Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent ...target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12‐deficient mice exhibit high‐fat diet (HFD)–induced and high‐fat high‐cholesterol diet–induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD‐induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal‐regulating kinase 1 (ASK1), which mediates the mitogen‐activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1‐related proteins, JUN N‐terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high‐fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.
Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene ...expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC.
circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization.
The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression.
We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.
In turbofan engine datasets, to address problems, such as noise interference, diverse data types, large data volumes, complex feature extraction, inability to effectively describe degradation trends, ...and poor remaining useful life (RUL) prognosis effects, a remaining useful life prognosis model combining an improved stack sparse autoencoder (imSSAE) and an improved echo state network (imESN) is proposed in this paper. First, the 3-sigma criterion is adopted to remove the noise and reconstruct the data, and then the deep features of the engine are extracted by using an imSSAE and fused into health indicator (HI) curves describing the engine degradation trend. Finally, an attention mechanism is introduced into an imESN to adaptively process different types of data and obtain the RUL. The experimental results based on the Commercial Modular Aero-Propulsion System Simulation (C-MAPSS) dataset show that compared with the other popular RUL prediction models, the combined model proposed in this paper has higher prediction accuracy, and the evaluation indices also show the effectiveness and superiority of the model.
The prognosis of the remaining useful life (RUL) of turbofan engine provides an important basis for predictive maintenance and remanufacturing, and plays a major role in reducing failure rate and ...maintenance costs. The main problem of traditional methods based on the single neural network of shallow machine learning is the RUL prognosis based on single feature extraction, and the prediction accuracy is generally not high, a method for predicting RUL based on the combination of one-dimensional convolutional neural networks with full convolutional layer (1-FCLCNN) and long short-term memory (LSTM) is proposed. In this method, LSTM and 1- FCLCNN are adopted to extract temporal and spatial features of FD001 andFD003 datasets generated by turbofan engine respectively. The fusion of these two kinds of features is for the input of the next convolutional neural networks (CNN) to obtain the target RUL. Compared with the currently popular RUL prediction models, the results show that the model proposed has higher prediction accuracy than other models in RUL prediction. The final evaluation index also shows the effectiveness and superiority of the model.
Diabetic cardiomyopathy is characterized by diabetes‐induced myocardial abnormalities, accompanied by inflammatory response and alterations in inflammation‐related signalling pathways. Kirenol, ...isolated from Herba Siegesbeckiae, has potent anti‐inflammatory properties. In this study, we aimed to investigate the cardioprotective effect of kirenol against DCM and underlying the potential mechanisms in a type 2 diabetes mellitus model. Kirenol treatment significantly decreased high glucose‐induced cardiofibroblasts proliferation and increased the cardiomyocytes viability, prevented the loss of mitochondrial membrane potential and further attenuated cardiomyocytes apoptosis, accompanied by a reduction in apoptosis‐related protein expression. Kirenol gavage could affect the expression of pro‐inflammatory cytokines in a dose‐dependent manner but not lower lipid profiles, and only decrease fasting plasma glucose, fasting plasma insulin and mean HbA1c levels in high‐dose kirenol‐treated group at some time‐points. Left ventricular dysfunction, hypertrophy, fibrosis and cell apoptosis, as structural and functional abnormalities, were ameliorated by kirenol administration. Moreover, in diabetic hearts, oral kirenol significantly attenuated activation of mitogen‐activated protein kinase subfamily and nuclear translocation of NF‐κB and Smad2/3 and decreased phosphorylation of IκBα and both fibrosis‐related and apoptosis‐related proteins. In an Electrophoretic mobility shift assay, the binding activities of NF‐κB, Smad3/4, SP1 and AP‐1 in the nucleus of diabetic myocardium were significantly down‐regulated by kirenol treatment. Additionally, high dose significantly enhanced myocardial Akt phosphorylation without intraperitoneal injection of insulin. Kirenol may have potent cardioprotective effects on treating for the established diabetic cardiomyopathy, which involves the inhibition of inflammation and fibrosis‐related signalling pathways and is independent of lowering hyperglycaemia, hyperinsulinemia and lipid profiles.
A palladium-catalyzed enantioselective Heck cyclization/dearomatization cascade via capturing the cyclized Heck π-allylpalladium intermediate by β-naphthols is reported, which provides a new strategy ...for the construction of chiral indole–terpenoid frameworks. This method affords indole-functionalized β-naphthalenone compounds bearing an all-carbon-substituted quaternary chiral center in excellent yields (up to 92%) and enantioselectivities (up to 94% ee). In addition, the utility of this method is showcased by the gram-scale syntheses and diverse transformations of the dearomatized products.
Bubble size contains important indication information that is closely related to flotation production conditions and process indicators. However, bubble images often have low contrast, noise, and ...many other shortcomings, making foam segmentation a difficult problem that the existing segmentation methods cannot solve. In this article, an improved watershed algorithm based on optimal labeling and edge constraints is proposed. Three algorithms are designed to obtain different initial tags, and then the extracted content of different tags is fused to obtain the combined foreground tag. To reduce the offset of the segmentation line, the edge operator is applied to extract the bubble boundary, and the boundary priori condition is used as a constraint to correct the segmentation line. Finally, the optimal segmentation line is obtained by fusing foreground markers and external constraints. Industrial experiments show that this method is effective and has a higher accuracy than the other methods. The average value and variance of rand index (RI) are 92.88% and 0.69, respectively.
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