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Tuning sterol extraction kinetics yields a renal-sparing polyene antifungal

Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model1. Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers2–6. Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification y ....

South Korea , Fungal Priority Pathogens List To Guide Research , Mcgraw Hill , Laboratory Standards Institute , Public Health Action World Organization , Clinical Pharmacology , Priority Pathogens List , Guide Research , Public Health Action , World Health Organization , Growth Design , Comprehensive Organic Synthesis , Drug Monit , Broth Dilution Antifungal Susceptibility Testing , Filamentous Fungi , Antifungal Susceptibility Testing ,

首届微软研究峰会开放注册，足不出户尽享全球学术盛宴-CSDN社区

以下内容是CSDN社区关于首届微软研究峰会开放注册，足不出户尽享全球学术盛宴相关内容，如果想了解更多关于微软技术栈社区其他内容，请访问CSDN社区。 ....

United States , Microsoft Institute , Science Research , Science Research For Microsoft , Microsoft Research , Science Microsoft Institute , Life Sciences , Research Microsoft , Guide Research , New Progress , Science The , New Crown , General Assembly , Field Interactive ,

山阳区：硬核赋能助企纾困

山阳区：硬核赋能助企纾困
jzrb.com - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from jzrb.com Daily Mail and Mail on Sunday newspapers.

Zheng Kobayashi , Jiaozuo Chinese River , Embassy Enterprise Service , Jiaozuo Yuntaishan , Union Guardian , Research Center , Medical Research Center , Sanyo District , Municipal City Hall , Service All , Guide Research , Hui Enterprise , Human Resources , Social Service , Limited Jiaozuo Chinese River , Limited Jiaozuo Yuntaishan , தொழிற்சங்கம் பாதுகாவலர் , ஆராய்ச்சி மையம் , மருத்துவ ஆராய்ச்சி மையம் , சேவை அனைத்தும் , மனிதன் வளங்கள் , சமூக சேவை ,

推动减污降碳协同增效 共促人与自然和谐共生_评论_中国环境

要深刻把握减污降碳协同增效的重大意义和科学内涵，完整、准确、全面贯彻新发展理念，站在构建高质量发展新格局的高度来整体谋划生态文明建设和经济社会发展，统筹污染物和温室气体协同减排，形成节约资源和保护环境的空间格局、产业结构、生产方式、生活方式，促进生态环境质量持续改善，努力建设人与自然和谐共生的现代化。
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Technology Innovation , Science Institute , Country Clean Energy , Central Committee , Order Earth , Transport Transportation , Integrated Management , Eleventh Five , Industrial Transport , Manufacturing Country , Guide Research , Sinopec Chemical ,

粮农组织 - 新闻报道: 立足水资源 管理全球森林

粮农组织 - 新闻报道: 立足水资源管理全球森林
fao.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from fao.org Daily Mail and Mail on Sunday newspapers.

United States , Liu Shirong , Service Do , Case Research , Basin Service , United Nations , Water Department , Research Center United States , Union European Commission , Watera Interactive Working Group , Water Management , Forest August Rome , New Guide , Forest Water Management Guide , Guidelines Forest , Forest Management , Forest Basin , Officer Maria , Interactive Working Group , Management Forest , Guide New , Guide Research , Case Research Guide , Forest Water ,