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| 1 | Generation and characterization of stable pig pregastrulation epiblast stem cell lines显示文摘Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model developme nt and livestock breeding.Despite on going attempts since the 1990s,no stably defined pig epiblast-derived stem cell line has bee n established.Here,guided by in sights from a large-scale sin gle-cell tran scriptome an alysis of pig embryos from embryonic day(E)0 to E14,specifically,the tracing of pluripotency changes during epiblast development,we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts(pgEpiSCs).Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK,JAK/STAT3,and Activin/Nodal pathways,pgEpiSCs maintain their pluripotency transcriptome features,similar to those of E10 epiblast cells,and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers.Strikingly,ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripote ncy marker genes in pgEpiSCs.I n practice,we con firmed that pgEpiSCs readily tolerate at least three rounds of successive gene editi ng and gene rated cloned gen e-edited live piglets.Our findings deliver on the long-a nticipated promise of pig pluripote nt stem cells and open new avenues for biological research,animal husbandry,and regenerative biomedicine. | Minglei Zhi Jinying Zhang Qianzi Tang Dawei Yu Shuai Gao Dengfeng Gao Pengliang Liu Jianxiong Guo Tang Hai Jie Gao Suying Cao Zimo Zhao Chongyang Li Xiaogang Weng Mengnan He Tianzhi Chen Yingjie Wang Keren Long Deling Jiao Guanglei Li Jiaman Zhang Yan Liu Yu Lin Daxin Pang Qianqian Zhu Naixin Chen Jingjing Huang Xinze Chen Yixuan Yao Jingcang Yang Zicong Xie Xianya Huang Mengxin Liu Ran Zhang Qiuyan Li Yiliang Miao Jianhui Tian Xingxu Huang Hongsheng Ouyang Bofeng Liu Wei Xie Qi Zhou Zhonghua Liu Caihong Zheng Mingzhou Li Jianyong Han | 2022 | Cell Research2022，32，4： | 3 |
| 2 | A triple-RBD-based mucosal vaccine provides broad protectionagainst SARS-CoV-2 variants of concern显示文摘The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broadspectrum protection against the initial infection and thereby curb the transmission potential.Here,we designed a chimeric tripleRBD immunogen,3Ro-NC,harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold.3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of concern.Notably,intranasal immunization with 3RoNC plus the mucosal adjuvant KFD(3Ro-NC+KFDi.n)elicits coordinated mucosal IgA and higher neutralizing antibody specificity(closer antigenic distance)against the Omicron variant.In Omicron-challenged human ACE2 transgenic mice,3Ro-NC+KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung(85.7-fold)and the nasal turbinate(13.6-fold).Nasal virologic control is highly correlated with RBD-specific secretory IgA antibodies.Our data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection,pathology and transmission potential. | Jingyi Yang Mei-Qin Liu Lin Liu Xian Li Mengxin Xu Haofeng Lin Shuning Liu Yunqi Hu Bei Li Bowen Liu Min Li Ying Sun Yao-Qing Chen Zheng-Li Shi Huimin Yan | 2022 | Cellular & Molecular Immunology2022，19，11： | 3 |
| 3 | Exome sequencing identifies rare mutations of LDLR and QTRT1 conferring risk for early-onset coronary artery disease in Chinese显示文摘Despite the advances made over the past decades,the known loci for coronary artery disease(CAD)still only explain<20%of the genetic variation in risk[1,2].The known loci with the strongest effects usually confer a 20%-37%increased CAD risk and the most loci modulate risk by≤10%[1].While most of the current data are from European populations,the use of trans-ethnic analyses could be helpful to identify additional loci.Genetic inheritance may impose a high burden on early-onset coronary artery disease(EOCAD). | Kang Yao Yuxiang Dai Juan Shen Yi Wang Huanjie Yang Runda Wu Qijun Liao Hongyi Wu Xiaodong Fang Shalaimaiti Shali Lili Xu Meng Hao Chenhao Lin Zhonghan Sun Yilian Liu Mengxin Li Zhen Wang Qiang Gao Shuning Zhang Chenguang Li Wei Gao Lei Ge Yunzeng Zou Aijun Sun Juying Qian Li Jin Shangyu Hong Yan Zheng Junbo Ge | 2022 | National Science Review2022，9，8： | 1 |
| 4 | SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer显示文摘Lymph node(LN)metastasis is one of the predominant metastatic routes of non-small cell lung cancer(NSCLC)and is considered as a leading cause for the unsatisfactory prognosis of patients.Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis,the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear.In this study,we employed high-throughput sequencing to identify a novel circular RNA(circRNA),circTLCD4-RWDD3,which was significantly upregulated in extracellular vesicles(EVs)from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort.Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo.Mechanically,circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9.Subsequently,circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif(SIM)of ALIX and activated ALIX to recruit ESCRT-III,thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs.Moreover,EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1,resulting in the lymphangiogenesis and LN metastasis of NSCLC.Importantly,blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo.Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC,suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC. | Xiayao Diao Chao Guo Hanhao Zheng Ke Zhao Yuming Luo Mingjie An Yan Lin Jiancheng Chen Yuanlong Li Yuting Li Xuehan Gao Jiaqi Zhang Mengxin Zhou Wenliang Bai Lei Liu Guige Wang Lanjun Zhang Xiaotian He Rusi Zhang Zhihua Li Changhao Chen Shanqing Li | 2023 | Signal Transduction and Targeted Therapy2023，8，12： | 0 |
| 5 | Dispensable role of CCL28 in Kras-mutated non-small cell lung cancer mouse models显示文摘Lung cancer is the most prevalent cancer and the leading cause of cancer-related deaths worldwide.More than 80%of lung cancer incidences are non-small cell lung cancer(NSCLC),including adenocarcinoma,squamous carcinoma and large-cell lung cancer[12].Although surgical resection is widely applied for patients with all types of NSCLC,different strategies such as radiotherapy and multimodal neoadjuvant chemotherapy are adopted to treat NSCLC.In addition,various mutations or copy number variations such as EGFR、MET,ALK,ROS1 and HER2 have been identified as key drivers of NSCLC,and targeting these mutations by small molecules or monoclonal antibodies significantly improves the prognosis of NSCLC patients.However;there are no targeted medicines for mutations of KRAS at the Glyl2 position。 | Dandan Lin Mengxin Zhang Hao Guo Yu Deng Bo Zhong Fei Liao Zhigao Xu | 2020 | Acta Biochimica et Biophysica Sinica2020，52，6： | 0 |
| 6 | The protective nasal boosting of a triple-RBD subunit vaccine against SARS-CoV-2 following inactivated virus vaccination显示文摘Dear Editor,Though COVID-19 vaccines have been developed and clinically deployed rapidly,new variants of concern(VOCs)are still emerging frequently and escalating around the world.More breakthrough infections occurred even vaccination rates are high.For possible ending of the pandemic,curbing infection and stopping transmission are priority. | Jingyi Yang Mei-Qin Liu Lin Liu Xian Li Mengxin Xu Haofeng Lin Min Li Huimin Yan Yao-Qing Chen Zheng-Li Shi | 2023 | Signal Transduction and Targeted Therapy2023，8，5： | 0 |
| 7 | IL2-inducible T-cell Kinase is Required for HBV-induced Type T Interferon Expression and Antiviral Response显示文摘Background and Aims:Hepatitis B is a vaccine-preventable liver infection caused by the hepatitis B virus(HBV),and is seen as a serious global health problem.HBV infection induces the expression of type I interferon(IFN),including IFN-αand IFN-β,which have anti-HBV activities,and have been used for HBV treatment.IL2-inducible T-cell kinase(ITK)is a tyrosine kinase,which regulates T-cell differentiation and activation,while its precise effects on type I IFN production during HBV infection remain unknown.Methods:We monitored the ITK expression in peripheral blood mononuclear cells(PBMCs)from healthy donors and patients with acute and chronic HBV infection.We used ITK inhibitor ibrutinib to treat hepatocytes and evaluated the type I IFN expression after HBV infection.We also administrated ibrutinib to mice and evaluated its effect on HBV infection in vivo.We generated ITK,suppressor of cytokine signaling 1(SOCS1)knockout and ITK/SOCS1 double knockout cells using CRISPR,and monitored the HBV-induced type I IFN production.Results:ITK and type I IFN were upregulated in patients with acute HBV infection.Inhibition of ITK by ibrutinib suppressed HBVinduced expression of type I IFN mRNA in mice.ITK knockout cells had decreased IRF3 activation but promoted the expression of SOCS1.ITK negatively regulated SOSC1 expression.The down regulation of type I IFN in ITK knockout cells after HBV stimulation was abolished in the absence of SOCS1.Conclusions:ITK regulated HBV-induced expression of type I IFN mRNA by modulating SOCS1. | Mengxin Lin Ruyi Guo Dawu Zeng Jiangfu Liu Minghui Zheng Zhijun Su | 2023 | Journal of Clinical and Translational Hepatology2023，11，4： | 0 |
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