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PMC11277516_p5
PMC11277516
sec[1]/p[1]
2. Adipose Tissue and Metabolic Health
4.203125
biomedical
Review
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It is important to understand the role of adipose tissue in glucose homeostasis. Thermogenic adipose tissue serves as a glucose sink under adrenergic stimulation, and the expression of glucose transporter type 4 (GLUT4) participates in peripheral glucose disposal . The key hormones released by adipose tissue include leptin, adiponectin, and resistin. Leptin increases energy expenditure, and its levels are correlated with adipose tissue mass. Obese states are characterized by leptin resistance, and consequently, increased leptin levels act as a compensatory mechanism . On the other hand, adiponectin suppresses hepatic glucose production and enhances muscle glucose uptake .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
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2. Adipose Tissue and Metabolic Health
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Recent studies have further elucidated the mechanisms linking adipose tissue dysfunction to metabolic disorders and obesity, highlighting the roles of impaired adipogenesis, altered adipokine secretion, chronic low-grade inflammation, increased FFA levels, and ectopic lipid accumulation . The balance between lipogenesis and lipolysis is disturbed in obesity due to adipose tissue inflammation and increased tumor necrosis factor alpha (TNFα) levels, which interfere with insulin signaling . The ectopic lipid accumulation in insulin-responsive metabolic tissues (also known as lipotoxicity) impairs insulin signaling .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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2.1. WAT and Metabolic Health
4.046875
biomedical
Study
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WAT is the main type of body fat, categorized into two key subgroups: subcutaneous WAT (sWAT), located under the skin, and visceral WAT (vWAT), found around the abdominal organs . sWAT is a main depot for lipid storage . It provides insulation, protection against infections, and mechanical stress relief . vWAT is usually present in small amounts in healthy individuals and is highly metabolically active, releasing FFAs into the bloodstream. In obesity, excess fat accumulates in the vWAT and other ectopic sites, such as around the heart, blood vessels, digestive organs, liver, and kidneys. This leads to insulin overproduction and resistance, inflammation, and fat deposits in the arteries .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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2.1. WAT and Metabolic Health
4.390625
biomedical
Study
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WAT is the primary site for energy storage, in the form of triacylglycerols, and exhibits high plasticity. Thus, WAT has the ability to expand, reduce, and remodel in response to various metabolic stimuli, such as diet, exercise, and obesity . The ability of sWAT expansion is the key determinant of metabolic dysregulation in obesity . When there is an energy imbalance, the physiological capacity of WAT to accommodate the excess fat is exceeded, triggering organelle stress, tissue hypoxia, the accumulation of extracellular matrix components, tissue infiltration by immune cells, mitochondrial dysfunction, and lipid droplet abnormalities . Moreover, WAT functions as an important endocrine organ by secreting various endocrine factors, such as adipokines, hormones, growth, and inflammatory, which regulate metabolic processes, inflammation, and insulin sensitivity. These secretions play crucial roles in maintaining energy balance and overall metabolic health.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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2.2. BAT and Metabolic Health
4.097656
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BAT’s uniqueness lies in its expression of uncoupled protein 1 (UCP1), an inner mitochondrial membrane protein responsible for thermogenesis by uncoupling the mitochondrial proton gradient from ATP production to generate heat . Another class of adipocytes, known as beige adipocytes, expresses UCP1 but utilizes UCP1-independent thermogenic mechanisms, such as Ca 2+ cycling .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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2.2. BAT and Metabolic Health
4.914063
biomedical
Study
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In addition to the regulation of thermogenesis, BAT is involved in crosstalk with several peripheral tissues, such as the liver, skeletal muscle, and immune cells, to regulate systemic energy balance and glucose homeostasis . It is interesting to note that BAT secretes BATokines, such as fibroblast growth factor 21 (FGF21), interleukin-6 (IL-6), growth differentiation factor 15 (GDF-15), and others . Studies have revealed that human pluripotent cells derived from brown adipocytes significantly improve glucose and lipid metabolism and prevent obesity . Recent studies have reported the association of human BAT with lower TG levels, blood glucose, and higher high-density lipoprotein (HDL) levels . In response to acute or mild cold exposure, BAT activation maintains the thermal demands through non-shivering thermogenesis . Cold acclimation increases the oxidative capacity of BAT, which correlates with a reduction in shivering thermogenesis. In addition, cold adaptation in BAT is also associated with mitochondrial remodeling and vascularization for adaptive thermogenesis and fatty oxidation through UCP1 during periods of high metabolic demands . The physiological regulation of BAT is mediated mainly via beta-3-adrenergic receptors present in brown adipocytes . Additionally, BAT has a critical role in glucose metabolism. The translocation of GLUT1 and GLUT4 to the plasma membrane of brown adipocytes is induced by the stimulation of adrenergic signaling by cold exposure . The uptake of glucose by BAT is also regulated by insulin signaling via the phosphatidylinositol 3-kinase (PI3K)–phosphoinositide-dependent kinase-1 (PDK1)–protein kinase B (PKB/Akt) signaling pathway, promoting the translocation of GLUT4 to the plasma membrane .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
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2.2. BAT and Metabolic Health
3.742188
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The major strategy for treating obesity and metabolic disorders is the manipulation of WAT to the human-like phenotype with increased thermogenic capacity, through a process called “adipocyte browning” .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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3. Effects of Climate Change on Adipose Tissue
4.128906
biomedical
Review
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Climate change significantly impacts adipose tissue function and metabolism, exacerbating the prevalence of obesity and metabolic disorders. The rising temperatures associated with global warming impair BAT thermogenesis, reducing energy expenditure and increasing adiposity . Furthermore, climate change-related factors, such as air pollution and altered dietary patterns, disrupt adipose tissue homeostasis, increasing the risk of metabolic dysfunction . The rise in temperatures also challenges thermoregulation in endothermic species, placing a burden on compensatory mechanisms and raising the risk of heat stress . These environmental stressors, along with extreme weather events and deforestation, further aggravate the issue by influencing nutrition, physical activity levels, and overall metabolic health .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
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3. Effects of Climate Change on Adipose Tissue
4.136719
biomedical
Review
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The role of adipose tissue in maintaining energy homeostasis is essential to the pathophysiology of metabolic disorders. Several reactions, such as vasoconstriction and piloerection, are known to maintain the core body temperature in mammals in response to thermal challenges . Shivering thermogenesis is an acute response to thermal stress, presenting as a continual contraction and relaxation of muscles. In contrast, non-shivering thermogenesis occurs in BAT, generating heat during chronic cold exposure, which is a long-term strategy to respond to cold challenges .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277516_p14
PMC11277516
sec[2]/p[2]
3. Effects of Climate Change on Adipose Tissue
4.320313
biomedical
Study
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It is important to note that the metabolic rate increases when the temperature is below the thermoneutral zone, due to the increased energy required to maintain body temperature . However, when the temperature exceeds the thermoneutral zone, the body’s cooling mechanisms activate energy expenditure . In addition to BAT, sWAT and inguinal WAT (iWAT) undergo morphological changes at different temperatures. For example, in cold environments, sWAT and iWAT undergo a browning process . Exposure to cold temperatures induces altered polarization of the macrophages in BAT. These polarized macrophages contribute to thermogenesis by producing catecholamines that directly activate β-adrenergic signaling in adipocytes . Briefly, cold exposure stimulates an increase in the oxidative metabolism rates of brown and beige adipocytes, resulting in an increased uptake of glucose and free fatty acids .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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3.1. Climate Change and Obesity
3.480469
biomedical
Study
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It is alarming that obesity affects more than 890 million adults (or one in eight people) globally . Notably, 61% of diabetic patients are obese. The global obesity rate has nearly tripled since 1975 . Global warming is caused by increased greenhouse gas (GHG) emissions, such as CO 2 , methane, nitrous oxide, ozone, and fluorinated gases such as chlorofluorocarbons (CFCs) and hydrofluorocarbons (HFCs) . The National Longitudinal Study of Adolescent to Adult Health (Add Health) demonstrated that the atmospheric temperature correlates with a slight increase in weight .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
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3.1. Climate Change and Obesity
4.085938
biomedical
Study
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The increase in oxidative metabolism due to greater metabolic demands and increased food intake may result from high GHG emissions . Obesity stems from many factors, such as high-calorie intake, physical inactivity, and decreased energy dissipation. Impaired thermogenesis is promoted by the reduced expression of the thermogenic genes encoding uncoupling proteins, thyroid hormone receptors, and β-adrenergic receptors, due to chemicals that disrupt hormone metabolism, which increase body weight .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999999
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3.1. Climate Change and Obesity
4.492188
biomedical
Study
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Several studies have found that thermogenesis, a process in which brown or beige adipocytes contribute to increased energy expenditure, varies among different populations , and some of these variations may be attributed to the environment . Increased time spent in the thermal neutral zone can lead to a loss of BAT and decreased thermogenic activity . It is established that thermogenesis plateaus above moderate physical activity levels. Regarding diet-induced thermogenesis, the energy released in the form of heat varies depending on the macronutrient composition of the food consumed. The thermic effect is lowest for fat (0–3%), followed by that for carbohydrates (5–10%), and is highest for protein (20–30%) . The variability in diet-induced thermogenesis can be attributed to factors such as sex, age, body composition, and hormonal status . Exposure to ambient temperature plays an important role in BAT activity. The increased time spent in the thermal comfort zone decreases energy expenditure and has potential obesogenic consequences. At high temperatures, the neuroendocrine mechanism reduces food intake and metabolism, leading to decreased thyroid activity and testosterone and cortisol levels .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999999
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3.1. Climate Change and Obesity
3.607422
biomedical
Other
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In contrast, low temperatures increase adrenal steroid hormone levels and the activity of the pituitary and thyroid glands. A rise in temperature negatively impacts agriculture, resulting in scarce fresh produce. Increased GHG emissions indirectly contribute to the higher production of processed foods due to multiple factors, such as the reduced availability and increased price of fresh food. The increased consumption of processed foods, characterized by their high levels of salt, sugar, and fat, leads to various health issues, including obesity and metabolic disorders . In addition, extreme temperatures negatively affect the level of physical activity, leading to a sedentary lifestyle .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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3.2. Climate Change and T2DM
4.414063
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Study
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Upon exposure to heat, the human body responds with peripheral vasodilation, increased sweat secretion to dissipate energy, and the redistribution of blood flow to the skin. These responses cause heat loss, aiming to maintain optimal body temperature . Elevated blood flow to the skin may result in dehydration and the impairment of insulin signaling and glucose disposal via the inhibition of cellular insulin action and a decrease in blood flow to insulin-sensitive tissues. Furthermore, dehydration promotes IR by disrupting downstream signaling pathways, such as PI3K and hyperosmotic inhibition of PKB activation. Strikingly, increased vasopressin levels due to dehydration stimulate glucose production in the liver and promote IR in the liver, adipose tissue, and pancreas . In T2DM, high temperatures may also disrupt thermoregulation by impairing the orthostatic response . Blauw et al. estimated that each degree of C increase in the outdoor temperature may be associated with 100,000 new diabetes cases annually in the United States .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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3.2. Climate Change and T2DM
3.927734
biomedical
Study
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Several studies have reported that air pollution increases IR and its associated complications . Air pollutants, such as ozone and fine particulate matter (PM), can cause diabetic complications . Fine particulate matter up to 2.5 μm (PM2.5) is a mixture of organic and inorganic chemicals generated from human and natural sources. It consists of carbonaceous nuclei that absorb polycyclic aromatic hydrocarbons and endotoxic metals from the atmosphere . PM2.5 is known to increase the risk of T2DM and its associated cardiovascular diseases (CVD) .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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4. Environmental Factors Affecting Adipose Tissue Metabolism
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Adipose tissue undergoes hyperplasia and hypertrophy in response to energy overload and temperature changes. Perinatal exposure to endocrine disruptors, such as DDT, may impair BAT thermogenesis and increase the risk of metabolic syndrome . In addition, air pollutants increase the risk of IR due to BAT mitochondrial dysfunction. The mechanism linking thermogenesis to the risk of IR involves the activation of peroxisome proliferator-activated receptor-gamma co-activator-1-alpha (PGC-1α), a master regulator of energy metabolism . Furthermore, the effects of DDT and DDE on BAT may be mediated by the aryl hydrocarbon receptor (AHR), a physiological carbon regulator of energy metabolism. AHR activation is increased by pro-inflammatory cytokines . In short, DDT and its metabolite DDE induce nuclear factor-kappa B (NF-κB) activation and the production of pro-inflammatory cytokines, which mediate the upregulation of the AHR .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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4.1. Air Pollutants and BAT
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Long-term exposure to PM2.5 has been shown to induce inflammation and decrease BAT weight, mitochondrial size in BAT, and mitochondrial number in WAT, changes associated with a process known as BAT “whitening” . Interestingly, homeobox protein C9 (HOXC9) and insulin-like growth factor binding protein 3 (IGFBP3) genes, characteristic of WAT, are upregulated in BAT, supporting the transformation of brown adipocytes to the WAT phenotype . Zhang et al. suggested that PM2.5 might impact BAT development through TNFα-mediated apoptosis and inflammation. BAT inflammation is associated with impaired insulin signaling, as evidenced by the decreased Ser437 phosphorylation of AKT in BAT . Additionally, long-term exposure to PM2.5 induces low-grade inflammation in the hypothalamus, indirectly causing BAT dysfunction. Other pollutants, such as mono-2-ethylhexyl phthalate (MEHP), promote adipocyte differentiation and induce obesity in mice . A study by Farrugia et al. suggested a correlation between bisphenol A (BPA) and obesity, diabetes, and metabolic disorders. In contrast, polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), have anti-obesogenic effects, increasing the rate of oxidative capacity in brown fat mitochondria via UCP1 upregulation .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
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4.1. Air Pollutants and BAT
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DDT and DDE impair BAT activity through multiple mechanisms, including reducing substrate transport and utilization, downregulating the expression of the genes involved in thermogenesis, inhibiting the deiodination of thyroxine (T4) to triiodothyronine (T3), and inducing IR and inflammatory pathways in BAT . In contrast, PFOA and PFOS increase mitochondrial oxidation via UCP1 upregulation in BAT, thereby decreasing food intake and body weight.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
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4.2. Temperature-Related Adaptations of BAT Function and Metabolism
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Changes in temperature alter the physiological and molecular aspects of adipose tissue to adjust to a new tissue homeostasis. Studies on mice have revealed that differences in metabolic rates have been observed due to thermal challenges. A gradual decrease in temperature from 30 °C to mild cold temperature (16–20 °C) to severe cold (5 °C) temperature causes a gradual increase in oxygen consumption . Thus, when the temperature is decreased, the rate of metabolism increases as more energy is required to maintain body temperature. On the other hand, energy expenditure is stimulated when the ambient temperature exceeds the thermoneutral zone and body-cooling mechanisms are activated .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
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4.2. Temperature-Related Adaptations of BAT Function and Metabolism
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One study demonstrated the effects that housing ob / ob mice at 14 °C, 22 °C, and 30 °C had on their core temperature and energy expenditure. In this case, the hypothermic phenotype of the ob / ob mice was partially rescued by leptin administration associated with decreased thermal conductance, proving the physiological effects of leptin in maintaining core body temperature under sub-thermoneutral conditions . The ambient temperature plays a crucial role in defining the metabolic phenotypes of mice. For example, nude mice exhibit reduced heat insulation and might activate compensatory thermogenic programs, such as BAT and beige adipocyte-mediated non-shivering thermogenesis (NST), leading to increased energy expenditure . It is well known that BAT activity improves obesity-induced metabolic dysfunction. However, a lack of brown adipocytes increases body weight, IR, and adipose tissue inflammation . BAT has multilocular brown adipocytes at room temperature, whereas in the thermoneutral (TN) zone, it has unilocular brown adipocytes. In addition, at cold temperatures, iWAT consists of multilocular adipocytes, indicating a browning event, which completely disappears in the TN zone . Furthermore, in the TN zone, whitened BAT exhibits decreased mitochondrial density and gene and protein expression .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277516_p26
PMC11277516
sec[3]/sec[1]/p[2]
4.2. Temperature-Related Adaptations of BAT Function and Metabolism
4.304688
biomedical
Study
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Exposure to cold induces the alternative polarization of the macrophages in BAT and beige adipose tissue (BeAT), which induces thermogenesis by producing catecholamines and directly activating β-adrenergic signaling in adipocytes . Another important feature is the alteration of immune cell composition; being in the TN zone systemically causes an accumulation of lymphocyte antigen 6 complex, locus G (LYG6) + monocytes in bone marrow. Additionally, there is an increase in the TNFα and IL-6 levels in the serum of mice . Conversely, cold exposure results in fewer activated monocytes and reduced T cell expression in autoimmunity .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277516_p27
PMC11277516
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4.2. Temperature-Related Adaptations of BAT Function and Metabolism
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biomedical
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Intermittent cold exposure (ICE) (exposing the body to low temperatures for short periods) is known to increase subcutaneous WAT and has variable effects on visceral WAT. ICE promotes weight loss maintenance and attenuates the positive energy balance during relapse by increasing energy expenditure in mice . Numerous studies have demonstrated that ICE increases BAT activation and reduces weight . ICE induces systemic responses to defend the core body temperature. For example, increased glucagon due to ICE acts as a browning stimulus via the activation of FGF21 secretion. The high expression of UCP1, high rates of substrate turnover, and abundant mitochondria are other alterations in the network of crosstalk underlying the physiological responses to ICE .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277516_p28
PMC11277516
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4.2. Temperature-Related Adaptations of BAT Function and Metabolism
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In BAT, the induction of UCP1 and peroxisome proliferator-activated receptor-gamma (PPARγ) expression increases the fat utilization capacity via the increased expression of lipoprotein lipase (LPL) . Furthermore, beige adipocytes, which are highly responsive to cold, have increased sensitivity to irisin secreted by muscles . It is essential to understand the effects of cold exposure on the secretory function of adipose tissue, particularly the modulatory role of adipokines in blood glucose and insulin sensitivity; however, direct evidence linking ICE and adipokine modulation is limited. Wang et al. reported that the combination of ICE and exercise in rats reduced IR and blood glucose levels. In addition, adipose triglyceride lipase (ATGL) and LPL activity in inguinal adipose tissue were shown to increase in response to ICE. Moreover, ICE enhances the capacity of skeletal muscles to oxidize FFAs via PGC1α and p38 MAPK upregulation . As much of the research is centered on rodent models, further research is needed on the effects of ICE on humans.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
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PMC11277516
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4.3. Air Pollutants and WAT Dysfunction
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Chronic exposure to PM2.5 is associated with WAT expansion and increased adiposity . In addition to stimulating adipogenesis, PM2.5 also decreases catecholamine-induced lipolysis. Additionally, PM2.5 exposure is associated with altered thyroid function and decreased T3 and T4 plasma levels . In skeletal muscles, PM2.5 exposure inhibits NO-dependent microvessel dilation and decreases mitochondrial oxidative capacity . Results from multiple rodent studies have suggested that exposure to PM2.5 induces adipocyte hypertrophy and WAT expansion. Notably, PM2.5 directly oxidizes organic molecules and stimulates reactive oxygen species (ROS) production, interfering with the mitochondrial respiratory chain in cells . The evidence suggests that long-term exposure to PM2.5 in rodents increases the expression of lipogenic genes, such as those encoding acetyl-CoA carboxylase (ACC) and diacylglycerol O-acyltransferase 2 (DGAT2), with an increase in PPARα and cAMP response element-binding protein alpha (CREB-α) .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999998
PMC11277516_p30
PMC11277516
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4.3. Air Pollutants and WAT Dysfunction
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Importantly, exposure to PM2.5 leads to hypothalamic inflammation associated with leptin resistance, decreased energy expenditure, and WAT accumulation . Additionally, it is associated with increased gut permeability, causing the migration of bacterial LPS and the release of pro-inflammatory molecules, stimulating WAT inflammation and adipogenesis. Moreover, chronic PM2.5 exposure causes a significant reduction in the mitochondrial number and size in WAT and BAT, suppressing PCG-1α and UCP1, and leading to impaired lipid metabolism, increased oxidative stress, mitochondrial dysfunction, and TG storage in white adipocytes .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277516_p31
PMC11277516
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4.4. Association between Climate Change, Air Pollution, and Altered Dietary Patterns
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biomedical
Review
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Unhealthy dietary habits, such as a high intake of fried and sugar-rich foods and a decreased consumption of red meat, fruits, and vegetables, contribute to central and global adiposity. Furthermore, these dietary habits are associated with sedentary behavior in adults . A high intake of white bread is also associated with central and global adiposity in adults . Studies have shown that food availability, access, and utilization can largely influence dietary patterns and lead to the consumption of high-calorie or processed foods. This also leads to an inadequate consumption of essential nutrients, such as proteins, vitamins, and minerals, contributing to dyslipidemia and increased central adiposity . Climate change also affects soil fertility, rain patterns, crop yields, food production, and nutrient bioavailability . It is important to note that there is a reciprocal and cyclical association between food production and climate change. Increased fertilizer use and deforestation lead to increased GHG emissions and climate change, subsequently decreasing food production . Weather events, such as drought, flooding, and heat waves, correlate with decreased rain patterns, reduced soil fertility, and acid rain due to increased fertilizer usage . Additionally, climate change alters supply chains, transportation, yield, biomass food composition, the quality of nutrition, and food prices. All these effects collectively increase the consumption of processed foods and high-calorie diets, thus elevating the incidence of abdominal adiposity .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277516_p32
PMC11277516
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4.4. Association between Climate Change, Air Pollution, and Altered Dietary Patterns
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biomedical
Review
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Air pollution can also influence dietary patterns by affecting food production, quality, and consumption. Exposure to air pollutants, such as PM2.5 and nitrogen oxides (NO x ), can reduce crop yields and nutrient content, potentially leading to the increased consumption of processed and energy-dense foods . Additionally, air pollution has been associated with increased oxidative stress and inflammation, which may alter appetite regulation and food preferences, promoting the consumption of high-calorie and high-fat foods . These changes in dietary patterns can further exacerbate the risk of obesity and metabolic disorders. Moreover, increased CO 2 concentrations in the atmosphere result in decreased plant protein content and micronutrients, such as calcium, iron, and zinc. For example, C3 grains and tubers, such as rice, wheat, barley, and potatoes, have experienced a 7–15% decrease in protein content . Thus, climate change and air pollution have a clear nutritional effect that can reduce or worsen food availability and dietary diversity.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999995
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5. Climate Change Adaptation and Mitigation Strategies
3.763672
biomedical
Review
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Climate change and air pollution are global threats that accelerate antimicrobial resistance, food and airborne diseases, and metabolic disorders. Climate change reduces crop yields and their micronutrient content, disrupting the food supply chain and increasing obesity rates . Minimizing GHG emissions will help to reduce climate change impacts to a large extent . The use of fossil fuels increases GHG emissions, obesity, and metabolic dysfunction. Increased physical activity, such as walking or biking, can decrease the prevalence of obesity . A sustainable diet with a low microenvironmental impact is safe and could help reduce obesity and its dire consequences. Reducing meat consumption can significantly decrease GHG generation, thus indirectly impacting crop growth .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999998
PMC11277516_p34
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5. Climate Change Adaptation and Mitigation Strategies
3.818359
biomedical
Review
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Incorporating plant-based proteins, such as soy, legumes, and nuts, into the diet has been suggested as a potential strategy with which to mitigate the effects of climate change and pollution-induced obesity . These protein sources have a lower environmental impact compared to animal-based proteins, and their consumption has been associated with better weight management and a reduced risk of obesity-related comorbidities. Furthermore, promoting active transportation, such as walking and cycling, can contribute to a decrease in air pollution, particularly in the form of PM2.5, which has been linked to an increased risk of obesity .
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999995
PMC11277516_p35
PMC11277516
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5. Climate Change Adaptation and Mitigation Strategies
3.990234
biomedical
Review
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Given the multiple threats posed by factors, such as heat, pollution, and extreme weather events, that exacerbate diabetes, the implementation of various mitigation strategies and individual adaptation measures is crucial. These strategies may include personal cooling techniques during periods of extreme heat, efforts to minimize the effects of air pollution through lifestyle modifications that reduce GHG emissions, and limiting outdoor activities or wearing face masks to minimize exposure to high levels of air pollution . Additionally, BAT activation in cold environments has been shown to increase lipid oxidation and glucose uptake in skeletal muscle, leading to improved insulin sensitivity . This highlights the potential benefits of cold exposure as a therapeutic approach to managing diabetes.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999994
PMC11277516_p36
PMC11277516
sec[4]/p[3]
5. Climate Change Adaptation and Mitigation Strategies
1.886719
biomedical
Other
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Moreover, shifting from vehicle transportation to cycling would increase physical activity levels and contribute to a reduction in GHG emissions, which might ultimately lower the risk of developing T2DM . Promoting active transportation and encouraging the adoption of low-carbon transportation models could have significant health benefits while simultaneously addressing environmental concerns.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999994
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6. Conclusions
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biomedical
Review
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This review highlights the significant impact of climate change and air pollution on adipose tissue dysfunction, obesity, and metabolic health. The rising temperatures associated with global warming can impair BAT thermogenesis and adaptive energy expenditure, contributing to increased adiposity. Air pollution, particularly exposure to PM2.5, can induce WAT inflammation, oxidative stress, and mitochondrial dysfunction, exacerbating the risk of IR and metabolic disorders. Furthermore, climate change and air pollution can alter dietary patterns, promoting the consumption of energy-dense and processed foods, further contributing to the obesity epidemic.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
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6. Conclusions
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biomedical
Other
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The bidirectional relationship between obesity and climate change is evident in the current literature. The impact of climate change, particularly the increase in ambient temperatures, is expected to contribute to higher rates of obesity and T2DM, partially due to reduced physical activity levels. As the global climate continues to change, developing and implementing individual and collective strategies will be crucial for minimizing the adverse effects on public health.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
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6. Conclusions
3.230469
biomedical
Other
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Reducing the adverse effects of climate change and air pollution on metabolic health requires the implementation of policies and interventions to reduce GHG emissions, improve air quality, and promote healthy dietary habits. These may include promoting renewable energy sources, applying energy-efficient technologies, and encouraging sustainable land-use practices. Furthermore, public health initiatives that focus on promoting healthy eating habits and reducing the intake of processed foods could contribute to individual health and environmental sustainability.
[ "Radoslav Stojchevski", "Preethi Chandrasekaran", "Nikola Hadzi-Petrushev", "Mitko Mladenov", "Dimiter Avtanski" ]
https://doi.org/10.3390/ijms25147849
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277528_p0
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1. Introduction
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Bacterial leaf streak (BLS) is one of the most important diseases of rice in Asia, Australia, and Africa. Xanthomonas oryzae pv. oryzicola ( Xoc ) is a bacterial pathogen responsible for BLS, which causes significant yield losses in rice fields, with estimates ranging from 10% to 30% in severely infected areas. This translates into substantial economic losses for farmers and the rice industry globally . Xoc is a Gram-negative bacterium and possesses a single polar flagellum, which plays important roles in bacterial motility and pathogenicity . The virulence mechanisms of Xoc are greatly complicated. There is little research on virulence mechanisms, and the control measures for BLS are poorly developed. Bacterial plant pathogens possess a range of pathogenicity factors, including type Ⅲ effector, extracellular polysaccharides (EPSs), lipopolysaccharides, extracellular enzymes, motility, and biofilm . These pathogenicity factors facilitate the infection of host tissues by the pathogen. The regulation of these pathogenicity factors is mediated by intricate regulatory mechanisms, including a two-component system (TCS). TCS plays a pivotal role in orchestrating the bacterial response to environmental cues and fine tuning the expression of virulence-associated genes, thereby ensuring the precise control of pathogenicity.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999994
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LuxR-family transcriptional regulators are generally 250 amino acids in size with a helix–turn–helix LuxR (HTH-LuxR) domain at the C-terminus and a variable domain at the N-terminus that interacts with signaling substances, for example, the quorum sensing (QS) system, TCSs, and other signals . The HTH-LuxR domain has the capacity to bind with a distinct gene promoter, thereby either stimulating or suppressing the expression of the intended genes. It is widely known that LuxR plays a role in the QS system. The N -acyl homoserine lactones (AHLs) are small, diffusible molecules used as communication signals in a large variety of proteobacteria . A typical AHLs-mediated QS system is composed of a LuxR protein and a cognate LuxI protein, which were first identified in Vibrio fischeri . This kind of LuxR-type protein has an N-terminal AHLs-binding domain and a C-terminal HTH-LuxR DNA-binding domain.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
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1. Introduction
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TCSs, comprising a membrane-bound histidine kinase sensor (HKs) and a cytoplasmic response regulator (RR), represent the primary molecular mechanisms utilized by prokaryotes to perceive and react to environmental cues . TCSs play an important role in the pathogenicity of microbes. In 1986, Ninfa et al. revealed in Escherichia coli ( E. coli ) a two-component signal transduction system, wherein the nitrogen-regulatory protein NRI is intricately regulated by the histidine kinase NRII, constituting a receptor–regulator pair that governs nitrogen metabolism. This marked the initial recognition of such a system by researchers . In Xanthomonads spp., the RpfC/RpfG, responsible for QS signal transduction, plays a role in positively regulating pathogenicity factors . In Xanthomonas campestris pv. vesicatoria , the function of HrpG was determined to occupy a pivotal position at the apex of the hrp gene regulatory cascade. The amino acid sequence of HrpG exhibits similarity to RR proteins belonging to the OmpR-family subclass of TCSs . By interacting with the downstream AraC-family transcription factor HrpX, HrpG regulates the expression of the type Ⅲ secretion system (T3SS), which is a crucial transportation machinery responsible for delivering effectors into host cells .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
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Bacteria display diverse locomotor patterns based on whether they reside in a liquid medium or are in contact with a solid substrate . In liquid environments, certain bacteria produce flagella and navigate in three dimensions as individual swimmers; however, upon encountering a solid surface, they initiate swift swarming locomotion in two dimensions across the substrate . Moreover, swimmer and swarmer cells exhibit physiological differences, as the transition to surfaces involves a period of immobility known as a lag phase, which could serve as a window for cellular differentiation triggered by surface contact . Swarming motility was first recorded for Proteus species and subsequently observed to be widespread among flagellated bacteria . Unlike swimming, bacteria exhibit a lag before moving. Bacteria must reach higher cell densities, and they generally require energy-rich media for swarming to begin . Flagella are the primary organelles responsible for bacterial motility in aqueous environments. Flagella are essential multi-functional structures composed primarily of a 39 kDa flagellin protein (FliC) and a 56 kDa flagellar cap protein (FliD). FliS acts as a flagellin protein (FliC) export chaperone. When the expression of these flagellar proteins is reduced, the bacteria are unable to assemble functional flagella, leading to a decrease in motility. In natural habitats, bacteria often compete with other microorganisms for resources and space. Decreased flagellar stability due to reduced gene expression can make bacteria more susceptible to these stresses, potentially reducing their survival rates in adverse conditions. For pathogenic bacteria, flagella play a crucial role in virulence, as they are involved in host cell attachment, invasion, and biofilm formation. This impairment can affect the ability of bacteria to colonize surfaces, move toward nutrients, or escape from harmful environments . In many bacteria, mutations that overcome these requirements map to TCSs or to regulators that increase flagella synthesis.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999995
PMC11277528_p4
PMC11277528
sec[0]/p[4]
1. Introduction
4.09375
biomedical
Study
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The formation of biofilms involves several phases: initial attachment, the establishment of microcolonies and macrocolonies, and ultimately, detachment or disassembly . EPSs play crucial roles throughout each of these stages: facilitating adhesion to surfaces, facilitating the formation of intricate structures by enhancing microbial interactions, and facilitating the release of these interactions to promote the dissolution of the biofilm. Bacteria are capable of producing multiple EPSs, which are significant in diverse strains and varying environmental conditions, encompassing surface substrate, nutritional availability, and flow rate .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999998
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1. Introduction
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These pathogenicity factors play a vital role in determining the virulence of Xoc , as they contribute significantly to its ability to cause disease. Typically, these pathogenicity factors are intricately regulated by the TCSs. Conducting a thorough study on TCSs and pathogenicity factors is highly imperative, as it offers crucial insights into the mechanisms underlying disease causation and virulence of Xoc .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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1. Introduction
4.417969
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Study
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Despite the crucial role TCSs play in regulating bacterial gene expression and cellular activities, their investigation in Xanthomonas spp. remains limited, necessitating further exploration to fully understand their functional significance within this genus. In this study, we identified the XOC_2507 regulator, a member of the LuxR family within the TCSs, in Xoc GX01 . Our objective was to elucidate the role of XOC_2507 in virulence, motility, EPS production, and biofilm formation in Xoc GX01 through gene knockdown experiments. Additionally, we aimed to explore the underlying mechanisms regulated by XOC_2507 expression using high-throughput transcriptional sequencing. RNA sequencing (RNA-Seq) analysis revealed that numerous genes involved in diverse functions were significantly differentially expressed in the ∆ XOC_2507 strain. Moreover, XOC_2507 can bind to the promoters of fliC , fliS and gumB in vitro. Herein, XOC_2507 is designated as VmsR (Virulence, Motility and Extracellular polysaccharides and Regulator). This study identifies a novel regulator, VmsR, which regulates the expression of virulence-associated flagella and EPS in Xoc .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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2.1. Identification of VmsR, a Putative LuxR-Type Regulator of Xoc, and Generation of vmsR Mutant and Its Complementary Strain
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An open-reading frame (ORF) encoding 210 amino acids residues was identified in the genome sequence of the Xoc GX01 , located from nucleotide 2453070 to 2453702, with the locus tag of XOC_2507 . In this study, the gene has been designated as vmsR , exhibiting a characteristic architecture that is typical of the LuxR family of response regulators. Specifically, it comprises a receiver domain situated at the N-terminus, responsible for signal reception, and a helix–turn–helix (HTH) domain positioned at the C-terminus, enabling DNA binding . The VmsR gene and the quorum-sensing signal receptor XocR exhibit no discernible similarities at the nucleotide or protein level ( Table S4 ). XocR possesses an Autoind_bind domain at the N-terminus and HTH-LuxR domain at the C-terminus . The xocR is located from nucleotide 1409638 to 1410402 with the locus tag of XOC1422 in the genome of Xoc BLS256 . The Autoind_bind domain binds AHLs, which are also known as autoinducers. The upstream of VmsR encompasses a gene cluster that is integral to the synthesis of flagellum, which is a vital component for bacterial motility and pathogenesis . To investigate the functional role of the VmsR regulator, the ∆ vmsR strain was constructed and analyzed .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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en
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2.1. Identification of VmsR, a Putative LuxR-Type Regulator of Xoc, and Generation of vmsR Mutant and Its Complementary Strain
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To determine the evolutionary relationship between VmsR and diverse Xanthomonads spp. LuxRs, a phylogenetic tree was constructed with MEGA11 software. We selected 22 LuxR-type regulatory proteins from diverse Xanthomonads species. Upon analysis, the 22 genes were systematically classified into two distinct categories. Taking VmsR of Xoc GX01 as the representative protein, it is classified into one category, while XocR of Xoc BLS256, as the representative protein, is grouped into a separate category . VmsR shares very close evolutionary relationships with the LuxR-type HTH regulators XOC_2369 of Xoc BLS256 . In addition, XocR has relatively close relationships with Xoc_3513 of Xoc GX01 . This suggests that the VmsR in Xoc GX01 is also a LuxR-type transcriptional regulator because it is an Xoc regulator that is different from XocR in the cognate strain Xoc BLS256.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.2. VmsR Positively Affects the Virulence of Xoc GX01
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To determine whether VmsR contributes to the virulence of Xoc GX01, the virulence of Xoc strains was tested in this work. The pathogenicity ability of wild-type strain GX01, mutant strain ∆ vmsR , and its complementary strain C∆ vmsR was evaluated by inoculation onto the leaf of Oryza sativa L. ssp. japonica cultivar Nipponbare. Fifteen days after inoculation, ∆ vmsR caused disease symptoms with a lesion length of 16.8 ± 1.64 mm, which was significantly less severe than that caused by the GX01 (lesion length 32.53 ± 2.16 mm). Notably, the C∆ vmsR strain exhibited virulence symptoms (lesion length 30.47 ± 1.82 mm) similar to those of the wild-type strain GX01 . This result indicates that C∆ vmsR could restore the impaired virulence of ∆ vmsR . These results suggest that VmsR positively regulates the pathogenic capacity demonstrated by Xoc GX01.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.3. VmsR Is an Important Regulator Involved in Various Cellular Processes of Xoc
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To determine whether VmsR plays a crucial role in virulence, we compared the ∆ vmsR with its wild-type strain Xoc GX01 through RNA-Seq. For all six samples analyzed (3 × ∆ vmsR and 3 × GX01), more than 80% of the total reads were successfully mapped back to the assembled transcriptome. From the total of 5006 genes obtained in the transcriptome of Xoc GX01, 140 genes were found to be statistically significant differentially expressed genes (DEGs) between ∆ vmsR and GX01 using a more stringent threshold (FDR ≤ 0.05 and |Fold Change| ≥ 2). Among these genes, 76 genes were upregulated and 64 genes were downregulated in ∆ vmsR .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.3. VmsR Is an Important Regulator Involved in Various Cellular Processes of Xoc
4.144531
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Study
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To gain a deeper understanding of the functionalities of genes regulated by VmsR, we performed a functional grouping analysis based on the genomic annotations of the Xoc GX01 . Based on the clusters of orthologous groups (COGs), out of the 140 DEGs in the ∆ vmsR strain, 104 were assigned to 15 various functional categories and 36 were predicted to encode hypothetical proteins or proteins that have not been given a functional category . The primary functional groupings are “cellular processes” and “pathogenicity and adaption”. In total, 18 and 11 genes fell into these two categories, respectively . Notably, 105 genes were assigned to “cell envelope and cell structure” (10) and “translation” (12). Table S3 shows a detailed categorization of DEGs.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.3. VmsR Is an Important Regulator Involved in Various Cellular Processes of Xoc
4.503906
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Consistent with the finding that LuxR regulates cell motility , the identified transcriptional profiles reveal that VmsR has a crucial impact on a number of genes that contribute to cell motility. Upon a thorough examination of the functional classification of the 140 DEGs identified in the ∆ vmsR mutant of Xoc GX01, it is evident that the pathways most significantly affected are those associated with cellular processes, which are fundamental to the survival, growth, and virulence of the bacterium. This observation underscores the central role that VmsR plays in regulating vital cellular activities, particularly those related to motility. Consequently, there is a pressing need to delve deeper into the regulatory mechanisms employed by VmsR in this regard. The pertinent gene clusters that are implicated in these processes are outlined as follows: The four flagellar-related DEGs consist of three genes, namely XOC_2502 / fliC , XOC_2503 / fliD , and XOC_2504 / fliS , which encode proteins integral to the formation of flagellar filaments. Additionally, there is a gene encoding the upstream regulator of flagella, flrA . Fourteen of the DEGs encode methyl-accepting chemotaxis proteins: XOC_2212 , XOC_2478 , XOC_2590 , XOC_2602 , XOC_2603 , XOC_2604 , XOC_2605 , XOC_2606 , XOC_2610 , XOC_2612 , XOC_2614 , XOC_2615 , XOC_2617 , and XOC_2861 . The expression levels of the mRNA for these genes corresponded closely with the RNA-Seq data . The findings demonstrate a significant role of VmsR in influencing the motility of Xoc . Taken together, the results from the transcriptome analysis reveal that VmsR acts as an essential regulator involved in many cellular processes in Xoc .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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2.4. Loss of vmsR in Xoc Enhanced the Swarming Motility but Impaired the Swimming Motility
4.117188
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Based on the RNA-Seq analysis, we hypothesize that VmsR is linked to bacterial motility. To validate this prediction, we conducted a study to measure the swarming and swimming motilities of Xoc GX01, the ∆ vmsR mutant strain, and the complementary strain C∆ vmsR . To assess swarming motility, Xoc strains were inoculated in a semi-solid NA medium containing 0.6% agar and incubated at 28 °C for 3 days. The wild-type strain GX01 exhibited an average bacterial colony diameter of up to 13.00 mm, which was significantly smaller than the 43.83 mm diameter observed for the ∆ vmsR strain. Notably, the C∆ vmsR strain exhibited a colony diameter averaging 13.33 mm, which is comparable to the wild-type strain GX01 .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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2.4. Loss of vmsR in Xoc Enhanced the Swarming Motility but Impaired the Swimming Motility
4.171875
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Bacterial swimming motility is dependent on the flagellum. To evaluate swimming motility, Xoc strains were inoculated in semi-solid basal medium with 0.25% agar and incubated at 28 °C for 3 days. The wild-type strain GX01 displayed a bacterial colony diameter averaging 40.17 mm, which was comparable to the 39.33 mm observed in the C∆ vmsR strain. The ∆ vmsR strain exhibited a significantly smaller colony diameter of 29.17 mm, as depicted in Figure 4 C,D. This reduction in swimming motility in the ∆ vmsR strain may be attributed, in part, to diminished flagellar biogenesis. Collectively, these findings indicate that VmsR plays contrasting roles in regulating swarming and swimming motility in Xoc GX01.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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2.5. VmsR Specifically Binds to the fliC and fliS Promoter In Vitro and Facilitates Their Expression
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The swimming motility of the ∆ vmsR strain has decreased. Bacterial swimming motility is fundamentally reliant on the flagellum, which is a complex organelle responsible for propelling the bacterium through its environment . The model of the flagellum structure is shown in Figure 5 A. The RNA-Seq analysis revealed the downregulation of three genes ( fliC , fliD , and fliS ) that are associated with flagella synthesis. The mRNA expression levels of the fliC , fliD and fliS genes were verified by RT-qPCR. As shown in Figure 5 B, the transcriptional levels of these genes were significantly reduced in the ∆ vmsR compared to GX01, and the expression patterns of these selected genes are all consistent with that observed in the data obtained from the transcriptome analysis .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.5. VmsR Specifically Binds to the fliC and fliS Promoter In Vitro and Facilitates Their Expression
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To determine if the transcriptional regulation of fliC , fliD , and fliS is mediated by the direct binding of VmsR to the promoter region, in vitro electrophoretic mobility shift assays (EMSAs) were performed. Purified recombinant VmsR-His 6 was incubated with 6′-carboxyfluorescein (6′-FAM)-labeled DNAs in binding buffer; then, the protein–DNA complexes were separated by electrophoresis in 4% polyacrylamide gel. The findings conclusively reveal that the recombinant VmsR-His6 exhibits a robust binding affinity to the fliC and fliS promoter regions, significantly impeding their migration within the polyacrylamide gel . Moreover, the observed shifted bands were displaced by an excess of unlabeled probes (10×, 50×, 100×), thus confirming the specificity of VmsR’s binding to the fliC and fliS promoter. To guarantee the specificity of VmsR binding, we incorporated a negative control promoter (the atsE promoter), which demonstrated no affinity for VmsR. As shown in Figure S2A , the EMSA results demonstrate that VmsR can directly bind to the promoter of fliC and fliS while failing to bind to the fliD promoter.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.5. VmsR Specifically Binds to the fliC and fliS Promoter In Vitro and Facilitates Their Expression
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These results supported the hypothesis that VmsR acts as a transcriptional activator of the fliC and fliS promoter. The reduced expression of fliD could been indirectly regulated by VmsR.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.6. EPS Production and Biofilm Formation of the ∆vmsR Strain Were Increased
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In the above results, we found an interesting phenomenon. The swimming motility and swarming motility of the ∆ vmsR strain were opposite. Liu et al. found that the self-secreted EPSs are essential for the swarming motility exhibited by Pseudoalteromonas sp. SM9913 . Consequently, EPS was measured qualitatively and quantitatively in this study. Compared with the wild-type strain, EPS production of the ∆ vmsR significantly increased both in qualitative and quantitative analysis. In terms of shape, the colony form of ∆ vmsR is fuller and shinier than wild-type strain GX01 and the complementary strain C∆ vmsR . EPS production was up to 12.96 g/L for the vmsR mutant, significantly greater than 6.383 g/L for the wild-type strain Xoc GX01, but similar to 7.45 g/L for the complementary strain C∆ vmsR .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.6. EPS Production and Biofilm Formation of the ∆vmsR Strain Were Increased
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[ 0.99951171875, 0.0002818107604980469, 0.0002677440643310547 ]
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It is firmly established that the biofilm formation process of numerous bacteria necessitates the presence of both EPSs and the type IV pilus (T4P). EPSs occupy a pivotal role in this biofilm formation. EPS constitutes part of the biofilm matrix that maintains and organizes bacterial biofilms, while the T4P facilitates surface attachment as adhesins . Biofilm formation was measured qualitatively and quantitatively in this study. When compared to the Xoc GX01 strain, the biofilm formation capacity of the ∆ vmsR mutant was observed to be significantly elevated . Quantification of the biofilm formation was achieved through the measurement of optical density at 590 nm (OD 590 ). Specifically, the mean OD 590 value for the ∆ vmsR mutant was 3.04, which significantly surpassed the values of 1.22 recorded for Xoc GX01 and 1.38 for the C∆ vmsR strain .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.6. EPS Production and Biofilm Formation of the ∆vmsR Strain Were Increased
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Taken together, the results indicate that VmsR negatively affects EPS production and biofilm formation in Xoc GX01. Furthermore, we hypothesize that the enhanced biofilm formation and swarming motility could be attributed to the increased production of EPS.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.7. VmsR Specifically Binds to the gumB Promoter In Vitro and Inhibits Its Expression
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EPS is encoded by a gene cluster with gumB serving as one of the primary genes within this cluster. The gumB gene plays a pivotal role in exporting the xanthan . The mRNA expression levels of gumB gene were verified by RT-qPCR. As shown in Figure 7 A, the transcriptional levels of gumB gene were significantly upregulated in the ∆ vmsR compared to GX01. To determine whether VmsR could directly regulate the gumB operon, in vitro EMSAs were conducted. Purified recombinant VmsR-His 6 was incubated with a 6′-FAM-labeled DNA (440 bp) spanning from bp −455 to −16 ( Table S2 ) relative to the translational initiation site (TIS) of the gumB operon. Then, the protein–DNA complexes were separated by electrophoresis in 4% polyacrylamide gel. A distinct shift band was observed with increasing concentrations of recombinant VmsR-His 6 . Competitive binding assays with unlabeled probes at various concentrations (10×, 50×, 100×) demonstrated competitive interactions, leading to progressively fainter or absent shift bands in the presence of non-fluorescent competitive probes . Taken together, these results illustrate that VmsR could specifically bind to the gumB operon promoter and repress the expression of gumB gene.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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2.7. VmsR Specifically Binds to the gumB Promoter In Vitro and Inhibits Its Expression
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Additionally, the putative consensus sequence recognized by VmsR using the MEME Suite ( https://meme-suite.org/meme/ ), with the promoter regions from fliC , fliS and gumB , identified the core DNA-binding sequence 5′-GTHGTGWWCSMWRWGKYTT-3′ (H: A/C/T; W: A/T; S: C/G; M: A/C; R: A/G; K: G/T; Y: C/T) .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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3. Discussion
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[ 0.99951171875, 0.00028061866760253906, 0.0002429485321044922 ]
[ 0.99951171875, 0.00023686885833740234, 0.00027108192443847656, 0.00007110834121704102 ]
In this work, we identified a LuxR-type transcriptional regulator VmsR, which acts as a global regulator influencing diverse cellular processes including cell motility, EPS production and biofilm formation in Xoc GX01. Specifically, we have identified VmsR as a key regulator of flagellum in Xoc . Our findings indicate that VmsR directly promotes the expression of fliC and fliS genes, revealing its crucial role in positively regulating motility and pathogenicity in Xoc .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999995
PMC11277528_p24
PMC11277528
sec[2]/p[1]
3. Discussion
4.390625
biomedical
Study
[ 0.99951171875, 0.0003218650817871094, 0.00025653839111328125 ]
[ 0.9990234375, 0.000331878662109375, 0.0005583763122558594, 0.0001004338264465332 ]
LuxR-type regulators are known to play a role not only in the QS system but also in other biological functions such as flagellar synthesis. For example, AcrR, a LuxR-type regulator, regulates flagellar assembly and contributes to the virulence, motility, biofilm formation, and growth ability of Acidovorax citrulli . VisN and VisR, two LuxR-type regulators in Sinorhizobium meliloti , act as global regulators of chemotaxis, flagellar, and motility genes . AclR, also a LuxR-type global regular, regulates the motility and virulence of A. citrulli . In accordance with the aforementioned LuxR-type regulators, VmsR similarly performs a crucial function in governing chemotaxis, flagellar assembly, and motility-associated genes. As demonstrated in our study, VmsR is a TCS response regulator, not a traditional QS system regulator. The vmsR mutant strain exhibits a reduced swimming motility but an increased swarming motility, EPS production, and biofilm production. This demonstrated that VmsR either positively or negatively regulated multiple biological functions of Xoc GX01.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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en
0.999995
PMC11277528_p25
PMC11277528
sec[2]/p[2]
3. Discussion
4.257813
biomedical
Study
[ 0.99951171875, 0.0003230571746826172, 0.00020372867584228516 ]
[ 0.99951171875, 0.0002123117446899414, 0.0003199577331542969, 0.00008541345596313477 ]
The flagellum is involved not only in the movement and chemotaxis of bacteria but also in several functions associated with bacterial pathogenicity, including biofilm formation, protein export, and adhesion . The flagellum also serves as a virulence factor in many bacterial pathogens. Steffens et al. found that the fliC mutant inhibited the motility and showed an increased xanthan production in Xcc JBL007 . In line with the aforementioned findings, the deletion of the vmsR gene in Xoc GX01 resulted in a significantly reduced expression of fliC , which was accompanied by an enhanced EPS production. In our study, the deletion of the vmsR gene led to a diminished expression of the fliC gene, potentially causing a reduction in swimming motility, which contributed significantly to the decreased virulence exhibited by the bacterium on rice. Our RNA-Seq data support the role that VmsR plays in flagellar biosynthesis because three genes involved in flagellar assembly were differentially expressed in the vmsR mutant strain in comparison with the wild-type strain.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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en
0.999997
PMC11277528_p26
PMC11277528
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3. Discussion
4.492188
biomedical
Study
[ 0.9990234375, 0.000614166259765625, 0.0002682209014892578 ]
[ 0.9990234375, 0.00037741661071777344, 0.00045990943908691406, 0.00018286705017089844 ]
In this study, ∆ vmsR exhibited a decrease in swimming motility and an increase in swarming motility. The result shows that VmsR plays an important role in the cell motility of Xoc GX01. Swimming motility is an individual movement in liquid or semi-solid media, and it requires flagella, which is a complex organelle responsible for propelling the bacterium through its environment . Song et al. discovered that flagellar instability results in a diminished virulence of Aeromonas veronii and correlates with its pathogenicity . In this study, three flagellar genes, namely fliC , fliD , and fliS , were downregulated through the RT-qPCR analysis. In vitro EMSA assay, VmsR can directly bind to the promoter of fliC and fliS . fliD encodes the HAP2/filament cap protein, which plays a pivotal role in regulating the assembly and stability of bacterial flagella. fliC encodes the H1 flagellin protein, which is a key component of the flagellar filament responsible for motility. FliS functions as a specific export chaperone for FliC, facilitating its translocation and assembly within the bacterial cell . In general, the expression of these genes is negatively regulated by the secretion of FlgM, which is a regulatory protein that modulates flagellar biosynthesis and function . FliS, on the other hand, operates as a non-canonical chaperone, fine-tuning FlgM’s activity to regulate the expression of late flagellar genes as well as motility and biofilm formation in Yersinia pseudotuberculosis . Therefore, we speculate that VmsR has positively regulated the expression of fliC and fliS . The deletion of the vmsR gene results in the instability of flagella, causing a decrease in the swimming motility. These results show that the flagellum is very important for pathogenic bacteria. Consequently, the reduction pathogenicity of ∆ vmsR may be caused by reduced flagellar synthesis.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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0.999997
PMC11277528_p27
PMC11277528
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3. Discussion
4.265625
biomedical
Study
[ 0.99951171875, 0.00020611286163330078, 0.00039958953857421875 ]
[ 0.9990234375, 0.0002951622009277344, 0.00039887428283691406, 0.00005894899368286133 ]
Swarming motility is a group movement on semi-solid medium, which requires both flagella and type Ⅳ pili . Swarming motility could increase the expression of virulence genes such as type Ⅲ effector and the type Ⅱ secretory system . Swarming motility, regulated by several genes and pathways like the QS system, is a complex bacterial behavior . One study showed that swarming is positively regulated by rhamnolipid production . As in other Xanthomonas , the difference of swimming motility and swarming motility remains unknown, requiring further research. Nevertheless, previous research has shown that the self-secreted EPS is positively correlated to the swarming behavior of Pseudoalteromonas sp. SM9913 . Consequently, the enhanced EPS production in the ∆ vmsR mutant may offer a plausible explanation for the remarkable swarming motility that has been observed.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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en
0.999998
PMC11277528_p28
PMC11277528
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3. Discussion
4.628906
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Study
[ 0.9990234375, 0.0005483627319335938, 0.0002827644348144531 ]
[ 0.9970703125, 0.0005021095275878906, 0.0023403167724609375, 0.00022494792938232422 ]
Biofilm is a critical virulence factor for many plant pathogens . When Xanthomonas citri was impaired in its ability to form a biofilm, it exhibited mitigated disease symptoms . Biofilm formation involves some adhesive molecules, such as polysaccharide or protein. EPS usually contributes to biofilm formation in Xoc . In general, the enhanced biofilm provides a protective barrier that could contribute to increased virulence by facilitating the colonization of host tissues and evasion of host immune responses. The mutant of rbdA in Pseudomonas aeruginosa PAO1 results in increased EPS production and biofilm formation . P. aeruginosa PAO1 has two operons, pel and psl , that have been reported to contribute to EPS production . They proved that the increased expression of the pel operon might contribute to the hyperbiofilm phenotype of the Δ rbdA mutant . Likewise, the mutation of bifA in P. aeruginosa elicits an enhanced biofilm phenotype. Furthermore, BifA has been demonstrated to regulate biofilm formation through modulating the expression of the pel operon . Consistent with the above studies, the EPS production and biofilm formation in the Δ vmsR mutant were increased, which are hypothesized to confer significant advantages to its pathogenicity. Nevertheless, the pathogenicity of the Δ vmsR mutant has decreased. We presume that EPS, being a co-pathogenic factor, does not necessarily exhibit a direct and positive correlation with pathogenicity. High levels of EPS production significantly contribute to the robustness of the biofilm structure, thereby potentially shielding the bacteria from host immune responses . However, this augmentation in robustness also diminishes the bacteria’s capacity to disperse, potentially reducing its virulence in dynamic environments. From an ecological long-term perspective, bacteria excrete substantial quantities of EPS as a strategic defense mechanism to evade the host’s immune system. This temporary state of defense, rather than aggression, facilitates the enhanced survival of the bacterial colony as a whole.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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0.999997
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3. Discussion
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Study
[ 0.99951171875, 0.0003485679626464844, 0.00025153160095214844 ]
[ 0.9990234375, 0.0002601146697998047, 0.0005612373352050781, 0.00009924173355102539 ]
Additionally, flagella are suggested to help E. coli overcome repulsive surface forces to establish initial contact . Flagella contribute to the early stages of biofilm formation in Bacillus cereus by facilitating surface attachment and microcolony formation . However, when E. coli express other surface structures like Curli or conjugative pili, flagella are not necessary for adhesion or biofilm development . This suggests that flagellar motility alone is not the key factor for promoting adhesion. On the other hand, flagella may serve a mechanosensory role in detecting surfaces, which triggers a transition from planktonic (free-swimming) to sessile (adherent) states, which are essential for biofilm formation . When surfaces are detected, flagella-mediated motility is downregulated, possibly due to the influence of the cellular messenger c-di-GMP, which is linked to both the suppression of motility and the promotion of robust biofilm formation . This dual role of flagella—both promoting initial surface contact and then downregulating motility upon surface detection—underscores a complex regulation where motility and biofilm formation are generally mutually exclusive. In this work, biofilm formation of the ∆ vmsR strain was increased significantly compared with the wild-type strain GX01, while the swimming of the ∆ vmsR strain was reduced. These results are consistent with the above studies. Motility and biofilm are mutually exclusive lifestyles, and shifts between the two are under the strict regulation of bacteria attempting to adapt to the complexity and variability of environmental conditions.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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en
0.999993
PMC11277528_p30
PMC11277528
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3. Discussion
4.210938
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Study
[ 0.99951171875, 0.0002772808074951172, 0.0004379749298095703 ]
[ 0.99951171875, 0.00018990039825439453, 0.00019371509552001953, 0.00005453824996948242 ]
Unexpectedly, EPS production has risen in ∆ vmsR , yet the gum gene is conspicuously absent from the DEGs. Similarly, this phenomenon aligns with the observation that the deletion of vemR conspicuously diminished EPS production despite the absence of any gum -related genes in the DEGs . In Xoc , the gum cluster, encompassing 13 genes ranging from gumB to gumN , is vital for EPS assembly, polymerization, and export . It has been demonstrated that in Xcc , EPS synthesis is initiated in the late-exponential growth phase and reaches maximal production during the stationary growth phase, and the expression of the gum genes mirrors the time course of EPS production . As described above, our transcriptome analysis used the bacterial cells in the mid-exponential growth phase. Therefore, this inconsistency is probably due to the employment of bacterial cells from different growth phases in the experiments.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
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0.999998
PMC11277528_p31
PMC11277528
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3. Discussion
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Study
[ 0.99951171875, 0.00025916099548339844, 0.00024199485778808594 ]
[ 0.74658203125, 0.0165863037109375, 0.236083984375, 0.000652313232421875 ]
Given their central role in bacterial physiology and pathogenesis, HKs represent promising targets for the development of novel antimicrobial agents . While the cognate HKs of VmsR remains unknown, further research efforts are likely to shed light on this important aspect of bacterial signaling. In addition, RR proteins can also be used as direct targets. Identifying the sensor kinase responsible for activating VmsR will not only deepen our understanding of TCS function but also have implications for the development of novel antibacterial strategies and biotechnology applications.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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0.999997
PMC11277528_p32
PMC11277528
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3. Discussion
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Study
[ 0.99951171875, 0.0002505779266357422, 0.00023818016052246094 ]
[ 0.9931640625, 0.0006508827209472656, 0.006229400634765625, 0.0001283884048461914 ]
In summary, the vmsR gene occupies a crucial position in the virulence of Xoc GX01, modulating swimming motility and flagellar formation positively, while suppressing EPS production and biofilm formation, either directly or indirectly. Transcriptomic investigations have further illuminated that VmsR adversely affects methyl-accepting chemotaxis proteins, which are integral to motility. The presence of a response regulatory domain at the N-terminus of VmsR suggests its potential to interact with a diverse array of signals regulating biological functions within Xoc GX01. However, the precise nature of these signals remains an enigma. Future research is imperative to decipher these signals and elucidate the underlying molecular mechanisms governing VmsR’s regulation in Xoc GX01, ultimately aiming to devise efficient control strategies against this significant bacterial pathogen.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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PMC11277528_p33
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4.1. Bacterial Strains, Culture Media and Growth Conditions
4.03125
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[ 0.99951171875, 0.00023865699768066406, 0.00020301342010498047 ]
[ 0.99755859375, 0.00218963623046875, 0.0003314018249511719, 0.00010406970977783203 ]
Xoc strains were routinely grown in nutrient broth (NB) medium (beef extract, 3 g/L; yeast extract, 1 g/L; polypeptone, 5 g/L) or on NB agar plates at 28 °C. E. coli strains were cultivated in Luria–Bertani (LB) medium or on LB agar plates at 37 °C. When necessary, antibiotics were added to medium at the following concentrations: kanamycin, 25 μg/mL; rifampicin, 50 μg/mL. The Xoc strains and plasmids used in this work are listed in Table S1 .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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4.2. Construction of the vmsR Deletion Mutant and Its Complementary Strain
4.160156
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[ 0.99951171875, 0.00031256675720214844, 0.00026726722717285156 ]
[ 0.99951171875, 0.0002925395965576172, 0.00017631053924560547, 0.0000622868537902832 ]
The vmsR gene was knocked out in Xoc GX01 using a homologous recombination method. The follow primers used in this study are listed in Table S2 . The 492 bp upstream and 522 bp downstream sequences of the vmsR gene were amplified from the Xoc wild-type strain GX01 genome using the vmsR -LF/LR and vmsR -RF/RR primers. The amplified DNA fragments were digested by corresponding restriction enzymes and cloned into pK18 mobsacB , which is a conjugative suicide plasmid in Xoc . Then, the resulting recombinant plasmids were created in E. coli strain DH5α and transferred to wild-type strain Xoc GX01 by electroporation (2 mm, 2.5 kV). Transconjugants were screened on NA medium with 10% sucrose and antibiotics (Rif r and Kam r ). Transconjugants were identified by external primers ( vmsR -LF and vmsR -RR) and vmsR ORF internal primers ( vmsR -inF and vmsR -inR). The successful transconjugants should satisfy the following two points at the same time: the combined fragment of upstream and downstream sequences was amplified by external primers, and no PCR product could be amplified by internal primers.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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4.2. Construction of the vmsR Deletion Mutant and Its Complementary Strain
4.128906
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[ 0.99951171875, 0.00026988983154296875, 0.00028443336486816406 ]
[ 0.9990234375, 0.0005946159362792969, 0.0001862049102783203, 0.0000699758529663086 ]
To complement the deletion mutant, the 989 bp sequence of the vmsR gene was amplified using the vmsR -cmF and vmsR -cmR primers. The PCR fragments were digested with the Xba Ⅰ/ Hin dⅢ restriction enzymes and ligated into Xba Ⅰ/ Hin dⅢ-digested pXUK, resulting in the recombinant plasmids. pXUK was derived from the endogenous plasmid pXOCgx01 isolated from Xoc GX01 . Recombinant plasmids were created in E. coli strain DH5α and transferred to the vmsR mutant of Xoc by electroporation (2 mm, 2.5 kV). Transconjugants were screened on NA medium with Rif r and Km r antibiotics. Transconjugants were identified by vmsR -cmF/R primers.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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4.3. Virulence Assay
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[ 0.99951171875, 0.00030517578125, 0.0003857612609863281 ]
[ 0.99951171875, 0.00024771690368652344, 0.00023734569549560547, 0.00004971027374267578 ]
The virulence of Xoc was determined by the pressure inoculation of leaves in rice . Xoc strains were grown in NB medium at 28 °C with shaking at 200 rpm until the value of OD 600 reached 0.8–1.0. The value of OD 600 was adapted to 0.5 using sterilized ddH 2 O. The above bacterial cell suspensions were inoculated into the leaves of 6-week-old rice plants using a needleless injector. Water-soaking symptoms were measured 15 days after inoculation. We also recorded the lesion length on at least 30 leaves.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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4.4. Assay for Swimming and Swarming Motilities
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[ 0.99951171875, 0.00023639202117919922, 0.00039649009704589844 ]
[ 0.9990234375, 0.0008463859558105469, 0.00016295909881591797, 0.000060558319091796875 ]
To determine the swimming and swarming motilities of the vmsR mutant strain and the wild-type strain Xoc GX01, Xoc strains were cultured in NB medium at 28 °C with shaking at 200 rpm until the value of OD 600 reached 1.0.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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PMC11277528_p38
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4.4. Assay for Swimming and Swarming Motilities
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[ 0.99951171875, 0.00031447410583496094, 0.00018548965454101562 ]
[ 0.9990234375, 0.0005464553833007812, 0.000278472900390625, 0.00007134675979614258 ]
For swimming motility, the value of OD 600 was adjusted to 1.0. A volume of 3 μL of each bacterial cell suspension was injected into the center of a basal medium plate containing 0.3% agar and then incubated at 28 °C for 3 days. For swarming motility, the value of OD 600 was adjusted to 0.2. A volume of 2 μL of each bacterial cell suspension was precisely dispensed onto the center of an NB medium plate containing 2% sucrose and 0.6% agar and then incubated at 28 °C for 3 days. Due to the low strength of the medium plate, the glass garden should be placed upward. After 3 days of incubation at 28 °C, the diameter of the bacterial colony on each plate was determined. In both swimming and swarming motility assays, each treatment involves three replications, and each experiment was repeated three times.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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PMC11277528_p39
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4.5. Determination of Biofilm Formation and EPS Production
4.097656
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[ 0.99951171875, 0.0002830028533935547, 0.00020420551300048828 ]
[ 0.99951171875, 0.000286102294921875, 0.0003075599670410156, 0.00005906820297241211 ]
Biofilm formation on glass surfaces was performed as described previously . Briefly, Xoc strains were grown in NB medium at 28 °C with shaking at 200 rpm until the value of OD 600 reached 1.0. The value of OD 600 was adapted to 0.5, and then 1.0 mL of cultures prepared as aforementioned was added in borosilicate glass tubes (100 mm * 15 mm). These cultures were incubated at 28 °C for 5 days without shaking. We removed the cell suspension from the borosilicate glass tubes and washed the glass tubes with sterile water three times. Then, 2.0 mL of 0.1% ( w / v ) crystal violet was added to these glass tubes for 30 min. To quantify the biofilm formation, stained biofilm solubilized with 2 mL absolute ethanol was measured with a spectrophotometer under OD 600 . Each treatment involved three replications, and the same experiment was repeated three times.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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PMC11277528_p40
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4.5. Determination of Biofilm Formation and EPS Production
4.082031
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[ 0.99951171875, 0.00031304359436035156, 0.00027751922607421875 ]
[ 0.99951171875, 0.0002065896987915039, 0.00021600723266601562, 0.00005161762237548828 ]
For analysis of EPS production on plates, the Xoc strains were cultured in NB medium at 28 °C with shaking at 200 rpm until the value of OD 600 reached 0.8–1.0. The value of OD 600 was adjusted to 0.2, and then 2 μL of each strain was inoculated onto the surface of NA plates containing 2% sucrose. After 48~72 h of incubation at 28 °C, the colony diameter of the Xoc strains was measured. To estimate EPS production, the Xoc strains were inoculated into 100 mL of NB liquid medium containing sucrose (2% w / v ) at 28 °C, 200 rpm for 5 days. EPS was precipitated from the culture supernatant with ethanol, dried at 55 °C and weighed as described. The results were observed after 5 days of incubation at 28 °C. Each treatment involves three replications, and the same experiment was repeated three times.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
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PMC11277528_p41
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4.6. Transcriptome Analysis
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[ 0.99951171875, 0.00025463104248046875, 0.00019216537475585938 ]
[ 0.99951171875, 0.0002779960632324219, 0.0003268718719482422, 0.00006276369094848633 ]
Xoc strains were cultured in NB medium at 28 °C with shaking at 200 rpm until the OD 600 value reached 1.0. Three biological replicates were derived from the bacteria solution. The bacterial cells were collected using high-speed centrifuge and then frozen with liquid nitrogen. The bacteria cells were sent to the PFOMIC Bioinformatics Company (Nanning, China) for library preparation and strand-specific transcriptome sequencing. Sequencing libraries were generated using the NEBNext ® Ultra TM Directional RNA Library Prep Kit for Illumina ® (NEB, USA) following the manufacture’s recommendations, and index codes were added to attribute sequences to each sample. HTSeq v0.6.1 was used to count the read numbers mapped to each gene. And then, the FPKM of each gene was calculated based on the length of the gene and the reads count mapped to this gene. FPKM, the expected number of Fragments Per Kilobase of transcript sequence per Millions base pairs sequenced, considers the effect of sequencing depth and gene length for the reads count at the same time, and it is currently the most commonly used method for estimating gene expression levels . Differential expression analysis of two conditions was performed using the DEGSeq R package (1.20.0). The p values were adjusted using the Benjamini and Hochberg method . A corrected FDR of 0.05 and log 2 (Fold Change) of 1 were set as the threshold for significantly differential expression.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277528_p42
PMC11277528
sec[3]/sec[6]/p[0]
4.7. RNA Isolation and Quantitative Reverse Transcription PCR Analysis of Gene Expression
4.125
biomedical
Study
[ 0.99951171875, 0.00026154518127441406, 0.0002123117446899414 ]
[ 0.99951171875, 0.00025153160095214844, 0.0002646446228027344, 0.000057816505432128906 ]
Xoc strains were grown in NB medium at 28 °C with shaking at 200 rpm until the value of OD 600 reached 1.0. The bacterial cells were collected using high-speed centrifuge and then washed three times with sterilized water. RNA was isolated from the Xoc strains using a TransZol Up Plus RNA Kit (TransGen, Beijing, China). To confirm the reality of the RNA-seq data, two-step quantitative reverse transcription PCR (RT-qPCR) was adapted in this work. First-strand cDNA was synthesized using RT SuperMix for qPCR (Vazyme Biotech, Nanjing, China). The cDNA was added as DNA templates into the PCR system with the 2 × RealStar Green Fast Mixture (GenStar, Beijing, China). The qPCR adapted a three-step amplification procedure. Firstly, the template cDNA was pre-denatured at 95 °C for 2 min. A total of 40 cycles were amplified by qPCR, and each cycle was performed using the following procedure: 95 °C for 15 s, 60 °C for 15 s, and 72 °C for 30 s. The 16S rRNA gene of X. oryzae pv. oryzicola was used as the internal control to verify the absence of significant variation at the cDNA level in the samples.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277528_p43
PMC11277528
sec[3]/sec[7]/p[0]
4.8. In Vitro Electrophoretic Mobility Shift Assay (EMSA)
4.242188
biomedical
Study
[ 0.99951171875, 0.0003006458282470703, 0.00018477439880371094 ]
[ 0.9990234375, 0.0005450248718261719, 0.000431060791015625, 0.00008755922317504883 ]
The EMSA represents a swift and precise technique for detecting interactions between proteins and nucleic acids. The principle is that the electrophoretic mobility of a protein–DNA complex is typically less than that of the free DNA . DNA probes were amplified by PCR with the corresponding primers . The 5′-end of the reverse primer was modified with 6′-FAM (Sangon Biotech, Shanghai, China). DNA fragments encoding the putative DNA-binding domain of VmsR were cloned into the plasmid pRSFDuet-1 to generate the recombinant plasmids. The recombinant plasmids were introduced into fresh competent cells of E. coli BL21 (DE3) Chemically Competent Cell (CD601, TransGen, Beijing, China). The recombinant plasmids were incubated in Luria–Bertani medium for 3 to 5 h at 37 °C with a shaking speed of 200 rpm, achieving an OD 600 of 0.6 to 0.8. Subsequently, 0.5 mM isopropyl-β-d-thiogalactoside (IPTG) (Solarbio Life Sciences, Beijing, China) was added, and the culture was further maintained for 12 h at 16 °C with a shaking speed of 120 rpm. E. coli BL21 (DE3) cells were collected and disrupted to extract the recombinant polypeptides. The recombinant proteins were purified by ProteinIso ® Ni-NTA Resin (TransGen, Beijing, China). The DNA probe (40 ng) was mixed with different amounts of recombinant protein (0–3 μg) in binding buffer (1 mM dithiothreitol, 0.1 mg/mL BSA, 50 mM KCl, 20 mM Tris-HCl, pH 8.0, 5% glycerol) and then reacted at 25 °C for 30 min. The protein–DNA complexes were separated by electrophoresis in 4% polyacrylamide gel (acrylamide/bisacrylamide, 29:1) in 0.5 × Tris-borate-EDTA (TBE) buffer (44.5 mM Tris base, 44.5 mM boric acid, and 1 mM EDTA, pH 8.0) and recorded with a Bio-Rad ChemiDoc™ MP Imaging System (Bio-Rad Laboratories, Hercules, CA, USA). For the competitive EMSA assay, DNA probes without 6′-FAM were substituted.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999995
PMC11277528_p44
PMC11277528
sec[3]/sec[7]/p[1]
4.8. In Vitro Electrophoretic Mobility Shift Assay (EMSA)
4.136719
biomedical
Study
[ 0.99951171875, 0.0002524852752685547, 0.0003306865692138672 ]
[ 0.99853515625, 0.0013980865478515625, 0.00019884109497070312, 0.0000699162483215332 ]
As shown in Table S2 , the fliC probe fragment measures 283 bp, encompassing the region from base pair −245 to +38, relative to the TIS of the fliC promoter. The fliD probe fragment spans 272 bp, extending from base pair −272 to −1 with respect to the TIS of the fliD promoter. Similarly, the fliS probe fragment encompasses 500 bp, covering the sequence from base pair −500 to −1, relative to the TIS of the fliS promoter.
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999998
PMC11277528_p45
PMC11277528
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5. Patents
1.007813
other
Other
[ 0.01305389404296875, 0.0017414093017578125, 0.9853515625 ]
[ 0.0026760101318359375, 0.99560546875, 0.0007843971252441406, 0.0006933212280273438 ]
China Invention Patent: Authorization Bulletin Number: CN112852839B .
[ "Yaqi Zhang", "Xiyao Zhao", "Jiuxiang Wang", "Lindong Liao", "Huajun Qin", "Rongbo Zhang", "Changyu Li", "Yongqiang He", "Sheng Huang" ]
https://doi.org/10.3390/ijms25147595
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999995
PMC11277541_p0
PMC11277541
sec[0]/p[0]
1. Introduction
4.054688
biomedical
Review
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[ 0.1243896484375, 0.10296630859375, 0.76953125, 0.003025054931640625 ]
Rubella is a contagious viral infection caused by the rubella virus, an RNA-virus belonging to the family Matonaviridae , genus Rubivirus , and humans are the only reservoir for rubella infection . Rubella infection has garnered significant attention in the field of public health due to its potential consequences, especially during pregnancy . While rubella infection is generally manageable in most individuals and sometimes may proceed asymptomatically, the real concern arises when the virus affects pregnant women. Rubella infection in pregnant women, particularly if contracted during the first trimester, can result in congenital rubella syndrome (CRS), the clinical manifestations of which include fetal growth restriction, cardiac defects, congenital cataract, sensorineural hearing loss and bone lesions .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999999
PMC11277541_p1
PMC11277541
sec[0]/p[1]
1. Introduction
4.375
biomedical
Review
[ 0.99658203125, 0.002826690673828125, 0.0004911422729492188 ]
[ 0.125, 0.06988525390625, 0.7958984375, 0.00905609130859375 ]
The virus is transmitted by direct droplet contact from nasopharyngeal secretions, replicates in the lymph tissue of the upper respiratory tract, and spreads hematogenously. Congenital infection occurs when maternal viremia allows hematogenous spread of the virus across the placenta. Acquired rubella is generally a mild, self-limited disease associated with a characteristic exanthem . Though asymptomatic in 25 to 50 percent of cases, affected individuals may experience mild, prodromal symptoms consisting of low-grade fever, conjunctivitis, coryza, sore throat, cough, and occasionally headache and malaise. These symptoms usually last one to five days before the onset of the rash. Rubella may also be associated with generalized, tender lymphadenopathy, particularly involving suboccipital, postauricular, and cervical nodes, which often becomes pronounced during the rash. The typical rash of rubella is an erythematous maculopapular eruption, which may be mildly pruritic and evolves into pinpoint papules similar to scarlet fever. The rash characteristically begins on the face and spreads to the trunk and extremities within hours. It lasts approximately one to three days and resolves first from the face and then from the body .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277541_p2
PMC11277541
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1. Introduction
4.152344
biomedical
Review
[ 0.9990234375, 0.0007333755493164062, 0.0004105567932128906 ]
[ 0.2125244140625, 0.01849365234375, 0.767578125, 0.0014934539794921875 ]
When a woman contracts rubella just before conception or within the first 8–10 weeks of pregnancy, it can result in fetal defects in up to 90% of cases, including miscarriage or stillbirth. Maternal–fetal transmission occurs via hematogenous spread and varies with gestational age. There is considerable pathologic evidence that suggests that the rubella virus spreads through the vascular system of the developing fetus after infecting the placenta. The resulting defects stem from cytopathic damage to blood vessels and ischemia in affected organs . The likelihood of birth defects decreases if the infection occurs later in pregnancy, and fetal abnormalities are rarely linked to maternal rubella after the 16th week, though sensorineural hearing loss can still occur if the infection happens as late as that. This syndrome, which can have severe consequences for pregnant women, is the only one preventable by vaccination .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277541_p3
PMC11277541
sec[0]/p[3]
1. Introduction
3.890625
biomedical
Study
[ 0.99951171875, 0.00023126602172851562, 0.00046372413635253906 ]
[ 0.84912109375, 0.036956787109375, 0.11346435546875, 0.0005240440368652344 ]
Over the past 10 years, significant efforts have been made to reduce the incidence of rubella infections worldwide. In the European region, between 2005 to 2019, the annual incidence of rubella dropped from 234.9 per 1 million people (206,359 cases) in 2005 to 0.67 per 1 million people (620 cases) in 2019. In 2019, Poland had the highest incidence, with 7.7 cases per 1 million people (292 cases), followed by Ukraine with 3.1 cases per 1 million people (138 cases). Cases of congenital rubella syndrome (CRS) were reduced by 50%, from 16 cases in 2005 to 8 cases in 2019 .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999999
PMC11277541_p4
PMC11277541
sec[0]/p[4]
1. Introduction
4.128906
biomedical
Review
[ 0.9931640625, 0.004344940185546875, 0.0024433135986328125 ]
[ 0.00928497314453125, 0.003490447998046875, 0.98681640625, 0.0005564689636230469 ]
The rubella vaccine is usually given as part of a measles–mumps–rubella vaccination (MMR). Because of the presence of live attenuated virus, MMR is strongly contraindicated during pregnancy and rubella immunization is appropriately recommended before the conception or in postpartum period in non-immune women. A sufficiently adequate wait time prior to conception after MMR vaccine administration corresponds to 4 weeks . However inadvertent administration of the MMR vaccine early in pregnancy is it not generally related to teratogenic effects: as noted in a 2014 review by Keller-Stanislawski et al., among over 3500 susceptible women who were inadvertently vaccinated against rubella just before or during the early stages of pregnancy, no cases of congenital rubella syndrome (CRS) were reported. It has been shown that the vaccine virus can be transmitted vertically to the fetus without causing any clinical symptoms . Thus, pregnancy termination is not recommended for individuals who are vaccinated during pregnancy (or become pregnant soon after vaccination) . Moreover, when the vaccination occurs during the post-partum period, breastfeeding is not contraindicated.
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999998
PMC11277541_p5
PMC11277541
sec[0]/p[5]
1. Introduction
2.234375
biomedical
Other
[ 0.98974609375, 0.0035552978515625, 0.00685882568359375 ]
[ 0.007427215576171875, 0.9248046875, 0.066162109375, 0.00162506103515625 ]
Despite increasing scientific evidence supporting the benefits and safety of immunization before, during, and after pregnancy, vaccine hesitancy persists because many people perceive vaccines to be unnecessary and unsafe .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277541_p6
PMC11277541
sec[0]/p[6]
1. Introduction
2.814453
biomedical
Other
[ 0.99365234375, 0.00417327880859375, 0.002269744873046875 ]
[ 0.311279296875, 0.537109375, 0.148193359375, 0.003604888916015625 ]
Various approaches have been taken to persuade patients who refuse vaccination during preconception period or pregnancy. It has been demonstrated that one of the most effective methods is recommendation from the attending gynecologist . The most effective communication strategy has proven to be explaining to the patient that not getting vaccinated seriously endangers the fetus or newborn child. Furthermore, emphasizing the importance of vaccination has been shown to be effective. In one study, 20% of pregnant people who received the influenza vaccine had previously refused it .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277541_p7
PMC11277541
sec[0]/p[7]
1. Introduction
3.984375
biomedical
Review
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[ 0.02227783203125, 0.1700439453125, 0.806640625, 0.001194000244140625 ]
According to the recommendations of the World Health Organization (WHO), several countries have endeavored to establish vaccination programs, surveillance and notification systems for rubella infection and CRS . Considering that a single dose of rubella-containing vaccine (RCV) can confer lifelong immunity, the WHO formulated a Global Vaccine Action Plan 2011–2020 (GVAP) . This plan included a target to achieve elimination of rubella in at least five of the six WHO regions by 2020 . Elimination of rubella is defined as the absence of endemic transmission in a defined geographical region or country for at least 36 months, documented by a well-performing surveillance system . In contrast to eradication, ongoing measures are necessary to prevent the re-establishment of transmission . The WHO recommends that countries that introduce RCV achieve and maintain a minimum coverage of at least 80%, with at least 1 dose of RCV delivered through routine services or campaigns.
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277541_p8
PMC11277541
sec[0]/p[8]
1. Introduction
3.699219
biomedical
Other
[ 0.99609375, 0.0014600753784179688, 0.0025272369384765625 ]
[ 0.049896240234375, 0.8447265625, 0.1041259765625, 0.0010890960693359375 ]
Until the disease is eliminated in all countries of the world, it will be necessary to maintain high vaccination coverage, and further strengthen the surveillance and investigation of reported cases, ensuring a rapid response to any imported case. Currently, only two WHO regions in the world are yet to achieve rubella elimination: the African region and the Eastern Mediterranean region . In November 2022, the WHO’s Regional Verification Commission declared the elimination of rubella infection in Italy, making it no longer endemic . In Italy, numerous efforts have been made to achieve rubella elimination, including mandatory vaccination for newborns since 2017. The National Plan for the Elimination of Measles and Congenital Rubella for the period 2010–2015, following the guidelines of the WHO’s European Regional Office, aimed to achieve a two-dose vaccine coverage of 95% and a percentage of susceptible women of childbearing age below 5% .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277541_p9
PMC11277541
sec[0]/p[9]
1. Introduction
3.638672
biomedical
Study
[ 0.99755859375, 0.0003261566162109375, 0.0022945404052734375 ]
[ 0.9990234375, 0.0005893707275390625, 0.00036025047302246094, 0.0000540614128112793 ]
In recent years, the main migration flows to Italy have originated from regions where rubella has not yet been eliminated and where no program is in place to achieve this goal . These flows have been particularly noted from Africa and the Middle East due to conflicts, political instability, and challenging economic conditions. In a recent study by Zenner et al., the implementation of the electronic Personal Health Record System, a health information system that records health data for newly arriving migrants, was examined in southern Europe. The analysis of these data highlighted the presence of a predominantly healthy population, but with a significant prevalence of both acute and chronic infectious diseases. Specifically, HIV, tuberculosis, and infectious hepatitis were more frequent among the older age group. This frequency could be attributed to the prevalence rates in the migrants’ countries of origin and the adverse conditions encountered during their migration journey .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277541_p10
PMC11277541
sec[0]/p[10]
1. Introduction
3.21875
biomedical
Other
[ 0.98046875, 0.0005116462707519531, 0.018890380859375 ]
[ 0.306396484375, 0.66748046875, 0.025604248046875, 0.0007100105285644531 ]
Millions of Syrian refugees have fled their country, seeking safety in neighboring countries such as Lebanon, Jordan, or in Europe. Ten percent of these have reached Europe in recent years . These migratory flows have the potential to reintroduce diseases into host countries where their incidence had significantly declined over time. These diseases include, for example, hepatitis A, which represents an emblematic case. The hepatitis A vaccine is safe and effective in preventing acute infection cases, providing immunity for at least 15 years once administered. In Europe, most countries do not include hepatitis A in their vaccination programs, unlike Middle Eastern states like Lebanon and Jordan, which are considered high–intermediate endemic countries for this infection . Paradoxically, therefore, the migration of these people could be riskier in Europe than in neighboring countries, as Europe is a low-endemic region, consequently having a large number of susceptible individuals.
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277541_p11
PMC11277541
sec[0]/p[11]
1. Introduction
4.03125
biomedical
Study
[ 0.99951171875, 0.00014507770538330078, 0.00028395652770996094 ]
[ 0.998046875, 0.0012302398681640625, 0.0007305145263671875, 0.00007015466690063477 ]
The increase in cases of infectious diseases related to migration flows has already been highlighted in Middle Eastern countries such as Lebanon . Following the Syrian refugee crisis and the lack of clean water in this region, a group of Lebanese researchers demonstrated the high prevalence of Entamoeba histolytica infection in children below one year old, as the cause of pediatric gastroenteritis. E. histolytica is usually transmitted via contaminated food and water, meaning that young infants should be less likely to frequently develop intestinal amebiasis. However, contaminated water used for milk preparation and hygiene can be ingested by infants during bathing or face washing. This fact highlights how unsanitary water supplies and poor hygiene conditions can affect the prevalence of E. histolytica infection in infants .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277541_p12
PMC11277541
sec[0]/p[12]
1. Introduction
1.475586
other
Other
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[ 0.06573486328125, 0.93310546875, 0.000774383544921875, 0.0005292892456054688 ]
In 2022, approximately 20.0% of births concerned mothers of non-Italian citizenship. The most represented geographical areas of origin were Africa (28.7%) and the European Union (19.6%). Mothers of Asian and South American origin make up 19.3% and 7.9% of foreign mothers, respectively .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277541_p13
PMC11277541
sec[0]/p[13]
1. Introduction
3.546875
biomedical
Study
[ 0.9990234375, 0.0004992485046386719, 0.0005655288696289062 ]
[ 0.99853515625, 0.0011081695556640625, 0.00019919872283935547, 0.00011485815048217773 ]
A seroepidemiologic study, conducted from 1 January 2008 to June 30 2009 on 489 immigrant women who were resident in Messina and aged between 18 and 45 years, showed an overall rate of seropositivity to rubella of 82.2%. This level of susceptibility to rubella virus infection in fertile immigrant women was still too high to meet the target of the WHO’s European Regional Office .
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999996
PMC11277541_p14
PMC11277541
sec[0]/p[14]
1. Introduction
1.470703
biomedical
Other
[ 0.556640625, 0.004772186279296875, 0.4384765625 ]
[ 0.017364501953125, 0.98095703125, 0.0009140968322753906, 0.0005321502685546875 ]
Regarding the vaccination coverage rate of pregnant women, these data are not available through the official channels of the Italian National Institute of Health.
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277541_p15
PMC11277541
sec[0]/p[15]
1. Introduction
3.617188
biomedical
Study
[ 0.99853515625, 0.0007805824279785156, 0.0005674362182617188 ]
[ 0.99853515625, 0.0009918212890625, 0.0002142190933227539, 0.00012814998626708984 ]
The aim of this study is to retrospectively assess rubella immunity in pregnant women who have attended three delivery centers in Rome over the past three years. The objective is to determine how many women are seronegative to rubella and are at risk of contracting the infection during pregnancy, thereby risking CRS for their newborns.
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999998
PMC11277541_p16
PMC11277541
sec[1]/p[0]
2. Materials and Methods
4.113281
biomedical
Study
[ 0.9990234375, 0.0006260871887207031, 0.00023949146270751953 ]
[ 0.99951171875, 0.0002428293228149414, 0.0003616809844970703, 0.00008511543273925781 ]
Data about the rubella serological status of 7937 non-consecutive pregnant women who delivered at three different hospitals in Rome, Italy, were collected from Isola Tiberina– Gemelli Isola Hospital, Fondazione Policlinico Universitario A. Gemelli IRCCS, and Sant’Eugenio Hospital. We have included only patients who delivered between January 2021 and May 2023 with a complete rubella test (IgM and IgG) performed during pregnancy or at the time of admission in hospital and considered only rubella tests that had been analyzed with the same method (Abbott Molecular Diagnostics, Des Plaines, USA, chemilumiscence, CLIA). The results were evaluated in terms of IgG positive (≥10 UI/mL), negative (≤4.9 UI/mL) and borderline (5–9.9 UI/mL); IgM positive (≥1.6 index), negative (<1.2 index) and borderline (1.2–1.59 index). All of the results with IgG and/or IgM borderline were excluded in order to categorize pregnant women as either receptive (both IgG and IgM negative) or immune (IgG positive—IgM negative) to rubella, avoiding non-interpretable rubella test results.
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999997
PMC11277541_p17
PMC11277541
sec[1]/p[1]
2. Materials and Methods
3.246094
biomedical
Study
[ 0.9990234375, 0.00034499168395996094, 0.0007052421569824219 ]
[ 0.9951171875, 0.004123687744140625, 0.00039958953857421875, 0.00012576580047607422 ]
Statistical analysis. Univariate analysis was performed to verify any difference between the study groups in terms of age distribution. Univariate analysis included the Student’s t test when appropriate for continuous variables. All statistical tests were two sided, and differences were considered significant at p < 0.05. Statistical analysis was performed by SPSS statistical software 29.0 (SPSS, Chicago, IL, USA).
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999995
PMC11277541_p18
PMC11277541
sec[1]/p[2]
2. Materials and Methods
1.404297
biomedical
Other
[ 0.94677734375, 0.04180908203125, 0.0115509033203125 ]
[ 0.03753662109375, 0.95166015625, 0.0010366439819335938, 0.00986480712890625 ]
All patients admitted to the hospital signed an informed consent that allows personal data to be used in anonymous form for clinical and scientific purposes.
[ "Anna Franca Cavaliere", "Marco Parasiliti", "Rita Franco", "Vitalba Gallitelli", "Federica Perelli", "Amelia Spanò", "Barbara Pallone", "Maria Grazia Serafini", "Fabrizio Signore", "Georgios Eleftheriou", "Giovanni Scambia", "Antonio Lanzone", "Annalisa Vidiri" ]
https://doi.org/10.3390/ijerph21070957
N/A
https://creativecommons.org/licenses/by/4.0/
en
0.999994