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Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review

World Journal of Hepatology 2024年第5期16卷 843-859页

作者： Michee M Bazie Mahamoudou Sanou Florencia Wendkuuni Djigma Tegwinde Rebeca Compaore Dorcas Obiri-Yeboah Benoît Kabamba Bolni Marius Nagalo Jacques Simpore Rasmata Ouédraogo Department of medicine Transmissible Diseases LaboratoryUniversitéJoseph KI-ZERBOOuagadougou 0000Burkina Faso Department of Biochemistry and Microbiology Molecular Biology and Genetics LaboratoryUniversity Joseph KI-ZERBOOuagadougou 0000Burkina Faso Infectious and parasitic disease laboratory Health Sciences Research InstituteIRSS/CNRSTNational Center for Scientific and Technological ResearchOuagadougou 0000Burkina Faso Department of Microbiology and Immunology School of Medical SciencesUniversity of Cape CoastPMBCape Coast 0000Ghana Department of Clinical Biology Virology LaboratoryCliniques Universitaires Saint LucUniversitéCatholique de LouvainBruxelles 0000Belgium Division of Hematology and Oncology Mayo ClinicAZ 0000United States

BACKGROUND Occult hepatitis B infection(OBI)is a globally prevalent infection,with its frequency being influenced by the prevalence of hepatitis B virus(HBV)infection in a particular geographic region,including Africa.OBI can be transmitted th-rough blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma(HCC).The associated HBV genotype influences the infection.AIM To highlight the genetic diversity and prevalence of OBI in Africa.METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed,Google Scholar,Science Direct,and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa.RESULTS The synthesis included 83 articles,revealing that the prevalence of OBI varied between countries and population groups,with the highest prevalence being 90.9%in patients with hepatitis C virus infection and 38%in blood donors,indicating an increased risk of HBV transmission through blood transfusions.Cases of OBI reactivation have been reported following chemotherapy.Genotype D is the predominant,followed by genotypes A and E.CONCLUSION This review highlights the prevalence of OBI in Africa,which varies across countries and population groups.The study also demonstrates that genotype D is the most prevalent.

关键词： Occult hepatitis B infection Blood transfusion Genetic diversity

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Clinical significance,molecular characterization,and immune microenvironment analysis of coagulation-related genes in clear cell renal cell carcinoma

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Cancer Innovation 2024年第1期3卷 29-49页

作者： Weihao Chen Xupeng Zhao Yongliang Lu Hanfeng Wang Xiyou Wang Yi Wang Chen Liang Zhuomin Jia Wei Ma Department of Urology The Third Medical Center of PLA General HospitalBeijingChina school of medicine Nankai UniversityTianjinChina medical Service Department The PLA General HospitalBeijingChina Senior Department of Otolaryngology-Head&Neck Surgery The Sixth Medical Center of PLA General HospitalBeijingChina

Background:Numerous studies have revealed a tight connection between tumor development and the coagulation system.However,the effects of coagulation on the prognosis and tumor microenvironment(TME)of clear cell renal cell carcinoma(ccRCC)remain poorly understood.Methods:We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns.Subsequently,we examined variations in the overall survival(OS),genomic profiles,and TME characteristics between these subtypes.To develop a prognostic coagulation-related risk score(CRRS)model,we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses.We also created a nomogram to aid in the clinical application of the risk score,evaluating the relationships between the CRRS and the immune microenvironment,responsiveness to immunotherapy,and targeted treatment.The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed.Results:There were significant differences in clinical features,prognostic stratification,genomic variation,and TME characteristics between the two coagulation-related subtypes.We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients.Significant variations in survival outcomes were observed between the high-and low-risk groups.The nomogram was proficient in predicting the 1-,3-,and 5-year OS.Additionally,the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC.Moreover,we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis.PLAUR knockdown notably inhibited ccRCC cell proliferation and migration.Conclusion:Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and

关键词： clear cell renal cell carcinoma coagulation immunotherapy risk score tumor immune microenvironment

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Design,synthesis,and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs

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Chinese Chemical Letters 2024年第6期35卷 344-348页

作者： Bairu Meng Zongji Zhuo Han Yu Sining Tao Zixuan Chen Erik De Clercq Christophe Pannecouque Dongwei Kang Peng Zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJi’nan 250012China laboratory of virology and Chemotherapy Rega Institute for Medical ResearchK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Ji’nan 250012China

Inspired by our previous studies to discover novel human immunodeficiency virus-1(HIV-1)nonnucleoside reverse transcriptase inhibitors(NNRTIs)by targeting the tolerant region II of the NNRTIs binding pocket(NNIBP),a series of novel benzo[4,5]thieno[2,3-d]pyrimidine derivatives were designed through structure-based drug design as novel potent HIV-1 NNRTIs.The results showed that compound16b was the most active inhibitor,exhibiting 50% effective concentration(EC50)values from 0.021μmol/L to 0.298μmol/L against wild-type(WT)and a panel of NNRTIs-resistant HIV-1 strains.Moreover,16b was demonstrated with a significantly low 50% cytotoxicity concentration(CC_(50))value(>200μmol/L)and high selectivity index(SI)values.In addition,16b yielded moderate reverse transcriptase(RT)enzyme inhibition with a 50% inhibition concentration(IC_(50))value of 0.183μmol/L,which demonstrated that it acted as HIV-1 NNRTIs.The binding mode of 16b with RT was also illustrated via molecular docking.Overall,this work provided a novel lead compound for developing potent HIV-1 NNRTIs.

关键词： HIV-1 NNRTIs DAPYs Tolerant region Ⅱ Drug design

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Supramolecular systems for bioapplications:recent research progress in China

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Science China Chemistry 2024年第5期67卷 1397-1441页

作者： Yue-Yang Liu Xiao-Yong Yu Yu-Chen Pan Hang Yin Shuang Chao Yujie Li He Ma Minzan Zuo Kun-Xu Teng Jun-Li Hou Yong Chen Dong-Sheng Guo Ruibing Wang Yuxin Pei Zhichao Pei Jiang-Fei Xu Xiao-Yu Hu Chunju Li Qing-Zheng Yang Leyong Wang Yu Liu Zhan-Ting Li State Key laboratory of Organometallic Chemistry Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional MoleculesShanghai Institute of Organic ChemistryChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200032China Department of Chemistry Fudan UniversityShanghai 200438China College of Chemistry State Key Laboratory of Elemento-Organic ChemistryCollaborative Innovation Center of Chemical Science and EngineeringNankai UniversityTianjin 300071China State Key laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China College of Chemistry&Pharmacy Northwest A&F UniversityYangling 712100China Key Lab of Organic Optoelectronics&molecular Engineering Department of ChemistryTsinghua UniversityBeijing 100084China College of Materials Science and Technology Nanjing University of Aeronautics and AstronauticsNanjing 211106China Key laboratory of Radiopharmaceuticals Ministry of EducationCollege of ChemistryBeijing Normal UniversityBeijing 100875China Tianjin Key laboratory of Structure and Performance for Functional Molecules College of ChemistryTianjin Normal UniversityTianjin 300387China State Key laboratory of Analytical Chemistry for Life Science Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Supramolecular systems feature dynamic,reversible and stimuli-responsive characteristics,which are not easily achieved by molecular entities.The last decade has witnessed tremendous advances in the investigations of supramolecular systems for various bioapplications,which include drug delivery,anticancer therapy,antibacterial therapy,photodynamic therapy,photothermal therapy,combination therapy,antidotes for residual drugs or toxins,and bioimaging and biosensing.Host-guest chemistry has played a key role in the development of such bioactive supramolecular systems,and natural macrocycles(such as cyclodextrins),synthetic macrocycles(such as calixarenes,cucurbit[n]urils,and pillararenes),and porous framework polymers(such as supramolecular organic frameworks and flexible organic frameworks)have been most successfully used as hosts to build different kinds of host-guest systems for attaining designed biofunctions.The self-assembly of rationally designed amphiphilic molecules,macromolecules and polymers represent another important approach for the construction of supramolecular architectures with advanced biofunctions.In this review,we summarize the important contributions made by Chinese researchers in this field,with emphasis on those reported in the past five years.

关键词： host-guest chemistry drug delivery anticancer and antibacterial photodynamic therapy photothermal therapy antidote transmembrane channel bioimaging and biosensing

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HIV-1 Protein Tat_(1–72) Impairs Neuronal Dendrites via Activation of PP1 and Regulation of the CREB/BDNF Pathway

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Virologica Sinica 2018年第3期33卷 261-269页

作者： Yu Liu Deyu Zhou Jiabin Feng Zhou Liu Yue Hu Chang Liu Xiaohong Kong laboratory of medical molecular virology School of Medicine Nankai University

Despite the success of combined antiretroviral therapy in recent years, the prevalence of human immunodeficiency virus(HIV)-associated neurocognitive disorders in people living with HIV-1 is increasing, significantly reducing the healthrelated quality of their lives. Although neurons cannot be infected by HIV-1, shed viral proteins such as transactivator of transcription(Tat) can cause dendritic damage. However, the detailed molecular mechanism of Tat-induced neuronal impairment remains unknown. In this study, we first showed that recombinant Tat(1–72 aa) induced neurotoxicity in primary cultured mouse neurons. Second, exposure to Tat_(1–72) was shown to reduce the length and number of dendrites in cultured neurons. Third, Tat_(1–72)(0–6 h) modulates protein phosphatase 1(PP1) expression and enhances its activity by decreasing the phosphorylation level of PP1 at Thr320. Finally, Tat_(1–72)(24 h) downregulates CREB activity and CREBmediated gene(BDNF, c-fos, Egr-1) expression. Together, these findings suggest that Tat_(1–72) might impair cognitive function by regulating the activity of PP1 and the CREB/BDNF pathway.

关键词：蛋白质磷酸酶 HIV-1 损害小径树突激活 c-fos Egr-1

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Stability of HIV-1 subtype B and C Tat is associated with variation in the carboxyl-terminal region

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Virologica Sinica 2016年第3期31卷 199-206页

作者： Xuechao Zhao Lingyu Qian Deyu Zhou Di Qi Chang Liu Xiaohong Kong laboratory of medical molecular virology School of MedicineNankai University

The multifunctional trans-activator Tat is an essential regulatory protein for HIV-1 replication and is characterized by high sequence diversity. Numerous experimental studies have examined Tat in HIV-1 subtype B, but research on subtype C Tat is lacking, despite the high prevalence of infections caused by subtype C worldwide. We hypothesized that amino acid differences contribute to functional differences among Tat proteins. In the present study, we found that subtype B NL4-3Tat and subtype C isolate HIV1084 i Tat exhibited differences in stability by overexpressing the fusion protein Tat-Flag. In addition, 1084 i Tat can activate LTR and NF-κB more efficiently than NL4-3 Tat. In analyses of the activities of the truncated forms of Tat, we found that the carboxylterminal region of Tat regulates its stability and transactivity. According to our results, we speculated that the differences in stability between B-Tat and C-Tat result in differences in transactivation ability.

关键词： HIV-1 TAT 稳定性 C亚型末端区域羧基转录活性 NF-κB

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A human monoclonal antibody neutralizes SARS-CoV-2 Omicron variants bytargeting the upstream region of spike protein HR2 motif

hLife

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hLife 2024年第3期2卷 126-140页

作者： Hang Su Jun Zhang Zhenfei Yi Sajid Khan Mian Peng Liang Ye Alan Bao Han Zhang Guangli Suo Qian Li Housheng Zheng Dandan Wu Thomas J.Kipps Lanfeng Wang Zhenghong Lin Suping Zhang Shenzhen Key laboratory of Precision medicine for Hematological Malignancies Guangdong Key Laboratory for Genome Stability andHuman Disease PreventionDepartment of PharmacologySchool of Basic Medical SciencesBase for International Science and TechnologyCooperation:Carson Cancer Stem Cell Vaccines R&D CenterInternational Cancer CenterShenzhen University Medical SchoolShenzhenUniversityGuangdongChina school of Life Sciences Chongqing UniversityChongqingChina The Center for Microbes Development and HealthCAS Key Laboratory of Molecular Virology&ImmunologyShanghai Institute of Immunityand InfectionChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina College of Life Sciences University of Chinese Academy of SciencesBeijingChina Department of Critical Care medicine Shenzhen Luohu People’s HospitalGuangdongChina university of California BerkeleyCaliforniaUSA Xenta Biomedical Science Co. LtdGuangdongChina CAS Key laboratory of Nano-Bio Interface Suzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesJiangsuChina Center of Novel Therapeutics University of CaliforniaSan DiegoCaliforniaUSA

The continuous emergence of new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants meansthere is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individuals remaining at risk of coronavirus disease 2019(COVID-19).Neutralizing monoclonal antibody(mAb)that binds to theconserved S2 subunit of the SARS-CoV-2 spike(S)protein alone,or in combination with mAb that binds to the receptor-binding domain(RBD)of S protein,might be effective in eliciting protection from infection by a variety of SARS-CoV2 variants.Using high-throughput single-cell immunoglobulin sequencing of B cells from COVID-19-convalescent donors,we identified a high-affinity S2-specific mAb-39,that could inhibit original SARS-CoV-2 strain,Omicron BA.1,BA.2.86,BA.4,BA.5,and EG.5.1 S protein-mediated membrane fusion,leading to the neutralization of these pseudoviralinfections.Moreover,mAb-39 could also improve the neutralizing activity of anti-RBD antibody against the highlyneutralization-resistant Omicron variants.molecular docking and point mutation analyses revealed that mAb-39 recognized epitopes within the conserved upstream region of the heptad repeat 2(HR2)motif of the S2 subunit.Collectively,these findings demonstrate that targeting the conserved upstream region of the HR2 motif(e.g.,using mAbs)provides anovel strategy for preventing the infection of SARS-CoV-2 and its variants.

关键词： coronavirus disease 2019(COVID-19) severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variants monoclonal antibody upstream region of heptad repeat 2(HR2) immunoglobulin repertoiresequencing

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Host protein atlastin-1 promotes human immunodeficiency virus(HIV-1)replication

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Virologica Sinica 2017年第4期32卷 338-341页

作者： W enyuan Shen Bin Liu Zhou Liu Jiabin Feng Chang Liu Xiaohong Kong laboratory of medical molecular virology school of medicinenankai university

Here we explored the contribution of atlastin- 1 （ATL 1）to HIV replication for the first time. HIV-1 encodes only15 proteins （Ayinde et al., 2010） and thus must exploitmultiple host cell functions for successful infection. Forexample, HIV-1 envelope （Env） glycoproteins are synthe-sized as a polyprotein precursor, known as gp 160, in theendoplasmic reticulum （ER）（Checkley et al., 2011）。

关键词：中国病毒学英文版

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Concurrent chemoradiotherapy using gemcitabine and nedaplatin in recurrent or locally advanced head and neck squamous cell carcinoma

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World Journal of Clinical Cases 2022年第11期10卷 3414-3425页

作者： Rui-Xue Huo Ying-Ying Jin Yong-Xue Zhuo Xiao-Tong Ji Yu Cui Xiao-Jing Wu Yi-Jia Wang Long Zhang Wen-Hua Zhang Yu-Mei Cai Cheng-Cheng Zheng Rui-Xue Cui Qian-Ye Wang Zhen Sun Feng-Wei Wang Department of Oncology Tianjin Union Medical CenterTianjin 300000China school of medicine Nankai UniversityTianjin 300000China laboratory of Oncologic molecular medicine Tianjin Union Medical CenterTianjin 300000China

BACKGROUND Patients with recurrent or locally advanced head and neck squamous cell carcinoma(HNSCC)typically have limited treatment options and poor prognosis.AIM To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC.METHODS This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days.Intensitymodulated radiation therapy with a conventional fraction was delivered 5 days per week.Objective response rate(ORR),disease control rate,and toxicity were observed as primary endpoints.Overall survival(OS)and progression free survival were recorded and analyzed as secondary endpoints.RESULTS A total of 24 patients with HNSCC were enrolled.During the median 22.4-mo follow-up,both ORR and disease control rate were 100%.The one-year OS was 75%,and one-year progression-free survival(PFS)was 66.7%(median PFS was 15.1 mo).Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients,and patients who achieved complete response had better survival than those in the PR group(all P<0.05).The most common grade 1-4(100%)or grade 3-4 toxicities(75%)were hematological,and the most common grade 3-4 non-hematological toxicity was mucositis in 17(71%)patients.CONCLUSION Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability.Considering the high adverse event rate,the optimized dose and schedule must be further explored.

关键词： Chemoradiotherapy Gemcitabine Nedaplatin Head and neck cancer Recurrent Locally advanced

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Evidence for the antisense transcription in the proviral R29-127 strain of bovine immunodeficiency virus

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Virologica Sinica 2015年第3期30卷 224-227页

作者： Bin Liu Xuechao Zhao Wenyuan Shen Xiaohong Kong laboratory of medical molecular virology school of medicine nankai university Tianjin 300071 China

Dear Editor,In the late stages of the retroviral life cycle,the transcription of viral pre-m RNA is initiated at the 5′long terminal repeat(5′LTR)and terminated at the 3′LTR;the full-length and spliced viral RNAs are transported out of the nucleus and serve as templates for the translation of viral proteins or alternatively as the full-length viral genome to be packaged into virus particles.

关键词： antisense terminated transcripts nucleus initiated length primer plasmid bovine transfection

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