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.     

Improvement of characteristics and freeze-thaw durability of solidified loess based on microbially induced carbonate precipitation

Bulletin of Engineering Geology and the Environment - Bio-cementation is currently applied to solidify sandy soils, but only few studies use it to cement loess soil particles. In this study, the...     

Effects of Different Short-Term UV-B Radiation Intensities on Metabolic Characteristics of Porphyra haitanensis

The effects of ultraviolet (UV) radiation, particularly UV-B on algae, have become an important issue as human-caused depletion of the protecting ozone layer has been reported. In this study, the effects of different short-term UV-B radiation on the growth, physiology, and metabolism of Porphyra haitanensis were examined. The growth of P. haitanensis decreased, and the bleaching phenomenon occurred in the thalli. The contents of total amino acids, soluble sugar, total protein, and mycosporine-like amino acids (MAAs) increased under different UV-B radiation intensities. The metabolic profiles of P. haitanensis differed between the control and UV-B radiation-treated groups. Most of the differential metabolites in P. haitanensis were significantly upregulated under UV-B exposure. Short-term enhanced UV-B irradiation significantly affected amino acid metabolism, carbohydrate metabolism, glutathione metabolism, and phenylpropane biosynthesis. The contents of phenylalanine, tyrosine, threonine, and serine were increased, suggesting that amino acid metabolism can promote the synthesis of UV-absorbing substances (such as phenols and MAAs) by providing precursor substances. The contents of sucrose, D-glucose-6-phosphate, and beta-D-fructose-6-phosphate were increased, suggesting that carbohydrate metabolism contributes to maintain energy supply for metabolic activity in response to UV-B exposure. Meanwhile, dehydroascorbic acid (DHA) was also significantly upregulated, denoting effective activation of the antioxidant system. To some extent, these results provide metabolic insights into the adaptive response mechanism of P. haitanensis to short-term enhanced UV-B radiation.     

从“流动的现代性”到“液态时尚”

本文主要通过齐格蒙·鲍曼的社会学著作《流动的现代性》(Liquid Modernity),讨论当代社会生活特性,并援引了原著中“Liquid”,即“液态、流动的”这一形容词,提出“液态时尚”这一与“流动的现代性”相适应的时尚概念。通过对“液态时尚”设计案例的分类分析,思考“液态时尚”在当代的社会意义和价值。     

Regulating the Interfacial Electronic Coupling of Fe2N via Orbital Steering for Hydrogen Evolution Catalysis

The capability of manipulating the interfacial electronic coupling is the key to achieving on-demand functionalities of catalysts. Herein, it is demonstrated that the electronic coupling of Fe₂N can be effectively regulated for hydrogen evolution reaction (HER) catalysis by vacancy-mediated orbital steering. Ex situ refined structural analysis reveals that the electronic and coordination states of Fe₂N can be well manipulated by nitrogen vacancies, which impressively exhibit strong correlation with the catalytic activities. Theoretical studies further indicate that the nitrogen vacancy can uniquely steer the orbital orientation of the active sites to tailor the electronic coupling and thus benefit the surface adsorption capability. This work sheds light on the understanding of the catalytic mechanism in real systems and could contribute to revolutionizing the current catalyst design for HER and beyond.     

城轨车辆一体式贯通道配套端墙结构设计及焊接工艺

阐述了一体式贯通道在城市轨道车辆中的应用及其机构组成、性能特点、安装方式和注意事项等方面的内容。针对一体式贯通道系统的安装要求,完成了车辆端墙结构的重新设计,并通过数值模拟的方法对电阻点焊接头剪切拉伸状态下焊点处应力分布进行分析,结合实际生产需要给出适合的焊接工艺以完成车体端墙结构的装配。结果表明,一体式贯通道优化了地铁车辆的美观度和实用性,数值模拟方法的应用能够有效评估点焊接头的承载能力,并可在实际生产中作为选择制定焊接工艺参数的有效依据,在积累城市轨道车辆设计经验的同时进一步提高了地铁车辆市场竞争力。     

节能和结构调整是当前影响行业发展的关键——平板玻璃行业2006年上半年发展形势分析与展望

"十五"期间,玻璃工业企业快速增长,但产品结构仍不能平衡,高质量的浮法玻璃仍有较大缺口,玻璃工业的能耗仍然很大,节能和结构调整势在必行.本文指出降低能耗,提高深加工率,发展功能玻璃等是行业发展的关键.     

马拉格锡矿巷道冒顶预测预报研究

通过对马拉格锡矿塘子凹矿段四条巷道冒顶事故多发地段进行岩体结构分析，从２９３个结构体中确定了１１个危险块体进行重点监测，避免了人身事故的发生，确保了生产安全。本文介绍的研究方法为个别危岩冒顶片帮的预测预报研究提供了一条有效的途径。