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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:58/0  |  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


  
The Linear Sensitivity of the North Atlantic Oscillation and Eddy-Driven Jet to SSTs 期刊论文
JOURNAL OF CLIMATE, 2019, 32 (19) : 6491-6511
作者:  Baker, Hugh S.;  Woollings, Tim;  Forest, Chris E.;  Allen, Myles R.
收藏  |  浏览/下载:14/0  |  提交时间:2019/11/27
Jets  North Atlantic Oscillation  Sea surface temperature  Regression analysis  Seasonal forecasting  General circulation models  
Historical and future storm surge around New Zealand: From the 19th century to the end of the 21st century 期刊论文
INTERNATIONAL JOURNAL OF CLIMATOLOGY, 2019
作者:  Cagigal, Laura;  Rueda, Ana;  Castanedo, Sonia;  Cid, Alba;  Perez, Jorge;  Stephens, Scott A.;  Coco, Giovanni;  Mendez, Fernando J.
收藏  |  浏览/下载:24/0  |  提交时间:2019/11/27
global climate models  multiple linear regression  statistical downscaling  storm surge  weather types  
How well are the downscaled CMIP5 models able to reproduce the monsoon precipitation over seven homogeneous zones of India? 期刊论文
INTERNATIONAL JOURNAL OF CLIMATOLOGY, 2019, 39 (7) : 3323-3333
作者:  Das, Lalu;  Akhter, Javed
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/26
CMIP5 models  perfect prognosis  performance metrics  principal component regression  quantile mapping  statistical downscaling  
Impacts of residential energy consumption on the health burden of household air pollution: Evidence from 135 countries 期刊论文
ENERGY POLICY, 2019, 128: 284-295
作者:  Wang, Qiang;  Kwan, Mei-Po;  Zhou, Kan;  Fan, Jie;  Wang, Yafei;  Zhan, Dongsheng
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/26
Burden from household air pollution  Residential energy consumption  Energy transition  Spatial regression models  
A fine-scale state-space model to understand drivers of forest fires in the Himalayan foothills 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2019, 432: 902-911
作者:  Murthy, Karthik K.;  Sinha, Samir Kumar;  Kaul, Rahul;  Vaidyanathan, Srinivas
收藏  |  浏览/下载:11/0  |  提交时间:2019/04/09
Forest fire  MODIS  Himalayan terai  Poisson regression  Zero-inflated negative binomial models  Anthropogenic influences  Fire management  
Selection of climate models for projection of spatiotemporal changes in temperature of Iraq with uncertainties 期刊论文
ATMOSPHERIC RESEARCH, 2018, 213: 509-522
作者:  Salman, Saleem A.;  Shahid, Shamsuddin;  Ismail, Tarmizi;  Ahmed, Kamal;  Wang, Xiao-Jun
收藏  |  浏览/下载:19/0  |  提交时间:2019/04/09
Temperature  Global circulation models  Systematic uncertainty  Representative concentration pathways  Quantile regression  Iraq  
Drought Monitoring of Southwestern China Using Insufficient GRACE Data for the Long-Term Mean Reference Frame under Global Change 期刊论文
JOURNAL OF CLIMATE, 2018, 31 (17) : 6897-6911
作者:  Zhao, Chuanpeng;  Huang, Yaohuan;  Li, Zhonghua;  Chen, Mingxing
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09
Principal components analysis  Regression analysis  Statistics  Time series  Adaptive models  
The effect of income on the energy mix: Are democracies more sustainable? 期刊论文
GLOBAL ENVIRONMENTAL CHANGE-HUMAN AND POLICY DIMENSIONS, 2018, 51: 10-21
作者:  Ramalho, Esmeralda A.;  Sequeira, Tiago Neves;  Santos, Marcelo Serra
收藏  |  浏览/下载:24/0  |  提交时间:2019/04/09
Democracy  Human development  Energy mix  Multivariate logit fractional regression models  Energy ladder  Renewable energies  
Evaluating anemometer drift: A statistical approach to correct biases in wind speed measurement 期刊论文
ATMOSPHERIC RESEARCH, 2018, 203: 175-188
作者:  Azorin-Molina, Cesar;  Asin, Jesus;  McVicar, Tim R.;  Minola, Lorenzo;  Lopez-Moreno, Juan I.;  Vicente-Serrano, Sergio M.;  Chen, Deliang
收藏  |  浏览/下载:19/0  |  提交时间:2019/04/09
Wind speed  Bearing ageing  Intercomparison  Regression models  Stilling phenomenon