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.     

豫西雷门沟钼矿水文地质条件分析及涌水量预测

豫西熊耳山雷门沟钼矿床位于东秦岭多金属成矿带东段,是已探明的超大型斑岩型钼矿,前人研究程度高、地质成果丰硕,但对矿床开采技术条件方面研究较少。本次通过地质调查工程、水文地质试验等方法,从水文地质角度,对雷门沟钼矿床水文地质条件进行研究,填补了该方面的空白,丰富了研究成果；采用水文地质比拟法预测未来矿坑最大排水量2613 m³/d,经实践检验结果较为可靠；总结的采坑排水量预测方法、含水层特点、矿床充水因素以及防治水措施,以期对该区域水文地质工作具有参考价值。     

快速灵敏的LC-MS/MS法测定人血浆中阿莫西林并应用于两种制剂的一致性评价

目的: 建立快速灵敏的LC-MS/MS法测定人血浆中阿莫西林浓度，并用于两种阿莫西林胶囊的一致性评价。方法: 采用岛津公司LCMS-8060型LC-MS/MS仪，以MRM模式测定阿莫西林（m/z 366.00/114.00）的浓度，d4-阿莫西林作内标（m/z 370.10/114.05），离子源为ESI源。色谱柱选用Waters ACQUITY BEH C18（2.1×50 mm，1.7 μm），梯度洗脱。血浆样本加入内标，经甲醇沉淀蛋白后取上清液进样检测。结果: 所建方法经验证，其线性、准确度、精密度、最低定量限、提取回收率、特异性、基质效应、稳定性等各项指标均符合CFDA的指导原则及最新核查标准要求，并较文献报道中的方法有处理简单、灵敏度高、色谱峰形好的优点。结论: 所建方法快速、灵敏，适用于人血浆中阿莫西林浓度的检测。用于一致性评价的样本实测，两种制剂生物等效。     

调频数字音频广播激励器技术指标测试技巧

中国调频频段数字音频广播(CDR)激励器及发射机测试标准已正式发布.CDR采用的是数模同播技术,相关指标测试方法比较复杂,具体测试步骤也较抽象.这里将实际测试积累的一些经验和技巧结合标准内容进行阐述,不但可提高测试效率也能帮助大家比较直观和深入的理解标准内容.     

PET熔体长距离输送影响因素探讨

介绍了PET熔体长距离输送工艺流程,重点分析易对PET熔体输送带来不利影响的因素,如熔体压力降、停留时间、管道粗糙度、焊缝品质等,并针对熔体输送的不利因素,提出了相应的解决方案,对熔体直纺设计、实践提供必要的参考。     

一种2,6-二甲基苯甲酸的改进合成方法

以2,6-二甲基苯胺为原料,通过重氮化反应制备2,6-二甲基苯腈,经水蒸汽蒸馏法提纯后,采用75%硫酸酸化,再经酸碱法对产物进行脱色和纯化得产物2,6-二甲基苯甲酸,总收率68.4%。工艺简单、操作安全、适合工业化生产。     

Experimental and numerical study on compressive performance of perforated brick masonry after fire exposure

This paper discusses the compressive performance of perforated brick masonry after fire exposure. Compressive strength tests of the mortar, clay perforated brick, and perforated brick masonry specimens were performed in accordance with ISO834 fire tests of different durations. The temperature distribution of the masonry materials and specimens was simulated using the finite element software ABAQUS, with the thermal parameters of masonry materials recommended by European standard Eurocode 6 and related literature. The compressive strength reduction factors of mortar and clay perforated brick exposed to different fire durations were calculated via the layered method suggested by European standard Eurocode 1. In addition, the compressive strength reduction factors after cooldown were obtained from the experimental data of the masonry materials, and by considering further reductions in the compressive strength after cooling from high temperatures. Experimental data of the masonry specimens were compared with the numerical results obtained using the reduction factors proposed in this work. The comparison revealed an overall acceptable approximation. Thus, the method presented in this paper can be used to evaluate the residual capacity of masonry structures after fire.     

一种实用的多数据库量子信息检索协议

针对目前量子私有信息检索不能适用与云存储的多数据库问题,基于现在成熟的量子密钥分发方法,提出了一种适合在多数据库环境下,实用的量子私有信息检索协议。对于不同大小的数据库,协议可通过调节参数θ和k,在保证数据库安全及用户隐私的情况下,完成信息的检索。性能分析结果表明,协议的通信复杂度低,检索成功率高、易于实施。     

子母车系统效率分析与验证

在子母车系统中,研究一台母车配合两台子车在同层进行复合作业的效率问题,提高系统作业效率计算的准确性,优化系统整体布局和物流设备的选择。首先分析一台母车配合两台子车在同层的循环复合作业过程;然后结合子母车的运动特性得到其作业效率计算模型;最后采用MATLAB工具计算效率模型分别在随机组合作业对和FEM9.851标准作业对的作业效率,通过对比验证,两种循环作业的效率绝对偏差符合工程实际。在工程实际中可以参照FEM9.851标准作业对代替随机组合作业对进行子母车系统的效率计算。     

Headspace fingerprinting approach to identify the major pathway influencing volatile patterns of vinasse-cured duck processed by high pressure,as well as its impact on physicochemical and sensory attributes

As a decisive attribute, flavour could be influenced by HP treatments through multiple physical and chemical pathways within the high pressure (HP)-assisted meat curing process. This investigation aimed to identify the major pathway influencing volatile flavour patterns of two representative vinasse-cured duck (VCD) products with HP treatments (150–300 MPa/15 min), including wet and dry types, by employing headspace fingerprinting as an untargeted approach. Results suggested that HP treatments greatly lowered moisture contents and increased Warner-Bratzler shear force and thiobarbituric acid reactive substances of the cured samples. According to multivariate models, the volatile flavour patterns of the HP-processed VCD could be clearly separated from the unprocessed samples, but the VCD pressurised at different intensities represented similar volatile fingerprinting, which was validated by e-nose analysis. The discriminant analysis (OPLS-DA) model outlined vinasse-derived ethanol, acetic acid, 3-methyl-1-butanol, 2-methyl-1-butanol, phenethyl alcohol and 2-methyl-3-octanone as the major discriminant aromas across the unpressurised and pressurised samples.