Real-Time analysis of exosome secretion of single cells with single molecule imaging

The exosome-mediated response can promote or restrain the diseases by regulating the intracellular pathways, making the exosome become an effective marker for diagnosis and therapeutic control at the single-cell level. However, real-time analysis is hard to be achieved with traditional approaches because the exosomes usually need to be enriched by ultracentrifugation for a measurable signal-to-noise ratio. Recently developed label-free single-molecule imaging approaches may become an real-time quantitative tool for the analysis of single exosomes and related secretion behaviors of single living cells owing to their extreme sensitivity.     

改进的遗传算法在同步器优化中的应用

汽车同步器是自动变速器的重要组成部分.对同步器的模拟优化能为同步器的设计生产提供重要的参考.为了获得一个较好的优化效果,提出了一种改进的遗传算法.通过对遗传算法选择过程的标准进行了改进,结合适应度函数与染色体之间差异,形成一种新的适应度函数.该函数同时考虑了选择压力和物种多样性.通过对函数中两个常量的调整,可以使算法在不同情况下可以有不同的偏重.引入两种典型测试函数的分别从高纬度变量和低纬度变量进行试验,分析改进算法中两个影响因子的作用.并与几类遗传算法进行比较,结果表明该改进的遗传算法能更快更稳定的找到较优的解.最后将改进选择策略结合自适应遗传算法对同步器进行优化,证明了该选择策略具有良好的鲁棒性和实效性.     

一种大量元素水溶肥料的制备及其在玉米上的喷施效果

根据玉米需肥特性设计氮磷钾比例,制备了含中微量元素的大量元素水溶肥料,产品氮、磷、钾比例为2∶1∶4,属于高钾中氮低磷型.在河北省安平县前子文村和浙江省新昌县孟家塘村玉米上开展了叶面喷施试验.结果表明:玉米生物学性能得到改善,玉米产量、出籽率、百粒重与容重得到提高;与空白对照相比,平均增产率为5.45％,平均纯增收896.40元/公顷,平均产投比为5.43∶1.     

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.     

药物相互作用研究在新药研发和审评决策中的应用

药物相互作用改变了剂量效应关系，可能会降低疗效或增加毒性，是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义，体内和体外研究的主要内容；梳理分析了2020年国家药品监督管理局（National Medical Products Administration, NMPA）和美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的新药药物相互作用研究情况，旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。     

转炉冶炼新国标螺纹钢HRB500E生产试验

中国钢铁工业“十二五”发展规划明确提出全面推广使用400、500 MPa高强度螺纹钢筋，促进建筑钢材升级换代和减量应用。本文通过化学成分设计确定了钢筋混凝土用HRB500E螺纹钢的化学成分，通过控制装入制度、供氧制度、造渣制度、温度及终点控制制度、出钢及脱氧合金化制度和吹氩处理等工艺，成功冶炼出了符合国标化学成分要求的钢液。生产试验结果表明，钢液具有较低的氧含量，并且生产试验过程中的钢铁料消耗、合金消耗和冶炼周期均在合理范围内，后续可以批量生产。     

Chemical durability and surface alteration of lanthanide zirconates (A2Zr2O7: A = La-Yb)

Chemical durability of lanthanide zirconates (A₂Zr₂O₇) (A = La-Yb) under near-field environments is important for evaluating their application as potential nuclear waste forms. In this work, A₂Zr₂O₇ (A = La-Yb) are synthesized by spark plasma sintering with controlled microstructure and their chemical durability are evaluated in a nitric acid solution (pH = 1). Scanning transmission electron microscopy analysis reveals an amorphous passivation film either enriched with Zr or lanthanide. The complex chemistry of the passivation films can be correlated with a transition in corrosion mechanisms from a preferential release of lanthanide in La₂Zr₂O₇ to a preferential release of Zr in Er₂Zr₂O₇ and Yb₂Zr₂O₇. These results suggest a dominant mechanism of incongruent dissolution and surface reorganization for the formation of passivation films. Strong correlations are identified between the leaching rates and cation ionic size, ionic potential, electronegativity differences between A-site cation and Zr, and bonding valence sum of oxygen, suggesting important impacts of structural and bonding characteristics in controlling chemical durability of lanthanide zirconates.     

高分子材料导热性能影响因素研究进展

介绍了高分子材料导热性能影响因素研究进展，重点阐释了聚合物基体的结构特性（链结构、分子间相互作用、取向、结晶度等）、导热填料（种类、含量、形态、尺寸等）以及制备方法等对高分子材料导热性能的影响。