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Autophagy is an essential cellular quality control process that has emerged as a critical one for vascular homeostasis. Here, we show that trichoplein (TCHP) links autophagy with endothelial cell (EC) function. TCHP localizes to centriolar satellites, where it binds and stabilizes PCM1. Loss of TCHP leads to delocalization and proteasome-dependent degradation of PCM1, further resulting in degradation of PCM1's binding partner GABARAP. Autophagic flux under basal conditions is impaired in THCP-depleted ECs, and SQSTM1/p62 (p62) accumulates. We further show that TCHP promotes autophagosome maturation and efficient clearance of p62 within lysosomes, without affecting their degradative capacity. Reduced TCHP and high p62 levels are detected in primary ECs from patients with coronary artery disease. This phenotype correlates with impaired EC function and can be ameliorated by NF-κB inhibition. Moreover, Tchp knock-out mice accumulate of p62 in the heart and cardiac vessels correlating with reduced cardiac vascularization. Taken together, our data reveal that TCHP regulates endothelial cell function via an autophagy-mediated mechanism. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.AIM Recently, FibroScan-AST (FAST) score was reported to be effective for identifying nonalcoholic steatohepatitis (NASH) with significant activity and fibrosis in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to confirm the diagnostic accuracy of FAST score of Japanese patients and compare the cut-off values and diagnostic accuracy between the FibroScan® M and XL probes. METHODS Eighty-two and 84 patients were included the verification and validation sets, respectively. All patients were diagnosed with NAFLD via biopsy by two central expert pathologists. DW71177 concentration Liver stiffness measurements and controlled attenuation parameter were performed, and diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS No significant difference existed in FAST score between the M and XL probes (0.489 vs 0.483, p=0.187). No significant difference existed in the area under the ROC between the two probes (M, 0.7598; XL, 0.7614; p=0.958). According to the Youden index, the cut-off value using the M probe was 0.57 with 68.2% sensitivity and 78.3% specificity. For the XL probe, the cut-off value was 0.56 with 68.2% sensitivity and 73.3% specificity. To obtain sensitivity and specificity values higher than 90%, cut-off values of 0.35 and 0.66 were chosen for the M probe and 0.32 and 0.63 were chosen for the XL probe. CONCLUSIONS There was no significant difference in diagnostic accuracy of FAST score between the FibroScan® M and XL probes. FAST score can be used to identify NASH with significant risk in Japanese patients regardless of probe selection. This article is protected by copyright. All rights reserved.BACKGROUND MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the early stage of acute ischemic stroke (AIS). The purpose of this study was to investigate the expression patterns of miRNAs in peripheral blood mononuclear cells (PBMCs) from AIS patients and further explore related molecular mechanisms in stroke-induced immunodeficiency syndrome (SIDS). METHODS The miRNA expression patterns of PBMCs were detected by miRNA microarray and validated by quantitative real-time PCR (qRT-PCR) in AIS patients and healthy controls (HCs). Bioinformatics methods and luciferase reporter assays were used to detect the downstream target genes. Following stimulation with lipopolysaccharide (LPS) and interleukin-4 (IL-4), the expression of miR-4443, tumor necrosis factor receptor-associated factor 4 (TRAF4) and the nuclear factor-κB (NF-κB) pathway were evaluated. Furthermore, transfection with miR-4443 mimic or inhibitor in the monocytes was to get insight into the mechanisms in SIDS. RESULTS The interleukin-10 (IL-10) in AIS patients was significantly higher than that of HCs. The miRNA microarray analysis and qRT-PCR validation showed only miR-4443 in 4 up-regulated miRNAs of PBMCs from AIS patients was differential expression, especially in monocytes. MiR-4443 was shown to directly interact with the 3'-UTR of TRAF4, resulting in suppression of TRAF4 protein expression. Furthermore, the expression of miR-4443 and TRAF4 was regulated by stimulation with LPS or IL-4. Additionally, overexpression of miR-4443 suppressed the TRAF4/Iκα/NF-κB signaling pathway to activate the expression of anti-inflammatory cytokines in monocytes. CONCLUSIONS The increased expression of miR-4443 induced monocyte dysfunction by targeting TRAF4, which may function as a crucial mediator in SIDS. This article is protected by copyright. All rights reserved.Genetic variation in a pathogen, including the causative agent of salmonellosis, Salmonella enterica, can occur as a result of eco-evolutionary forces triggered by dissimilarities of ecological niches. Here, we applied comparative genomics to study 90 antimicrobial resistant (AMR) S. enterica isolates from bovine and human hosts in New York and Washington states to understand host- and geographic-associated population structure. Results revealed distinct presence/absence profiles of functional genes and pseudogenes (e.g., virulence genes) associated with bovine and human isolates. Notably, bovine isolates contained significantly more transposase genes but fewer transposase pseudogenes than human isolates, suggesting the occurrence of large-scale transposition in genomes of bovine and human isolates at different times. The high correlation between transposase genes and AMR genes, as well as plasmid replicons, highlights the potential role of horizontally transferred transposons in promoting adaptation to antibiotics. By contrast, a number of potentially geographic-associated single-nucleotide polymorphisms (SNPs), rather than geographic-associated genes, were identified. Interestingly, 38% of these SNPs were in genes annotated as cell surface protein-encoding genes, including some essential for antibiotic resistance and host colonization. Overall, different evolutionary forces and limited recent inter-population transmission appear to shape AMR S. enterica population structure in different hosts and geographic origins. © 2020 Society for Applied Microbiology and John Wiley & Sons Ltd.