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.     

电磁精细探测法在隐伏型导水地质裂缝勘探中的应用

针对传统隐伏型导水地质裂缝勘探方法存在勘测精度较差的问题,提出电磁精细探测法探析隐伏型导水地质裂缝。依照屏蔽系数、实测场强和理论场强数据绘制综合曲线图,通过该图获取隐伏型导水地质裂缝所处位置几何阴影范围,采用层析成像法得到网格化的工作面,获取隐伏型导水地质图像。通过图像直接观测隐伏型导水地质工作面裂缝所处位置,在此基础上,观测四个电磁场分量,采用正交电磁场分量计算介质视电阻率,依据计算视电阻率数值和视电阻率分布状态研究裂缝发育情况和裂缝富水程度。结果表明:采用该方法能较为精准地获取隐伏型导水地质裂缝位置。通过裂缝位置进一步检测出隐伏型导水地质裂缝最大发育高度为63.5 m。当视电阻数值不断增加时,隐伏型导水地质裂缝和裂缝富水性逐渐减小,与实际情况较为相符,说明该种方法探析效果较好。     

Effect of CuSO4 on the Hydromechanical Behavior of Compacted Tailings

Laboratory tests, including compressibility, permeability, and microstructure tests, were conducted on tailings samples using custom-designed test apparatus to investigate the effect of metal contamination (Cu²⁺) on the hydromechanical behavior of compacted tailings. Infiltrating samples with various dry densities with distilled water or CuSO₄ solution at various concentrations showed that the void ratio of compacted tailings decreased with increased dry density. An increase in the metal contaminant concentrations from 0 to 0.1 mol/L increased the compression coefficient of the tailings from 0.14 to 0.84 MPa^?1 under a vertical load of 0.01 to 2.0 MPa, while the yield stress of the tailings decreased from 204.3 to 98.7 kPa, respectively. The linear relationship between permeability coefficient (k) and void ratio (e) is described by k?=???6.48?+?17.17e. Microstructure test results showed that the diffusion double layer thinned, and the surface potential decreased, indicating that the contaminant of Cu²⁺ enhanced the compressibility and permeability of the tailings. The microstructure test results also showed that the amount of fine-grained soil in the copper tailings was significantly less after the hydromechanical test. Therefore, the permeability and compressibility of copper tailings increased. The experimental results are in good agreement with the estimated results.

     

Visual Detection of Adenosine Triphosphate by Taylor Rising: A Simple Point-of-Care Testing Method Based on Rolling Circle Amplification

Rapid and sensitive point-of-care testing (POCT) is an extremely critical mission in practical applications, especially for rigorous military medicine, home health care, and in the third world. Here, we report a visual POCT method for adenosine triphosphate (ATP) detection based on Taylor rising in the corner of quadratic geometries between two rod surfaces. We discuss the principle of Taylor rising, demonstrating that it is significantly influenced by contact angle, surface tension, and density of the sample, which are controlled by ATP-dependent rolling circle amplification (RCA). In the presence of ATP, RCA reaction effectively suppresses Taylor-rising behavior, due to the increased contact angle, density, and decreased surface tension. Without addition of ATP, untriggered RCA reaction is favorable for Taylor rising, resulting in a significant height. With this proposed method, visual sensitive detection of ATP without the aid of other instruments is realized with only a 5 μL droplet, which has good selectivity and a low detection limit (17 nM). Importantly, this visual method provides a promising POCT tool for user-friendly molecular diagnostics.     

内插法在相关干涉仪测向体制中的应用

测向误差的减小一直以来都是无线电测向精度提高的一个难点,对于不同的测向体制所采用的减小测向误差的方法都不尽相同。本文主要介绍的是相关干涉仪测向体制的基本原理以及通过内插法的应用来减小测向误差的方法。     

铜基化合物的可见光催化研究进展

与传统贵金属光催化剂相比，铜基光催化剂具有价格低廉、绿色环保、反应条件温和、光催化活性可调节等优势，受到合成化学家们广泛关注。本文简述了铜基催化剂的光催化历史，回顾了近五年来铜基化合物在可见光催化领域的研究成果与进展，总结了铜基催化剂的独立光催化机理与协同光催化机理；简要阐述了铜催化剂在不同类型反应中的应用，重点讨论了铜(Ⅰ)催化剂在烯烃官能化、碳-碳偶联、碳-杂偶联、原位催化等反应中的应用研究，表明铜基化合物在光催化合成领域具有很大的应用潜力。对未来的研究工作进行了展望，指出拓展催化剂的反应适用性、探索催化剂的氧化还原能力、进一步开发催化剂在手性合成中的应用将是该领域的研究重点。     

高密度聚乙烯/铅硼复合材料屏蔽性能和力学性能研究

研究了高密度聚乙烯/铅硼复合材料的屏蔽性能和力学性能，通过屏蔽仿真比较了密度及碳化硼（B4C）含量对屏蔽性能的影响，通过试验比较了B4C含量对屏蔽性能、弯曲强度及冲击强度的影响。仿真结果表明,随聚乙烯/铅硼复合材料密度升高，快中子屏蔽性能下降，热中子屏蔽性能和γ屏蔽性能提高；保持聚乙烯/铅硼复合材料密度不变，随B4C含量的提高，中子屏蔽性能提高而γ屏蔽性能下降;实验数据表明,随B4C含量的升高，高密度聚乙烯/铅硼材料的快中子屏蔽性能、热中子屏蔽性能升高，γ屏蔽系数下降，冲击强度和弯曲强度下降明显，屏蔽性能测试结果和仿真结果规律性相符；综合仿真结果和实验数据表明，含B4C 2 %左右的高密度聚乙烯/铅硼复合材料同时具有较好的屏蔽性能和力学性能。