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Whether the stomach influences the progression of nonalcoholic steatohepatitis (NASH) remains largely unknown. Ghrelin, a 28‐amino acid gastric hormone, is critical for the regulation of energy metabolism and inflammation. We investigated whether ghrelin affects the progression of NASH. NASH was induced with lipopolysaccharide (LPS; 240 μg/kg/day) in male C57BL/6J mice with high‐fat diet (HFD). Ghrelin (11 nmol/kg/day) was administrated by a subcutaneous mini‐pump. Liver steatosis, inflammation, and fibrosis were assessed. Kupffer cells and hepatocytes isolated from wild type, GHSR1a−/− or PPARγ+/− mice were cocultured to determine the cellular and molecular mechanism by which ghrelin ameliorates NASH. A low concentration of LPS activates the Kupffer cells, leading to the development of NASH in mice fed HFD. Ghrelin blocked the progression of NASH induced by LPS via GHSR1a‐mediated attenuation of Kupffer cells M1 polarization. GHSR1a was detected in Kupffer cells isolated from wild‐type mice but not in GHSR1a deficient animals. Upon binding with ghrelin, internalization of GHSR1a occurred. Ghrelin reduced levels of tumor necrosis factor‐α and inducible nitricoxide synthase while increasing Arg1 in Kupffer cells treated with LPS. Ghrelin markedly attenuated the upregulation of lipid accumulation induced by the supernatant of Kupffer cells under both basal and LPS‐treated conditions. Deficiency of PPARγ significantly reduced the effect of LPS on the hepatic steatosis in mice and in cultured hepatocytes. Our studies indicate that the stomach may improve the development of NASH via ghrelin. Ghrelin may serve as a marker and therapeutic target for NASH. [ABSTRACT FROM AUTHOR]

The big data stored in massive open online course (MOOC) platforms have become a posed challenge in the Learning Analytics field to analyze the learning behavior of learners, and predict their respective performance, related especially to video lecture data, since most learners view the same online lecture videos. This helps to conduct a comprehensive analysis of such behaviors and explore various learning patterns in MOOC video interactions. This paper aims at presenting a visual analysis, which enables course instructors and education experts to analyze clickstream data that were generated by learner interaction with course videos. It also aims at predicting learner performance, which is a vital decision‐making problem, by addressing their issues and improving the educational process. This paper uses a long short‐term memory network (LSTM) on implicit features extracted from video‐clickstreams data to predict learners' performance and enable instructors to make measures for timely intervention. Results show that the accuracy rate of the proposed model is 89%–95% throughout course weeks. The proposed LSTM model outperforms baseline Deep learning (GRU) and simple recurrent neural network by accuracy of 90.30% in the "Mining of Massive Datasets" course, and the "Automata Theory" accuracy is 89%. [ABSTRACT FROM AUTHOR]

This study comprehensively investigated the impact of indoor carbon dioxide (CO2) concentration on sleep quality. Three experimental conditions (800, 1900, 3000 ppm) were created in chambers decorated as bedroom and other environmental parameters that may influence the sleep quality were under strict control. Sleep quality of 12 subjects (6 men and 6 women) was monitored for 54 consecutive days through sleep quality questionnaire and physiological measures. Both subjective and physiological results showed that sleep quality decreased significantly with the increase of CO2 concentration, and the comprehensive questionnaire score at 3000 ppm was only 80.8% of that at 800 ppm. A linear positive correlation was found between sleep onset latency (SOL) and CO2 concentration, while a linear negative correlation occurred between slow‐wave sleep (SWS) and CO2 concentration. In addition, in the same sleep environment, men had higher subjective questionnaire scores after wake‐up, longer SWS and shorter SOL, which lead to a better sleep quality compared with women, and there was a significant gender difference in sleep quality at 800 ppm (P <.05). [ABSTRACT FROM AUTHOR]

ETV5 is an ETS transcription factor that has been associated with obesity in genomic association studies. However, little is known about the role of ETV5 in hepatic lipid metabolism and nonalcoholic fatty liver disease. In the current study, we found that ETV5 protein expression was increased in diet- and genetically induced steatotic liver. ETV5 responded to the nutrient status in a mammalian target of rapamycin complex 1 (mTORC1)-dependent manner and in turn, regulated mTORC1 activity. Both viral-mediated and genetic depletion of ETV5 in mice led to increased lipid accumulation in the liver. RNA sequencing analysis revealed that peroxisome proliferator-activated receptor (PPAR) signaling and fatty acid degradation/metabolism pathways were significantly downregulated in ETV5-deficient hepatocytes in vivo and in vitro. Mechanistically, ETV5 could bind to the PPAR response element region of downstream genes and enhance its transactivity. Collectively, our study identifies ETV5 as a novel transcription factor for the regulation of hepatic fatty acid metabolism, which is required for the optimal β-oxidation process. ETV5 may provide a therapeutic target for the treatment of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Aims Sustained activation of β-adrenergic signalling induces cardiac fibrosis, which marks progression to heart failure. GHSR (growth hormone secretagogue receptor) is the receptor for ghrelin, which is an orexigenic gastric hormone with newly defined cardiovascular effects. The present study determined the effects of GHSR deficiency in a mouse model of isoproterenol (ISO)-induced cardiac fibrosis and examined the underlying mechanism. Methods and results Histochemical studies showed that GHSR deficiency exacerbated cardiac fibrosis. Quantitative RT–PCR, western blotting, and immunofluorescence staining demonstrated that cardiac fibroblasts isolated from GHSR−/− mice exhibited increased expression of marker genes for myofibroblast trans-differentiation (α-SMA, SM22, and calponin) upon transforming growth factor-β treatment compared to wild-type mice. RNA-sequencing of heart transcriptomes revealed that differentially expressed genes in GHSR−/− hearts were enriched in such biological processes as extracellular matrix organization, inflammatory response, lipid metabolism, cell cycle, migration, and adhesion. Particularly, GHSR deficiency increased Wnt/β-catenin pathway activation in ISO-induced myocardial fibrosis. In addition, loss of GHSR in macrophages instigated inflammasome activation with increased cleavage and release of interleukin-18. Conclusion These results for the first time demonstrated that GHSR deficiency aggravated ISO-induced cardiac fibrosis, suggesting that GHSR was a potential target for the intervention of cardiac fibrosis. [ABSTRACT FROM AUTHOR]

The N6-methyladenosine (m6A) RNA modification is essential during embryonic development of various organs. However, its role in embryonic and early postnatal islet development remains unknown. Mice in which RNA methyltransferase-like 3/14 (Mettl3/14) were deleted in Ngn3+ endocrine progenitors (Mettl3/14nKO ) developed hyperglycemia and hypoinsulinemia at 2 weeks after birth. We found that Mettl3/14 specifically regulated both functional maturation and mass expansion of neonatal β-cells before weaning. Transcriptome and m6A methylome analyses provided m6A-dependent mechanisms in regulating cell identity, insulin secretion, and proliferation in neonatal β-cells. Importantly, we found that Mettl3/14 were dispensable for β-cell differentiation but directly regulated essential transcription factor MafA expression at least partially via modulating its mRNA stability. Failure to maintain this modification impacted the ability to fulfill β-cell functional maturity. In both diabetic db/db mice and patients with type 2 diabetes (T2D), decreased Mettl3/14 expression in β-cells was observed, suggesting its possible role in T2D. Our study unraveled the essential role of Mettl3/14 in neonatal β-cell development and functional maturation, both of which determined functional β-cell mass and glycemic control in adulthood. [ABSTRACT FROM AUTHOR]

This study investigates the morphological changes in cyanobacterial and microbial distribution characteristics of surface sediments, throughout different cyanobacterial blooms periods in Zhushan Bay, Taihu Lake. Comparative microscopic analysis of cyanobacterial morphology (n = 36) was performed during the formation period (W1), stationary period (W2), decline period (W3) and decomposition period (W4). Simultaneously, sequence analysis was performed on microbial 16S rRNA genes in sediments (n = 36) by high-throughput sequencing. The coverage of the sequencing library was very high (100%) indicating that the sequencing results well represented the microbes present in samples, among which the species richness in W4 was the highest, while the species distribution uniformity was low. The microbial abundance distribution in all four periods showed that Firmicutes (33.45%), Cyanobacteria (30.44%), Proteobacteria (27.17%) and Bacteroidetes (7.2%) were the dominant flora, with W1 dominated by Cyanobacteria, W2 dominated by Firmicutes, W3 dominated by Proteobacteria and Cyanobacteria, and W4 dominated by Proteobacteria. There were significant differences in microbial species abundance and distribution observed during each cyanobacterial bloom period and synchronous microorganisms in the sediment regulated bacterial abundance and distribution through signal transduction of various proteases. The findings of this study help to establish the impact of cyanobacteria blooms on the sediment environment and benefit the comprehensive assessment of hazard presented by cyanobacteria to the aquatic environment. [ABSTRACT FROM AUTHOR]

Lipotoxicity has been shown to induce the loss of functional β-cell mass and lead to type 2 diabetes, but the mechanism remains unknown. In this study, we aim to explore the role of secretagogin (SCGN) in lipotoxicity-induced β-cell injury. Our results indicate that ox-LDL treatment leads to autophagic cell death, as evidenced by decreased cell viability, aggravated cell apoptosis, and the accumulation of the p62 protein in MIN6 cells. LysoTracker Red staining, TEM and mRFP-GFP-LC3 assays demonstrate that autophagic flux is blocked in ox-LDL-treated MIN6 cells. Intriguingly, SCGN is significantly decreased in MIN6 cells under lipotoxic conditions. Additionally, siRNA-guided SCGN knockdown blocks autophagic flux triggered by rapamycin, while SCGN restoration alleviates autophagic flux retardation and mitigates cell apoptosis. The physical interaction between SCGN and SNAP29 is validated by bioinformatics analysis, coimmunoprecipitation assay and SCGN knockdown test. Downregulation of SCGN expression reduces the interaction of these two proteins. Taken together, our results indicate that ox-LDL treatment induces apoptotic β-cell death by blocking autophagic flux dependent on SCGN downregulation. SCGN administration prevents lipotoxic β-cell injury and may be a potential therapeutic strategy to promote β-cell expansion in type 2 diabetes.