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Molybdenum disulfide has attracted significant research attention as a nanocatalyst for hydrogen evolution reaction. In this study, the effects of nanoribbons on the catalytic performance of molybdenum disulfide in the hydrogen evolution reaction are evaluated via the density functional theory. Co is considered to be an effective promoter of Mo-based catalysts. Thus, the promotion of the Mo-edge was studied here in a number of Co-substituted surface models. The results show that the electronic structure of the molybdenum disulfide nanoribbons changed after doping with Co atoms; this change significantly reduced the Gibbs free energy of the hydrogen evolution reaction and improved the reaction activity. In addition, the effects of stress regulation on the catalyst were analyzed. Tensile and compressive stresses were applied to the catalyst in the x direction. The results indicate that the distance between atoms changed owing to the effects of stress, and changes were also observed in the electronic properties. The insights obtained from this study will be helpful to further improve the activity of catalysts. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a kind of noncoding RNA, which plays an essential role in gene regulation by binding to messenger RNAs (mRNAs). Accurate and rapid identification of miRNA target genes is helpful to reveal the mechanism of transcriptome regulation, which is of great significance for the study of cancer and other diseases. Many bioinformatics methods have been proposed to solve this problem, but the previous research did not further study the encoding of the nucleotide sequence. In this paper, we developed a novel method combining word embedding and deep learning for human miRNA targets at the site-level prediction, which is inspired by the similarity between natural language and biological sequences. First, the word2vec model was used to mine the distribution representation of miRNAs and mRNAs. Then, the embedding is extracted automatically via the stacked bidirectional long short-term memory (BiLSTM) network. By testing, our method can effectively improve the accuracy, sensitivity, specificity, and F -measure of other methods. Through our research, it is proved that the distributed representation can improve the accuracy of the deep learning model and better solve the miRNA target site prediction problem. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well as genetic and environmental factors. Liraglutide has been used to control blood sugar. But the impact of liraglutide on T2DM-associated NAFLD remains unclear. In this study, we investigated the impact and potential molecular mechanisms of inhibiting ferroptosis for liraglutide improves T2DM-associated NAFLD. Methods: Mice were fed on high-fat-diet and injected with streptozotocin to mimic T2DM-associated NAFLD and gene expression in liver was analysed by RNA-seq. The fast blood glucose was measured during the period of liraglutide and ferrostatin-1 administration. Hematoxylin and eosin staining was used to evaluate the pathological changes in the liver. The occurrence of hepatic ferroptosis was measured by lipid peroxidation in vivo. The mechanism of liraglutide inhibition ferroptosis was investigated by in vitro cell culture. Results: Liraglutide not only improved glucose metabolism, but also ameliorated tissue damage in the livers. Transcriptomic analysis indicated that liraglutide regulates lipid metabolism related signaling including AMPK and ACC. Furthermore, ferroptosis inhibitor rather than other cell death inhibitors rescued liver cell viability in the presence of high glucose. Mechanistically, liraglutide-induced activation of AMPK phosphorylated ACC, while AMPK inhibitor compound C blocked the liraglutide-mediated suppression of ferroptosis. Moreover, ferroptosis inhibitor restored liver function in T2DM mice in vivo. Conclusions: These findings indicate that liraglutide ameliorates the T2DM-associated NAFLD, which possibly through the activation of AMPK/ACC pathway and inhibition of ferroptosis. [ABSTRACT FROM AUTHOR]

Based on our super-slip groove design, three-dimensional numerical models for liquid film under boundary conditions of no slip and super slip at the groove bottom of spiral groove, Tesla groove, and double spiral groove liquid film seals were established. The evolution characteristics of cavitation under different rotational speeds and ambient temperatures were studied, and visualization experiments were carried out through a self-built cavitation visualization test bench. The findings reveal that the super-slip design demonstrates groove universality, preserving the integrity of the liquid film while significantly reducing cavitation rate, enhancing opening force, minimizing leakage, and lowering liquid film temperature. Notably, the experimental observations align closely with the numerical results. • Visualization experiments have verified the accuracy of numerical simulation method for super-slip groove liquid film seals. • The proposed super-slip groove design offers groove universality. • The super-slip groove design significantly mitigates cavitation and enhances the performance of liquid film seals. [ABSTRACT FROM AUTHOR]

• CUS induced down-regulation of RAGE and GLT-1 in hippocampus DG. • RAGE knockdown in hippocampus DG elicited depressive-like behaviors. • RAGE knockdown caused down-regulation of GLT-1, p-CREB and p-p65. • RAGE signaling in hippocampus involved in dysfunction of GLT-1 induced by CUS. A pivotal role of glutamatergic neurotransmission in the pathophysiology of major depressive disorder (MDD) has been supported in preclinical and clinical studies. Glutamate transporters are responsible for rapid uptake of glutamate to maintain glutamate homeostasis. Down-regulation of glutamate transporters has been reported in MDD patients and animal models. However, the mechanism for stress-induced modulation of glutamate transporter expression is poorly understood. Receptor for advanced glycosylation end products (RAGE), a member of immunoglobulin family, is found expressed widely in brain and play important roles in neuronal development, neurite growth, neurogenesis and neuroinflammation. Our study showed chronic unpredictable stress (CUS) induced depressive-like behaviors and reduced RAGE expression in hippocampus DG, CA1 and CA3 areas. The protein levels of GLT-1, p-CREB and p-p65 decreased in hippocampus DG as well. Knockdown of RAGE expression in hippocampus DG with RAGE shRNA lentivirus particles induced depressive-like behaviors. Meanwhile, the protein and mRNA levels of GLT-1 were significantly decreased as well as phosphorylation of CREB and p65. Neither CUS nor RAGE knockdown altered GLAST protein and mRNA levels. These findings suggested that RAGE/CREB-NF-κB signaling pathway in hippocampus DG involved in modulation of GLT-1 expression, which possibly contributed to the depressive-like behavior induced by CUS. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a metabolic disease that is characterized by elevated blood sugar. Although glucagon-like peptide-1 receptor agonists (GLP-1RA) lower blood glucose in a glucose-dependent manner, most of them are macromolecule polypeptides. Macromolecular peptides are relatively expensive and inconvenient compared with small molecules. Therefore, this study sought to identify the small molecules binding to GLP-1R via cell membrane chromatography (CMC), confirm their agonistic activity, and further study its beneficial effects in a mouse model of type 2 diabetes mellitus (T2DM) induced by a combination of high-fat diet and streptozotocin. We used CMC, calcium imaging and molecular docking techniques to screen and identify the potential small molecule Schisandrin B (Sch B), which exhibits a strong binding effect to GLP-1R, from the small molecule library of traditional Chinese medicine. Through in-vitro experiments, we found that Sch B stimulated insulin secretion in β-TC-6 cells, while GLP-1R antagonist Exendin9-39, adenylate cyclase inhibitor SQ22536, and protein kinase A (PKA) inhibitor H89 could significantly inhibit the insulin secretion induced by Sch B. In vivo, Sch B significantly improved fasting blood glucose levels, intraperitoneal glucose tolerance test damage, and the status of pancreatic tissue damage, and reduced serum insulin levels, total cholesterol, triglyceride and low density lipoprotein in T2DM mice. These results indicate that Sch B alleviates T2DM by promoting insulin release through the GLP-1R/cAMP/PKA signaling pathway, suggesting that Sch B may be a potential GLP-1RA, which is expected to provide a new therapeutic strategy for the prevention and treatment of T2DM. [Display omitted] • We screen out the small molecules binding to GLP-1R by cell membrane chromatography. • Sch B stimulates insulin secretion both in vivo and in vitro. • Sch B stimulates insulin secretion through GLP-1R/cAMP/PKA signaling pathway. [ABSTRACT FROM AUTHOR]

The incidence of diabetic cognitive dysfunction is increasing year by year, and it has gradually become a research hot spot. Studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists can improve cognitive dysfunction in diabetic patients. This study focuses on whether small molecule GLP-1R agonists from traditional Chinese medicine (TCM) can improve the diabetic cognitive dysfunction. The small molecules from TCM were screened by cell membrane chromatography (CMC) with GLP-1R-HEK293 cell membrane column. MTT assay, flow cytometry, immunofluorescence cytochemistry and other methods were used to determine the effects of mollugin on the apoptosis rate and reactive oxygen species (ROS) level of high glucose (HG)/hydrogen peroxide (H 2 O 2) induced PC12 cells. Real-Time PCR was used to detect mRNA expression in mouse cerebral cortex. Water maze test was further used to confirm the effect of mollugin on cognitive dysfunction in T2DM mice. Mollugin bound to GLP-1R, promoted Ca2+ influx, increased insulin secretion and cAMP content in β-TC-6 cells. Mollugin enhanced the cell viability, ameliorated apoptosis, reduced intracellular ROS levels in HG/H 2 O 2 -injured PC12 cells. Mollugin reduced the T2DM mice's escape latency, improved neuronal cell damage, decreased the expression of Pik3ca, Akt1 and Mapk1 mRNA in the cerebral cortex tissue. The results suggest that mollugin could improve cognitive dysfunction in T2DM mice through activating GLP-1R/cAMP/PKA signal pathway. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is strongly associated with an increased risk of developing cognitive dysfunction. Numerous studies have indicated that erythropoietin (EPO) has neurotrophic effects. Ferroptosis has been reported to be associated with diabetic cognitive dysfunction. However, the impact of EPO on T2DM-associated cognitive dysfunction and its protective mechanism remain unclear. To evaluate the effects of EPO on diabetes-associated cognitive dysfunction, we constructed a T2DM mouse model and found that EPO not only decreased fasting blood glucose but also ameliorated hippocampal damage in the brain. The Morris water maze test indicated that EPO improved cognitive impairments in diabetic mice. Moreover, a ferroptosis inhibitor improved cognitive dysfunction in mice with T2DM in vivo. Furthermore, a ferroptosis inhibitor, but not other cell death inhibitors, mostly rescued high-glucose damaged PC12 cell viability. EPO had a similar effect as the ferroptosis inhibitor, which increased cell viability in the presence of a ferroptosis inducer. In addition, EPO reduced lipid peroxidation, iron levels, and regulated ferroptosis-related expression of proteins in vivo and in vitro. These findings indicate that EPO ameliorates T2DM-associated cognitive dysfunction, which might be related to decreasing iron overload and inhibiting ferroptosis. • Erythropoietin mitigated cognitive dysfunction in T2DM mice. • Erythropoietin inhibits ferroptosis in high-glucose-treated PC12 cells. • Erythropoietin regulated ferroptosis-related proteins in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Recent studies have shown that erythropoietin (EPO) is an effective neuroprotective and neurotrophic agent for neurological disorders, such as traumatic brain injury and Alzheimer's disease. However, the effectiveness of EPO administration against diabetic cognitive impairments has rarely been examined. In this study, we investigated the effects of EPO on streptozotocin (STZ)-induced male C57BL/6 J mice. Then, we sought to clarify the mechanisms of EPO-mediated neuroprotection in high-glucose (HG)-stimulated HT22 cells. In vivo , we found that STZ-induced diabetic mice showed impaired spatial learning and memory, which was alleviated by EPO treatment. EPO also significantly lowered elevated fasting blood glucose levels, improved pancreatic and hippocampal damage, and restored oxidative stress in the STZ-induced diabetic mice. In vitro, EPO markedly increased cell viability, restrained the expression of pro-apoptotic Bax, enhanced the expression of pro-caspase 3, anti-apoptotic Bcl-2, brain-derived neurotrophic factor (BDNF) and postsynaptic density 95 (PSD-95), and attenuated the upregulation of N -methyl-d-aspartic acid (NMDA) receptor subunits NR1, NR2A and NR2B in HG-induced HT22 cells. The protective effects of EPO was obviously abolished by treatment with an NMDA receptor agonist. Our findings revealed that EPO impedes hippocampal and synaptic damage and neuronal apoptosis by regulating BDNF and PSD-95 expression through NMDA receptors, thereby ameliorating cognitive impairments in mice with T1DM. • EPO alleviates cognitive impairments in STZ-induced diabetic mice. • EPO mitigates the hippocampal and synaptic injuries of diabetic mice. • EPO regulates synapse-associated proteins via NMDA receptors in vitro. [ABSTRACT FROM AUTHOR]