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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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Mingming Yang Siwei Long Yunzhong Zhu Haozhe Ma Shaopeng Lin Jiliang Quan Biao Wang 《Ceramics International》2021,47(2):1970-1975
LiNbO3 crystals activated by Sm3+ and co-doped with Zr4+ (Sm:Zr:LN) or Hf4+ (Sm:Hf:LN) were prepared by the Czochralski method. Detailed investigation on spectroscopic properties was conducted on the frame of Judd-Ofelt (J-O) theory. The J-O intensity parameters Ωi (i = 2, 4, 6), fluorescence branching ratios and radiative lifetime of excited level 4G5/2 were determined. Furthermore, the thermal stability of the strong orange-red emissions obtained under near-UV excitation in both crystals was evaluated. As high as 100% and 97% of integrated intensities at room temperature in Sm:Zr:LN and Sm:Hf:LN respectively were retained at 423 K, demonstrating the suppressed thermal attenuation. The temperature sensing performance based on fluorescence intensity ratio strategy was degraded at higher temperatures with relatively low sensitivities, while the shift of CIE chromaticity coordinates of Sm:Zr:LN and Sm:Hf:LN in the orange-red region was insignificant, demonstrating the color constancy with increasing temperature. With the efficient and thermally stable orange-red luminescence, Sm:Zr:LN and Sm:Hf:LN could serve as promising candidate materials for near-UV excited white light-emitting diodes. 相似文献
4.
Sangmin Lee Biao Che Meiling Tai Wanzhao Li Shin-Hyun Kim 《Advanced functional materials》2021,31(42):2105477
Hydrogel shells that compartmentalize the water core from the aqueous surrounding provide molecular selectivity on size and charge in transmembrane transport. It is highly demanding to produce thin hydrogel shells to minimize diffusion length and maximize core volume. Here, internal osmosis in water-in-oil-in-water-in-oil (W/O/W/O) triple-emulsion droplets is used to produce thin hydrogel shells enclosing a large water core. The triple-emulsion droplets are prepared to have an ultrathin middle oil layer using a capillary microfluidic device. The innermost water droplet has a higher osmolarity than the outer water layer containing photopolymerizable hydrogel precursors, which pumps water from the outer layer to the core through the ultrathin oil layer by the osmosis. Therefore, the outer layer gets thinner and hydrogel precursors are enriched while the size of the triple-emulsion droplets remains unchanged. Through photopolymerization of precursors and phase transfer from oil to water, hydrogel shells enclosing water core are produced in the water environment; the oil layer is ruptured for molecular exchange through the shells. The thickness and composition of the hydrogel shells are precisely controllable by the osmotic conditions. The shells show a high permeation rate due to the thinness as well as controlled cut-off threshold of permeation for neutral and charged molecules. 相似文献
5.
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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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
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