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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
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Telecommunication Systems - Machine to Machine technology has a broad application prospect in the 5G network, but there is a bottleneck in the energy consumption of intelligent devices powered by... 相似文献
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High purity AlN fiber is a promising thermal conductive material. In this work, AlN fibers were prepared using solution blow spinning followed by nitridation under N2 or NH3 atmosphere. Soluble polymer, such as polyaluminoxane, and allyl-functional novolac resin were adopted as raw materials to form homogeneous distribution of Al2O3 and C nanoparticles within the fibers, which could inhibit the growth of alumina crystal and promote their nitridation process. The effect of nitriding atmosphere on the fiber morphology was investigated. XRD results showed that complete nitridation was achieved at 1300 °C in the NH3 or at 1500 °C in the N2 atmosphere. Hollowed fiber structure was observed when fiber was nitrided in N2 at high temperature, which was caused by gaseous Al gas diffusion, and this phenomenon was eliminated in NH3 atmosphere. The nitridation mechanisms in different atmosphere were analyzed in detail. It was demonstrated that the nitridation of Al2O3 fibers in the NH3 atmosphere offered the favored AlN morphology and chemical quality. Flexible AlN fiber with O content of 0.7 wt% was achieved after nitriding in NH3 at 1400 °C. The high quality AlN can be used in thermal conductive composite materials. 相似文献
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采煤机作为综采工作面的关键设备,其性能直接决定工作面的生产能力,为进一步提升工作面生产能力,在研究滚筒采煤机装煤理论的基础上,基于现有工作面采煤机的参数分别对滚筒位置参数和摇臂厚度对采煤机装煤性能的影响机理进行研究,为后续改进采煤机的结构参数和生产过程中位置参数奠定扎实的理论基础. 相似文献
5.
Xuewu Li Lin Zhang Tian Shi Weining Yu Jinhui Shao Xuegang Zhou Yuxing He Binbin Zhang 《工业材料与腐蚀》2021,72(5):951-959
Ti-based amorphous metallic glasses have excellent mechanical, physical, and chemical properties, which is an important development direction and research hotspot of metal composite reinforcement. As a stable, simple, efficient, and large-scale preparation technology of metallic powders, the gas atomization process provides an effective way of preparing amorphous metallic glasses. In this study, the controllable fabrication of a Ti-based amorphous powder, with high efficiency, has been realized by using gas atomization. The scanning electron microscope, energy-dispersive spectrometer, and X-ray diffraction are used to analyze surface morphology, element distribution, and phase structure, respectively. A microhardness tester is used to measure the mechanical property. An electrochemical workstation is used to characterize corrosion behavior. The results show that as-prepared microparticles are more uniform and exhibit good amorphous characteristics. The mechanical test shows that the hardness of amorphous powder is significantly increased as compared with that before preparation, which has the prospect of being an important part of engineering reinforced materials. Further electrochemical measurement shows that the corrosion resistance of the as-prepared sample is also significantly improved. This study has laid a solid foundation for expanding applications of Ti-based metallic glasses, especially in heavy-duty and corrosive domains. 相似文献
6.
Kang Luan Meijin He Bojie Xu Pengwei Wang Jiajia Zhou Binbin Hu Lei Jiang Huan Liu 《Advanced functional materials》2021,31(26):2010634
In nature, the feathers of the goose Anser cygnoides domesticus stay superhydrophobic over a long term, thought as the main reason for keeping the surface clean. However, contaminants, especially those that are oleophilic or trapped within textures, cannot be removed off the superhydrophobic feathers spontaneously. Here, a different self-cleaning strategy based on superhydrophilic feathers is revealed that is imparted by self-coating of the amphiphilic saliva, which enables removing away low-surface-tension and/or small-size contaminants by forming directional water sheeting depending on their unique anisotropic microstructures. Particularly, the surface superhydrophilicity is switchable to superhydrophobicity upon exposure to air for maintaining a clean surface for a long time, which is further enhanced by coating with self-secreted preening oil. By alternate switching between a transient superhydrophilicity and a long-term stable superhydrophobicity, the goose feathers exhibit an integrated smart self-cleaning strategy, which is also shared by other aquatic birds. An attractive point is the re-entrant structure of the feathers, which facilitates not only liquid spreading on superhydrophilic feathers, but also long-term stability of the cleaned surface by shedding water droplets off the superhydrophobicity feathers. Thus, artificial self-cleaning microtextures are developed. The result renews the common knowledge on the self-cleaning of aquatic bird feathers, offering inspiration for developing bioinspired self-cleaning microtextures and coatings. 相似文献
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The slight-alkalization of generator internal cooling water (GICW) is widely used to inhibit the corrosion of hollow copper conductor and thereby ensure the safe operation of the generator. CO2 inleakage is increasingly identified as a potential security risk for GICW system. In this paper, the influence of CO2 inleakage on the slight-alkalization of GICW was theoretically discussed. Based on the equilibriums of the CO2-NaOH-H2O system, CO2 inleakage saturation was derived to quantify the amount of the dissolved CO2 in GICW. This parameter can be directly calculated with the measured conductivity and the [Na+] of GICW. The influence of CO2 inleakage on the slight-alkalization conditioning of GICW and the measurement of its water quality parameters were then analyzed. The more severe the inleakage, the narrower the water quality operation ranges of GICW, resulting in the more difficult the slight-alkalization conditioning of GICW. The temperature calibrations of the conductivity and the pH value of GICW show non-linear correlations with the amount of CO2 inleakage and the NaOH dosage. This study provides insights into the influence of CO2 inleakage on the slight-alkalization of GICW, which can serve as the theoretical basis for the actual slight-alkalization when CO2 inleakage occurs. 相似文献