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Prediabetes is a high-risk condition for type 2 diabetes (T2D). Pancreatic β-cells adapt to impaired glucose regulation in prediabetes by increasing insulin secretion and β-cell mass expansion. In people with prediabetes, metformin has been shown to prevent prediabetes conversion to diabetes. However, emerging evidence indicates that metformin has negative effects on β-cell function and survival. Our previous study established the Nile rat (NR) as a model for prediabetes, recapitulating characteristics of human β-cell compensation in function and mass expansion. In this study, we investigated the action of metformin on β-cells in vivo and in vitro. A 7-week metformin treatment improved glucose tolerance by reducing hepatic glucose output and enhancing insulin secretion. Although high-dose metformin inhibited β-cell glucose-stimulated insulin secretion in vitro, stimulation of β-cell insulin secretion was preserved in metformin-treated NRs via an indirect mechanism. Moreover, β-cells in NRs receiving metformin exhibited increased endoplasmic reticulum (ER) chaperones and alleviated apoptotic unfold protein response (UPR) without changes in the expression of cell identity genes. Additionally, metformin did not suppress β-cell mass compensation or proliferation. Taken together, despite the conflicting role indicated by in vitro studies, administration of metformin does not exert a negative effect on β-cell function or cell mass and, instead, early metformin treatment may help protect β-cells from exhaustion and decompensation.  相似文献   
33.
Parkinson’s disease (PD) is a neurodegenerative disorder that affects 1% of the population over the age of 60. Diabetes Mellitus (DM) is a metabolic disorder that affects approximately 25% of adults over the age of 60. Recent studies showed that DM increases the risk of developing PD. The link between DM and PD has been discussed in the literature in relation to different mechanisms including mitochondrial dysfunction, oxidative stress, and protein aggregation. In this paper, we review the common microRNA (miRNA) biomarkers of both diseases. miRNAs play an important role in cell differentiation, development, the regulation of the cell cycle, and apoptosis. They are also involved in the pathology of many diseases. miRNAs can mediate the insulin pathway and glucose absorption. miRNAs can also regulate PD-related genes. Therefore, exploring the common miRNA biomarkers of both PD and DM can shed a light on how these two diseases are correlated, and targeting miRNAs is a potential therapeutic opportunity for both diseases.  相似文献   
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The evolution of new SARS-CoV-2 variants around the globe has made the COVID-19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to the receptor-binding motif (RBM) of the receptor-binding domain (RBD) spike glycoprotein, i. e. L452R-E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant's pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R-E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic-stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural-dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS-CoV-2 variants.  相似文献   
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学术英文写作是当今电子信息专业研究生必修的一门课程。然而传统的以教师为中心的灌输式教学已不能跟上网络迅猛发展的趋势,尤其是当疫情来临的特殊形势下。此外,现有的学术英文写作教学研究仅提供宏观的设计,缺乏具体的实际可操作性。为此,本文以引言写作逻辑为教学模块案例,探索了如何充分利用网络资源的优势,开展以学生为中心的课前课中课下有机融合的灵活的教学设计。所探索的引言写作技巧和详实的教学设计,为模块化网络教学提供一个切实可行的参考方案。  相似文献   
37.
采用整体式控制爆破拆除方案对华电扬州电厂钢筋混凝土框-排架结构厂房进行了爆破拆除。爆破前,对汽机房、厂房外墙和楼梯进行了预处理。将厂房划分为3个爆区,采用非电多回路网格式爆破网路,依靠东侧锅炉房倒塌施加在西侧锅炉房上的倾覆力矩,有效地克服了西侧锅炉房向西倒的难题,可为同类工程提供一定的参考。  相似文献   
38.
This work explored the feasibility of Li decoration on the B4CN3 monolayer for hydrogen (H2) storage performance using first-principles calculations. The results of density functional theory (DFT) calculations showed that each Li atom decorated on the B4CN3 monolayer can physically adsorb four H2 molecules with an average adsorption energy of ?0.23 eV/H2, and the corresponding theoretical gravimetric density could reach as high as 12.7 wt%. Moreover, the H2 desorption behaviors of Li-decorated B4CN3 monolayer at temperatures of 100, 200, 300 and 400 K were simulated via molecular dynamics (MD) methods. The results showed that the structure was stable within the prescribed temperature range, and a large amount of H2 could be released at 300 K, indicative of the reversibility of hydrogen storage. The above findings demonstrate that the Li-decorated B4CN3 monolayer can serve as a favorable candidate material for high-capacity reversible hydrogen storage application.  相似文献   
39.
Water electrolysis is the most clean and high-efficiency technology for production of hydrogen, an ultimate clean energy in future. Highly efficient non-noble electrocatalysts for hydrogen evolution reaction (HER) are desirable for large scale production of hydrogen by water electrolysis. Especially, exposing as many active sites as possible is a vital way to improve activities of the catalysts. Herein, a series of new hydrangea like composite catalysts of ultrathin Mo2S3 nanosheets assembled uprightly and interlacedly on N, S-dual-doped graphitic biocarbon spheres were facilely prepared. The unique structure endowed the catalysts highly exposed edge active sites and prominently high activities for HER. Especially, the optimized catalyst Mo2S3/NSCS-50 exhibited as low as 106 mV of overpotential at 10 mA/cm2 (denoted as ?10). The catalyst also showed low Tafel slope of 53 mV/dec, low electron transfer resistance of 34 Ω and high stability evidenced by the result that the current density only attenuated 11.7% after 10 h i-t test. The catalyst has shown broad prospect for commercial application in water electrolysis.  相似文献   
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