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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PMC11278529_p32
|
PMC11278529
|
sec[2]/sec[4]/p[0]
|
3.5. Gravimetric Corrosion Testing—Immersion and Salt Spray Test
| 4.039063 |
biomedical
|
Study
|
[
0.94384765625,
0.0008211135864257812,
0.055450439453125
] |
[
0.99951171875,
0.00039196014404296875,
0.0001837015151977539,
0.000043272972106933594
] |
The results of the gravimetric corrosion tests are listed in Table 4 , including the p-value of the t-test. Significant changes are marked with an *. Both tests demonstrate corrosion rates of the same order of magnitude. In both tests, the specimens treated at 320 °C for 2 h and 650 °C for 2 h show no significant difference compared to the as-built specimen. The specimens treated at 800 °C for 2 h + 400 °C for 4 h exhibit an average reduction in corrosion rate of 21% in the salt spray test and 15% in the immersion test. However, a statistically significant difference is observed only in the immersion test. It should be noted that the values for the specimens treated at 800 °C for 2 h + 400 °C for 4 h in both the immersion test and salt spray test are close to the significance threshold. Therefore, within the current test setting, it cannot definitively be determined whether there is a minor difference in the corrosion rate or no difference at all.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278529_p33
|
PMC11278529
|
sec[3]/p[0]
|
4. Discussion
| 2.605469 |
biomedical
|
Study
|
[
0.53369140625,
0.00148773193359375,
0.464599609375
] |
[
0.98291015625,
0.016265869140625,
0.0005564689636230469,
0.00021457672119140625
] |
A significant influence of the heat treatments on the CuSn10 was found. Treatment at 320 °C for 2 h did not change the visual impression of the metallographically produced microstructure, but did lead to an increase in hardness. The clear difference between with and against the build-up direction in the micrograph is still clearly visible, which is why a reduction in anisotropy cannot be assumed.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278529_p34
|
PMC11278529
|
sec[3]/p[1]
|
4. Discussion
| 2.568359 |
biomedical
|
Study
|
[
0.748046875,
0.0013017654418945312,
0.25048828125
] |
[
0.90771484375,
0.0911865234375,
0.0007462501525878906,
0.0003902912139892578
] |
This change can be explained by a phase transformation in which the β’ phase in the microstructure of α, β’, and δ transforms into δ. The δ phase is significantly more brittle . In addition, the specimen required a significantly longer exposure time to the etchant compared to the untreated specimen.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278529_p35
|
PMC11278529
|
sec[3]/p[2]
|
4. Discussion
| 3.878906 |
biomedical
|
Study
|
[
0.9091796875,
0.0006914138793945312,
0.09033203125
] |
[
0.9970703125,
0.002323150634765625,
0.0003254413604736328,
0.00006902217864990234
] |
The heat treatment at 650 °C for 2 h caused a significant change in the microstructure. From the originally fine, process-typical microstructure with visible melting traces, uniform grains formed, indicating significant grain growth. A preferred direction was no longer discernible, suggesting the reduction in anisotropy. The hardness of the specimen decreased, indicating a transformation in the δ-phase into the α-phase, a process that was documented several times in the literature .
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278529_p36
|
PMC11278529
|
sec[3]/p[3]
|
4. Discussion
| 2.972656 |
biomedical
|
Study
|
[
0.7451171875,
0.0011539459228515625,
0.253662109375
] |
[
0.9638671875,
0.03558349609375,
0.00045418739318847656,
0.0002765655517578125
] |
In the treatment at 800 °C for 2 h followed by 400 °C for 4 h, precipitations with increased tin content formed at the grain boundaries, leading to a slightly increased hardness level. Such precipitations are known from casting and often consist of α- and δ-phases . Additionally, no anisotropy was recognisable and further grain growth occurred.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278529_p37
|
PMC11278529
|
sec[3]/p[4]
|
4. Discussion
| 3.171875 |
other
|
Study
|
[
0.48193359375,
0.0010318756103515625,
0.51708984375
] |
[
0.9931640625,
0.00626373291015625,
0.000652313232421875,
0.00014722347259521484
] |
The conducted investigations to assess corrosion behaviour are only partially comparable, as different salt concentrations and exposure conditions as well as accelerated and unaccelerated methods were used. Nevertheless, all results—as shown in Figure 14 —fall within the same corrosion protection category (Level 2; material loss 0.1 to 0.5 mm/year) for the classification of copper materials according to the German Copper Institute (DKI). The DKI classifications for copper materials were chosen because they are more detailed than the more well-known DECHEMA table for corrosion progress. According to DECHEMA, the tested material would fall into class + (material loss 0.1 to 1 mm/year) . This indicates that the heat treatments and the differences in the tested environmental conditions only result in differences that are technically insignificant.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278529_p38
|
PMC11278529
|
sec[3]/p[5]
|
4. Discussion
| 4.074219 |
biomedical
|
Study
|
[
0.98388671875,
0.0005335807800292969,
0.01551055908203125
] |
[
0.99951171875,
0.0003094673156738281,
0.0001685619354248047,
0.00004178285598754883
] |
Information on the passivation process is provided by comparing the LSV measurement after 900 s with the LSV measurement after 60 h. The OCP after 60 h is −0.180 V instead of −0.245 V as observed after the 900 s measurement. This increase can be explained by the formation of a passivation layer and its protective effect. Although it was not possible to determine the corrosion parameters on the passivated layer, the comparison with the LSV measurements at 900 s OCP in Figure 15 shows their influence. The corrosion currents are generally lower, indicating a reduced corrosion rate, and the repeatability is significantly reduced, suggesting an uneven formation of the passivation layer.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278529_p39
|
PMC11278529
|
sec[3]/p[6]
|
4. Discussion
| 2.585938 |
biomedical
|
Study
|
[
0.84130859375,
0.0014476776123046875,
0.1571044921875
] |
[
0.9921875,
0.007152557373046875,
0.00039458274841308594,
0.00019681453704833984
] |
The measurements indicated that heat treatments at 320 °C for 2 h and 650 °C for 2 h have no impact on the corrosion rate. All tests showed no difference compared to the as-built condition. Accordingly, the detected changes in microstructure have no effect on the corrosion resistance in a saline environment.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278529_p40
|
PMC11278529
|
sec[3]/p[7]
|
4. Discussion
| 4.09375 |
biomedical
|
Study
|
[
0.99267578125,
0.0004677772521972656,
0.006626129150390625
] |
[
0.99951171875,
0.000209808349609375,
0.000152587890625,
0.000035881996154785156
] |
Specimens treated at 800 °C for 2 h + 400 °C for 4 h displayed an anomaly during the 60 h OCP measurement. This suggests that the passivation process might differ. This is also supported by the chemical composition of the measurement surface, where only the specimens treated at 800 °C for 2 h + 400 °C for 4 h showed a higher chlorine content. Furthermore, these specimens exhibited a trend towards higher corrosion resistance in the gravimetric corrosion tests, although this was only significant in the immersion test. It should be noted that the specimen size used is only somewhat suitable for detecting such fine differences. Since differences between the specimens treated at 800 °C for 2 h + 400 °C for 4 h and the as-built condition appeared in several different tests, a slight difference can be expected, which is not technically relevant under the tested environmental conditions.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278529_p41
|
PMC11278529
|
sec[3]/p[8]
|
4. Discussion
| 3.357422 |
biomedical
|
Study
|
[
0.87548828125,
0.0011892318725585938,
0.12335205078125
] |
[
0.99609375,
0.0031375885009765625,
0.0005164146423339844,
0.00012385845184326172
] |
In combination with the microstructure analysis and the direction-dependent LSV measurement, it suggests that changes in phase composition, grain size, and orientation do not affect the corrosion behaviour under the tested conditions. Only the tin-containing precipitates seemed to influence the corrosion behaviour, although this influence is not technically significant. This behaviour cannot be easily generalised to other media, as indicated by observations during etching, where resistance to etching agents generally increased due to the heat treatments.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278529_p42
|
PMC11278529
|
sec[3]/p[9]
|
4. Discussion
| 4.019531 |
biomedical
|
Study
|
[
0.9599609375,
0.0004911422729492188,
0.03961181640625
] |
[
0.9990234375,
0.000591278076171875,
0.00017905235290527344,
0.00004214048385620117
] |
The influence of heat treatments on hardness as shown in could be reproduced in this study. Notably, in , after heat treatments at 800 °C for 2 h and 400 °C for 4 h, the microstructure of the specimen changed from a columnar grain to an equiaxed grain with numerous annealing twins. The same heat treatment in the present study led to significant precipitations at the grain boundaries. The reported tin contents of 11.01 wt.% in compared to 10.8 wt.% in the present study cannot account for the difference. One possibility for the discrepancies could be the allowable 0.5 wt.% of other elements from the supplier in the present study. Along with potential unreported additional elements in , this could result in a sufficient difference in the chemical composition of the materials.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278529_p43
|
PMC11278529
|
sec[3]/p[10]
|
4. Discussion
| 2.03125 |
biomedical
|
Study
|
[
0.759765625,
0.0014019012451171875,
0.239013671875
] |
[
0.499755859375,
0.493896484375,
0.005390167236328125,
0.0009045600891113281
] |
Comparisons between different corrosion behaviour studies are often difficult. This is because corrosion tests are often set up differently to reproduce various conditions, as many factors can influence corrosion behaviour. In addition, there is the influence of the different manufacturing parameters in the LPBF process, as well as variations between material batches and suppliers.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278529_p44
|
PMC11278529
|
sec[3]/p[11]
|
4. Discussion
| 4.148438 |
biomedical
|
Study
|
[
0.99560546875,
0.0003859996795654297,
0.003864288330078125
] |
[
0.99951171875,
0.0001811981201171875,
0.00018334388732910156,
0.000033974647521972656
] |
In , the corrosion behaviour was investigated using LSV measurements on five specimens. A standard three-electrode system was employed, utilising a GAMRY Interface 1000 (UK) potentiated in a 3.5 wt.% NaCl solution. A Saturated Calomel Electrode (SCE) served as the reference electrode, while a graphite electrode was used as the counter electrode. Similarly, the corrosion behaviour in the as-built condition was investigated in using a comparable setup, within a measurement potential range from −0.25 to 1.5 VSCE and a scan rate of 0.5 mV/s, also in a 3.5% NaCl solution. In , the corrosion behaviour of LPBF-manufactured CuSn10 was examined both in the as-built condition and after heat treatments at 600 °C for 1 h and 800 °C for 1 h. In each condition, three specimens with polished surfaces were tested. During the LSV investigations, the open circuit potential was recorded for 60 h, followed by an LSV measurement in the potential range from -1.5 to 0 VSCE with a scan rate of 1.67 mV/s. A standard three electrode corrosion cell was used for the tests, featuring a saturated calomel electrode (SCE) as the reference electrode, a platinum counter electrode, and a CHI-604C corrosion tester (CH Instruments, Inc., Bee Cave, TX, USA).
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278529_p45
|
PMC11278529
|
sec[3]/p[12]
|
4. Discussion
| 2.054688 |
biomedical
|
Study
|
[
0.87060546875,
0.0011663436889648438,
0.1282958984375
] |
[
0.95068359375,
0.046112060546875,
0.0024662017822265625,
0.0005135536193847656
] |
For a comprehensive between-study assessment, I corr and E corr are plotted and compared in Figure 16 , as not all studies determined a corrosion rate.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278529_p46
|
PMC11278529
|
sec[3]/p[13]
|
4. Discussion
| 4.164063 |
biomedical
|
Study
|
[
0.9892578125,
0.0004456043243408203,
0.01025390625
] |
[
0.99951171875,
0.00020694732666015625,
0.0002720355987548828,
0.000035762786865234375
] |
E corr and I corr from are comparable with the values of the present study, which is also reflected in the comparable corrosion rate of 0.111 mm/year (indicated in the paper: 4.388 mpy). The results from show substantially differing values. In the as-built condition, a considerably higher I corr and a markedly lower E corr were measured compared to both and the present study. Furthermore, demonstrated a significant change in corrosion behaviour due to thermal post treatment, which could not be replicated here, neither with 900 s of OCP measurements nor, as in , with 60 h of OCP measurements. The experimental setups are comparable; however, there are notable differences in the scan rate (1.67 mV/s in versus 0.5 mV/s in this study) and the measurement range (−1.5 to 0 VSCE in versus −0.5 to 1.5 VSCE in this study). When comparing the 60 h OCP measurements between and the present study, it is apparent that significant differences already emerge, which can only be attributed to the test material itself. The as-built material investigated in behaves similarly to all the specimens measured here, whereas the heat-treated specimens in start the measurement with a slightly higher OCP and reach a stable potential after approximately 8 h (instead of 30 h). This suggests a difference in the test material, such as varying chemical composition or influences from the LPBF manufacturing process. Although this does not exclude the impact of the LSV measurement settings, it indicates that the material itself differs.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278529_p47
|
PMC11278529
|
sec[3]/p[14]
|
4. Discussion
| 4.140625 |
biomedical
|
Study
|
[
0.99755859375,
0.0002942085266113281,
0.0022792816162109375
] |
[
0.99951171875,
0.0001537799835205078,
0.00020778179168701172,
0.000032067298889160156
] |
In , alongside electrochemical measurements, a gravimetric method was also used to investigate corrosion. For this purpose, three specimens were weighed and immersed in a 3.5 wt.% NaCl solution for 24 h. After drying and cleaning, they were weighed again. This process was repeated a total of eleven times. The individual data points were approximated using a linear function and used to determine the corrosion rate in terms of mass per unit area per unit time. Using a density of 8.74 g/cm 3 , the following corrosion rates can be calculated: 0.256 mm/year ( R 2 = 0.98) (indicated in the paper: 0.612 mg/cm 2 ·day) for the as-built state, and for the treatments at 600 °C and 800 °C, corrosion rates of 0.196 mm/year ( R 2 = 0.96) (indicated in the paper: 0.469 mg/cm 2 ·day) and 0.195 mm/year ( R 2 = 0.96) (indicated in the paper: 0.469 mg/cm 2 ·day), respectively. Similarly to the electrical chemical tests in , the corrosion resistance improved with heat treatments, which could not be reproduced in the present study. Given the limited influence of the experimental setup, the difference between and the present study can be attributed to the tested material. Generally, the corrosion rates calculated in fall within the same corrosion class (corrosion rate: 0.1 to 0.5 mm/year) as all other measurements investigated.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278529_p48
|
PMC11278529
|
sec[4]/p[0]
|
5. Conclusions
| 2 |
biomedical
|
Other
|
[
0.982421875,
0.0035076141357421875,
0.014312744140625
] |
[
0.2034912109375,
0.7890625,
0.004100799560546875,
0.0032825469970703125
] |
Corrosion investigation in saline solution
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
it
| 0.714283 |
PMC11278529_p49
|
PMC11278529
|
sec[4]/p[1]
|
5. Conclusions
| 1.617188 |
biomedical
|
Other
|
[
0.80126953125,
0.0027618408203125,
0.1961669921875
] |
[
0.05499267578125,
0.9423828125,
0.0019817352294921875,
0.0007181167602539062
] |
Microstructure and hardness:
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278529_p50
|
PMC11278529
|
sec[4]/p[2]
|
5. Conclusions
| 2.128906 |
other
|
Study
|
[
0.341552734375,
0.0012807846069335938,
0.6572265625
] |
[
0.94580078125,
0.052581787109375,
0.0010461807250976562,
0.00039577484130859375
] |
In the extensive corrosion investigations conducted in this study, no impact of heat treatments on corrosion behaviour was detected. However, since such influences were demonstrated in other studies, future research should aim to identify the causes of these differences in the material. It is important to determine whether these differences are due to the chemical composition or to the effects of additive manufacturing, which may occur only with certain combinations of manufacturing parameters.
|
[
"Robert Kremer",
"Johannes Etzkorn",
"Somayeh Khani",
"Tamara Appel",
"Johannes Buhl",
"Heinz Palkowski"
] |
https://doi.org/10.3390/ma17143525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057671_p0
|
39057671
|
sec[0]/p[0]
|
1. Pancreatic Cancer
| 4.363281 |
biomedical
|
Study
|
[
0.99853515625,
0.0006232261657714844,
0.0008602142333984375
] |
[
0.490966796875,
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The pancreas, a retroperitoneal organ, is composed of exocrine and endocrine cells . Around 80% of the tissue mass forms the exocrine pancreas. It comprises acinar and duct cells. Centro acinar cells are located near the ducts in the acinar cells. The acinar cells are responsible for synthesizing and secreting zymogens into the ductal lumen . They assist in the production of isotonic, alkaline pancreatic juice (pH 8), consisting of enzymes such as amylase and trypsin , which is essential for food digestion . It plays a crucial role in regulating protein, carbohydrate digestion, and glucose homeostasis. On the other hand, the endocrine pancreas contributes to hormonal secretion, thus regulating glucose homeostasis and glandular secretions . Islets of Langerhans have alpha, beta, delta, epsilon, and upsilon cells . They are involved in several hormonal products like glucagon, somatostatin, proinsulin, insulin, amylin, pancreatic polypeptide (PP), and C-peptide, and perform endocrine functions .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057671_p1
|
39057671
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sec[0]/p[1]
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1. Pancreatic Cancer
| 4.328125 |
biomedical
|
Review
|
[
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Pancreatic cancer (PC) is an aggressive disease, accounting for 7% of deaths in cancer patients , and is the third leading cause of cancer-related death in males and females and is projected to become the second by 2030 . In 2020, 466,003 (4.7%) cases were diagnosed with PC . In 2022, the number of cases with PC-associated mortality within North America in both genders was found to be 56,044, as shown in Figure 1 . An estimated number of 64,050 new cases and 50,550 deaths were associated with pancreatic cancer in 2023 . Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer (PC), as it represents around 90% of the cases . With no induced changes in hormonal secretion, it originates from exocrine tissue . Primarily, PC does not give rise to obstructive symptoms or pain because of the large surrounding pancreatic space. This can be one of the explanations for why PC is diagnosed at late, inoperable, and incurable stages . At present, there is no best way to screen PC at an earlier stage. Identification and systematic examination of individuals at risk of developing PC is the only diagnostic approach . PC is a malignant digestive tract tumor considered to have the worst prognosis, with rising morbidity and mortality rates . Identifying precursor lesions can help understand genomic characteristics associated with PC progression from earlier to advanced stages . Non-invasive, pancreatic intraepithelial neoplasia (PanIN) lesions can be classified into PanIN-1A, PanIN-1B, and PanIN-2, whereas PanIN-3 is an advanced lesion. These all have diverse cytology and architecture. PanIN1-A is a flat lesion with low-grade dysplasia, PanIN1-B is a micropapillary type of lesion with low-grade dysplasia, and PanIN-2 has a frequent papillary formation with cell enlargement and nuclear crowding, and is hyperchromatic with lack in polarity. PanIN-3 exhibits luminal necrosis and severe nuclear atypia . Low-grade lesions can be found in patients with chronic pancreatitis and observed with low risk of PC . High-grade PanIN-3 lesions are observed with a high risk of PC and are found in patients with invasive PDAC . Around 60% of PCs are prevalent in the pancreatic head, which is near various bile tracts . Maintaining the idea that bile acids (BAs) play an important role in PC development , we performed a thorough literature search to bring forth this review describing the contribution of BAs in PC.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p2
|
39057671
|
sec[0]/p[2]
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1. Pancreatic Cancer
| 4.308594 |
biomedical
|
Review
|
[
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[
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Several studies have reported that the development and progression of PC is associated with numerous risk factors. Some of these risk factors are obesity, alcohol consumption, radiation, dietary factors, race, gender, smoking, blood group, occupational hazards, age, genetic aberrations, family history/ hereditary pancreatitis, ethnicity, chronic pancreatitis , Peutz–Jeghers syndrome, gall stones , hormonal abnormality, allergy, and diabetes mellitus . Risk factors like diet, smoking, and alcohol consumption can be controlled and are called modifiable, whereas, age, blood group, gender, genetic aberrations, and family history/ hereditary pancreatitis are a few examples of non-modifiable risk factors . Acute pancreatitis (AP) is considered to be an early symptom of PC . Based on studies, a survival rate of 20% in patients diagnosed with PC, compared to 28% in patients diagnosed with PC and AP (both), has been recorded over one year . Dietary fat can induce BA secretion into the duodenum and elevate the fecal BA concentration . Absorption of dietary fat, fat-soluble vitamins, and regulation of cholesterol metabolism can be affected by BAs . Proper functioning of intestinal tight junctions and trans-epithelial permeability is regulated by normal intestinal flora by redistributing Toll-like receptor 2 protein (TLR-2) . BAs can alter intestinal flora due to a high-fat diet leading to mucosal permeability . High permeability leads BAs into blood circulation, allowing the translocation of gut microbes and associated products into the bloodstream, followed by chronic local and systemic inflammation . High anti-oxidants in fruits and vegetables can help reduce inflammation and oxidative stress caused by various PC-associated risk factors .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057671_p3
|
39057671
|
sec[0]/p[3]
|
1. Pancreatic Cancer
| 4.410156 |
biomedical
|
Study
|
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Tobacco smoking is one of the many important causes that favor PC development . According to Talimini et al. , the smoker population is presented with a severe risk of developing PC when compared with non-smokers . Hermann et al. revealed the effects of nicotine on PC development in a mouse model with active forms of Kirsten rat sarcoma virus gene (KRAS) expression. In their study, nicotine-activated AKT-ERK-MYC signaling led to dedifferentiation, loss of differentiation in acinar cells, enhanced aggressiveness in cancer cells and increased numbers of circulating cancer cells, hyperactivation of oncogenic KRAS, and inhibition of Gata6 promoter activity accompanied by loss of GATA6 protein, altered gene expression and functional characteristics . Protein kinase B (PKB), also known as Akt, is a group of three serine/threonine-specific protein kinases. It plays a crucial role in various cellular processes such as cell migration, regulation of gene expression, cell survival, and cell proliferation. Another important protein, extracellular signal-regulated kinase (ERK), belongs to the mitogen-activated protein kinase family and is involved in controlling blood vessel constriction and the growth of vascular smooth muscle cells. Additionally, the MYC proto-oncogene is a critical molecular factor in both the initiation and perpetuation of tumorigenesis.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057671_p4
|
39057671
|
sec[0]/p[4]
|
1. Pancreatic Cancer
| 4.363281 |
biomedical
|
Study
|
[
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[
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Some PC-associated mutations stimulated by nicotine include those of KRAS, p53, COX-2, p16INK4A (also known as P16 and MTS1), and SMAD4 . Alcohol consumption can stimulate blood and intestinal BA levels by two pathways : first by increasing cholesterol 7α-hydroxylase synthesis , and second, by reducing feedback inhibition of BA synthesis by interrupting the enterohepatic circulation of BAs . Different research models have been developed by researchers to explore various aspects of PC. For example, morphological and genetic observation, when combined, can serve as a progression model for PC . Depending on the cancer history of an individual’s family, risk prediction statistical models such as PancPRO (a statistical model) can help understand the risk related to PC development . Based on various heritability studies, >20% of PC cases are due to variations in inherited sequences . According to the International Agency for Research on Cancer (IARC), in 2022, the highest PC-associated mortality and incidence rates in both genders were found in Asia, followed by Europe, North America, Latin America, the Caribbean, Africa, and Oceania, as shown in Figure 2 . Among white and Asian populations, KRAS is the most frequently mutated gene, followed by TP53, whereas in Black or African American populations, TP53 is the most mutated gene, followed by KRAS . In addition to KRAS and TP53, several other genes are mutated in PC. We have attempted to explore the interactions between these genes using various exploratory tools . The development of PC can be affected by inflammation of the Islets of Langerhans, products of activated macrophages, neutrophil granulocytes, diabetes, reactive oxygen species (ROS), insulin resistance, and growth promotion .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057671_p5
|
39057671
|
sec[1]/p[0]
|
2. Genetic Alterations in PC
| 4.859375 |
biomedical
|
Study
|
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A frequently occurring form of PC is PDAC . Generally, a nonmalignant fibrotic pancreatic tissue revealing atrophy and dilated ducts surrounds PDAC . Some PDACs present as firm white-yellowish masses of the pancreatic head with poor demarcation . Overall, the 5-year survival rate of PC patients is reported as very poor, i.e., ~11.5% . KRAS, a proto-oncogene, is involved in the proliferation, differentiation, metabolism, and survival of cancer cells. From 90% to 95% of PC cases are seen with KRAS mutation . Mutations in the KRAS gene can occur when a single nucleotide base is changed, inserted, or deleted in the DNA or RNA sequence of an organism. These mutations often happen at codon 12 (G12), codon 13 (G13), or codon 61 (Q61). The most common mutation, G12D, is present in 40% of pancreatic cancer patients. This mutation results in a GAT sequence replacing the normal GGT sequence, leading to the production of aspartic acid instead of glycine. Other prevalent mutations include G12V, which produces valine, and G12R, which produces arginine. The inactivation of tumor-suppressing genes such as SMAD4, P53, P16, and PTEN promotes the initiation and development of PC . Some genes are frequently mutated, whereas some are rare. Mutations of a proto-oncogene (KRAS) and tumor suppressors (TP53, SMAD4) are frequent in PC and associated with cell cycle dysregulation . Mutations of tumor suppressors like BRCA and mismatch-repairing genes, such as LKB1/STK11, AKT (AKT2), or Protein kinase B (PKB) (serine-threonine kinases), are rare genetic events .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 1 |
39057671_p6
|
39057671
|
sec[1]/p[1]
|
2. Genetic Alterations in PC
| 4.226563 |
biomedical
|
Study
|
[
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Based on genomic analysis, KRAS, CHEK2, BARD1, BRCA1, and BRCA2 , the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 , and CDKN2A, NBN, SMAD4, ATM , PALB2 STK11 , TP53, and MUTYH/MYH are some of the genes associated with PC. Among these, TP53, KRAS, SMAD4, and CDKN2A are four major driver genes of PC . SWI/SNF complexes are PDAC epigenetic drivers with multi-subunit complexes . They are involved in chromatin remodeling, DNA repair, and regulation of transcription . Genes like ARID1B, ARID2, PBRM1, SMARCA2, and SMARCA4 (also called transcriptional activator BRG1) are associated with the encoding of multi-component SWI/SNF complexes. As reported by various studies, these encoding genes are mutated in human PDAC . Interactions between some of the commonly occurring mutated genes are shown in Figure 3 , and functions of these genes in a non-mutated (healthy) form are shown in Table 1 of this paper.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
39057671_p7
|
39057671
|
sec[1]/p[2]
|
2. Genetic Alterations in PC
| 4.71875 |
biomedical
|
Study
|
[
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Dysregulation in signaling pathways, oncogenes, and tumor suppressor genes contributes to the malignancy of PC . In PC, high incidences of RAS mutations are identified . In a study conducted by Jones et al. , ~63 genetic alterations were found in PC. These alterations were associated with 12 pathways and processes such as DNA damage control, wingless-type MMTV integration site family (Wnt), neurogenic locus notch homolog protein (Notch), apoptosis, KRAS, small GTPase signaling, integrin, hedgehog, invasion, homophilic cell adhesion, Jun N-terminal kinase (JNK), control of G1/S phase transition, and transforming growth factor-β (TGF-β) . KRAS and Wnt have an important role in cell proliferation and transcription, TP53 contributes to apoptosis, and SMAD, P16, and CDKN2A are regulators of the cell cycle . Mutation of KRAS, neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), and Harvey rat sarcoma viral oncogene homolog (HRAS) are located in codon 12, with a frequency of 20 to 100% in tumor progression . Polyphenic effects including cell proliferation, migration, and survival are promoted by small GTP-binding cytoplasmic proteins encoded by RAS family proteins . Based on studies, KRAS-mutated PC cell lines such as MiaPaca and Capan1 are often identified with loss of the wildtype KRAS allele . In cancer cell lines like Panc1 and SU8686, mutated alleles, when compared with wild-type alleles, are presented with suppressed expression . With the loss of the wildtype allele and late occurrence, a missense mutation in sequence coding of TP53 is reported in over 50% of cases diagnosed with PC . Heavily glycosylated proteins known as mucins (MUC) possess the ability to build selective molecular barriers at the epithelial surface and are crucial for regulating morphogenesis. These proteins contribute to cellular growth, adhesion, differentiation, immunity, transformation, and invasion . Twenty-one mucin genes are found in humans and used as potential diagnostic tools for PC. In PC, MUC4, 5AC, and 1 are revealed to be highly expressed and associated with poor outcomes. These genes can serve as promising biomarkers for PC progression . BAs can induce changes in the expression of mucins and play an important role in cancer progression . As reported by studies, MUC4 undergoes overexpression in the presence of BAs and enhances the carcinogenic potential of PDAC cells .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057671_p8
|
39057671
|
sec[1]/p[3]
|
2. Genetic Alterations in PC
| 4.347656 |
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BAs can act on different types of pancreatic cells, for example, duct cells, and can alter ductal secretion by inducing pathological Ca 2+ signals . A large Ca 2+ signal aberration in pancreatic acinar cells is found to be caused by BAs like taurolithocholic acid 3-sulfate (TLC-S). This allows depletion of intracellular Ca 2+ stores as well as enhanced entry of Ca 2+ . In acinar cells, an increase in Ca 2+ is associated with cell necrosis and vacuolization, as well as untimely intracellular enzyme activation . BAs can act as pathological agents, and their signaling can affect various pathological conditions . They can give rise to mitochondrial dysfunction, abnormal activation of intra-cellular trypsin, cytoskeletal damage, activation of nuclear factor- kappa B, acute pancreatitis, cell injury, and cell necrosis .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057671_p9
|
39057671
|
sec[1]/p[4]
|
2. Genetic Alterations in PC
| 4.363281 |
biomedical
|
Study
|
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The pancreas has both exocrine and endocrine functions . Acute pancreatitis (AP) is associated with the development of PC . Pancreatic stellate cells (PSCs) not only interact with cancer cells but are also related to pancreatic fibrosis . According to Xu et al. , PSCs can promote cancer metastasis . The stromal reaction produced by PSCs can enhance the development and progression of PC . As reported by Pries et al. , taurocholate is a suppressor of BA production and is more potent than cholate . In a study by Ferdek et al. , cholate and taurocholate were shown to be inducers of necrosis and Ca 2+ signaling in stellate cells. Acinar cells are reported to be affected by taurolithocholic acid 3-sulfate. Extracellular Ca 2+ is one of the core requirements to mediate Ca 2+ signals and necrosis . Bradykinin-induced signals in stellate cells can promote pancreatic damage mediated by BAs and have crucial involvement in acute biliary pancreatitis . Platelet endothelial cell adhesion molecule-1 (PECAM-1), also known as cluster of differentiation (CD31), is important for cellular immunity, cell proliferation, migration, and apoptosis . In a current study, staining of endothelial cell marker CD31 revealed an increase in endothelial cell number and confirmed the presence of CD31 in the peritumoral stroma of PC .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p10
|
39057671
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sec[2]/p[0]
|
3. What Are Bile Acids?
| 4.523438 |
biomedical
|
Study
|
[
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Bile is a yellow-greenish fluid, synthesized in liver hepatocytes, carried to the duodenum via bile ducts, and helps in lipid metabolism . Its constituents are bile acids , cholesterol, amino acids, vitamins, lecithin, toxins, bilirubin, and heavy metals . BAs conjugated with glycine or taurine are involved in the synthesis of bile salts. Thus, BAs are building blocks of bile salts. These are saturated, hydroxylated C-24 cyclopentanophenanthrene sterols . These are synthesized from cholesterol in perivenous hepatocytes surrounding the central hepatic vein , and affiliated with cholesterol-derived sterols . They are crucial for dietary lipid solubilization and absorption of fat-soluble vitamins such as A, D, E, and K . BAs are natural products that can be isolated in pure form . Hydroxylation of the steroid ring and the presence of the carboxyl group side chain make BA polarity higher than that of cholesterol . Due to the amphipathic character of BAs, they are known as natural detergents . They are strong digestive surfactants that act as emulsifiers to promote lipid absorption .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p11
|
39057671
|
sec[2]/p[1]
|
3. What Are Bile Acids?
| 5.097656 |
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|
Study
|
[
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The main constituents of BAs are organic molecules (phospholipids, proteins, bile salts, cholesterol), water, and electrolytes . The release of stored bile from the gallbladder depends on bile flow in the duodenum . The hormone Cholecystokinin (CCK) regulates bile flow in the duodenum . Any type of blockage in the extrahepatic biliary system can result in biliary obstruction . Biliary obstruction is one of the core characteristics of PC . It can result not only in renal failure and hepatic dysfunction but also in infections, bleeding complications, and nutritional inadequacy . BAs are formed as an end-product of cholesterol catabolism . They act as nutrient signaling hormones by activating receptors such as nuclear receptors (pregnane X receptor, farnesoid X receptor) and G-protein coupled receptors (muscarinic receptors, sphingosine-1 phosphate receptor 2) to promote digestion, transportation, and metabolism of various nutrients . BAs are important for the absorption and excretion of cholesterol as well as the maintenance of plasma cholesterol levels . Farnesoid X receptor (FXR) serves as a critical nuclear receptor activated by bile acids (BAR) and is predominantly expressed in the liver and intestine. When FXR becomes active in the liver, it triggers the enhanced expression of specific target genes. These genes encompass ATP-binding cassette, sub-family B member 11 (ABCB11), which plays a key role in the bile salt export pump, and ATP-binding cassette, sub-family B member 4 (ABCB4), which serves as a phospholipid transporter. These transporters function to decrease the levels of bile salts and lipids within cells by accelerating their transport into the bile. FXR activation depends on the activation of the AKT signaling pathway . BAs act on the FXR target gene known as small heterodimeric partners (SHP) and possess the ability to deorphanize BAs associated with FXR . Activation of Protein kinase C, zeta (PKCζ) is reported as a helping act of taurocholic acid (TCA) towards activation of SHP . As discussed above, the synthesis of BAs takes place in the liver. Their metabolism involves hepatic endogenous and xenobiotic metabolism along with interaction with constitutive androstane receptor (CAR) and PXR . Their excretion involves multiple organs but at present, physiological regulation of BA metabolism is unknown . BAs can disrupt the mucosal barrier to diffusion and are considered as pro-carcinogenic molecules .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057671_p12
|
39057671
|
sec[2]/p[2]
|
3. What Are Bile Acids?
| 4.667969 |
biomedical
|
Study
|
[
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Bile is constituted by greater than 60% of glycine-conjugated BAs (pKa values of 4.3–5.2) and ~20% of taurine-conjugated BAs (pKa values of 1.8–1.9) . The ratio between both BAs is 3:1 . Taurine-conjugated BAs can act as carcinogens ; their properties such as solubility, frequent cell contact, and cross-talk upgrade their carcinogenicity . Non-conjugated BAs are more carcinogenic than conjugated BAs . Approximately 95% of BAs undergo intestinal (terminal ileal) active reabsorption and are carried to the liver . The level of BAs in plasma can be co-related with a fecal concentration of BAs . An enhanced level of BAs such as hydrophobic 12a-hydroxylated BAs and deoxycholic acid in type 2 diabetes have been reported in the literature . BAs act as ligands for various receptors like FXR , PXR, vitamin D receptor, and androstane receptor . For example: chenodeoxycholic acid (CDCA) acts as a potent agonist for FRX, whereas deoxycholic acids (DCA) and lithocholic acid (LCA) act with low affinity on the same receptor . Expression of FXR is majorly reported in reproductive tissues, liver, kidney, pancreas, reproductive tissues, and intestines .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057671_p13
|
39057671
|
sec[2]/p[3]
|
3. What Are Bile Acids?
| 4.789063 |
biomedical
|
Study
|
[
0.9990234375,
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Synthesis of BAs is a multistage process that includes a series of enzymatic reactions . Primary pathways for cholesterol catabolism are represented by BAs . In BA-associated synthetic pathways, immediate products are termed primary BAs such as chenodeoxycholic acid and cholic acid. Intestinal bacterial flora act on these primary BAs to form secondary BAs such as lithocholic acid and deoxycholic acids . Formation of primary BAs involves cholesterol 7α-hydroxylase (CYP7A1), a cytochrome P450 enzyme that promotes hydroxylation of cholesterol . CYP7A1 controls the conversion of cholesterol to BAs. Another pathway of BA formation is an “acidic or alternative” pathway controlled by CYP27A1. It mediates the conversion of oxysterols to BAs . CYP7A1 is regulated by BAs, whereas CYP27A1 is not. The conversion of BA intermediates into chenodeoxycholic acid or cholic acid is controlled by CYP8B1 . The overall hydrophobicity of the BA pool is determined by the ratio of cholic acid to chenodeoxycholic acid. CYP8B1-mediated hydroxylation assists in the formation of hydrophilic cholic acid molecules . There are 17 sets of enzymes in hepatocytes that are essential for the removal of side chains, steroid core modification, and formation of a conjugated form of taurine or glycine . Passive or carrier-mediated transport processes mediate the reabsorption of BAs into the intestinal proximal region , whereas apical sodium-dependent bile acid transporter (ASBT) supports the recovery of BAs in the distal ileum .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p14
|
39057671
|
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|
4. Contribution of Bile Acids in Pancreatic Cancer
| 3.902344 |
biomedical
|
Study
|
[
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[
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In 1940, BAs (deoxycholic acid, deoxycholate) were reported to induce cancer in rodents and were proposed as carcinogens . Rodents, when induced with BAs, presented with malignant spindle-celled tumors. Epidemiological studies confirmed an association between BAs and cancer . Both primary and secondary BAs are contributors to tumorigenesis, and the level of variations strictly depends on the cancer type .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
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|
39057671
|
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|
4. Contribution of Bile Acids in Pancreatic Cancer
| 4.097656 |
biomedical
|
Study
|
[
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The role of BAs in PC is not clear . An increase in BA level can elevate ROS production, oxidative stress, cell membrane damage, activation of downstream signaling (EGFR, NF-κB, PKC), and DNA mutations. This promotes aggressive neoplastic cell growth in organs such as the stomach, colon, and others . Enhanced levels of BAs can result in BA reflux in the pancreatic duct and can affect acinar cells, thus promoting pancreatic adenocarcinoma progression . Factors such as smoking, alcohol consumption, and high-fat diet possess the ability to elevate BA levels. BA-associated dysregulated metabolism can result in gallstone formation .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057671_p16
|
39057671
|
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|
4. Contribution of Bile Acids in Pancreatic Cancer
| 4.148438 |
biomedical
|
Study
|
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Secretion of BAs is strongly regulated by gastric acid. As reported by Adachi et al. , bile reflux into the pancreatic ducts can lead to accelerated kinetics of epithelial cells and promote the development of pancreatic intraductal papillary carcinoma (IPC) . Based on studies, BAs can induce pancreatic adenocarcinoma and mediate progression at multiple stages . Pancreatitis caused by restricted bile flow (which occurs in gallstone formation) is a risk factor for pancreatic adenocarcinoma . Pre-malignant pancreatic ductal cells, on treatment with BAs, can result in tumorigenesis .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
39057671_p17
|
39057671
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|
4. Contribution of Bile Acids in Pancreatic Cancer
| 4.367188 |
biomedical
|
Study
|
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BAs can increase the expression of COX-2 or mucins and can mediate the development of cancer . Higher levels of BAs such as unconjugated cholic acids were reported by Rees et al. in patients with adenocarcinoma of the pancreas. Such studies promote an understanding of cancer biology and the role of metabolites such as BAs in cancer cells . In a study conducted by Sarkar et al. , levels of sphingosine-1-phosphate receptor 2 (S1PR2) and PC progression were shown to be raised by conjugated bile acids (CBAs) . BAs in PC are associated with dysregulation of the cell cycle, cell membrane disruption, activation and expression of inflammatory mediators, and reduction of apoptosis . In multiple studies, the occurrence of PDAC has been reported majorly in pancreatic heads from ductal cells. With tumor progression, the flow of bile is hindered, leading to the development of obstructive jaundice. It elevates the serum level of BAs. Enhanced levels of BAs have carcinogenic potential and can result in gastrointestinal cancer .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057671_p18
|
39057671
|
sec[3]/p[4]
|
4. Contribution of Bile Acids in Pancreatic Cancer
| 4.277344 |
biomedical
|
Study
|
[
0.99951171875,
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[
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] |
In a study conducted by Gál et al. , BAs were able to induce MUC4 overexpression and promote carcinogenesis . They reported an elevated level of serum BAs such as taurochenodeoxycholic acid, glycochenodeoxycholic acid, glycocholic acid, and taurocholic acid in patients diagnosed with PDAC . Overexpression of MUC20 and 1 are associated with poor survival in PDAC patients . The presence of MUC5B, 13, and 5AC can be found in PDAC and pancreatic intraepithelial neoplasia, whereas they are absent in normal pancreas . Aberrant expression of MUC17 in PC is not uncommon . MUC4 is reported with aberrant expression in premalignant and malignant pancreatic lesions . It can act as an intramembrane ligand for v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2/Erb-B2/HER2/neu) and promote antiapoptotic function of MUC4 . It can alter the actin organization, enhance invasiveness, and inhibit integrin-mediated cell adhesion. Silencing of MUC4 can dysregulate genes associated with growth and metastasis: for example, plakoglobin, caspase 3, 2, and 7, thrombomodulin, neuregulin-2, Liver Intestine-cadherin (LI-cadherin), S100 calcium-binding protein A4 (S100A4), AnnexinA1 (ANXA1), Ras-related C3 botulinum toxin substrate 1 (RAC1), and carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) . The contribution of BAs in PC is explained in Figure 4 of this paper.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057671_p19
|
39057671
|
sec[3]/p[5]
|
4. Contribution of Bile Acids in Pancreatic Cancer
| 4.285156 |
biomedical
|
Study
|
[
0.99951171875,
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[
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0.00067901611328125,
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Iron is one of the many crucial trace elements in the body. BAs possess the ability to solubilize iron in the duodenum and promote its absorption . Bile salts have cholanic ring 7 alpha-OH and/or 12 alpha-OH groups that afford high affinity towards iron . In 2012, Dixon et al. first proposed iron-mediated cell death known as ferroptosis (FPT). It is a new mode of non-apoptotic cell death . In FPT, ROS such as peroxides (ROOH and H 2 O 2 ), superoxide (O 2 •), and free radicals (RO• and HO•) are generated enormously by Fenton reaction (Fe 2+ reacts with hydrogen peroxide) . Based on various studies, FPT has been identified in PC . Higher levels of iron may result in lipid peroxidation (LP) . LP is one of the characteristics of FPT . Hence, connecting these dots, there is a possibility that BAs are associated with FPT in PC and contribute to its growth.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057671_p20
|
39057671
|
sec[3]/p[6]
|
4. Contribution of Bile Acids in Pancreatic Cancer
| 4.292969 |
biomedical
|
Study
|
[
0.99951171875,
0.00015354156494140625,
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[
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Gastrointestinal microbial flora contains around 1014 bacteria and is associated with 99% of multi-functional genes . Microbial flora is associated with the size and composition of the BA pool, and the BA pool can affect the diversity of gut microbiota . The gut microbiome comprises various phyla and genera. Examples of phyla include Bacteroidetes , Firmicutes , Fusobacteria , Proteobacteria , Verrucomicrobia , and Actinobacteria . Examples of genera are Clostridium , Pepto streptococcus , Bacteroides , Lactobacillus , Bifidobacterium , Methanobrevibacter , Ruminococcus , Eubacterium , and Propionibacterium . Based on a study conducted by Nejman et al. , bacterial DNA is identified in more than 60% of PC. The sources of this DNA include Klebsiella pneumoniae , Fusobacterium nucleatum , Enterobacter asburiae , and Citrobacter freundii . Poly-β-1,6-N-acetyl-d-glucosamine (PNAG) is a bacterial surface polysaccharide and an essential component of biofilm . In K. pneumoniae , the formation of biofilm and production of PNAG are stimulated by bile salts .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p21
|
39057671
|
sec[3]/p[7]
|
4. Contribution of Bile Acids in Pancreatic Cancer
| 4.253906 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.99560546875,
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] |
The BA pool and microbial flora have been shown to work closely along with higher chances of contributing to PC growth and development. A total BA pool of around 1.5–4 g undergoes recycling 4–14 times every day with a recovery rate of 95% in enterohepatic circulation and a contribution of 5% to fecal loss . Microbiota plays an important role in the transformation of primary BA to secondary BA . Functional-centered changes in gut microbiota can negatively influence BA levels and are associated with the development of cancers such as PC . For example, infection by C. freundii can cause disbalance in intestinal microbiota, bile acid synthesis, and pathogenic bacterial colonization. This results in inflammation and the disruption of tissue structure .
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p22
|
39057671
|
sec[3]/p[8]
|
4. Contribution of Bile Acids in Pancreatic Cancer
| 4.523438 |
biomedical
|
Study
|
[
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[
0.5830078125,
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] |
Based on various studies, Glucagon-like peptide-1 (GLP-1) is vigorously secreted by BAs . GLP-1 is a long peptide hormone comprising 30–31 amino acids. Its effect is mediated by various GLP-1 receptors located in the pancreas . Studies have confirmed the involvement of GLP-1 in the proliferation of pancreatic β-cells . GLP-1 mimetics such as exenatide and liraglutide have been reported with pancreatitis as one of their side effects . The glucagon-like peptide-1 receptor (GLP-1R) is a G-protein-coupled receptor that is expressed particularly in pancreatic islet cells bound to the plasma membrane of pancreatic acinar cells . These are involved in the initiation and progression of cancer as well as associated oxidative stress and inflammation . Glucagon-like peptide-1 receptor agonists (GLP-1RAs) work by pancreatic GLP-1 receptor activation . Activation of GLP-1R directly contributes to cell proliferation and increases cell survival . GLP-1RAs are associated with the regulation of crucial molecular pathways . These are also involved in indirect cancer growth . An endocrine neoplasm of the pancreas is called insulinoma . Studies have revealed an immense expression of GLP-1R with an incidence rate of >90% on benign insulinoma cell surfaces . A high risk of pancreatitis and PC is associated with GLP-1RAs . In this aspect, BAs and GLP-1 are associated with PC growth and development. However, there is a need for detailed research aimed at shedding light on the contribution of BAs to the development of PC due to their interaction and involvement with GLP1.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p23
|
39057671
|
sec[4]/p[0]
|
5. Conclusions and Future Direction
| 4.023438 |
biomedical
|
Review
|
[
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Pancreatic cancer is often diagnosed at an advanced stage, making early detection uncommon. There is ongoing debate about whether elevated bile acids are harmful or beneficial for pancreatic cancer. However, bile acids are closely linked to the development of pancreatic cancer. They are associated with many risk factors for pancreatic cancer, including alcohol consumption, smoking, high-fat diet/obesity, gallstones, pancreatitis, diabetes, and hypertriglyceridemia. Aside from their systemic effects, bile acids also have local tissue effects and can directly activate cancer signaling pathways. In the future, bile acids are likely to be recognized as signaling molecules in pancreatic cancer. Understanding how bile acids promote the progression of pancreatic cancer can aid in the development of new therapeutic targets and effective strategies for diagnosis and treatment.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p24
|
39057671
|
sec[4]/p[1]
|
5. Conclusions and Future Direction
| 3.9375 |
biomedical
|
Review
|
[
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Multiple studies have suggested that bile acids may act as cancer promoters in pancreatic cancer. For instance, pancreatic ductal adenocarcinoma (PDAC) is often associated with elevated levels of bile acids in the bloodstream. However, the impact of bile acids on the progression of pancreatic cancer has not been comprehensively assessed. Many questions remain unanswered, and further research, including oncological and physiological experiments, is necessary to confirm the role of bile acids in the development of pancreatic cancer. Detailed research studies are increasingly important to improve our understanding of pancreatic cancer’s biology, with the role of metabolites such as bile acids being crucial.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057671_p25
|
39057671
|
sec[4]/p[2]
|
5. Conclusions and Future Direction
| 4 |
biomedical
|
Review
|
[
0.99853515625,
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[
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Bile acids have the potential to induce changes in various cellular proteins, receptors, signaling pathways, and molecules. Moreover, they can affect normal calcium and iron levels in the body. However, research on the role of bile acids in iron metabolism or ferritin processing is limited and requires scientific investigation. Additionally, the relationship between Glucagon-like peptide-1 and its receptors must be explored to understand its contribution to pancreatic cancer. The connection between bile acids, microbiomes, and pancreatic cancer is an area that requires in-depth research. The specific connections between pancreatic cancer and bile acids in cancer cell biology have not been fully explored. Therefore, both laboratory research and clinical studies in this area are important. The results of clinical trials can complement and validate laboratory findings, ultimately benefiting patients with pancreatic cancer.
|
[
"Bharti Sharma",
"Kate Twelker",
"Cecilia Nguyen",
"Scott Ellis",
"Navin D. Bhatia",
"Zachary Kuschner",
"Andrew Agriantonis",
"George Agriantonis",
"Monique Arnold",
"Jasmine Dave",
"Juan Mestre",
"Zahra Shafaee",
"Shalini Arora",
"Hima Ghanta",
"Jennifer Whittington"
] |
https://doi.org/10.3390/metabo14070348
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278557_p0
|
PMC11278557
|
sec[0]/p[0]
|
1. Introduction
| 4.078125 |
biomedical
|
Study
|
[
0.998046875,
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Salmo trutta fario Linnaeus belongs to Salmonidae , Salmoninae , Salmo . It is native to Europe, northern Africa, and western Asia and was introduced into the Yadong area of Tibet in the late 19th century. Following long-term adaptation, Salmo trutta fario Linnaeus has successfully reproduced and thrived in its natural environment, maintaining a stable population. This species holds significant economic value in Tibet and is classified as a second-class protected animal in the Tibet Autonomous Region . In recent years, the widespread adoption of standardized intensive breeding practices has led to the extensive use of antibiotics for disease prevention and treatment. However, this has resulted in significant antibiotic residues and the proliferation of antibiotic-resistant bacteria, posing challenges for effectively managing diseases in breeding production. As a result, the intestinal flora of fish is disrupted and their immune system is compromised. Additionally, the presence of residual antibiotics in aquatic products may constitute a potential risk to human health . To address the challenges related to aquaculture diseases and food safety, and to ensure the sustainable and healthy development of aquaculture, there is a growing focus on researching environmentally friendly, safe, and effective alternatives to antibiotics.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p1
|
PMC11278557
|
sec[0]/p[1]
|
1. Introduction
| 4.140625 |
biomedical
|
Review
|
[
0.998046875,
0.0007185935974121094,
0.0013189315795898438
] |
[
0.2196044921875,
0.0015630722045898438,
0.7783203125,
0.00042629241943359375
] |
The word probiotics, which is derived from the Greek word “pro bios” that means “for life” , refers to a group of organisms that are a normal part of the intestinal tract and can create compounds with positive effects. Probiotics, as microbial feed additives, confer health benefits to the host by modulating intestinal microbiota. They are frequently used in aquaculture because of their capacity to synthesize a variety of extracellular enzymes that have a positive impact on host immunology, growth performance, and feed conversion . Additionally, many probiotics provide vitamins, fatty acids, and essential amino acids to the host . Several studies have shown that probiotics, alone or in combination, can enhance local or systemic immunity in fish . Microorganisms commonly used as probiotics in aquaculture include yeast, bacteria, and algae . Kosaza evaluated whether boosting the diet with Bacillus toyoda could accelerate the growth rate of yellowtail for the first time in aquaculture . The findings of Vazirzadeh et al. demonstrated that the addition of Saccharomyces cerevisiae to the feed of rainbow trout improved immunity and FCR, providing a significant positive effect on immunomodulation, as well as resistance to pathogenic bacterial infections . These findings suggest that probiotics are promising natural products for increasing the sustainability and efficiency of aquaculture.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278557_p2
|
PMC11278557
|
sec[0]/p[2]
|
1. Introduction
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.00028967857360839844,
0.00027251243591308594
] |
[
0.99951171875,
0.00015985965728759766,
0.0004868507385253906,
0.00006681680679321289
] |
Therefore, this study employed metagenomics to investigate the impact of different probiotics ( Saccharomyces cerevisiae (SC), Bacillus licheniformis (BL), and lactic acid bacteria (LAB)) on the functional diversity of intestinal flora. Concurrently, non-targeted metabolomics was utilized to analyze changes in intestinal microbial metabolites following the addition of these probiotics, enhancing our understanding of previously unknown microbial metabolites. Ultimately, through integrated multi-omics analysis, this study offers new insights into the role of different probiotics in aquaculture and sheds light on the mechanisms by which probiotics promote the growth, development, and disease resistance of Salvelinus asiaticus.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278557_p3
|
PMC11278557
|
sec[1]/sec[0]/sec[0]/p[0]
|
S. trutta and Trial Design
| 4.140625 |
biomedical
|
Study
|
[
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0.0015125274658203125
] |
[
0.99951171875,
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] |
S. trutta were sourced from the Yarlung Zangbo River Fishery Resources Breeding Base in Lhasa, Tibet Autonomous Region. Prior to experimental feeding, 360 healthy S. trutta with an average weight of 84.57 ± 1.83 g were selected and raised in a cement pond (10 m × 2.0 m × 1.2 m) for 10 days. Proprietary feed formulations were selected ( Tables S1 and S2 ). Then, after 24 h of starvation, the salmon were randomly assigned to 12 cages (2.0 m × 1.0 m × 1.2 m), the water level was controlled by 0.6 m, and 30 S. trutta were divided into four groups and placed into each cage, with three replicates in each group. The control group was fed basic feed, and SC, BL, and LAB probiotics were added to the treatment group. Probiotics were purchased from Cangzhou Yihong Biotechnology Co., Ltd., Cangzhou, China, and the effective viable count was 1.0 × 10 7 CFU/g. The feed after adding probiotics was stored in a refrigerator at 4 °C. Feeding twice daily, with each feeding comprising 3% of their body weight, was implemented. The water temperature was maintained at 10~12 °C, and dissolved oxygen of 6.2~7.3 mg/L. The main components of LAB were Lactobacillus acidophilus and Lactobacillus plantarum . An experimental feeding trial was carried out over a 3-month period. In addition, the unfed residual bait was collected in time after feeding every day, and the actual feed intake was calculated according to the initial feeding amount after drying.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278557_p4
|
PMC11278557
|
sec[1]/sec[1]/p[0]
|
2.2. Feed and Sample Collection
| 3.994141 |
biomedical
|
Study
|
[
0.99951171875,
0.00034046173095703125,
0.0003333091735839844
] |
[
0.9990234375,
0.000759124755859375,
0.00018799304962158203,
0.0000845789909362793
] |
At the end of animal study, after 24 h of fasting, all S. trutta were euthanized by administered intramuscularly with Tricaine methanesulfonate (MS-222) (MCE Co., Ltd., Malta, NJ, USA) at a concentration of 130 mg/L. Five tails were randomly selected in each cage, and 50 mg of intestinal contents were sampled from the same region of the distal intestine. Samples were immediately frozen on dry ice and subsequently transferred to a −80 °C freezer within hours. Each sample was kept on dry ice during transportation.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p5
|
PMC11278557
|
sec[1]/sec[2]/p[0]
|
2.3. Growth Performance Analysis
| 4.054688 |
biomedical
|
Study
|
[
0.99951171875,
0.0002536773681640625,
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[
0.99951171875,
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0.00005918741226196289
] |
The initial weight, length, fatness, and liver index of each fish were measured, and the number of surviving fish in the different probiotic supplementation groups was calculated. WG (final weight in g − initial weight in g), SGR ((ln (final weight in g) − ln (initial weight in g) × 100)/t (days)), hepatic steatosis index (HSI; liver weight in g/body weight in g) × 100), and condition factor (K = (W/L 3 ) × 100) were recorded .
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p6
|
PMC11278557
|
sec[1]/sec[3]/sec[0]/p[0]
|
2.4.1. Genomic DNA Extraction, Library Preparation, and Sequencing
| 4.148438 |
biomedical
|
Study
|
[
0.99951171875,
0.0002982616424560547,
0.00017774105072021484
] |
[
0.9990234375,
0.0005035400390625,
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0.00008761882781982422
] |
Genomic DNA extraction and shotgun metagenomic sequencing were carried out at Biomarker Technologie Co., Ltd. (Beijing, China). Total microbial genomic DNA was extracted from the gut using the CTAB method. The NanoDrop ND-1000 spectrophotometer (Invitrogen, Qubit3.0, Waltham, MA, USA) and agarose gel electrophoresis were used to evaluate the quality and quantity of the extracted DNA. The qualified DNA was used to construct the shotgun metagenomic sequencing library with VAHTS ® Universal Plus DNA Library Pren Kit (Illumina, San Diego, CA, USA). The library passed the QSEP-400 inspection for quality and was quantified using Qubit 3.0 for the library concentration. Illumina Novaseq (Illumina, San Diego, CA, USA) was used as the sequencing platform. The cluster density was within 1.255–1.412 K cluster/mm 2 range, and the sequencing operational error rate was <0.05.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p7
|
PMC11278557
|
sec[1]/sec[3]/sec[1]/p[0]
|
2.4.2. Metagenomic De Novo Assembly, Gene Prediction, and Annotation
| 4.1875 |
biomedical
|
Study
|
[
0.99951171875,
0.00023221969604492188,
0.000171661376953125
] |
[
0.9990234375,
0.00048279762268066406,
0.0004897117614746094,
0.00008690357208251953
] |
Clean reads were obtained by filtering the original sequence obtained by sequencing, and MEGAHIT v0.1-beta was used to assemble the macroscopic group. Quast 5.0.0 software evaluated the assembly results. The encoding area in the genome was identified using agnemark software by default parameters (-A-D-F-G). To obtain a non-redundant gene catalog, redundancy was removed using MMseq2v2 software with the similarity threshold set at 95 and the threshold set to 90. Protein sequences of non-redundant genes and the Nr database were used to align with BLAST to find the most similar sequences in the Nr database and annotate. Protein sequences of non-redundant genes and protein sequences included in the KEGG database were used for BLAST alignment (diamond v0.9.29 alignment screening threshold E-value 1 × 10 −5 ), and functional genes were annotated. The beta diversity of microbial composition was assessed using Bray–Curtis distance metrics and displayed through principal coordinate analysis (PCoA) and non-metric multidimensional scaling (NMDS) hierarchical clustering . According to the abundance and variation of each species in each sample, the correlation analysis (including positive and negative correlation) was performed by using the Spearman algorithm, and statistical tests were performed to filter the data groups with a correlation greater than 0.5, and p -values less than 0.05, and correlation network diagrams were plotted. Use Python 3.11.2 to analyze and visualize data.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278557_p8
|
PMC11278557
|
sec[1]/sec[4]/sec[0]/p[0]
|
2.5.1. Metabolite Extraction and Treatment
| 4.117188 |
biomedical
|
Study
|
[
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[
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] |
Intestinal samples were weighed 50 mg, ground in a 2 mL Eppendorf tube containing steel beads, added 1 mL precooled mixtures of methanol, acetonitrile and water ( v / v / v , 2:2:1) for 10 min at 45 Hz in a grinding mill and then placed for 1 h into ice baths with ultrasonic shaking. Subsequently, the mixture was placed at −20 °C for 1 h and centrifuged at 4 °C and 12,000 rpm for 15 min. The 500 μL supernatant was taken, dried and redissolved using a mixture of 160 μL acetonitrile and water (volume ratio: 1:1), vortexed for 30 s, ultrasonic in ice baths for 10 min and then centrifuged at 4 °C, 12,000 rpm for 15 min. Additionally, quality control (QC) samples are normalized by pooling aliquots from all representative samples and used for data normalization.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278557_p9
|
PMC11278557
|
sec[1]/sec[4]/sec[1]/p[0]
|
2.5.2. LC-MS/MS Analysis
| 3.972656 |
biomedical
|
Other
|
[
0.998046875,
0.0010805130004882812,
0.000873565673828125
] |
[
0.31494140625,
0.68212890625,
0.0017337799072265625,
0.0011644363403320312
] |
Waters Xevo G2-XS QTOF (Waters Co. Ltd., Milford, MA, USA) high-resolution mass spectrometer can collect primary and secondary mass spectrometry data in MSe mode under the control of the acquisition software (MassLynx V4.2, Waters). In each data acquisition cycle, dual-channel data acquisition can be performed on both low collision energy and high collision energy at the same time. The low collision energy is 2 V, the high collision energy range is 10~40 V, and the scanning frequency is 0.2 s for a mass spectrum. The parameters of the ESI ion source are as follows: capillary voltage, 2000 V (positive ion mode) or −1500 V (negative ion mode); cone voltage, 30 V; ion source temperature, 150 °C; desolvent gas temperature, 500 °C; backflush gas flow rate, 50 L/h; desolventizing gas flow rate, 800 L/h.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278557_p10
|
PMC11278557
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sec[1]/sec[4]/sec[2]/p[0]
|
2.5.3. Data Preprocessing and Annotation
| 4.003906 |
biomedical
|
Study
|
[
0.99951171875,
0.00017881393432617188,
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] |
[
0.990234375,
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0.00038313865661621094,
0.0001729726791381836
] |
The raw data collected using MassLynx V4.2 was processed by Progenesis QI v3.0 software for peak extraction, peak alignment, and other data processing operations, based on the Progenesis QI software online METLIN database and Biomark’s self-built library for identification, and at the same time, theoretical fragment identification and mass deviation were all within 100 ppm.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278557_p11
|
PMC11278557
|
sec[1]/sec[4]/sec[3]/p[0]
|
2.5.4. Data Analysis
| 4.113281 |
biomedical
|
Study
|
[
0.99951171875,
0.00028133392333984375,
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] |
[
0.99951171875,
0.0001862049102783203,
0.00039839744567871094,
0.00007295608520507812
] |
After normalizing the original peak area information with the total peak area, follow-up analysis was performed. Principal component analysis and Spearman correlation analysis were used to determine the reproducibility of the group samples and quantitative control samples. The identified compounds were categorized and pathway information was retrieved in KEGG, HMDB, and lipidmaps databases, the multiplicity of differences was calculated and compared based on the grouping information, and the t -test was used to calculate the significance of difference p value of each compound. OPLS-DA modeling was performed using the R language package ropls, and 200 permutation tests were performed to verify the reliability of the model. The VIP value of the model was calculated using multiple cross-validation. The method of combining the difference multiple, the p -values and the VIP value of the OPLS-DA model was adopted to screen the differential metabolites. The screening criteria were fold change (FC) >1, p -value, and VIP > 1. The differential metabolites of KEGG pathway enrichment significance were calculated using hypergeometric distribution test.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278557_p12
|
PMC11278557
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sec[1]/sec[5]/p[0]
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2.6. Correlation Analysis between Microbiome and Metabolome
| 3.935547 |
biomedical
|
Study
|
[
0.99951171875,
0.0001531839370727539,
0.0002601146697998047
] |
[
0.99853515625,
0.001026153564453125,
0.0003044605255126953,
0.00006729364395141602
] |
Correlation analysis between metabolome and microbiome was calculated by Top20 differential metabolites with the lowest p -values. Bacteria as Top20 abundance microorganisms under genus level which accounted for more than 80% of the microbial sequence reads and metabolites were deduced from the differential KEGG metabolic pathways.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278557_p13
|
PMC11278557
|
sec[2]/sec[0]/p[0]
|
3.1. Survival and Growth Performance Analysis
| 4.085938 |
biomedical
|
Study
|
[
0.9990234375,
0.000331878662109375,
0.0005965232849121094
] |
[
0.99951171875,
0.00015652179718017578,
0.000232696533203125,
0.000045180320739746094
] |
The survival rate, growth parameters, fatness, and liver index of S. trutta reared with each probiotic are listed in Table 1 . Our results showed that the addition of probiotics improved the survival rate of S. trutta ( p < 0.05). There were no significant differences among the liver body indices of BL, SC, LAB, and CON groups. Compared to the control group, the probiotic-supplemented group showed a significant increase in body weight and length ( p < 0.05). Additionally, only the BL group showed a significant increase in probiotic-supplemented S. trutta fat compared to the control group ( p < 0.05).
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278557_p14
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PMC11278557
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sec[2]/sec[1]/p[0]
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3.2. Effect of Probiotics Addition on Intestinal Microbial Composition and Function in S. trutta
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.00031065940856933594,
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[
0.99951171875,
0.00014734268188476562,
0.0004189014434814453,
0.00006514787673950195
] |
To achieve a comprehensive comparison, we used metagenomics to detect the gut microbial composition, diversity, richness, and functional enrichment. First of all, taxonomic alpha diversity was estimated using the Shannon index, ACE index, Simpson index, and Chao1 index . The NMDS analysis, based on β diversity, showed variations in the distances among samples’ passing points. The lower the stress value, the better. The CON, SC, BL, and LAB samples demonstrated some overlap , indicating that there might be some difference among the gut microbiota components in each group. Then, using principal component analysis (PCA) to conveniently observe the variation law between samples, the results showed significant separation and some degree of clustering of bacterial community composition among the four groups .
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278557_p15
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PMC11278557
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sec[2]/sec[1]/p[1]
|
3.2. Effect of Probiotics Addition on Intestinal Microbial Composition and Function in S. trutta
| 4.132813 |
biomedical
|
Study
|
[
0.99951171875,
0.00030112266540527344,
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] |
[
0.99951171875,
0.00014448165893554688,
0.00032806396484375,
0.00005602836608886719
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Then, to further observe the effect of probiotic addition on the gut microbiota of S. trutta , we investigated the microbial species and their relative abundance at the genus and species levels. As shown in Figure 1 D,E, the community structure and abundance of all bacteria in these groups were very similar and mainly comprised of Acinetobacter and Pseudomonas. Compared with CON, the abundance of Hepatospora , Aeromonas , and Rhizoctonia were decreased and the abundance of Pseudomonas , Rhizopus , and Alcanivorax were increased in LAB. The abundance of Rhizoctonia genus was decreased and Aeromonas , Hepatospora , and Alcanivorax were increased in BL. The abundance of Rhizoctonia was decreased and Rhizopus was increased in SC. At the species level, consistent increases or decreases were observed in all samples at the genus level . Random forest analysis can identify key species that differ between samples. The random forest analysis showed that the key species with the top five differences were Paenibacillus , Kuraishia , Gloeocapsa , Candidatus_Amoebophilus , and Glarea .
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p16
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sec[2]/sec[2]/p[0]
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3.3. Functional Prediction of Microbe Community
| 4.09375 |
biomedical
|
Study
|
[
0.99951171875,
0.00025200843811035156,
0.0002627372741699219
] |
[
0.99951171875,
0.00013387203216552734,
0.0002779960632324219,
0.0000508427619934082
] |
To further understand the functional differences between CON and microorganisms, KEGG analysis of differentially functional genes was performed according to the criterion of nonparametric testing ( p < 0.05). The results showed that “oxidative phosphorylation, phosphatidylinositol signaling, inositol phosphate metabolism, and penicillin and cephalosporin biosynthesis” pathways decreased after the addition of BL probiotics . In addition, we were able to learn that the production of fatty acids, as well as abundance of the hippo signaling pathway, were altered after the addition of probiotics . Additionally, compared with CON, increased enrichment was observed in “Glycosphingolipid biosynthesis ganglio series and Styrene degradation” and decreased enrichment was observed in “Spliceosome and Phagosome” after LAB addition .
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278557_p17
|
PMC11278557
|
sec[2]/sec[3]/p[0]
|
3.4. Quality Control
| 4.152344 |
biomedical
|
Study
|
[
0.99951171875,
0.0002359151840209961,
0.00023686885833740234
] |
[
0.99951171875,
0.0001876354217529297,
0.0003750324249267578,
0.000054955482482910156
] |
PCA is an unsupervised pattern recognition method for statistical analysis of multidimensional data that converts a set of potentially correlated variables into a set of linearly uncorrelated variables through orthogonal transformation. The PCA of samples provided a preliminary understanding of the overall metabolic differences between groups and the magnitude of variability between samples within groups. As shown in Figure 3 A, the PCoA results indicated that the CON group was significantly separated from the BL and LAB groups, whereas it was not significantly separated from the SC group, and the sample distribution of the CON group converged. The OPLS-DA model is a latent variable regression method based on the covariance between predictor variables and the response. The prediction parameters of the evaluation model were R 2 X, R 2 Y, and Q 2 Y, where R 2 X and R 2 Y represent the interpretation rate of the established model to X and Y matrices, respectively, and Q 2 Y represents the predictive ability of the model. The closer that R 2 Y and Q 2 Y of the index are to 1, the more stable and reliable the model is, and the differential metabolites can be screened by this model. The R 2 Y and Q 2 Y values of OPLS-DA were 0.998 and 0.441, respectively, in the BL group compared to those in the control group . The R 2 Y and Q 2 Y values of OPLS-DA were 0.981 and 0.41, respectively, in the SC group compared with those in the control group . Compared to the control group, the R 2 Y and Q 2 Y values of OPLS-DA in the LAB group were 0.977 and 0.164, respectively .
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278557_p18
|
PMC11278557
|
sec[2]/sec[4]/p[0]
|
3.5. Analysis of Differential Metabolites and Their KEGG Enrichment in Control and Probiotic-Treated Groups
| 4.003906 |
biomedical
|
Study
|
[
0.99951171875,
0.00022685527801513672,
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] |
[
0.99951171875,
0.0003643035888671875,
0.00019598007202148438,
0.00005263090133666992
] |
At FC = 1 and p -value = 0.05, there were 199 differential metabolites in the BL group compared to the control group, of which 102 metabolites were upregulated and 97 were downregulated . Compared to the control group, there were 63 differential metabolites in the SC group, of which 25 were upregulated and 38 were downregulated . There were 30 differential metabolites in the LAB group compared to those in the control group, of which 14 were upregulated and 16 were downregulated .
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278557_p19
|
PMC11278557
|
sec[2]/sec[4]/p[1]
|
3.5. Analysis of Differential Metabolites and Their KEGG Enrichment in Control and Probiotic-Treated Groups
| 4.132813 |
biomedical
|
Study
|
[
0.99951171875,
0.0002467632293701172,
0.0001844167709350586
] |
[
0.9990234375,
0.00018012523651123047,
0.0005135536193847656,
0.00006705522537231445
] |
Complex metabolic reactions and their regulation in organisms are not performed alone and are often performed by different genes and proteins to form complex pathways and networks, and their mutual influence and regulation eventually lead to systemic changes in the metabolome. The KEGG database was used to study genes, expression information, and metabolite content in the overall network. The results are shown in Figure 5 . Metabolism of arginine and proline; digestion and absorption of fat, lipids, and atherosclerosis; biosynthesis of neomycin, kanamycin, and gentamicin; and the mTOR signaling pathway were enriched after the addition of BL probiotics . After adding SC probiotics, the inflammatory mediator regulation of TRP channels, CAMP signaling pathway, and neomycin, kanamycin, and gentamicin biosynthesis signal pathways were enriched. Additionally, some amino acid metabolic pathways were enriched . In the LAB group, the biosynthesis of unsaturated fatty acids; aldosterone-regulated sodium reabsorption; and cutin, suberin, and wax biosynthesis signal pathways were enriched . Overall, after the addition of probiotics, pathways related to inflammation, amino acid metabolism, and fatty acid metabolism were enriched, indicating that probiotics play a role in intestinal inflammation and fat metabolism.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278557_p20
|
PMC11278557
|
sec[2]/sec[5]/p[0]
|
3.6. Correlation Analysis between Microbiome and Metabolism
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.00031375885009765625,
0.00020456314086914062
] |
[
0.99951171875,
0.00016760826110839844,
0.00035858154296875,
0.00006526708602905273
] |
To investigate the association between specific metabolites and the presence of microbes, we verified the correlation between the intestinal microbiota and metabolites in the control group and groups treated with different probiotics. Correlation analysis was performed by calculating the Spearman’s correlation coefficients and p -values. Otherwise, metabolites from different metabolic pathways were selected. As shown in Figure 5 A, in the BL treatment group compared to the control group, Hepatospora was negatively correlated with Toxin T2 tetrol, 4-Hydroxynonenal, Glutaminylproline, and L-glutamyl 5-phosphate, and Acinetobacter was positively correlated with L-beta-aspartyl-L-leucine and negatively correlated with Celgosivi. Finally, the classification showed that most differential metabolites included lipids, lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. When the SC-treated group was compared to the control group, the results showed that Enterococcus was negatively correlated with cannabigerolate and 3-(4’-Methylthio) butylmalic acid, and Psilocybe was positively correlated with L-Pyridosine . Similar to the BL group, the correlated metabolites in the SC group were mainly clustered as lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. We speculated that organoheterocyclic compounds may be related to the production of antimicrobial substances in the gut that counteract bacterial cell walls.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278557_p21
|
PMC11278557
|
sec[2]/sec[5]/p[1]
|
3.6. Correlation Analysis between Microbiome and Metabolism
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.00022733211517333984,
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] |
[
0.99951171875,
0.00020575523376464844,
0.00023412704467773438,
0.0000508427619934082
] |
In the LAB-treated group, Aquifex showed a positive correlation with Maraviroc, L-pyridosine, PG(16:0/0:0)[U], N-oleoyl tryptophan, and 41-O-demethylrapamycin and a negative correlation with cortisone . Many microorganisms and their metabolites were negatively and positively correlated. These metabolites were classified into lipids, benzenes, and amino acids. Interestingly, this result was consistent with the pathways enriched by differential metabolites, suggesting that lipid anabolism in the gut of Adonis salmon changed mainly after the addition of probiotics. Furthermore, most of these metabolites are benzene molecules, which may be antimicrobial substances produced in the intestine, thus boosting intestinal immunity.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p22
|
PMC11278557
|
sec[3]/p[0]
|
4. Discussion
| 4.148438 |
biomedical
|
Study
|
[
0.99951171875,
0.0003082752227783203,
0.0002143383026123047
] |
[
0.9990234375,
0.00015342235565185547,
0.0005197525024414062,
0.00007390975952148438
] |
In this study, we investigated the effects of probiotic supplementation on the intestinal microbiota and metabolomes of fish. Our results revealed noteworthy differences in the intestinal function, gut microbiota composition, and metabolite profiles between the control and probiotic-supplemented groups. Correlation analysis further confirmed significant associations between the microbial community and a multitude of metabolites. To elucidate these findings, we employed advanced techniques such as deep sequencing-based metagenomics and untargeted metabolomics, enabling us to visually illustrate alterations in both the microbial community and metabolite profiles. Collectively, our findings shed light on the intricate relationship between probiotic supplementation and distinctive functional and metabolic characteristics of the gut microbiota in S. trutta .
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278557_p23
|
PMC11278557
|
sec[3]/p[1]
|
4. Discussion
| 4.117188 |
biomedical
|
Study
|
[
0.99951171875,
0.000209808349609375,
0.00046825408935546875
] |
[
0.99755859375,
0.00028228759765625,
0.0021190643310546875,
0.00006264448165893555
] |
Fish are susceptible to different types of bacterial, fungal, and parasitic infections during their growth and development, which are threats to fish health. Probiotics have been shown to be positive promoters of growth, survival, and health in aquatic animals . As natural products, probiotics have a great potential to improve the efficiency and sustainability of aquaculture production . Saccharomyces cerevisiae is one of the most popular probiotics in extract or whole cell form, and it is considered an important source of products with probiotic activity . Many studies have shown that it can promote fish growth, development, and feed utilization and improve intestinal health and intestinal mucosal flora . The results of this study showed that the body weight and length of S. trutta significantly increased after the addition of SC, indicating that SC could promote the growth and development of S. trutta . As the most commonly used beneficial probiotics in animal diets, lactic acid bacteria significantly contribute to maintaining the intestinal ecosystem and stimulating the host immune system . Bacillus licheniformis is also widely added to aquaculture feeds because of its resistance to harsh environments and ability to produce various enzymes . Some researchers have demonstrated that the growth of grass carp improved after supplementation with Bacillus Licheniformis , which is consistent with the results of this study. These findings suggest that probiotics promote the growth and development of S. trutta . Therefore, probiotics as feed additives can also provide economic benefits for industrial farming of fisheries.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p24
|
PMC11278557
|
sec[3]/p[2]
|
4. Discussion
| 4.164063 |
biomedical
|
Study
|
[
0.99951171875,
0.0002684593200683594,
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] |
[
0.9990234375,
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Notably, the addition of probiotics altered the gut microbial composition and diversity in S. trutta , and the three most abundant groups were Pseudomonas , Acinetobacter , and Rhizophagus . Compared to the control group, the SC group Rhizophagus_irregulari and Rhizoctonia_solani decreased. Rhizophagus rickettsii is an aggressive, soil-borne, semi-viviparous trophic pathogen that can destroy many plants . However, no such studies have been conducted on fish. We speculated that it may also be harmful to fish. Notably, the level of Hepatospora abundance decreased after the addition of LAB. Hepatospora are intracellular parasites that infect epithelial cells of the liver, bile, and pancreas in animals . Ding performed transcriptome sequencing before and after infection and found that the differentially expressed genes were mainly enriched in amino acid metabolism and fatty acid biosynthesis . This result is consistent with the pathways enriched by differential metabolites identified in the metabolome sequencing results of this experiment. The results for the gut microbes were consistent with those of other studies, suggesting that probiotics have a positive effect on gut health.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p25
|
PMC11278557
|
sec[3]/p[3]
|
4. Discussion
| 4.195313 |
biomedical
|
Study
|
[
0.99951171875,
0.00024628639221191406,
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] |
[
0.9990234375,
0.00019860267639160156,
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Analysis of macrogenomic results has provided a clear understanding of the changes in the intestinal flora following probiotic addition; however, these changes in the intestinal flora lead to changes in certain metabolites that we do not understand. Studies have also highlighted that the metabolites of gut microbes, such as bile acids, short-chain fatty acids, and amino acids, play a particularly important role in gut health . Therefore, we next performed metabolomics to gain a comprehensive understanding of the mechanism of action of probiotics. Bacillus licheniformis has been shown to have anti-inflammatory and antioxidant effects and to improve lipid synthesis and beta fatty acid oxidation . Similar results were obtained in the present study, where the addition of BL resulted in an enrichment of differential metabolites compared to the control group, mainly in the metabolism of arginine and proline; digestion and absorption of lipids; atherosclerosis; biosynthesis of neomycin, kanamycin, and gentamicin; and regulation of TR channels by inflammatory mediators. Bacillus licheniformis has demonstrated the ability to regulate intestinal sub-health by reshaping the intestinal flora, reducing inflammation, and regulating the intestinal flora balance . Additionally, after the addition of SC, the differential metabolites were mainly in the pathways of inflammatory mediators regulating TRP channels, as well as amino acid metabolism, compared to the control group. This addition enhances resistance and immunity against pathogens . The probiotic Lactobacillus is generally considered beneficial to both humans and animals, and we found that the addition of Lactobacillus affected lipid and amino acid metabolism in S. trutta .
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278557_p26
|
PMC11278557
|
sec[3]/p[4]
|
4. Discussion
| 4.207031 |
biomedical
|
Study
|
[
0.99951171875,
0.00027370452880859375,
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] |
[
0.99658203125,
0.0002865791320800781,
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0.00010216236114501953
] |
The gut microbiota is a complex biological system that plays crucial roles in animals, including the digestion of complex molecules, synthesis of vitamins, and modulation of the immune system . The integration of multiple omics approaches, such as metagenomics and metabolomics, has led to significant advancements in the study of the relationship between gut microbiota and health-related diseases, overcoming the limitations of single-omics studies . Previous research has indicated a direct correlation between the differences in gut microbiota composition and significant changes in the metabolomics landscape, including lipid and lipid-related metabolites, amino acids, bile acids, and steroid-related metabolites, after supplementation with probiotics in rainbow trout . In this study, we also observed significant changes in the joint analysis of the microbiota and metabolites in the different probiotic treatment groups, particularly in lipid synthesis and metabolism, organoheterocyclic compounds, and organic acid derivatives. The gut microbiota has a significant effect on lipid synthesis and metabolism. Many probiotics have been shown to provide vitamins, fatty acids, and essential amino acids to the host . They can also be considered supplementary sources of nutrients . Probiotics improve feed consumption and nutrient absorption, thereby promoting animal growth.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278557_p27
|
PMC11278557
|
sec[4]/p[0]
|
5. Conclusions
| 4.136719 |
biomedical
|
Study
|
[
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[
0.9990234375,
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In conclusion, this study provides evidence that probiotic supplements may improve the growth performance of S. trutta by promoting intestinal health. Our findings indicate that probiotic supplementation increases the diversity and richness of the gut microbiota, leading to dynamic changes in microbial composition. Additionally, we investigated the potential mechanisms underlying the interactions between the host and gut microbiome, although the specific molecular regulation mechanism of growth performance changes in S. trutta induced by probiotics needs to be further investigated. Overall, our study highlights the use of multi-omics approaches to comprehensively examine complex host–microbiome interactions, allowing for a more thorough evaluation and exploration of the functional potential of probiotics compared to previous studies. This research contributes to a better understanding of the biological significance and regulatory mechanisms of probiotic supplementation in aquatic animals such as salmon.
|
[
"Mengjuan Chen",
"Zhitong Wang",
"Hui He",
"Wenjia He",
"Zihao Zhang",
"Shuaijie Sun",
"Wanliang Wang"
] |
https://doi.org/10.3390/microorganisms12071410
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p0
|
PMC11278569
|
sec[0]/p[0]
|
1. Introduction
| 3.929688 |
biomedical
|
Study
|
[
0.99462890625,
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] |
[
0.62744140625,
0.3642578125,
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] |
Microbial fuel cells (MFCs) represent a method of generating electrical power via microbial processes by the connection of an anaerobic anode to an aerobic cathode . These processes generally involve anaerobic bacteria oxidizing organic matter and subsequently producing electrical current . The ocean floor ecosystem contains diverse and abundant microbial activity . A Benthic MFC (BMFC) functions similarly to an MFC with the added specification of making use of bacteria that naturally occupy this ecological niche in a marine environment .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p1
|
PMC11278569
|
sec[0]/p[1]
|
1. Introduction
| 3.671875 |
biomedical
|
Other
|
[
0.9951171875,
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] |
[
0.2998046875,
0.69677734375,
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] |
Some anaerobic bacteria are able to expel their terminal electrons to the external environment; these are exoelectrogens . It is these expelled electrons that are captured by the anode of a BMFC. This is performed via a conductive capture anode connected to a nearby cathode by a resistive load, thus obtaining usable electrical power from the bacteria. Typical voltage ranges for this arrangement span from 0.2 to 1 V . This technique is applied in practice with applications such as low-draw sensors .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p2
|
PMC11278569
|
sec[0]/p[2]
|
1. Introduction
| 3.501953 |
biomedical
|
Study
|
[
0.63427734375,
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[
0.81689453125,
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0.00028777122497558594
] |
Typical BMFCs have been shown to produce low amounts of power in the range of 3–40 mW/m 2 in situ and as high as 1 W/m 2 in laboratory environments with optimal conditions including nutrition being provided . Regarding the in situ BMFCs, there have been various attempts to improve the resulting power densities via various strategies such as altering the cathode (e.g., increasing the size) , altering the anode , altering both electrodes , changing the electrode spacing, coating the electrodes in cerium , using carbon felt as the anode material , using organic additives such as acetate , and supplying alternative food sources like chitin .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p3
|
PMC11278569
|
sec[0]/p[3]
|
1. Introduction
| 2.994141 |
biomedical
|
Study
|
[
0.982421875,
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[
0.7470703125,
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] |
Alternative optimization approaches involve bacterial concentration, anode geometry, or the minimization of the distance from the cells to the anode . Optimizing bacterial concentration would intuitively increase power production proportionally. However, there are diminishing returns (or even decreases) associated with this approach due to the ecological constraints on the bacterial communities .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p4
|
PMC11278569
|
sec[0]/p[4]
|
1. Introduction
| 3.898438 |
biomedical
|
Study
|
[
0.9990234375,
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[
0.68017578125,
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] |
Due to the size of bacteria, they live in a world dominated by viscous forces, characterized by low Reynolds numbers, typically values less than 1 . The environment created within microfluidic devices can also be characterized by low Reynolds numbers which matches the needs of the microbes . Making use of these low Reynolds number regimes is common practice in fields such as biotechnology , cell culture work , biomedical diagnostic tools , and embedded electric measurements . Microscale MFCs are generating lots of interest due to the potential benefits to capture efficiency and the continuing efforts to maximize power density .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p5
|
PMC11278569
|
sec[0]/p[5]
|
1. Introduction
| 4.039063 |
biomedical
|
Study
|
[
0.99951171875,
0.00014960765838623047,
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] |
[
0.97607421875,
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0.00017058849334716797
] |
A united approach, joining microfluidics chips and living microbial systems, can be used to improve the characterization of Microfluidic BMFC (MBMFC) relevant microbial responses . This can be performed by depositing a metal electrode on glass, then using that surface as the substrate for an elastomer microfluidic chip . Elastomer microfluidic chips such as these boast key benefits such as biocompatibility, fluidic control, visibility, and critically, the minimization of the distance between the bacteria and the anode .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p6
|
PMC11278569
|
sec[0]/p[6]
|
1. Introduction
| 4.097656 |
biomedical
|
Study
|
[
0.9990234375,
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[
0.99951171875,
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This approach was successfully used to constrain the bacteria to be within 90 μ m of the capturing electrode in a proof-of-concept experiment yielding an increase in generated power by roughly a factor of four . This showed that the shortening of distance between the electron emission and capture significantly improved the power production capabilities of MBMFCs. This was performed with a PDMS (polydimethylsiloxane) cast as the physical structure of the microfluidic component. The capturing electrode was chromium in a fractal pattern. The test devices were prepared with a single-input single-output microfluidic design with dendritic branching . They were placed in sediment collected from the San Diego Bay. Steady-state power densities as high as 80 mW/m 2 were recorded . It follows that further confinement of the bacteria could further increase the performance.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p7
|
PMC11278569
|
sec[0]/p[7]
|
1. Introduction
| 2.910156 |
biomedical
|
Other
|
[
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[
0.324462890625,
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] |
However, these test devices were difficult and time-consuming to fabricate, thus presenting the problem of how to upscale effectively. Depending on the applications, thousands or even tens of thousands of these test devices would need to be implemented together for practical use. Even if they are easy to produce in small numbers, the cost of producing enough of them and assembling them would still be a significant deterrent. Thus, a pathway is needed to allow for efficient upscaling. Three-dimensional printing offers just such a pathway to upscale microfluidic devices such as these .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p8
|
PMC11278569
|
sec[0]/p[8]
|
1. Introduction
| 3.988281 |
biomedical
|
Study
|
[
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[
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The 3D printing of embedded negative features, such as three-dimensional networks of microfluidic channels, requires the removal of the sacrificial support material inherent to 3D printing. We previously addressed this via a clearing methodology developed specifically for this application . This technique is based on the combination of vibration, heating, and chemicals injected into the microchannels. The methodology works reliably when the microchannels are wider than 200 μ m across .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p9
|
PMC11278569
|
sec[0]/p[9]
|
1. Introduction
| 3.464844 |
biomedical
|
Other
|
[
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[
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Another key development leading to the practical use of 3D printing in microfluidic applications like these is predictable manufacturing. Using PolyJet technology , we have highly reproducible fabrication. Thus, planning is now possible around the systematic recurrent discrepancies between dimensions on a CAD model and their analog in an associated 3D print . Reproducibility and the consequent predictability are critical for industrial applications as well as further research and development.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p10
|
PMC11278569
|
sec[0]/p[10]
|
1. Introduction
| 4.160156 |
biomedical
|
Study
|
[
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[
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The next hurdle to address was embedding electrical wiring in the microfluidic network. We initially approached this task via a self-assembly technique applied to square microfluidic channels with flanges on the sides . After removing the sacrificial material , the microchannel was filled with a hydrophobic fluid. Next, the hydrophobic fluid was flushed out of the central area of the microchannel with a hydrophilic fluid at moderate pressure, while the hydrophobic fluid in the flanges remained in place due to higher surface tension and fluidic resistance in the flanges . The next step was for the hydrophobic fluid to be conductive, e.g., nanoparticle-spiked resin to be cured in position post-self-assembly. This could then act as a pair of wires that run parallel to the microchannel. With a square channel 200 μ m across, this achieved roughly the same maximal spacing between any bacterium and the nearest electrode as the one that previously increased the power output by a factor of four . This approach using resin spiked with conductive nanoparticles was hindered by the mixed fluid being too viscous to feed into the microchannel.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p11
|
PMC11278569
|
sec[0]/p[11]
|
1. Introduction
| 4.023438 |
biomedical
|
Study
|
[
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[
0.990234375,
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] |
An alternative method was developed based on deposition of conductive particles directly inside the microchannels. This led to Carbon Nano Fiber (CNF) distributed wiring throughout the entire volume of a microchannel . Importantly, carbon is a biocompatible electrode material. Additionally, this approach maintains some key benefits of that self-assembly method: access is only needed through a fluidic inlet; the wiring is performed via fluidic injection, and can thus be potentially automated in the future; and acceptable conductivity is achievable.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278569_p12
|
PMC11278569
|
sec[0]/p[12]
|
1. Introduction
| 3.591797 |
biomedical
|
Study
|
[
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[
0.87890625,
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] |
In this scheme, the capturing anode is distributed throughout the volume of the microchannels. This further minimizes the distance from an emitted electron to the nearest electrode, as the bacteria and wiring occupy portions of the same physical space. This scheme provides a definite improvement to the separation distance compared to the preceding work . With these developments, the key fundamental prerequisite developments such as fabrication and wiring methods have now been addressed.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p13
|
PMC11278569
|
sec[0]/p[13]
|
1. Introduction
| 4.054688 |
biomedical
|
Study
|
[
0.99951171875,
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[
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Herein, we present a monolithically 3D-printed microfluidic device containing a binary branching microfluidic network with embedded CNF wiring as the biocompatible volumetrically distributed electrode. The typical achieved electric conductivity per dry microchannel is 4 S/m. This device is an important step in the further development of MBMFCs. In the future, this can be further developed and optimized before being used as an integral unit element within modular macro-scale MBMFCs. As such, this represents a major step in the advancement of this technology and carries strong promise for the future of MBMFCs.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278569_p14
|
PMC11278569
|
sec[0]/p[14]
|
1. Introduction
| 1.369141 |
other
|
Other
|
[
0.1396484375,
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0.85888671875
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[
0.01160430908203125,
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] |
The potential applications include energy at the sea floor or near the sea floor. The end goal is to stack these small-scale units to make microbial condominiums to eventually obtain 1 W of power at the sea floor.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11278569_p15
|
PMC11278569
|
sec[1]/p[0]
|
2. Materials and Methods
| 3.935547 |
biomedical
|
Study
|
[
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[
0.95751953125,
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Chip Architecture . The test chips discussed herein can be seen in Figure 1 . We call them `comb’ chips due to their visual resemblance to a hair comb. They are designed within an outer frame defined by a rectangular prism of dimensions 100 × 70 × 5 mm. The bottom portion of the comb chips houses 32 identical microfluidic channels (0.8 × 0.8 mm cross section) that form the fluidic outlets. The upper portion is dedicated to a dendritic branching structure that connects the single common inlet port to all the 32 outlets. The total internal volume of the microfluidic network as defined by SOLIDWORKS is 1040 mm 3 .
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p16
|
PMC11278569
|
sec[1]/p[1]
|
2. Materials and Methods
| 4.042969 |
biomedical
|
Study
|
[
0.99755859375,
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[
0.89306640625,
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0.0002586841583251953
] |
Chip Fabrication . These chips are designed in SOLIDWORKS 2022 , then converted into STL files for compatibility with our 3D printer: Stratasys Objet500 Connex 1 (Stratasys Ltd., Rehovot, Israel). The models are laid flat on the print bed and oriented to keep the microchannels in the bottom portion of the design parallel to the primary axis. This maximizes the print quality . Devices are printed in batches to produce a total of 10. The material used for the main structure of the chip is VeroClear-RGD810, a clear hard resin chosen for its optical clarity, chemical resilience, and mechanical rigidity. Additional materials used during printing are SUP706B for the sacrificial material, and AGILUS30 BLACK FLX985 for the labels.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p17
|
PMC11278569
|
sec[1]/p[2]
|
2. Materials and Methods
| 3.486328 |
biomedical
|
Other
|
[
0.982421875,
0.0010251998901367188,
0.0163726806640625
] |
[
0.416015625,
0.58203125,
0.0013341903686523438,
0.00048804283142089844
] |
Support Material Removal . After printing, the chips are put through our previously published clearing procedure . Briefly, this process includes the flushing of channels and sonication of the chips in a 10% NaOH aqueous solution as well as heating at 80 °C. They are then cleaned of any residual chemicals and carefully inspected. This procedure successfully clears each of the 320 total channels.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p18
|
PMC11278569
|
sec[1]/p[3]
|
2. Materials and Methods
| 4.0625 |
biomedical
|
Study
|
[
0.99658203125,
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[
0.75146484375,
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0.00040221214294433594
] |
Chip Wiring . Once the test chips are cleared of support material, the next step in the process is electrical wiring. This is accomplished by depositing CNFs throughout the volume of the microchannels . Briefly, the CNFs are implanted by injecting a solution of CNFs in isopropyl alcohol into the entire internal volume of the chips. Next, the chips are heated to evaporate the alcohol while leaving the CNFs in place. This process is iterated 10 times, incrementally improving conductivity. Lastly, a naked copper wire is inserted in parallel to a plastic Luer-Stub adapter into the primary inlet and epoxied in place. This allows for simultaneous fluidic and electrical access to the internal network of microchannels via the primary inlet. See Test and Evaluation, MBMFC construction for a wiring description during the test and evaluation phase.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278569_p19
|
PMC11278569
|
sec[1]/p[4]
|
2. Materials and Methods
| 2.587891 |
biomedical
|
Other
|
[
0.8740234375,
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0.124755859375
] |
[
0.3994140625,
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0.0014553070068359375,
0.0005340576171875
] |
Electrical Characterization . All electrical measurements are taken via a benchtop source meter . For each datapoint, the instrument takes 100 sample measurements automatically and calculates the mean value and the standard deviation. These are then recorded as the corresponding measured value and its error bar, respectively. All electrical measurements are taken in this way.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p20
|
PMC11278569
|
sec[1]/p[5]
|
2. Materials and Methods
| 4.070313 |
biomedical
|
Study
|
[
0.97802734375,
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[
0.9990234375,
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The set of 10 comb chips have a total of 320 outlet channels. It is impractical to measure the resistance of each channel after each CNF iteration. Additionally, measuring each channel is unnecessary, as the purpose of intermediate measurements is to track the progression of the wiring, so representative subsets are sufficient. The chips can be conceptually broken into four segments as defined by the second branching event, where the segments are made up of channels 1–8, 9–16, 17–24, and 25–32, respectively, as shown in Figure 4 B. Every measurement taken has one lead inserted into the common inlet port and the other lead inserted in one of the 32 outlet ports. For each of the four measurements taken between CNF iterations, the other lead is inserted in a randomly chosen channel in the corresponding segment. The average of the four measurements taken per chip is plotted for each comb chip as a function of injection cycle count in Figure 4 A. All electrical measurements are taken when the channel is dry. Figure 4 A shows convergence towards a saturated resistance value on the order of tens of k Ω , along with a reduction in variation between individual chips as the injection iteration number increases.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278569_p21
|
PMC11278569
|
sec[1]/p[6]
|
2. Materials and Methods
| 4.082031 |
biomedical
|
Study
|
[
0.9921875,
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[
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Cold Room Setup . In the area wherein the experiment is set to run, a header tank with a constant flow of seawater is continuously filled and connected to a PVC line. Figure 2 shows a photograph of the cold room setup. The PVC line has triple differential flow configurations spaced for each experiment, also made out of PVC and connected to vinyl tubing. These configurations allow the water flow for each individual MFC in the experiment to be adjusted without affecting the others so that the optimal amount of water is constantly supplied. Just behind the water flow PVC is another line identical in length that has individual holes, adjustable valves, as well as tubing. This ensures that each MFC also has adequate oxygen flow for the aerobically necessary cathodic reaction. The MFCs (inside their respective 1 L beakers) are placed inside a plastic tub, 3 at a time, which fits them and separates the experiment properly. The tubes for water and oxygen are clamped to the beaker so that they are slightly penetrating the water surface. The experiment is left to run, and the water flow/oxygen flow/separation of the MFC components within the beakers are tightly and constantly monitored.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p22
|
PMC11278569
|
sec[1]/p[7]
|
2. Materials and Methods
| 3.962891 |
biomedical
|
Study
|
[
0.998046875,
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] |
[
0.72314453125,
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PBS and Acetate Solution, Anode Preparation, and Electronic Connections . Acetate is often used as a bacterial food source, as it is a single carbon compound easily used as a food source by many exoelectrogens. A 50 mM phosphate buffer solution (PBS) is used to create a 1 g/L sodium acetate solution via dissolution with subsequent stirring. This is accomplished by adding 5 mL of sodium acetate solution to 5 mL of seawater and mixing. Next, 5 mL of 50 mM PBS is added to 5 mL of seawater and mixed. A total of six anodes are used—three anodes are injected with 2 mL of the PBS–acetate–seawater solution, and three anodes are injected with 2 mL of the PBS–seawater solution.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278569_p23
|
PMC11278569
|
sec[1]/p[8]
|
2. Materials and Methods
| 3.960938 |
biomedical
|
Study
|
[
0.99755859375,
0.0005898475646972656,
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[
0.61669921875,
0.38134765625,
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] |
The microfluidic microbial fuel cell anodes are connected to a patented electrical regulation system which measures the open circuit voltage potential of the benthic microbial fuel cell (BMFC) between the anode and cathode for the first 3 days. This potentiostat then sets the appropriate load resistor value, in this case 10 kΩ, to maintain the voltage. Power is determined using current multiplied by operating voltage.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p24
|
PMC11278569
|
sec[1]/p[9]
|
2. Materials and Methods
| 3.613281 |
biomedical
|
Study
|
[
0.83154296875,
0.0010776519775390625,
0.1671142578125
] |
[
0.974609375,
0.0247955322265625,
0.000396728515625,
0.0001863241195678711
] |
MBMFC Construction . To assess the applicability of the design, six MBMFC devices are tested at NIWC Pacific. All six anodes are crimped to titanium wire and are covered with marine grade heat shrink. Any exposed copper wire from the anodes is coated with clear nail polish to minimize corrosion. Approximately 500 mL of sediment is placed in a 1 L glass beaker. All six anodes are submerged into the sediment with only the top 1/4 of the anode plastic exposed. A carbon cloth cathode for each is sewn to copper wire, heatshrunk with marine grade heat shrink and is submerged just beneath the water surface. For the duration of the experiment, a steady flow of ocean salt water and aeration is supplied to each of the six anodes. Figure 3 shows a schematic of the experimental setup.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278569_p25
|
PMC11278569
|
sec[1]/p[10]
|
2. Materials and Methods
| 3.208984 |
biomedical
|
Other
|
[
0.98583984375,
0.0008745193481445312,
0.01334381103515625
] |
[
0.315673828125,
0.6826171875,
0.0008525848388671875,
0.0007166862487792969
] |
Sediment Supernatant . San Diego Bay sediment is obtained from the Marine Corp Recruit Depot located at 32°44′20.65″ N, 177°12′31.42″ W. Two 50 mL conical tubes are filled roughly three-quarters full with sediment slurry. The tubes are then centrifuged for 2 min at 500 RCF and then another 2 min at 700 RFC to pellet out the sediment/debris, leaving the bacterial inoculate in the supernatant. This supernatant is then decanted into another conical tube for the subsequent treatments.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278569_p26
|
PMC11278569
|
sec[2]/sec[0]/p[0]
|
3.1. Chip Design
| 4.167969 |
biomedical
|
Study
|
[
0.998046875,
0.00025177001953125,
0.0018711090087890625
] |
[
0.98291015625,
0.01617431640625,
0.0006184577941894531,
0.00010919570922851562
] |
To minimize the cumulative fluidic resistance of the comb chip’s microchannels, the branching connections are designed to avoid sharp changes in direction. This results in the streamlined and naturalistic appearance of the network of microfluidic channels. The channel arclengths are non-uniform . As measured from the channel’s centerline in SOLIDWORKS, the set of arclengths contains a maximum of 100.89 mm, a minimum of 86.44 mm, and a mean of 93.14 mm. Additional features include the outlet ports being designed to minimize head loss for the internal flow, an increase in size near the inlet to allow for easier processing and wiring, and a robust minimum spacing of 2.23 mm between channels.
|
[
"Terak Hornik",
"Maxwell Terry",
"Michael Krause",
"Jeffrey K. Catterlin",
"Kevin L. Joiner",
"Samuel Aragon",
"Angelica Sarmiento",
"Yolanda Meriah Arias-Thode",
"Emil P. Kartalov"
] |
https://doi.org/10.3390/mi15070870
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |