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An HBV-encoded miRNA activates innate immunity to restrict HBV replication

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Journal of Molecular Cell Biology 2020年第4期12卷 263-276页

作者： Xiaoqing Zhao Lu Sun Ting Mu Jianying Yi Chaoqun Ma Hong Xie Min Liu Hua Tang Tianjin Life Science research Center Tianjin Key Laboratory of Inflammation BiologyCollaborative Innovation Center of Tianjin for Medical EpigeneticsDepartment of Pathogen BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Department of Laboratory Medicine General HospitalTianjin Medical UniversityTianjin 300070China

We previously identified that hepatitis B virus(HBV)encodes a microRNA(HBV-miR-3)that restrains HBV replication by targeting the HBV ***,whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains ***,we examined the vital functions of HBV-miR-3 in the innate immune response after HBV *** found that HBV-miR-3 expression gradually increased in a dose-and time-dependent manner in HBV-infected HepG2-NTCP ***-miR-3 activated the JAK/STAT signaling pathway by downregulating SOCS5 in hepatocytes,thereby enhancing the IFN-induced anti-HBV *** addition,HBVmiR-3 in exosomes facilitated the Ml polarization of ***,exosomes containing HBV-miR-3 enhanced the secretion of IL-6 via inhibiting the SOCS5-mediated ubiquitination of *** short,these results demonstrate that HBV-miR-3 activates the innate immune response to restrain HBV replication by multiple pathways,which may suppress HBV-induced acute liver cell injury and affect the progression of persistent HBV infection.

关键词： hepatitis B virus HBV-miR-3 IFN M1 polarization IL-6

Cell membrane anchoring strategies for HIV gene therapy

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Cellular & Molecular Immunology 2023年第6期20卷 683-685页

作者： Yani Gong Yuxian He NHC Key Laboratory of Systems Biology of pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina Center for AIDS research Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Very recently,the Dusseldorf University Hospital in Germany reported the third patient who was cured of HIV after CCR5△32 hematopoietic stem cell transplantation(HSCT)[1].There is increasing evidence that a cure can be achieved through infusion of HIV-resistant cells for gene *** this goal,we focus on cell membrane anchoring strategies by glycosylphosphatidylinositol(GPl),as illustrated in *** example,genetically anchoring the single-domain antibody m36.4(nanobody)that targets the coreceptor-binding site of gp120 through the GPl attachment signal might render modified cells fully resistant to HIV infection,block HIV-1 envelope-mediated cell-cell fusion and cell-cell viral transmission,and interfere with viral genesis[2].

关键词： infusion render HIV

Coherent Addressing of Single Molecular Electron Spin Qubits

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Chinese Journal of Chemistry 2024年第22期42卷 2895-2901页

作者： Xiya Du Aimei Zhou Lei Sun Department of Chemistry Schoolof Science and Research Centerfor Industries of the FutureWestlake University600 Dunyu RoadHangzhouZhejiang 310030China Institute of Natural Sciences Westlake Institute of Advanced Study18 Shilongshan RoadHangzhouZhejiang 310024China Key Laboratory for Quantum Materials of Zhejiang Province Department of PhysicsSchool of ScienceWestlake University600 Dunyu RoadHangzhouZhejiang 310030China

With rational designability,versatile tunability,and quantum coherence,molecular electron spin qubits could offer new opportunities for quantum information science,enabling simplified implementation of quantum algorithms and chemical-specific quantum *** development of these transformative technologies relies on coherent addressing of single molecular electron spin qubits with high initialization,manipulation,and readout *** is unfeasible to conventional electron spin resonance spectroscopy,which is widely used for coherent addressing of ensemble electron spins,due to its low initialization efficiency and readout *** advantage of single spin detectability of single-molecule spectroscopy,scanning tunneling microscopy,atomic force microscopy,and quantum metrology,several strategies have been developed to empower electron spin resonance spectroscopy with single qubit *** this Emerging Topic,we introduce principles and technical implementation of strategies for coherent addressing of single molecular electron spin qubits,discuss their potential applicability in quantum technologies,and point out their challenges in terms of scalability,molecular design,and/or decoherence *** discuss future directions to overcome these challenges and to improve single qubit addressing technologies,which will facilitate the advancement of molecular quantum information science.

关键词： Quantum information science Electron spin qubit Quantum coherence Single-molecule studies EPR spectroscopy

Organizing interdisciplinary teaching team to promote curriculum construction of basic medicine experimental design

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中国病理生理杂志 2013年第10期29卷 1881-1882页

作者： XIE Ke-ming JIANG Xing-hong LIU Li-min SUN Xiao-dong HUANG Rui Department of Pathology and Pathophysiolosy Department of Neurobiology Department of pathogen Biology Medical College of Soochow University Suzhou 215123 China

While offering a entire class of students the course of basic medicine experimental design,the teacher is required to guide simultaneously multiple research groups of them at a limited period of time in conducting independently design of interdisciplinary experimental research,selecting and revising the optimal designs,putting these projects into *** this teaching process,the course is expected to improve students’ability to carry out scientific research and *** is apparently difficult for an assigned teacher who has been engaged in a certain discipline to be responsible for the whole teaching process and to achieve the teaching goal of this *** fact,whether the curriculum can be run effectively is not only dependent on the active participation of teachers and students,but also the overall and firm support from university’s *** spite of that,the teacher’s role in the curriculum is still *** the present report,the pathophysiology discipline was responsible for the work of both interdisciplinary teaching team construction and the curriculum *** team included the multiple disciplinary teachers of basic medical science,the specialist teachers of scientific research methodology such as medical statistics,medical literature retrieval,laboratory animal science and senior *** is favorable for this form to successfully conduct the curriculum of basic medicine experimental design by making full advantages of this multiple disciplinary *** significance of the teaching team construction,its tasks,the manner of teaching quality assessment and the operational mechanism are described in this *** is believed to be a new form of teachers’team construction of higher medical schools.

关键词：课程建设教学过程实验设计跨学科药物教师角色运行机制组织

Local heroes or villains:tissue-resident memory T cells in human health and disease

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Cellular & Molecular Immunology 2020年第2期17卷 113-122页

作者： S.C.Sasson C.L.Gordon S.N.Christo P.Klenerman L.K.Mackay Translational Gastroenterology Unit Nuffield Department of MedicineUniversity of OxfordOxfordUK Department of Microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneMelbourneVICAustralia Department of Infectious Diseases Austin HealthMelbourneVICAustralia Peter Medawar Building for pathogen research University of OxfordOxfordUK

Tissue-resident memory T(T_(RM))cells are increasingly associated with the outcomes of health and disease.T_(RM) cells can mediate local immune protection against infections and cancer,which has led to interest in T_(RM) cells as targets for vaccination and ***,these cells have also been implicated in mediating detrimental pro-inflammatory responses in autoimmune skin diseases such as psoriasis,alopecia areata,and ***,we summarize the biology of T_(RM) cells established in animal models and in translational human *** review the beneficial effects of T_(RM) cells in mediating protective responses against infection and cancer and the adverse role of T_(RM) cells in driving pathology in autoimmunity.A further understanding of the breadth and mechanisms of T_(RM) cell activity is essential for the safe design of strategies that manipulate T_(RM) cells,such that protective responses can be enhanced without unwanted tissue damage,and pathogenic T_(RM) cells can be eliminated without losing local immunity.

关键词： human T cells tissue-resident memory immunity

Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction

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Journal of Molecular Cell Biology 2021年第3期13卷 225-227页

作者： Mukhtar Sadykov Tobias Mourier Qingtian Guan Arnab Pain King Abdullah University of Science and Technology(KAUST) Pathogen Genomics LaboratoryBiological and Environmental Science and Engineering(BESE)Thuwal-Jeddah 23955-6900Saudi Arabia research Center for Zoonosis Control Global Institution for Collaborative Research and Education(GI-CoRE)Hokkaido UniversityN20 W10 Kita-KuSapporo 001-0020Japan

Dear Editor,The apolipoprotein B editing complex(APOBEC)protein family members are host antiviral enzymes known for catalyzing cytosine to uracil(C>U)deamination in foreign single-stranded DNA(ssDNA)and RNA(ssRNA)(Blanc and Davidson,2010;Salter and Smith,2018).Enzymatic target motifs for most of the APOBEC enzymes have been experimentally identified,among which the most common ones are 5′-[T/U]C-3′and 5′-CC-3′for DNA/RNA substrates(Salter and Smith,2018;McDaniel et al.,2020).It was recently suggested that SARS-CoV-2 undergoes genome editing by host-dependent RNA-editing proteins such as APOBEC(Di Giorgio et al.,2020;Rice et al.,2020;Simmonds,2020;Schmidt et al.,2021).

关键词： al. APOB editing

Dynamic Proteome Changes of Shigella flexneri 2a During Transition from Exponential Growth to Stationary Phase

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Genomics, Proteomics & Bioinformatics 2007年第2期5卷 111-120页

作者： Li Zhu Xian-Kai Liu Ge Zhao Yi-Dan Zhi Xin Bu Tian-Yi Ying Er-Ling Feng Jie Wang Xue-Min Zhang Pei-Tang Huang Heng-Liang Wang State Key Laboratory of pathogen and Biosecurity Beijing Institute of Biotechnology Beijing 100071 China National Center of Biomedical Analysis Beijing 100850 China

Shigella flexneri is an infectious pathogen that causes dysentery to human, which remains a serious threat to public health, particularly in developing countries. In this study, the global protein expression patterns of S. flexneri during transition from exponential growth to stationary phase in vitro were analyzed by using 2-D PAGE combined with MALDI-TOF MS. In a time-course experiment with five time points, the relative abundance of 49 protein spots varied significantly. Interestingly, a putative outer membrane protein YciD （OmpW） was almost not detected in the exponential growth phase but became one of the most abundant proteins in the whole stationary-phase proteome. Some proteins regulated by the global regulator FNR were also significantly induced （such as AnsB, AspA, FrdAB, and KatG） or repressed （such as AceEF, OmpX, SodA, and SucAB） during the growth phase transition. These proteins may be the key effectors of the bacterial cell cycle or play important roles in the cellular maintenance and stress responses. Our expression profile data provide valuable information for the study of bacterial physiology and form the basis for future proteomic analyses of this pathogen.

关键词： Shigella flexneri proteomics growth phase

Synthetic TLR4 agonist as a potential immunotherapy for melioidosis

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Open Journal of Immunology 2013年第1期3卷 1-9页

作者： Zi Yan Tan Alvin K. L. Khah Siew Hoon Sim Vidhya Novem Yichun Liu Gek-Yen Gladys Tan Host-pathogen Interaction Laboratory Defence Medical & Environmental Research Institute DSO National Laboratories Singapore City Singapore

Melioidosis, an infection caused by Gram-negative Burkholderia pseudomallei (Bp), has high clinical recurrence and mortality rates associated with pneumonia and sepsis. With the limitations in current therapeutic options and the lack of available human vaccines, development of novel countermeasures against Bp infection is vital. In this study, we evaluated the efficacy of an aminoalkyl glucosaminide 4-phosphate (AGP), a synthetic toll like receptor 4 agonist (CRX-527), in conferring protection against melioidosis in a murine model. Survival data showed 66% of mice treated with AGP prior to lethal intranasal Bp challenge survived and presented no signs of illness over a 3 months period. In contrast, all control mice succumbed to infection within 4 days. Kinetic study on organ bacterial burden demonstrated mice treated with AGP had dramatically reduced bacterial loads in both the lungs and spleens as compared to control mice. Notably, all but one AGP-treated mouse had no Bp growth in the blood as compared to overwhelming bacteraemia found in all control mice. The protective effect of CRX-527 was associated with a transient increase in pulmonary cytokine/ chemokine levels, which boosted the host’s innate immunity. This enabled rapid clearance of the pulmonary and systemic bacterial burden and prevented the development of sepsis. This study demonstrated the potential use of TLR4 agonist as a prophylactic immunotherapy in preventing melioidosis.

关键词： Melioidosis AGP Pneumonia Sepsis TLR4 Agonist Bukholderia pseudomallei

Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第9期21卷 813-825页

作者： Jiaxin Han Wentao Kuai Liu Yang Xuemei Tao Yuekui Wang Minghui Zeng Yuqin Li Yuqiang Mi Ningning Zhang Wei Lu Liang Xu Clinical School of the Tianjin Second People's Hospital Tianjin Medical UniversityTianjin 300192China Department of Hepatology Tianjin Second People's HospitalTianjin 300192China Tianjin Institute of Hepatology Tianjin 300192China Department of Hepatobiliary Oncology Liver Cancer CenterTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Centerfor CancerTianjin300060China

Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were *** were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB *** median overall survival was not *** percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB *** MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all ***:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

关键词： Metabolic dysfunction-associated steatotic liver disease chronic hepatitis B hepatocellular carcinoma immunotherapy efficacy