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The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8^(+)T-cell immunity 被引量:1
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作者 Jizhang Yu Jikai Cui +12 位作者 Xi Zhang Heng Xu Zhang Chen Yuan Li yuqing niu Song Wang Shuan Ran Yanqiang Zou Weicong Ye Dan Zhang Cheng Zhou Jiahong Xia Jie Wu 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2023年第12期1445-1456,共12页
Immune checkpoint blockade(ICB),including anti-cytotoxic T-lymphocyte associated protein 4(CTLA-4),benefits only a limited number of patients with cancer.Understanding the in-depth regulatory mechanism of CTLA-4 prote... Immune checkpoint blockade(ICB),including anti-cytotoxic T-lymphocyte associated protein 4(CTLA-4),benefits only a limited number of patients with cancer.Understanding the in-depth regulatory mechanism of CTLA-4 protein stability and its functional significance may help identify ICB resistance mechanisms and assist in the development of novel immunotherapeutic modalities to improve ICB efficacy.Here,we identified that TNF receptor-associated factor 6(TRAF6)mediates Lys63-linked ubiquitination and subsequent lysosomal degradation of CTLA-4.Moreover,by using TRAF6-deficient mice and retroviral overexpression experiments,we demonstrated that TRAF6 promotes CTLA-4 degradation in a T-cell-intrinsic manner,which is dependent on the RING domain of TRAF6.This intrinsic regulatory mechanism contributes to CD8+T-cell-mediated antitumor immunity in vivo.Additionally,by using an OX40 agonist,we demonstrated that the OX40-TRAF6 axis is responsible for CTLA-4 degradation,thereby controlling antitumor immunity in both tumor-bearing mice and patients with cancer.Overall,our findings demonstrate that the OX40-TRAF6 axis promotes CTLA-4 degradation and is a potential therapeutic target for the improvement of T-cell-based immunotherapies. 展开更多
关键词 Antitumor immunity CD8^(+)T cell T-cell-based immunotherapy TRAF6 CTLA-4
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锶在黑云母上的吸附及影响因素研究 被引量:1
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作者 胡娜 牛玉清 +5 位作者 常明凯 鲜东帆 周万强 周根茂 杨小雨 刘春立 《中国科学:化学》 CAS CSCD 北大核心 2020年第4期498-506,共9页
本文通过静态批式吸附实验研究了离子强度、pH、温度以及共存离子等对Sr2+在黑云母上吸附的影响.结果表明,当pH在3.0~5.0之间时, Sr2+在黑云母上的吸附可忽略;当pH在5.0~10.0之间时,随着pH的增加, Sr2+在黑云母上的吸附百分比迅速上升.... 本文通过静态批式吸附实验研究了离子强度、pH、温度以及共存离子等对Sr2+在黑云母上吸附的影响.结果表明,当pH在3.0~5.0之间时, Sr2+在黑云母上的吸附可忽略;当pH在5.0~10.0之间时,随着pH的增加, Sr2+在黑云母上的吸附百分比迅速上升.随着离子强度的增大, Sr2+在黑云母上的吸附百分比逐渐降低. Sr2+在黑云母上的吸附动力学和吸附等温线分别符合准二级动力学模型和Freundlich等温吸附模型. X射线光电子能谱分析结果表明, Sr2+主要是与黑云母表面的铁羟基发生了配合作用. 展开更多
关键词 黑云母 吸附 环境放射化学
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Precise large deviations for sums of random vectors with dependent components of consistently varying tails 被引量:1
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作者 Xinmei SHEN yuqing niu Hailan TIAN 《Frontiers of Mathematics in China》 SCIE CSCD 2017年第3期711-732,共22页
Let {Xi = (X1,i,...,Xm,i)T, i ≥ 1} be a sequence of independent and identically distributed nonnegative m-dimensional random vectors. The univariate marginal distributions of these vectors have consistently varying... Let {Xi = (X1,i,...,Xm,i)T, i ≥ 1} be a sequence of independent and identically distributed nonnegative m-dimensional random vectors. The univariate marginal distributions of these vectors have consistently varying tails and finite means. Here, the components of X1 are allowed to be generally dependent. Moreover, let N(.) be a nonnegative integer-valued process, independent of the sequence {Xi, i ≥ 1}. Under several mild assumptions, precise large deviations for Sn =∑i=1 n Xi and SN(t) =∑i=1 N(t) Xi are investigated. Meanwhile, some simulation examples are also given to illustrate the results. 展开更多
关键词 Precise large deviations MULTI-DIMENSIONAL consistently varying distributions random sums
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