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1.
Dr. Jie Zang Dr. Fei Ye Dr. Sara M. Ø. Solbak Dr. Lars J. Høj Prof. Mingjie Zhang Prof. Anders Bach 《ChemMedChem》2021,16(6):949-954
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. 相似文献
2.
Shimei Fu Song Xue Jun Chen Shuai Shang Hui Xiao Yu Zang Xuexi Tang 《International journal of molecular sciences》2021,22(4)
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. 相似文献
3.
Xian Yu Wang Cuicui Wang Ge Smith Leemiller Cheng Haitao 《Holz als Roh- und Werkstoff》2022,80(2):355-365
European Journal of Wood and Wood Products - To obtain the optimum balance between performance and cost, white mud (lime mud) was incorporated into the shell layer of core–shell structured... 相似文献
4.
6.
综述了铁素体与铁素体异种金属焊缝(dissimilar metal welds,DMWs)接头界面组织及其影响。结果表明,在焊后热处理或运行温度下的铁素体钢DMWs接头的不均匀界面组织中,通常会形成脱碳层和增碳层。在铁素体钢DMWs焊接接头界面组织影响因素中,焊缝金属的化学成分有重要影响;焊后热处理规范(温度和时间)、工作温度下运行时间的影响较为突出;焊接工艺参数的影响亦不可忽略。异种钢接头界面处近缝区裂纹的产生,以及接头的蠕变强度随Larson Miller 参数增大而下降等不利影响,均为异种钢界面碳迁移行为所导致。焊缝成分控制法是接头界面组织控制或改善的必要条件,而脱碳层部位转移法能有效防止裂纹发生,亦是接头安全运行的重要工艺措施之一。 相似文献
7.
Xu Wang Yujie Zhong Qian Sun Dongqing Qi Fuxue Yan Quangang Xian Dong Wang Kui Du Jingyang Wang 《Journal of the American Ceramic Society》2019,102(4):2176-2186
The microstructure evolution and growth behavior of the Al2O3/Y3Al5O12(YAG)/ZrO2 ternary eutectic ceramics during directional solidification were well investigated. During directional solidification of the Al2O3/YAG/ZrO2 ternary eutectic ceramics, {} Al2O3 paralleled with {001}ZrO2 while they did not parallel with {001}YAG at the same time in the competitive growth stage. All of the interfaces parallel to each other finally. The area percentage of the Al2O3/ZrO2 and YAG/ZrO2 interfaces are 40.4 ± 0.2% and 30.8 ± 0.1%, respectively, higher than that of the Al2O3/YAG (28.8 ± 0.2%). The content of Al2O3 and YAG phases are 39.9% and 41.1%, respectively, almost double of that of ZrO2. The interfaces of Al2O3/ZrO2 and YAG/ZrO2 are shorter and more dispersed than that of the Al2O3/YAG. It was found that the interfacial energy of Al2O3/ZrO2 and YAG/ZrO2 interfaces are lower than that of Al2O3/YAG. It can be concluded that interfacial energy plays a decisive role in affecting the crystallographic orientation and interfaces distribution in the Al2O3/YAG/ZrO2 eutectic since the interfaces of Al2O3/ZrO2 and YAG/ZrO2 with lower interfacial energy can be formed more easily during directional solidification. Therefore, the contents of Al2O3/ZrO2 and YAG/ZrO2 interfaces are higher. This study can provide theoretical guidance for interface design of multi-phase materials. 相似文献
8.
In this study, 30 subjects were exposed to different combinations of air temperature (Ta: 24, 27, and 30°C) and CO2 level (8000, 10 000, and 12 000 ppm) in a high-humidity (RH: 85%) underground climate chamber. Subjective assessments, physiological responses, and cognitive performance were investigated. The results showed that as compared with exposure to Ta = 24°C, exposure to 30°C at all CO2 levels caused subjects to feel uncomfortably warm and experience stronger odor intensity, while increased mental effort and greater intensity of acute health symptoms were reported. However, no significant effects of Ta on task performance or physiological responses were found. This indicated that subjects had to exert more effort to maintain their performance in an uncomfortably warm environment. Increasing CO2 from 8000 to 12 000 ppm at all Ta caused subjects to report higher rates of headache, fatigue, agitation, and feeling depressed, although the results were statistically significant only at 24 and 27°C. The text typing performance and systolic blood pressure (SBP) decreased significantly at this exposure, whereas diastolic blood pressure (DBP) and thermal discomfort increased significantly. These effects suggest higher arousal/stress. No significant interaction effect of Ta and CO2 concentration on human responses was identified. 相似文献
9.
Yunxia Liu Hui Wang Daiyan Chen Lin Gao Xin Wang Xian Jian Chunhong Mu Xin Xu Yujie Zhao Liangjun Yin 《Ceramics International》2021,47(3):3244-3251
Chemical stability of phosphors is critical to the efficiency and lifetime of the white light-emitting diodes. Therefore, many strategies have been adopted to improve the stability of phosphors. However, it is still lack of report on the improvement of thermal stability and hydrolysis resistance of phosphors by a single layer coating. Due to the high transmittance and high chemical inertness of graphene, it was coated on the surface of Sr2Si5N8:Eu2+ phosphor by chemical vapor deposition, aiming to improve its thermal stability and hydrolysis resistance. The chemical composition and microstructure of the coating were characterized and analyzed. A nanoscale carbon layer was attached on the surface of Sr2Si5N8:Eu2+ phosphor particles in an amorphous state. In coated Sr2Si5N8:Eu2+ phosphor, the oxidation degree of Eu2+ to Eu3+ was significantly suppressed. At the same time, the surface of Sr2Si5N8:Eu2+ particle turned from hydrophilic to hydrophobic after carbon coating, and consequently the hydrolysis resistance of Sr2Si5N8:Eu2+ phosphor was greatly improved. After tests at 85 °C and 85% humidity for 200 h, the carbon coated Sr2Si5N8:Eu2+ phosphor still maintained about 95% of its initial luminous intensity as compared with 35% of the uncoated. By observing the in-situ microstructure evolution of coated phosphor in air-water vapor environment, remained presence of the carbon layer even at 500 °C explained the excellent chemical stability of carbon coated Sr2Si5N8:Eu2+ phosphor in complex environment. These results indicate that a nanoscale carbon layer can be used to provide superior thermal stability and hydrolysis resistance of (oxy) nitrides phosphors. 相似文献
10.
为研究碳纤维复合材料(CFRP)对水泥砂浆的加固效果,针对普通水泥砂浆和CFRP布端面约束水泥砂浆,采用分离式霍普金森压杆(SHPB)分别进行恒定气压(0.3 MPa)和递增气压(0.2、0.3、0.4、0.5 MPa)循环冲击压缩试验,分析了试件的应力-应变曲线、破坏形态和能量特征.结果表明:与普通水泥砂浆试件相比,CFRP布端面约束水泥砂浆试件的循环冲击次数、峰值应力和峰值应变均有显著提高,且其峰值应力随着应变率的提高而增大;CFRP布的断裂部位主要发生在碳纤维横向连接处,CFRP布减缓了试件内部裂缝的产生,提高了试件的延性,表现出更好的抗冲击能力,试件的残余强度增加;端面粘贴CFRP布可以提高水泥砂浆的能量吸收能力,在相同冲击气压作用下,CFRP布端面约束水泥砂浆产生裂纹所需的能量高于普通水泥砂浆. 相似文献