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| 1 | Super-resolution fluorescence-assisted diffraction computational tomography reveals the threedimensional landscape of the cellular organelle interactome显示文摘The emergence of super-resolution(SR)fluorescence microscopy has rejuvenated the search for new cellular substructures.However,SR fluorescence microscopy achieves high contrast at the expense of a holistic view of the interacting partners and surrounding environment.Thus,we developed SR fluorescence-assisted diffraction computational tomography(SR-FACT),which combines label-free three-dimensional optical diffraction tomography(ODT)with two-dimensional fluorescence Hessian structured illumination microscopy.The ODT module is capable of resolving the mitochondria,lipid droplets,the nuclear membrane,chromosomes,the tubular endoplasmic reticulum,and lysosomes.Using dual-mode correlated live-cell imaging for a prolonged period of time,we observed novel subcellular structures named dark-vacuole bodies,the majority of which originate from densely populated perinuclear regions,and intensively interact with organelles such as the mitochondria and the nuclear membrane before ultimately collapsing into the plasma membrane.This work demonstrates the unique capabilities of SR-FACT,which suggests its wide applicability in cell biology in general. | Dashan Dong Xiaoshuai Huang Liuju Li Heng Mao Yanquan Mo Guangyi Zhang Zhe Zhang Jiayu Shen Wei Liu Zeming Wu Guanghui Liu Yanmei Liu Hong Yang Qihuang Gong Kebin Shi Liangyi Chen | 2020 | Light(Science & Applications)2020，9，1： | 7 |
| 2 | 细胞核内病毒RNA受体SAFA连接天然免疫和染色质重塑显示文摘文章简介天然免疫免疫从上世纪发现模式识别受体在现在一直学界研究的热点,而细胞核内的天然免疫识别和调节机制还不为人所知。本研究揭示了SAFA作为一个新型的细胞核内病毒双链RNA(dsRNA)监测器,连接染色质重塑和抗病毒天然免疫反应。该研究显示多种病毒感染宿主细胞后,在细胞核中产生dsRNA,被SAFA监测结合,引起SAFA发生寡聚化。 | Lili Cao Shengde Liu Yunfei Li Guang Yang Yujie Luo Siji Li Hongqiang Du Yingchi Zhao Dandan Wang Jingxuan Chen Zeming Zhang Mo Li Songying Ouyang Xiang Gao Yujie Sun Zekun Wang Long Yang Rongtuan Lin Penghua Wang 游富平 | 2020 | 科学新闻2020，，2： | 0 |
| 3 | A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis显示文摘Pleural and peritoneal metastasis accompanied by malignant pleural effusion(MPE)or malignant ascites(MA)is frequent in patients with advanced solid tumors that originate from the lung,breast,gastrointestinal tract and ovary.Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination in serous cavities.However,malignant effusions constitute an immune-suppressive environment that potentially induces CAR-T cell dysfunction.Here,we demonstrated that the anti-tumor cytotoxicity of conventional 2nd-generation CAR-T cells was significantly inhibited by both the cellular and non-cellular components of MPE/MA,which was primarily attributed to impaired CAR-T cell proliferation and cytokine production in MPE/MA environment.Interestingly,we found that PD-L1 was widely expressed on freshly-isolated MPE/MA cells.Based on this feature,a novel PD-L1-targeting chimeric switch receptor(PD-L1.BB CSR)was designed,which can bind to PD-L1,switching the inhibitory signal into an additional 4-1BB signal.When co-expressed with a 2nd-generation CAR,PD-L1.BB CSR-modified CAR-T cells displayed superior fitness and enhanced functions in both culture medium and MPE/MA environment,causing rapid and durable eradication of pleural and peritoneal metastatic tumors in xenograft models.Further investigations revealed elevated expressions of T-cell activation,proliferation,and cytotoxicity-related genes,and we confirmed that PD-L1 scFv and 4-1BB intracellular domain,the two important components of PD-L1.BB CSR,were both necessary for the functional improvements of CAR-T cells.Overall,our study shed light on the clinical application of PD-L1.BB CSR-modified dual-targeting CAR-T cells.Based on this study,a phase I clinical trial was initiated in patients with pleural or peritoneal metastasis(NCT04684459). | Qizhi Ma Xia He Benxia Zhang Fuchun Guo Xuejin Ou Qiyu Yang Pei Shu Yue Chen Kai Li Ge Gao Yajuan Zhu Diyuan Qin Jie Tang Xiaoyu Li Meng Jing Jian Zhao Zeming Mo Ning Liu Yao Zeng Kexun Zhou Mingyang Feng Weiting Liao Wanting Lei Qiu Li Dan Li Yongsheng Wang | 2022 | Signal Transduction and Targeted Therapy2022，7，12： | 0 |
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