Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

深共融溶剂催化制备二酯类化合物

二酯类化合物广泛应用于有机中间体、药物、增塑剂、香料等领域,开发其绿色、高效的合成新方法具有重要意义.报道了以二元羧酸(或二羧酸酐)和脂肪醇为原料,以深共融溶剂(DESs)为催化剂催化合成二酯类化合物.以n(氯化胆碱):n(对甲苯磺酸)=1:2为催化剂,产率最高可达95％,并且DESs使用8次后产率仍保持在88％以上.运用1HNMR和13CNMR对产物进行了结构表征.该方法具有操作简单、产率高、易分离和催化剂可循环使用等优点.     

Matrix Manipulation of Directly-Synthesized PbS Quantum Dot Inks Enabled by Coordination Engineering

The direct-synthesis of conductive PbS quantum dot (QD) ink is facile, scalable, and low-cost, boosting the future commercialization of optoelectronics based on colloidal QDs. However, manipulating the QD matrix structures still is a challenge, which limits the corresponding QD solar cell performance. Here, for the first time a coordination-engineering strategy to finely adjust the matrix thickness around the QDs is presented, in which halogen salts are introduced into the reaction to convert the excessive insulating lead iodide into soluble iodoplumbate species. As a result, the obtained QD film exhibits shrunk insulating shells, leading to higher charge carrier transport and superior surface passivation compared to the control devices. A significantly improved power-conversion efficiency from 10.52% to 12.12% can be achieved after the matrix engineering. Therefore, the work shows high significance in promoting the practical application of directly synthesized PbS QD inks in large-area low-cost optoelectronic devices.     

工艺参数对动态流量控制法挤压弯管应力的影响

采用有限元模拟和实验研究了挤压钛合金弯曲管件。通过实验验证了工件的形状和尺寸精度,并通过有限元模拟分析了工艺参数对挤出过程中变形体的平均压应力分布情况和挤出弯管件的曲率半径的影响规律。结果表明:有限元模拟中,弯管件的曲率半径误差为6.03%,弯管直径误差为3.82%;在靠近定径带处,平均压应力呈非均匀分布;在焊合腔内,靠近细分流孔区域的平均压应力小于靠近粗分流孔区域的平均压应力,平均压应力的大小顺序在通过粗、细分流孔前后相反;在模具结构固定不变时,弯管件的曲率半径随挤压速度的减小而增大,不随挤压温度的变化而变化。     

变压器内部故障在线检测方法仿真及误差分析

为研究变压器内部故障在线检测方法的有效性及抗干扰性,搭建实际变压器的非线性三维有限元模型.对变压器常见几种类型的内部故障进行详细的结构仿真,通过"场-路耦合法"构建各类型故障的ΔV-I1轨迹.同时,通过对正常绕组的测量信号设置一定的误差,构建了考虑测量误差时的误差轨迹.在此基础上,将正常时的标准轨迹、误差轨迹和各种类型的故障轨迹进行对比分析,通过对ΔV-I1轨迹特征差异的定性分析与定量计算,验证该方法在实际应用中的有效性,总结判断各类型故障的规则,同时针对测量误差所造成的干扰提出了建议.     

爆炸冲击波载荷下预制孔铝板的动态响应

为研究爆炸冲击波对破片穿孔后板结构的毁伤效应,使用激波管为冲击波加载设备,对不同孔形的预制孔铝板进行冲击波加载.利用三维数字图像相关(3 D-DIC)技术,分析固支预制孔方形铝板在冲击波加载条件下的动态响应,得到预制孔铝板的动态响应和变形失效过程.结合3 D-DIC结果分析孔形对靶板刚度、破坏形式、承载能力的影响.结果表明:圆形孔靶板刚度最大,圆形孔靶板的极限承载能力最大,菱形孔靶板极限承载能力最差;孔形对撕裂破坏的影响主要体现在孔的角点在靶板分布上.该实验结果对固支板结构的抗爆设计具有一定参考价值.     

Corrosion behaviour of Mg-Gd-Y-Zn-Ag alloy components with different sizes after cooling

The corrosion behaviour of Mg-6Gd-3Y-1Zn-0.3Ag (wt.%) alloy components with different sizes after cooling was investigated. The alloys in the small components (SC) cooled fast, which were composed of α-Mg matrix and coarse long-period stacking ordered (LPSO) phases. The alloys in the large components (LC) cooled slowly, and there were thin lamellar LPSO phases precipitating inside the grains, except for α-Mg matrix and coarse LPSO phases. The hydrogen evolution test revealed that the corrosion rate of LC sample was higher than that of SC sample. Electrochemical impedance spectroscopy (EIS) test showed that the surface film on LC alloys provided worse protection. The corrosion morphologies indicated that the precipitation of the thin lamellar LPSO phases in LC sample caused severe micro-galvanic corrosion, which accelerated the rupture of the surface film.