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.     

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.     

Preparation and the effects of ion irradiation on bulk SiOC ceramics

Bulk SiOC ceramics were prepared by spark plasma sintering of polymer-derived SiOC powders, and the effects of ion irradiation on their microstructures and properties were investigated in detail. High sintering temperature was conducive to low open porosity, high bulk density, nucleation and growth of β-SiC nanodomains, and graphitization of free carbon clusters in the SiOC ceramics. Ordering of the nanodomanins is beneficial for improving hardness and modulus of the ceramics. After 70 keV He ion irradiations, the β-SiC nanocrystals and graphitic clusters were partially amorphized, and their average grain size decreased by 13.6% and 50.9%, respectively. But no bubbling or peeling occurred on the irradiated sample surface, the hardness and modulus barely changed, indicating the SiOC ceramics are promising as radiation-tolerant materials.     

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.     

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。     

新型钛系聚酯催化剂的催化性能研究

合成了一种应用型钛系聚酯(PET)催化剂TY,考察了在PET合成中催化剂TY对酯化时间、缩聚时间、产品性能等的影响;并与传统锑系催化剂三氧化二锑(Sb2O3)的性能进行了对比。结果表明:钛系催化剂TY不仅能缩短酯化时间和聚合时间,而且催化剂用量少、催化活性高;钛系催化剂TY用量为20~25μg/g时,催化活性最佳,催化剂TY 20~25μg/g的催化活性相当于Sb2O3350~400μg/g的催化活性;钛系催化剂合成的PET切片的特性黏数达0.683 d L/g,与锑系PET相比,色相L值提高达71.68,b值相差不大,端羧基含量及二甘醇含量降低,结晶行为及热性能相当;钛系催化剂TY适合无重金属聚酯的工业生产,工业应用性强。     

A visco-elastoplastic constitutive model for large deformation response of polycarbonate over a wide range of strain rates and temperatures

The principal purpose in this paper is to present a combined experimental and analytical study to understand the mechanical behavior of polycarbonate (PC) under a wide range of temperatures (−40 °C to 100 °C) and strain rates (0.001 up to 5000 s⁻¹). Firstly, the experiments were conducted to obtain stress-strain response from low to high rates and temperatures. Then a robust physically consistent rate and temperature-dependent constitutive model is proposed to characterize large deformation mechanical behavior of PC. According to viscoelastic theory, a nonlinear-viscoelastic model is employed to understand the elastic response. Yielding behavior is described via cooperative model. As respect to post-yield regime, it is described by the conflict and interaction between softening and hardening behavior based on the integral-form softening and kinematic hardening model. The proposed constitutive model is successfully validated by the excellent agreement between model prediction and experiment results.     

Biosorption mechanism of Zn2+ from aqueous solution by spent substrates of pleurotus ostreatus

To solve the problem of heavy metal pollution and agricultural wastes reclamation, spent substrate of pleurotus ostreatus (SSPO) was used as adsorbent to remove Zn²⁺ from aqueous solution. The biosorption of zinc ions on SSPO was studied as a function of the solution pH, temperature and initial Zn²⁺ concentration. The equilibrium sorption data were well represented by linear Langmuir isotherm models with R² value of 0.9955 and non-linear Freundlich with R² value of 0.9973. The BET surface area of SSPO can reach 51.16m²g^?1. SEM-EDX and XRD revealed that (NH₄)₂Zn·H₂O and Zn₂PO₄(OH) were the main compounds in metal-loaded SSPO. FTIR analysis indicated the governing functional groups such as O-H, N-H and P=O played an important role in biosorption. The desorption studies showed the reversibility of SSPO. The results indicate that SSPO is a potential adsorbent in wastewater treatment due to its great sorption capacity and low cost.