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排序方式: 共有6993条查询结果,搜索用时 15 毫秒
941.
Chalada Suebsuwong Daniel M. Pinkas Soumya S. Ray Joshua C. Bufton Bing Dai Alex N. Bullock Alexei Degterev Gregory D. Cuny 《Bioorganic & medicinal chemistry letters》2018,28(4):577-583
Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171. We report development of CSR35 that displayed >10-fold selective inhibition of RIPK2 versus VEGFR2, the target of regorafenib. A co-crystal structure of CSR35 with RIPK2 revealed a resolved activation loop with an ionic interaction between the carboxylic acid installed in the inhibitor and the side-chain of Lys169. Our data provides principle feasibility of developing activation loop targeting type II inhibitors as a complementary strategy for achieving improved selectivity. 相似文献
942.
Ji Cheng Jianping Guo Zhiwei Wang Brian J. North Kaixiong Tao Xiangpeng Dai Wenyi Wei 《生物化学与生物物理学报:癌评论》2018,1869(1):11-28
Cullin 3-RING ligases (CRL3) play pivotal roles in the regulation of various physiological and pathological processes, including neoplastic events. The substrate adaptors of CRL3 typically contain a BTB domain that mediates the interaction between Cullin 3 and target substrates to promote their ubiquitination and subsequent degradation. The biological implications of CRL3 adaptor proteins have been well described where they have been found to play a role as either an oncogene, tumor suppressor, or can mediate either of these effects in a context-dependent manner. Among the extensively studied CRL3-based E3 ligases, the role of the adaptor protein SPOP (speckle type BTB/POZ protein) in tumorigenesis appears to be tissue or cellular context dependent. Specifically, SPOP acts as a tumor suppressor via destabilizing downstream oncoproteins in many malignancies, especially in prostate cancer. However, SPOP has largely an oncogenic role in kidney cancer. Keap1, another well-characterized CRL3 adaptor protein, likely serves as a tumor suppressor within diverse malignancies, mainly due to its specific turnover of its downstream oncogenic substrate, NRF2 (nuclear factor erythroid 2-related factor 2). In accordance with the physiological role the various CRL3 adaptors exhibit, several pharmacological agents have been developed to disrupt its E3 ligase activity, therefore blocking its potential oncogenic activity to mitigate tumorigenesis. 相似文献
943.
Compound C induces protective autophagy in human cholangiocarcinoma cells via Akt/mTOR‐independent pathway
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944.
945.
Expression plasticity and evolutionary changes extensively shape the sugar‐mimic alkaloid adaptation of nondigestive glucosidase in lepidopteran mulberry‐specialist insects
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![点击此处可从《Molecular ecology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Liangen Shi Xiangping Dai Yajie Chen Hongqing Xie Min Feng Yuyin Chen Huabing Wang 《Molecular ecology》2018,27(13):2858-2870
946.
Sufang Han Zhifeng Xiao Xing Li Huan Zhao Bin Wang Zhixue Qiu Zhi Li Xin Mei Bai Xu Caixia Fan Bing Chen Jin Han Yanzheng Gu Huilin Yang Qin Shi Jianwu Dai 《中国科学:生命科学英文版》2018,(1)
Traumatic spinal cord injury(SCI) is a major challenge in the clinic. In this study, we sought to examine the synergistic effects of linear ordered collagen scaffold(LOCS) and human placenta-derived mesenchymal stem cells(hPMSCs) when transplanted into completely transected beagle dogs. After 36 weeks observation, we found that LOCS+hPMSCs implants promoted better hindlimb locomotor recovery than was observed in the non-treatment(control) group and LOCS group. Histological analysis showed that the regenerated tissue after treatment was well integrated with the host tissue, and dramatically reduced the volume of cystic and chondroitin sulfate proteoglycans(CSPGs) expression. Furthermore, the LOCS+hPMSCs group also showed more neuron-specific βIII-tubulin(Tuj-1)-and NeuN-positive neurons in the lesion area, as well as axonal regeneration, remyelination and synapse formation in the lesion site. Additionally, dogs in the LOCS+hPMSCs group experienced enhanced sprouting of both ascending(CGRP-positive) sensory fibers and descending(5-HT-and TH-positive) motor fibers at the lesion area. All these data together suggested that the combined treatment had beneficial effects on neuronal regeneration and functional improvement in a canine complete transection model. Therefore, LOCS+hPMSCs implantation holds a great promise for bridging the nerve defect and may be clinically useful in the near future. 相似文献
947.
Three new oplopane sesquiterpenes, knorringianalarins D – F ( 1 – 3 , respectively), and five known analogues ( 4 – 8 , respectively), were isolated from the roots and rhizomes of Ligularia knorringiana. The structures of three new compounds were identified as 4‐acetoxy‐11α,12‐epoxy‐2β‐hydroxy‐3β‐(2‐methylbutyryloxy)‐9α‐(4‐methylsenecioyloxy)oplop‐10(14)‐ene ( 1 ), 3β,4‐diacetoxy‐9α‐(4‐acetoxy‐4‐methylsenecioyloxy)‐11α,12‐epoxy‐8α‐(2‐methylbutyryloxy)oplop‐10(14)‐ene ( 2 ), and (1R,5R,6R,7R,9R)‐5,9,11‐trihydroxy‐4,15‐dinoroplop‐10(14)‐en‐3‐one ( 3 ) based on spectroscopic methods including 1D‐ and 2D‐NMR, mass spectrometry, and CD spectroscopy techniques. All compounds were evaluated for their anti‐complementary activity on the classical pathway of the complement system in vitro. Among which, three oplopane sesquiterpenes ( 3 , 7 , and 8 ) exhibited better anti‐complementary effects with CH50 values ranging from 0.33 to 0.89 mm , which are plausible candidates for developing potent anti‐complementary agents. 相似文献
948.
Hierarchically Porous,Ultrathick, “Breathable” Wood‐Derived Cathode for Lithium‐Oxygen Batteries
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Huiyu Song Shaomao Xu Yiju Li Jiaqi Dai Amy Gong Mingwei Zhu Chunliang Zhu Chaoji Chen Yanan Chen Yonggang Yao Boyang Liu Jianwei Song Glenn Pastel Liangbing Hu 《Liver Transplantation》2018,8(4)
In this work, a hierarchically porous and ultrathick “breathable” wood‐based cathode for high‐performance Li‐O2 batteries is developed. The 3D carbon matrix obtained from the carbonized and activated wood (denoted as CA‐wood) serves as a superconductive current collector and an ideal porous host for accommodating catalysts. The ruthenium (Ru) nanoparticles are uniformly anchored on the porous wall of the aligned microchannels (denoted as CA‐wood/Ru). The aligned open microchannels inside the carbon matrix contribute to unimpeded oxygen gas diffusion. Moreover, the hierarchical pores on the microchannel walls can be facilely impregnated by electrolyte, forming a continuous supply of electrolyte. As a result, numerous ideal triphase active sites are formed where electrolyte, oxygen, and catalyst accumulate on the porous walls of microchannels. Benefiting from the numerous well‐balanced triple‐phase active sites, the assembled Li‐O2 battery with the CA‐wood/Ru cathode (thickness: ≈700 µm) shows a high specific area capacity of 8.58 mA h cm?2 at 0.1 mA cm?2. Moreover, the areal capacity can be further increased to 56.0 mA h cm?2 by using an ultrathick CA‐wood/Ru cathode with a thickness of ≈3.4 mm. The facile ultrathick wood‐based cathodes can be applied to other cathodes to achieve a super high areal capacity without sacrificing the electrochemical performance. 相似文献
949.
Supercapacitors: Large‐Scale Conductive Yarns Based on Twistable Korean Traditional Paper (Hanji) for Supercapacitor Applications: Toward High‐Performance Paper Supercapacitors (Adv. Energy Mater. 27/2018)
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950.
Long‐term nitrogen fertilization decreases bacterial diversity and favors the growth of Actinobacteria and Proteobacteria in agro‐ecosystems across the globe
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Zhongmin Dai Weiqin Su Huaihai Chen Albert Barberán Haochun Zhao Mengjie Yu Lu Yu Philip C. Brookes Christopher W. Schadt Scott X. Chang Jianming Xu 《Global Change Biology》2018,24(8):3452-3461
Long‐term elevated nitrogen (N) input from anthropogenic sources may cause soil acidification and decrease crop yield, yet the response of the belowground microbial community to long‐term N input alone or in combination with phosphorus (P) and potassium (K) is poorly understood. We explored the effect of long‐term N and NPK fertilization on soil bacterial diversity and community composition using meta‐analysis of a global dataset. Nitrogen fertilization decreased soil pH, and increased soil organic carbon (C) and available N contents. Bacterial taxonomic diversity was decreased by N fertilization alone, but was increased by NPK fertilization. The effect of N fertilization on bacterial diversity varied with soil texture and water management, but was independent of crop type or N application rate. Changes in bacterial diversity were positively related to both soil pH and organic C content under N fertilization alone, but only to soil organic C under NPK fertilization. Microbial biomass C decreased with decreasing bacterial diversity under long‐term N fertilization. Nitrogen fertilization increased the relative abundance of Proteobacteria and Actinobacteria, but reduced the abundance of Acidobacteria, consistent with the general life history strategy theory for bacteria. The positive correlation between N application rate and the relative abundance of Actinobacteria indicates that increased N availability favored the growth of Actinobacteria. This first global analysis of long‐term N and NPK fertilization that differentially affects bacterial diversity and community composition provides a reference for nutrient management strategies for maintaining belowground microbial diversity in agro‐ecosystems worldwide. 相似文献