Primary and secondary resistance to immune checkpoint blockade(ICB)reduces its efficacy.The mechanisms underlying immunotherapy resistance are highly complex.In non-small cell lung cancer(NSCLC),these mechanisms are p...Primary and secondary resistance to immune checkpoint blockade(ICB)reduces its efficacy.The mechanisms underlying immunotherapy resistance are highly complex.In non-small cell lung cancer(NSCLC),these mechanisms are primarily associated with the loss of programmed cell death-ligand 1(PD-L1)expression,genetic mutations,circular RNA axis and transcription factor regulation,antigen presentation disorders,and dysregulation of signaling pathways.Additionally,alterations in the tumor microenvironment(TME)play a pivotal role in driving immunotherapy resistance.Primary resistance is mainly attributed to TME alterations,including mutations and comutations,modulation of T cell infiltration,enrichment of M2 tumor-associated macrophages(M2-TAMs)and mucosal-associated invariant T(MAIT)cells,vascular endothelial growth factor(VEGF),and pulmonary fibrosis.Acquired resistance mainly stems from changes in cellular infiltration patterns leading to“cold”or“hot”tumors,altered interferon(IFN)signaling pathway expression,involvement of extracellular vesicles(EVs),and oxidative stress responses,as well as post-treatment gene mutations and circadian rhythm disruption(CRD).This review presents an overview of various mechanisms underlying resistance to ICB,elucidates the alterations in the TME during primary,adaptive,and acquired resistance,and discusses existing strategies for overcoming ICB resistance.展开更多
This article presents a comprehensive review of China's policy system for the management of natural hazard-induced disasters from 1949 to 2016 through a quantitative bibliometric analysis of 5472 policy documents ...This article presents a comprehensive review of China's policy system for the management of natural hazard-induced disasters from 1949 to 2016 through a quantitative bibliometric analysis of 5472 policy documents on such disasters. It identifies four phases of China's evolving disaster management system, which focused on agriculture, economic development, government and professional capacity building, and disaster governance,respectively. Characteristics of policies and contributing factors of policy change in each of the four phases are discussed in depth. This article provides a quantitative foundation for understanding the dynamic policy change of the disaster management system in China with a particular emphasis on the governance capacity and may serve as a basis for exploring the potential pathways of transformation according to the Sendai Framework for Disaster Risk Reduction 2015–2030 and the Sustainable Development Goals.展开更多
基金supported by grants from the Ministry of Science and Technology,RPC(No.2023YFC3503302)the Shanghai Municipal Commission of Science and Technology(No.22Y31920400)the National Natural Science Foundation of China(No.82474484).
文摘Primary and secondary resistance to immune checkpoint blockade(ICB)reduces its efficacy.The mechanisms underlying immunotherapy resistance are highly complex.In non-small cell lung cancer(NSCLC),these mechanisms are primarily associated with the loss of programmed cell death-ligand 1(PD-L1)expression,genetic mutations,circular RNA axis and transcription factor regulation,antigen presentation disorders,and dysregulation of signaling pathways.Additionally,alterations in the tumor microenvironment(TME)play a pivotal role in driving immunotherapy resistance.Primary resistance is mainly attributed to TME alterations,including mutations and comutations,modulation of T cell infiltration,enrichment of M2 tumor-associated macrophages(M2-TAMs)and mucosal-associated invariant T(MAIT)cells,vascular endothelial growth factor(VEGF),and pulmonary fibrosis.Acquired resistance mainly stems from changes in cellular infiltration patterns leading to“cold”or“hot”tumors,altered interferon(IFN)signaling pathway expression,involvement of extracellular vesicles(EVs),and oxidative stress responses,as well as post-treatment gene mutations and circadian rhythm disruption(CRD).This review presents an overview of various mechanisms underlying resistance to ICB,elucidates the alterations in the TME during primary,adaptive,and acquired resistance,and discusses existing strategies for overcoming ICB resistance.
基金the support of the National Social Science Fund of China for Outstanding Project(#10AGL011)the Fundamental Research Funds for the Central Universities
文摘This article presents a comprehensive review of China's policy system for the management of natural hazard-induced disasters from 1949 to 2016 through a quantitative bibliometric analysis of 5472 policy documents on such disasters. It identifies four phases of China's evolving disaster management system, which focused on agriculture, economic development, government and professional capacity building, and disaster governance,respectively. Characteristics of policies and contributing factors of policy change in each of the four phases are discussed in depth. This article provides a quantitative foundation for understanding the dynamic policy change of the disaster management system in China with a particular emphasis on the governance capacity and may serve as a basis for exploring the potential pathways of transformation according to the Sendai Framework for Disaster Risk Reduction 2015–2030 and the Sustainable Development Goals.
