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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.
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
3.
Nianxiu Duan Junjun Li Sha Song Feng Wang Yiwei Yang Di Nie Caifen Wang Yingjie Sheng Yali Tao Jie Gao Can Xu Yan Wei Yong Gan 《Advanced functional materials》2021,31(46):2100605
Tumor-specific enhanced delivery of chemotherapeutics and modulators to tumor cells and activated pancreatic stellate cells (aPSCs), respectively, represents safer and more effective therapy for pancreatic cancer. Herein, a membrane type 1-matrix metalloproteinase (MT1-MMP)-cleavable spacer is used to assemble low-density cRGDfK onto thermosensitive liposomes loaded with phosphorylated calcipotriol (PCAL) and doxorubicin (DOX), yielding MR-T-PD. The liposome-linked cRGDfK prodrug on MR-T-PD surface is first activated by MT1-MMP, which is selectively expressed on tumor endothelial cells, to release cRGDfK. The free cRGDfK specifically promotes tumor angiogenesis, leading to 3.4-fold higher accumulation and a wider distribution of MR-T-PD in tumors. Furthermore, MR-T-PD rapidly releases PCAL and DOX into the interstitium under heat treatment. The released DOX enters tumor cells to induce apoptosis, whereas the PCAL prodrug is converted to CAL by alkaline phosphatase on the surface of aPSCs; CAL can then enter aPSCs to induce quiescence and promote the antitumor effect of DOX. Finally, by enhancing the exposure of DOX and CAL to tumor cells and aPSCs, respectively, in a tumor-specific manner, MR-T-PD exerts superior efficacy (a 5.9-fold decrease in tumor weight) without causing additional side effects. Overall, this prodrug-based smart liposome system represents a promising paradigm for pancreatic cancer therapy. 相似文献
4.
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
5.
Nengbing Long Yanqing Fu Tianxiang Xu Dashuang Ding Shaoqian Zhang Shengzhi Sun Shiliang Kang Tiefeng Xu Shixun Dai Qiuhua Nie Changgui Lin 《Journal of the European Ceramic Society》2021,41(8):4584-4589
The confinement of CsPbX3 (X = Cl, Br, and I) perovskite nanocrystals (NCs) in a stabilized inorganic glass matrix is a new strategy for improving their long-term stability and promoting their applications in the optoelectronic field. Here, in situ nanocrystallization strategy is developed to precipitate CsPbBr3?xIx NCs with arbitrary I/Br ratio among an elaborately designed GeS2–Sb2S3-based chalcogenide glass matrix. Spherical CsPbBr3?xIx NCs are homogeneously distributed in the glass matrix after thermal treatment. The photoluminescence (PL) spectra show that the emission peaks of CsPbBr3?xIx NCs can be tuned from 570 nm to 722 nm with the replacement of Br by I. The fs transient absorption (TA) spectra reveal that there exists some structural defects in the NCs, leading to short PL decay life. This work would shed light on confining CsPbX3 NCs into glassy matrices, facilitating their future applications in photoelectronic fields. 相似文献
6.
Haijuan Nan Tetiana M. Stepanova Natalia V. Kondratiuk Yuanyang Nie Bo Li 《International Journal of Food Science & Technology》2022,57(8):5532-5541
The gel-forming ability of myofibrillar protein (MP) is highly correlated with the characteristics of emulsified meat products. Incorporation of Agaricus bisporus (Ab) powder into MP gels may enhance its gel properties to facilitate the development of a novel and safe meat product. Therefore, this study investigated the effects of Ab powder on gel strength, water holding capacity (WHC), texture, rheological behaviour, LF-NMR spin–spin relaxation (T2), microstructure and protein secondary structure of the MP gel system. The results indicated that the gel strength, WHC, G' value and G" value were significantly improved when the addition of Ab powder increased from 0% to 6% (P < 0.05). Meanwhile, the T2 relaxation time was shortened, and free water was transformed into immobilised water. The texture of the gel was improved when 1%–4% Ab powder was added compared to the control. Furthermore, Ab filled in the gel network and promoted the unfolding of MP α-helix and the formation of MP β-sheet during the thermal denaturation of MP, leading to a dense aggregated network structure. The study suggested that Ab could be a promising ingredient in improving chicken MP's gel properties and developing fat-reduced meat products. 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