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Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity 期刊论文
Science, 2020
作者:  Ellen Shrock;  Eric Fujimura;  Tomasz Kula;  Richard T. Timms;  I-Hsiu Lee;  Yumei Leng;  Matthew L. Robinson;  Brandon M. Sie;  Mamie Z. Li;  Yuezhou Chen;  Jennifer Logue;  Adam Zuiani;  Denise McCulloch;  Felipe J. N. Lelis;  Stephanie Henson;  Daniel R. Monaco;  Meghan Travers;  Shaghayegh Habibi;  William A. Clarke;  Patrizio Caturegli;  Oliver Laeyendecker;  Alicja Piechocka-Trocha;  Jonathan Z. Li;  Ashok Khatri;  Helen Y. Chu;  MGH COVID-19 Collection &;  amp;  Processing Team16‡;  Alexandra-Chloé Villani;  Kyle Kays;  Marcia B. Goldberg;  Nir Hacohen;  Michael R. Filbin;  Xu G. Yu;  Bruce D. Walker;  Duane R. Wesemann;  H. Benjamin Larman;  James A. Lederer;  Stephen J. Elledge
收藏  |  浏览/下载:11/0  |  提交时间:2020/11/30
COVID-19 in children and young people 期刊论文
Science, 2020
作者:  Matthew D. Snape;  Russell M. Viner
收藏  |  浏览/下载:10/0  |  提交时间:2020/10/20
Conformational states dynamically populated by a kinase determine its function 期刊论文
Science, 2020
作者:  Tao Xie;  Tamjeed Saleh;  Paolo Rossi;  Charalampos G. Kalodimos
收藏  |  浏览/下载:0/0  |  提交时间:2020/10/12
Measurement report: Amino acids in fine and coarse atmospheric aerosol: concentrations, compositions, sources and possible bacterial degradation state 期刊论文
Atmospheric Chemistry and Physics, 2020
作者:  Ren-guo Zhu, Hua-Yun Xiao, Li Luo, Hongwei Xiao, Zequn Wen, Yuwen Zhu, Xiaozheng Fang, Yuanyuan Pan, and Zhenping Chen
收藏  |  浏览/下载:13/0  |  提交时间:2020/08/09
Ethics of controlled human infection to address COVID-19 期刊论文
Science, 2020
作者:  Seema K. Shah;  Franklin G. Miller;  Thomas C. Darton;  Devan Duenas;  Claudia Emerson;  Holly Fernandez Lynch;  Euzebiusz Jamrozik;  Nancy S. Jecker;  Dorcas Kamuya;  Melissa Kapulu;  Jonathan Kimmelman;  Douglas MacKay;  Matthew J. Memoli;  Sean C. Murphy;  Ricardo Palacios;  Thomas L. Richie;  Meta Roestenberg;  Abha Saxena;  Katherine Saylor;  Michael J. Selgelid;  Vina Vaswani;  Annette Rid
收藏  |  浏览/下载:10/0  |  提交时间:2020/05/25
A bioorthogonal system reveals antitumour immune function of pyroptosis 期刊论文
NATURE, 2020
作者:  Kim, Sungchul;  Loeff, Luuk;  Colombo, Sabina;  Jergic, Slobodan;  Brouns, Stan J. J.;  Joo, Chirlmin
收藏  |  浏览/下载:49/0  |  提交时间:2020/07/03

Bioorthogonal chemistry capable of operating in live animals is needed to investigate biological processes such as cell death and immunity. Recent studies have identified a gasdermin family of pore-forming proteins that executes inflammasome-dependent and -independent pyroptosis(1-5). Pyroptosis is proinflammatory, but its effect on antitumour immunity is unknown. Here we establish a bioorthogonal chemical system, in which a cancer-imaging probe phenylalanine trifluoroborate (Phe-BF3) that can enter cells desilylates and '  cleaves'  a designed linker that contains a silyl ether. This system enabled the controlled release of a drug from an antibody-drug conjugate in mice. When combined with nanoparticle-mediated delivery, desilylation catalysed by Phe-BF3 could release a client protein-including an active gasdermin-from a nanoparticle conjugate, selectively into tumour cells in mice. We applied this bioorthogonal system to gasdermin, which revealed that pyroptosis of less than 15% of tumour cells was sufficient to clear the entire 4T1 mammary tumour graft. The tumour regression was absent in immune-deficient mice or upon T cell depletion, and was correlated with augmented antitumour immune responses. The injection of a reduced, ineffective dose of nanoparticle-conjugated gasdermin along with Phe-BF3 sensitized 4T1 tumours to anti-PD1 therapy. Our bioorthogonal system based on Phe-BF3 desilylation is therefore a powerful tool for chemical biology  our application of this system suggests that pyroptosis-induced inflammation triggers robust antitumour immunity and can synergize with checkpoint blockade.


In mouse models of cancer, a biorthogonal chemical system based on desilylation catalysed by phenylalanine trifluoroborate enables the controlled release of gasdermin to induce pyroptosis selectively in tumour cells