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IL2-inducible T-cell Kinase is Required for HBV-induced Type T Interferon Expression and Antiviral Response

Journal of Clinical and Translational Hepatology 2023年第4期11卷 918-924页

作者： mengxin lin Ruyi Guo Dawu Zeng Jiangfu Liu Minghui Zheng Zhijun Su Department of Infectious Disease Quanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhouFujianChina Liver Research Center Quanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhouFujianChina

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.

关键词： HBV ITK Type I IFN SOCS1

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Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li mengxin Xu Jingyi Yang Li Zhou lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen Wuhan Institute of Virology Chinese Academy of SciencesWuhanChina Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic.Here,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year.This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant.Based upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)vaccine.With a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions.To meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including JN.1.Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

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韧性安全文化下建筑工人知识转移与安全绩效的实证研究

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工程管理学报 2024年第1期38卷 118-123页

作者：林陵娜张孟欣苏州科技大学土木工程学院江苏苏州215000

基于韧性安全文化视角,构建建筑工人安全培训-韧性安全文化-知识转移行为-安全绩效的关系模型,旨在有效促进建筑工人提高安全培训知识和技能的交流,从而提升安全绩效。使用SmartPLS 3.0软件对262份有效数据进行处理和分析。结果显示,韧... 详细信息

基于韧性安全文化视角,构建建筑工人安全培训-韧性安全文化-知识转移行为-安全绩效的关系模型,旨在有效促进建筑工人提高安全培训知识和技能的交流,从而提升安全绩效。使用SmartPLS 3.0软件对262份有效数据进行处理和分析。结果显示,韧性安全文化促进知识转移,进而对安全绩效产生积极的影响;安全培训所获得的知识能够持续提升组织的安全绩效。此外,知识转移行为在安全培训和安全绩效间起到部分中介作用;韧性安全文化在安全培训和知识转移行为间起到部分中介作用。研究提供了建立建筑行业组织开放式学习和交流环境的新思路,丰富了建筑工人知识转移行为的理论体系。

关键词：韧性安全文化知识转移行为安全绩效 PLS

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认知偏差:“双减”政策下家校合作共育的障碍及突破

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西安文理学院学报（社会科学版） 2024年第1期27卷 53-59页

作者：徐梦鑫马香莲蔺春利宝鸡文理学院教育学院陕西宝鸡721013

“双减”政策下家校合作共育可以很好地解放学生,能够持续深入地推进教育改革。有效开展家校合作共育有助于教育在目标与方向上保持一致,形成教育合力有助于实现学生的全面发展、促进学生健康成长也有利于整合教育资源、构建教育的良好... 详细信息

“双减”政策下家校合作共育可以很好地解放学生,能够持续深入地推进教育改革。有效开展家校合作共育有助于教育在目标与方向上保持一致,形成教育合力有助于实现学生的全面发展、促进学生健康成长也有利于整合教育资源、构建教育的良好生态。然而,目前双减政策执行过程中家校双方在各自责任的理解上存在偏差,导致家校合作的实施效果不太理想。在认知方面,学校对家长在青少年儿童全面发展中的影响认识不够全面、教师对家校合作中自身的责任认识不清、家长没有全面认识到家庭教育对青少年儿童的价值和意义。要突破合作共育的现实困境,需要从学校、教师、家长三方面提出具体的改进措施即转变教育观念,确保学生获得优质教育;树立正确的边界意识,把握好合作的“度”;改变家长的观念,促进青少年全面发展。

关键词：家校合作共育认知偏差 “双减”政策下

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The protective nasal boosting of a triple-RBD subunit vaccine against SARS-CoV-2 following inactivated virus vaccination

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2051-2053页

作者： Jingyi Yang Mei-Qin Liu lin Liu Xian Li mengxin Xu Haofeng lin Min Li Huimin Yan Yao-Qing Chen Zheng-Li Shi Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghai201508China Wuhan Institute of Virology Chinese Academy of SciencesWuhan430071China School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversitySun Yat-sen UniversityShenzhenGuangdong518107China

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.

关键词： vaccination protective nasal

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A triple-RBD-based mucosal vaccine provides broad protectionagainst SARS-CoV-2 variants of concern

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Cellular & Molecular Immunology 2022年第11期19卷 1279-1289页

作者： 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 Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan University201508 ShanghaiChina Wuhan Institute of Virology Chinese Academy of Sciences430071 WuhanChina University of Chinese Academy of Sciences 100049 BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107 GuangdongChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhou 215123 JiangsuChina Key Laboratory of Tropical Disease Control(Sun Yat-sen University) Ministry of EducationGuangzhouChina

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.

关键词： SARS-CoV-2 Mucosal vaccine Intranasal immunization Triple-RBD Flagellin adjuvant Variant of concern

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白牛肝菌、白松露、松茸中多糖和氨基酸含量对比

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香料香精化妆品 2024年第3期 178-183页

作者：冯孟鑫马恺悦高家敏林铌马长华石钺张凤兰中国食品药品检定研究院北京100050 北京中医药大学北京102488 中国医学科学院药用植物研究所北京100193

以白牛肝菌、白松露、松茸烘干片为研究对象,分别采用苯酚-硫酸法和异硫氰酸苯酯衍生化法对其多糖、氨基酸的含量及氨基酸种类进行了测定和对比分析。结果表明白牛肝菌、白松露、松茸烘干片中多糖含量分别为质量分数3.739%、2.739%、4.3... 详细信息

以白牛肝菌、白松露、松茸烘干片为研究对象,分别采用苯酚-硫酸法和异硫氰酸苯酯衍生化法对其多糖、氨基酸的含量及氨基酸种类进行了测定和对比分析。结果表明白牛肝菌、白松露、松茸烘干片中多糖含量分别为质量分数3.739%、2.739%、4.378%,总氨基酸质量比含量分别为124.83、88.76、33.29 mg/g。三者均含有赖氨酸(Lys)等17种游离氨基酸,但同一种氨基酸在三者中的含量差异较大。提示3种不同品种的珍稀食用菌中多糖和氨基酸含量具有一定的差异,但总体而言其多糖含量均较高,且氨基酸种类齐全、含量丰富。

关键词：食用菌多糖氨基酸苯酚-硫酸法异硫氰酸苯酯衍生化法

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水稻香型抗病恢复系的分子鉴定及其应用

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中国农学通报 2024年第18期40卷 90-95页

作者：张玉婷王泓超梁莹莹匡梦鑫吴欣蒋云林程祖锌林荔辉福建农林大学作物遗传育种与综合利用教育部重点实验室福州350002 福建省特种作物育种与利用工程技术研究中心福州350002

提高水稻恢复系的稻米品质及稻瘟病抗性,是培育高产、优质、抗病的杂交稻新组合基础。采用香味fgr基因和稻瘟病抗性基因Pi-1、Pi-9和Pi-kh紧密连锁的分子标记,对香型品种‘玉针香’与抗病恢复系‘福恢683’‘、金恢1131’杂交获得的265... 详细信息

提高水稻恢复系的稻米品质及稻瘟病抗性,是培育高产、优质、抗病的杂交稻新组合基础。采用香味fgr基因和稻瘟病抗性基因Pi-1、Pi-9和Pi-kh紧密连锁的分子标记,对香型品种‘玉针香’与抗病恢复系‘福恢683’‘、金恢1131’杂交获得的265个F_(6)代恢复株系进行香味和稻瘟病抗性基因的分子标记辅助选择,筛选出携带上述4个目的基因的6个优良恢复株系,通过综合性状考察,育成了中抗稻瘟病的香型恢复系‘润香’,并配组出高产、优质的香型黑米杂交稻新组合‘紫两优润香’先后通过广西(桂审稻2021200号)和福建省(闽审稻20220024)农作物新品种审定。该品种表现出高产、优质和广适应特性,具有较大的推广应用潜力。本研究表明,分子标记辅助选择是一种在水稻香味和稻瘟病抗性定向改良中的快速而有效的现代生物育种技术。

关键词：水稻恢复系稻瘟病香味分子鉴定

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SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5887-5903页

作者： 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 Department of Thoracic Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalState Key Laboratory of Oncology in South ChinaGuangzhouGuangdongP.R.China Department of General Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongP.R.China Cancer Center Renmin Hospital of Wuhan UniversityWuhanHubeiP.R.China Department of Thoracic Surgery Sun Yat-sen University Cancer CenterSun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Medical Oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China

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.

关键词： metastasis inhibited lymphatic

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Exome sequencing identifies rare mutations of LDLR and QTRT1 conferring risk for early-onset coronary artery disease in Chinese

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National Science Review 2022年第8期9卷 22-25页

作者： 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 Department of Cardiology Zhongshan HospitalFudan University Shanghai Institute of Cardiovascular Disease BGI Genomics BGI-Shenzhen State Key Laboratory of Genetic Engineering School of Life Sciences and Human PhenomeInstituteFudan University BGI-Shenzhen State Key Laboratory of Genetic Engineering School of Life Sciences and Human Phenome InstituteFudan University

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).

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