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.     

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。     

Adaptive Synchronization-Based Approach for Finite-Time Parameters Identification of Genetic Regulatory Networks

Neural Processing Letters - This paper presents an approach to identify the unknown parameters of genetic regulatory network (GRN) in finite-time. The adaptive synchronization-based method is used...     

水泥窑烟气脱硫系统节能降耗措施探讨

水泥窑烟气为满足高硫条件下排放达标，多采用窑灰-石膏湿法烟气脱硫。其工艺系统相对复杂，在脱除SO2的同时，要消耗水、电等资源，因此，节能降耗对提升脱硫系统的经济性具有重要意义。本文通过对水、电从工艺、设备选型和运行维护三方面探讨了水泥窑烟气脱硫系统节能降耗措施。     

Measuring the disparity among scientific disciplines using Library of Congress Subject Headings

Scientometrics - Examining the relationships among scientific disciplines is important today, but existing methods are limited by the contents and structure of their bibliographic databases. We...     

Ferulic acid and EGCG alter the structural characteristics of ovalbumin and its application in mineral loading

This study aims to fabricate mineral-loading nanocarriers using natural materials. The interaction patterns between ovalbumin (OVA) and four water-soluble polyphenols, namely ferulic acid (FA), (-)-Epigallo-catechin 3-gallate (EGCG), gallic acid (GA) and epicatechin (EC), were investigated. Results showed that the optimised conditions for preparing stable OVA–polyphenol complexes are at the OVA–polyphenol ratio of 4:1 at pH 6, under which OVA–FA and OVA–EGCG showed the highest stability and mineral-loading capacity among four OVA–polyphenol complexes. The fluorescence results indicated that the addition of EGCG and FA induced a significant fluorescence quenching to OVA. The interaction between OVA and polyphenols involved hydrogen bonding, hydrophobic interaction and electrostatic interaction. Fourier transform infrared spectroscopy (FTIR) analysis suggested that both FA and EGCG enhanced the stability and orderliness of the structure of OVA. The transmission electron microscopy images also exhibited the spherical structure of OVA after the addition of FA and EGCG. Furthermore, scanning electron microscope–energy dispersive X-ray spectrum results suggested that OVA–FA and OVA–EGCG complexes were better mineral carriers than OVA–GA and OVA–EC. This study may serve as the theoretical support for the promising application of OVA in the fabrication of mineral-loading nanocarriers in functional food and pharmaceutic.