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• Fecal TMAO levels are associated with NAFLD severity. • TMAO promotes the progression of NAFLD models in vitro and in vivo. • TMAO exacerbates intestinal barrier damage and inflammation at various levels. • TMAO promotes endothelial dysfunction and capillarization of LSECs. • TMAO promotes M1 macrophage while inhibiting M2 macrophage polarization. Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, with the gut microbiota and its metabolites are important regulators of its progression. Trimethylamine N-oxide (TMAO), a metabolite of the gut microbiota, has been closely associated with various metabolic diseases, but its relationship with NAFLD remains to be elucidated. In this study, we found that fecal TMAO levels correlated with NAFLD severity. Moreover, TMAO promoted lipid deposition in HepG2 fatty liver cells and exacerbated hepatic steatosis in NAFLD rats. In the colon, TMAO undermined the structure and function of the intestinal barrier at various levels, further activated the TLR4/MyD88/NF-κB pathway, and inhibited the WNT/β-catenin pathway. In the liver, TMAO induced endothelial dysfunction with capillarization of liver sinusoidal endothelial cells, while modulating macrophage polarization. In conclusion, our study suggests that gut microbiota metabolite TMAO promotes NAFLD progression by impairing the gut and liver and that targeting TMAO could be an alternative therapeutic strategy for NAFLD. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most pressing health issues in today's society. As such, it is imperative that the scientific community devise effective methods to inhibit the proliferation and metastasis of CRC cells. Ferroptosis is a recently discovered regulatory cell death mode mainly manifested by dysregulation of cellular iron metabolism and mitochondrial lipid peroxidation. ACADSB is a member of the acyl‐CoA dehydrogenase. This study finds that ACADSB is lowly expressed in CRC tissues. Its expression is negatively correlated with N‐ and M‐stage CRC but positively correlated with the overall survival rate of CRC patients. In addition, it finds that ACADSB is found in the mitochondria of cells. Overexpression of ACADSB inhibits CRC cell migration, invasion, and proliferation, while ACADSB knockdown has the opposite effect. More importantly, the study finds that ACADSB negatively regulates expression of glutathione reductase and glutathione peroxidase 4, the two main enzymes responsible for clearing glutathione (GSH) in CRC cells. ACADSB overexpression enhances the concentration of malondialdehyde, Fe+, superoxide dismutase, and lipid peroxidation in CRC cells, but reduces the concentration of GSH. This is significant, as all of these are important indicators of ferroptosis. Evaluating the data as a whole, this paper speculates that ACADSB affects CRC cell migration, invasion, and proliferation by regulating CRC cell ferroptosis. [ABSTRACT FROM AUTHOR]

Purpose: To determine the population attributable fraction (PAF) of fatty liver disease (FLD) for type 2 diabetes mellitus (T2DM) and compare it to the PAFs of other metabolic abnormalities. Methods: We conducted a 10-year retrospective cohort study of 33,346 individuals in Karamay Central Hospital of Xinjiang. Individuals were followed up for T2DM occurrence based on FBS. The PAFs of FLD were calculated generally and respectively in different sex and age groups. A comparison of the PAF of FLD and that of other metabolic abnormalities, as well as the PAFs of FLD in different groups classified based on age and sex, was performed using Cox regression. Results: During an average follow-up period of 3.71 years, 1486 T2DM were diagnosed. The incidence density of T2DM was 1.2/100 person-years, and cumulative incidence rate was 4456.31/100,000 person-years. Partial PAF (PAFp) of FLD in the entire population was 23.11%. In the male population, PAFp was higher at 30–40 years old. In the female population, it was higher when age ≥ 60 years old. In multivariable Cox regression model, FLD, male sex, age ≥ 45 years old, overweight, hypertriglyceridaemia, and systolic hypertension were independent risk factors for T2DM, with corresponding PAFp of 25.00%, 24.99%, 36.47%, 24.96%, 5.71%, and 6.76%, respectively. Age ≥ 45 years old showed the highest PAFp and adjusted hazard ratio, followed by FLD. Conclusions: FLD contributes more to T2DM incidence than other metabolic disorders. Particular attention should be given to male populations of 30–40 and female populations above 60 for FLD prevention and treatment. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide but still lacks specific treatment modalities. The gut microbiota and its metabolites have been shown to be intimately involved in NAFLD development, participating in and regulating disease progression. Trimethylamine N-oxide (TMAO), a metabolite highly dependent on the gut microbiota, has been shown to play deleterious regulatory roles in cardiovascular disease, but the relationship between it and NAFLD lacks validation from basic experiments. This research applied TMAO intervention by constructing fatty liver cell models in vitro to observe its effect on fatty liver cells and potential key genes and performed siRNA interference on the gene to verify the action. The results showed that TMAO intervention promoted the appearance of more red-stained lipid droplets in Oil-red O staining results, increased triglyceride (TG) levels and increased mRNA levels of liver fibrosis-related genes, and also identified one of the key genes, keratin17 (KRT17) via transcriptomics. Following the reduction in its expression level, under the same treatment, there were decreased red-stained lipid droplets, decreased TG levels, decreased indicators of impaired liver function as well as decreased mRNA levels of liver fibrosis-related genes. In conclusion, the gut microbiota metabolite TMAO could promote lipid deposition and fibrosis process via the KRT17 gene in fatty liver cells in vitro. • TMAO promotes lipid deposition in fatty liver cells in vitro. • TMAO promotes the fibrosis process of fatty liver cells in vitro. • KRT17 is the critical gene in the action of TMAO. • Reduced KRT17 expression levels diminish the cell-promoting effect of TMAO. [ABSTRACT FROM AUTHOR]

Based on the survey data for 2120 inbound and domestic tourists at the Shanghai World Expo, a structural equation model was constructed for the relationship among tourists' perceived value dimensions, behavioral intention and revisit intention. Additionally, the influence of tourists' perceived value dimensions on the behavioral intention and revisit intention was explored. The results show that the utilitarian value and enjoyment value significantly affect the inbound and domestic tourists' behavioral intention, while the convenience value and aesthetic value have no significant influence. The service value only significantly affects the domestic tourists' behavioral intention, and the aesthetic value only significantly affects the inbound tourists' behavioral intention. The utilitarian value, service value and enjoyment value significantly affect the inbound and domestic tourists' revisit intention, while the convenience value only significantly affects the domestic tourists' revisit intention. The utilitarian value is the primary factor affecting the inbound tourists' behavioral intention and revisit intention, and the perceived price has no significant effect on either inbound or domestic tourists' behavioral intention or revisit intention. The study explores the relationships between tourists' perceived value, behavioral intention and revisit intention, analyzes the divergence and causation, theoretically enriches the research field of tourism geography and behavioral geography, and has great practical significance to the sustainable development of mega events in China, including the further development of the Shanghai World Expo. [ABSTRACT FROM AUTHOR]

• Aeration triggers while PFOS restructures assembly of rhizospheric organic matter. • PFOS-protein cored nanocapsules with lipid-carbohydrate shells are obtained. • Bioavailability of PFOS and proteins is reduced by PFOS-protein cored nanocapsules. • AFM IR-mapping uncovers chemical structure and fate of PFOS-nanocapsule assemblies. • Eco-effect of PFAS can only be understood when assembly structure is clarified. Ubiquitous presence of the extremely persistent pollutants, per- and polyfluoroalkyl substances, is drawing ever-increasing concerns for their high eco-environmental risks which, however, are insufficiently considered based on the assembly characteristics of those amphiphilic molecules in environment. This study investigated the re-organization and self-assembly of perfluorooctane sulfonate (PFOS) and macronutrient molecules from rhizospheric organic (RhO) matter induced with a common operation of aeration. Atomic force microscopy (AFM) with infrared spectroscopy (IR)-mapping clearly showed that, after aeration and stabilization, RhO nanocapsules (∼ 1000 nm or smaller) with a core of PFOS-protein complexes coated by "lipid-carbohydrate" layers were observed whereas the capsule structure with a lipid core surrounded by "protein-carbohydrate-protein" multilayers was obtained in the absence of PFOS. It is aeration that exerted the disassociation of pristine RhO components, after which the environmental concentration PFOS restructured the self-assembly structure in a conspicuous "disorder-to-order" transition. AFM IR-mapping analysis of faeces combined with quantification of component uptake denoted the decreased ingestion and utilization of both PFOS and proteins compared with lipids and carbohydrates when Daphnia magna were fed with RhO nanocapsules. RhO nanocapsules acted as double-edged swords via simultaneously impeding the bioaccessibility of hazardous PFOS molecules and macronutrient proteins; and the latter might be more significant, which caused a malnutrition status within merely 48 h. Elucidating the assembly structure of natural organic matter and environmental concentration PFOS, the finding of this work could be a crucial supplementation to the high-dose-dependent eco-effect investigations on PFOS. [Display omitted] [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) serves a critical role in regulating gene expression and has been associated with various diseases; however, its role in the differentiation of endothelial progenitor cells (EPCs) remains unclear. The present study used liquid chromatography with tandem mass spectrometry and immunofluorescence assays to quantify the levels of m6A in human peripheral blood-derived EPCs (HPB-EPCs) before and after differentiation into mature cells. The present study performed Cell Counting Kit 8, Transwell, and tube formation assays to determine the effects of overexpression and knockdown of Wilms' tumor 1-associated protein (WTAP) on HPB-EPCs. The results revealed that the level of m6A modification was significantly increased during HPB-EPCs differentiation, and WTAP exhibited the most significant alteration among the enzymes involved in m6A regulation. When WTAP was overexpressed in HPB-EPCs, cell proliferation, invasion, and the formation of tubes were improved, whereas WTAP knockdown yielded the opposite effects. In conclusion, the present study highlighted the involvement of m6A in regulating EPC differentiation, with WTAP acting as a promoter of EPC differentiation. [ABSTRACT FROM AUTHOR]

• Bacteria removal by functionalized microbubbles is an interface-dependent process. • Adhesion-related VFs may facilitate cell capture by functionalized microbubbles. • Motility-related VFs weaken bubble performance unless motility structure is damaged. • Membrane structure related to antibiotic resistance impacts microbubble performance. • Organic matter in municipal wastewater enhances cell capture but consumes O 3 -CCMBs. The frequent occurrence of epidemics around the world gives rise to increasing concerns of the pollution of pathogens and antibiotic resistant bacteria in water. This study investigated the impacts of virulence factors (VFs) on the removal of antibiotic resistant and pathogenic bacteria from municipal wastewater by ozone-free or ozone-encapsulated Fe(III)-coagulant-modified colloidal microbubbles (O 3 _free-CCMBs or O 3 -CCMBs). The highly interface-dependent process was initiated with cell-capture on the microbubble surface where the as-collected cells could be further inactivated with the bubble-released ozone and oxidative species if O 3 -CCMBs were used. The microbiome sequencing analyses denote that the O 3 _free-CCMB performance of antibiotic resistant and pathogenic bacteria removal was dependent on the virulence phenotypes related to cell-surface properties or structures. The adhesion-related VFs facilitated the effective attachment between cells and the coagulant-modified bubble-surface, which further enhanced cell inactivation by bubble-released ozone. On the contrary, the motility-related VFs might help cells to escape from the bubble capture by locomotion; however, this could be overcome by O 3 -CCMB-induced oxidative demolition of the movement structures. Besides, the microbubble performance was also impacted with the cell-membrane structure related to antibiotic resistance (i.e., efflux pumps) and the dissolved organic matter through promoting the surface-capture and decreasing the oxidation efficacy. The ozone-encapsulated microbubbles with surface functionalization are robust and promising tools in hampering antibiotic resistance and pathogenicity dissemination from wastewater to surface water environment; and awareness should be raised for the influence of virulence signatures on its performance. [Display omitted] [ABSTRACT FROM AUTHOR]