A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

In Situ Observation of Phase Transformations in the Coarse-Grained Heat-Affected Zone of P91 Heat-Resistant Steel During Simulated Welding Process

Metallurgical and Materials Transactions A - The solid-state phase transformation in the coarse-grained heat-affected zone of P91 steel under simulated welding thermal cycle has been investigated...     

Semantic Hierarchy Emerges in Deep Generative Representations for Scene Synthesis

International Journal of Computer Vision - Despite the great success of Generative Adversarial Networks (GANs) in synthesizing images, there lacks enough understanding of how photo-realistic images...     

Suppressing Ion Migration across Perovskite Grain Boundaries by Polymer Additives

Passivation of organometal halide perovskites with polar molecules has been recently demonstrated to improve the photovoltaic device efficiency and stability. However, the mechanism is still elusive. Here, it is found that both polymers with large and small dipole moment of 3.7 D and 0.6 D have negligible defect passivation effect on the MAPbI₃ perovskite films as evidenced by photothermal deflection spectroscopy. The photovoltaic devices with and without the polymer additives also have comparable power conversion efficiencies around 19%. However, devices with the additives have noticeable improvement in stability under continuous light irradiation. It is found that although the initial mobile ion concentrations are comparable in both devices with and without the additives, the additives can strongly suppress the ion migration during the device operation. This contributes to the significantly enhanced electrical-field stress tolerance of the perovskite solar cells (PVSCs). The PVSCs with polymer additives can operate up to −2 V reverse voltage bias which is much larger than the breakdown voltage of −0.5 V that has been commonly observed. This study provides insight into the role of additives in perovskites and the corresponding device degradation mechanism.     

Zinc-Deficiency Induced g-C3N4 Nanosheets: Photocatalytic Nitrogen Fixation Study and Carrier Dynamics

Catalysis Letters - g-C3N4 has great application prospect in the field of photocatalytic nitrogen fixation owing to the advantages of abundant raw materials, low toxicity, low consumption, high...     

Aqueous-based,high-density nanoporous carbon xerogels with high specific surface area for supercapacitors

Journal of Porous Materials - Electrode materials with high density for assembling supercapacitors with high volumetric capacitance are urgently needed. Herein, nanoporous carbon xerogels (NPCXs)...     

基于决策树方法的混凝土泵车液压油超温分析与识别

工程机械的液压油超温由于设备规模大,影响因素多,导致运行过程中存在较强的不确定性.本文以混凝土泵车为研究对象,基于决策树算法分析了造成液压油异常高温的原因,了解了导致液压油超温的主要原因与各参数对液压油温度的贡献度.通过决策树模型(测试精度93.4％)找出了典型的超温原因,实施整改措施后液压油超温率降低7.4％,超温得到控制,降低了设备因液压油超温带来的潜在风险.数据挖掘在工程机械领域的应用大大提高了故障分析效率,明确了问题方向,为故障诊断与性能分析提供了一种新的思路.     

核电站结构模块组装工艺实践与分析

AP系列核电建设引入了"模块化"施工的理念,以国内某核电站2台机组CA20模块为例,从实践经验出发,介绍卧式和立式2种组装工艺,对2种工艺的特点进行分析对比,提出结构模块组装工作的相关建议,为后续同类型核电项目施工提供参考.