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251.
Zeynep Eroglu Sheri L. Holmen Qing Chen Nikhil I. Khushalani Ravi Amaravadi Reena Thomas Kamran A. Ahmed Hussein Tawbi Sunandana Chandra Joseph Markowitz Inna Smalley James K. C. Liu Yian Ann Chen Yana G. Najjar Florian A. Karreth Daniel Abate‐Daga Isabella C. Glitza Jeffrey A. Sosman Vernon K. Sondak Marcus Bosenberg Meenhard Herlyn Michael B. Atkins Harriet Kluger Kim Margolin Peter A. Forsyth Michael A. Davies Keiran S. M. Smalley 《Pigment cell & melanoma research》2019,32(3):458-469
In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area. 相似文献
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Gemma V. White Emma V. Edgar Duncan S. Holmes Xiao Qing Lewell John Liddle Oxana Polyakova Kathrine J. Smith James H. Thorpe Ann L. Walker Yichen Wang Robert J. Young Alain Hovnanian 《Bioorganic & medicinal chemistry letters》2019,29(6):821-825
Netherton syndrome (NS) is a rare and debilitating severe autosomal recessive genetic skin disease with high mortality rates particularly in neonates. NS is caused by loss-of-function SPINK5 mutations leading to unregulated kallikrein 5 (KLK5) and kallikrein 7 (KLK7) activity. Furthermore, KLK5 inhibition has been proposed as a potential therapeutic treatment for NS. Identification of potent and selective KLK5 inhibitors would enable further exploration of the disease biology and could ultimately lead to a treatment for NS. This publication describes how fragmentation of known trypsin-like serine protease (TLSP) inhibitors resulted in the identification of a series of phenolic amidine-based KLK5 inhibitors 1. X-ray crystallography was used to find alternatives to the phenol interaction leading to identification of carbonyl analogues such as lactam 13 and benzimidazole 15. These reversible inhibitors, with selectivity over KLK1 (10–100 fold), provided novel starting points for the guided growth towards suitable tool molecules for the exploration of KLK5 biology. 相似文献
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Hongyan Liu Xiaoming Qiang Qing Song Wei Li Yuxi He Chanyuan Ye Zhenghuai Tan Yong Deng 《Bioorganic & medicinal chemistry》2019,27(6):991-1001
A series of 4′-OH flurbiprofen Mannich base derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound 8n demonstrated the best inhibitory effects on self-induced Aβ1-42 aggregation (65.03% at 25.0?μM). Moreover, this representative compound also exhibited good antioxidant activity, biometal chelating ability and anti-neuroinflammatory activity in vitro. Furthermore, compound 8n displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 8n as promising candidate for further development of multi-functional drugs against AD. 相似文献
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Shutao Zheng Qing Liu Rong Ma Doudou Tan Tongxue Shen Xiao Zhang Xiaomei Lu 《Cell biology international》2019,43(6):634-641
KIAA1377 has been found to be linked with lymph node metastasis in esophageal squamous cell carcinoma (SCC) in our previous study; however, the regulation of KIAA1377 remains far from understood. Herein, to understand the regulation of KIAA1377 from the angle of microRNA (miRNA)–messenger RNA (mRNA) modulation in the setting of SCC cells, the basal level of KIAA1377 was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot analysis in KYSE‐150 and HeLa cells; biological roles of KIAA1377 contributing in the proliferation, migration, and invasion were evaluated using 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT), wound‐healing and Transwell assays, respectively, after KIAA1377 was knocked out mediated by the CRISPR‐Cas9 system. Bioinformatic prediction revealed that let‐7b‐5p was a putative miRNA regulating KIAA1377, which was ensuingly validated by the luciferase reporter assay; after which, variation of KIAA1377 expression was further verified by qRT‐PCR and western blot analysis. Moreover, the biological roles of let‐7b‐5p in proliferation, migration, and invasion of KYSE‐150 and HeLa cells were also evaluated. It was exhibited that KIAA1377 was able to promote the proliferation and motility of both KYSE‐150 and HeLa cells, which can be reverted by re‐expression of let‐7b‐5p. The luciferase reporter assay verified that let‐7b‐5p can diametrically target KIAA1377. Collectively, our data demonstrated that let‐7b‐5p can directly but negatively regulate KIAA1377 in SCC cell lines, Ecal109, and HeLa cells. 相似文献
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Pharmaceuticals and personal care products (PPCPs) exist and are often grouped into categories according to their functional mechanism and effect on human health. In this study, six types of PPCPs were detected and characterized in the drinking water of Shanghai, covering 35 water treatment plants. The PPCPs concentrations were ranged from 2.57 ng/L to 19.4 ng/L and over 10 ng/L in nearly half of the samples. Hormones, blockers, and veterinary drugs were considered to contribute negligibly to the overall pollution from PPCPs for their low concentrations. However, dicyclohexylamine and psycholeptics were detected in all samples, with a maximum concentration of 11.8 ng/L, 7.82 ng/L, and 9.07 ng/L for dicyclohexylamine, sertraline, and sulpiride, respectively. In addition, high toxicity antitumor drug cyclophosphamide was detected in one-third of the samples and the highest concentration was 3.72 ng/L.
In all, the four PPCPs evaluated accounted for over 80% of the detected PPCPs levels. Therefore, it was determined that the major PPCPs are contributing to water pollution in the region. While these compounds do not pose a potential human health risk at their present levels, close attention should be paid to the use of these PPCPs and their discharge into drinking water source. 相似文献
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景观生态学在风景园林领域应用的研究进展 总被引:2,自引:0,他引:2
作为我国风景园林学科的三大基础理论之一,景观生态学是风景园林师从经验规划/设计转向循证规划/设计的利器.本文根据国内外已有研究,挖掘景观生态学在风景园林领域的应用优势与必要性;基于文献分析法,从规划设计研究主体、科学基础以及景观性能与人类福祉三方面总结景观生态学在风景园林领域的研究热点与进展,并提出面向规划设计实践需求的景观生态学应用研究优先议题,包括服务多学科与多部门的景观内涵与分类体系研究、面向管理决策的景观性能评估与参数量化研究、应对人居环境与规划设计不确定性的景观格局-生态过程研究,以及提升人类福祉的景观格局-过程-服务耦合研究.开展景观生态学与风景园林领域的交叉融合研究,有利于深化并推动景观生态学综合研究成果向应用实践的转化,对于构建风景园林领域实践性科学研究体系具有重要参考价值. 相似文献