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Adsorption,in vitro digestion and human gut microbiota regulation characteristics of three Poria cocos polysaccharides

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Food Science and Human Wellness 2024年第3期13卷 1685-1697页

作者： Fangming zhang hui Zheng Tao Zheng pan xu Yao xu Yuxin Cao Fan Jia Yiqiong Zeng Yubing Fan Kai He Xinwen Dai Fengfei Hou Yong yang college of pharmacy Hunan University of Chinese MedicineChangsha 410208China School of Pharmaceutical Science Hunan University of MedicineHuaihua 418000China Hunan Fuling Engineering Technology Research Center Huaihua 418100China

Poria cocos(PC)is a famous traditional Chinese medicine(TCM)and a widely used healthcare ingredient,which has antiobesity,enhancing immunity and improving sleep ***,only water-soluble poria polysaccharide(WSP)is extracted and applied for clinical application,while insoluble polysaccharide(alkali-soluble poria polysaccharide,ASP)is discarded as herb ***,the whole PC has also been historically utilized as functional herbal *** the beneficial role of dietary fiber and the traditional use of PC,ASP may also contribute substantially to the therapy function of *** to WSP,little attention has been paid to ASP and ASP modified product carboxymethyl poria polysaccharide(CMP)which has been used as an antitumor adjuvant *** this study,the oil,cholesterol,metal ions and polyphenols adsorption ability,in vitro simulated digestive and the gut microbiota fermentation characteristics of WSP,ASP and CMP were studied to evaluate the functional values of three *** polysaccharides(PCPs).The results showed that all three PCPs had good adsorption capacity on cholesterol,polyphenols and metal ions(Cd^(2+)/Zn^(2+)/Mg^(2+)),among which ASP showed the highest capacity than WSP and *** adsorption capacity of all three PCPs on heavy metal ions(Cd^(2+)/Zn^(2+))was stronger than that of non-heavy metal ions(Mg^(2+));The in vitro digestibility of all three PCPs was very low,but WSP was slightly higher than ASP and CMP;Moreover,the indigestible residue of all three PCPs could improve the richness and diversity of gut microbiota,among which ASP had the greatest *** general,ASP and CMP could significantly promote the proliferation of some probiotics and inhibit the growth of some harmful *** gut microbiota diversity of CMP was reduced,but the richness of probiotics,especially Parabacteroides distasonis was significantly enhanced compared with the ASP group,and the growth of harmful bacteria Klebsiella pneumoniae was inh

关键词： Poria cocos polysaccharides Alkali-soluble poria polysaccharide Carboxymethyl poria polysaccharide Adsorption characteristics In vitro simulated digestion In vitro simulated gut microbiota fermentation

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization

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Science China(Life Sciences) 2024年第5期67卷 1010-1026页

作者： Ziyue qin Yanxing Han Yifei Du Yixuan zhang Yifeng Bian Ruyu Wang haoran Wang Fanyi Guo Hua Yuan Yongchu pan Jianliang Jin Qigang Zhou Yuli Wang Feng Han Yan xu Jiandong Jiang Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjing 210029China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing 210029China State Key Laboratoryof BioactiveSubstances andFunction of Natural Medicine Instituteof Materia MedicaChinese Academyof MedicalSciencesandPeking Union MedicalCollegeBeijing100050China Gusu school Nanjing medical universitySuzhou 215002China Key Laboratory of Cardiovascular&Cerebrovascular Medicine Drug Target and Drug Discovery CenterSchool of PharmacyNanjing Medical UniversityNanjing 211166 China Department of Orthodontics The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Department of Human Anatomy Research Centre for Bone and Stem CellsKey Laboratory for Aging&DiseaseThe State Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjing 211166China Department of Clinical Pharmacology School of PharmacyNanjing Medical UniversityNanjing Jiangsu211166China Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Department of Virology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Alveolar bone regeneration has been strongly linked to macrophage polarization.M1 macrophages aggravate alveolar bone loss,whereas M2 macrophages reverse this ***(BBR),a natural alkaloid isolated and refined from Chinese medicinal plants,has shown therapeutic effects in treating metabolic *** this study,we first discovered that culture supernatant(CS)collected from BBR-treated human bone marrow mesenchymal stem cells(HBMSCs)ameliorated periodontal alveolar bone *** from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in *** clarify the underlying mechanism,the bioactive materials were applied to different animal *** discovered macrophage colony-stimulating factor(M-CSF),which regulates macrophage polarization and promotes bone formation,a key macromolecule in the *** of pure M-CSF attenuated experimental periodontal alveolar bone loss in ***-stimulating factor 1 receptor(CSF1R)inhibitor or anti-human M-CSF(M-CSF neutralizing antibody,Nab)abolished the therapeutic effects of the CS of BBR-treated ***,AKT phosphorylation in macrophages was activated by the CS,and the AKT activator reversed the negative effect of the CSF1R inhibitor or *** results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT *** studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction ***,our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

关键词： berberine human bone marrow mesenchymal stem cells alveolar bone regeneration macrophage colony-stimulating factor AKT phosphorylation

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羧甲基茯苓多糖的生物活性与食品应用

食品与机械 2024年第6期40卷 213-220页

作者：徐攀张芳铭郑慧戴鑫汶杨勇湖南中医药大学药学院湖南长沙410208 湖南省茯苓工程技术研究中心湖南怀化418100

羧甲基茯苓多糖(CMP)是茯苓水不溶性多糖的羧甲基化修饰产物,具有调节免疫、抑菌抗炎、抗肿瘤、抗氧化、肝损伤保护和调节肠道菌群等多种生物活性,在功能性食品、活性分子载体、药物等领域有着广泛的应用前景。文章聚焦近年来国内外对CM... 详细信息

羧甲基茯苓多糖(CMP)是茯苓水不溶性多糖的羧甲基化修饰产物,具有调节免疫、抑菌抗炎、抗肿瘤、抗氧化、肝损伤保护和调节肠道菌群等多种生物活性,在功能性食品、活性分子载体、药物等领域有着广泛的应用前景。文章聚焦近年来国内外对CMP的研究,综述了CMP的生物活性、制备鉴定和应用开发,并对CMP的未来发展方向进行了展望。

关键词：羧甲基茯苓多糖(CMP) 生物活性制备方法健康应用

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2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-Glucoside modulates CHEK2 and CCND1 alternative splicing to inhibit MCF-7 cells proliferation

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Traditional Medicine Research 2024年第1期9卷 33-46页

作者： hui Shen You-Zhi zhang Peng-Yu Wang Shuo zhang Huan pan Bei-Bei Liu Long-Sheng xu Jian-Fen Shen Department of Central Laboratory The First Affiliated Hospital of Jiaxing UniversityJiaxing 314000China School of pharmacy Xianning Medical CollegeHubei University of Science and TechnologyXianning 437100China Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province Xianning Medical CollegeHubei University of Science and TechnologyXianning 437100China

Background:In our previous study,we observed a synergistic effect of 2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-glucoside combined with adriamycin to induce apoptosis in MCF-7 breast cancer ***,the underlying mechanisms of epigenetic modifications,such as alternative splicing,have not been *** this study,we aimed to investigate the mechanism by which THSG inhibits MCF-7 cell proliferation using full-length transcriptome ***:First,cell viability was examined using the methyl thiazolyl tetrazolium method and full-length transcriptome sequencing was performed to identify genes and *** Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify the principal pathways and targets of *** cytometry analysis of cell cycle distribution was ***,the analysis of alternative splicing and domains of the key proteins was *** polymerase chain reaction and western blotting were performed for ***:THSG showed significant cytotoxic activity in MCF-7 ***-length transcriptome sequencing revealed differential alternative splicing with 173 upregulated and 263 downregulated *** analysis identified distinct differential expression of genes(CHEK2-211 and CCND1-201)involved in the cell cycle in the THSG-treated ***,alternative splicing types of CHEK2(mutually exclusive exon)and CCND1(intron retention).We found that THSG downregulated mRNA expression,as confirmed by quantitative polymerase chain reaction ***,protein structural analysis revealed that THSG treatment led to the generation of CHK2-211,which was the result of a mutation in the amino acid residues(GLU-150,ASN-151)of the CHEK2 domain(VAL-150,GLY-151).and CyclinD1-201 were obtained when an amino acid(ASP-267)in the domain was lost in ***,molecular docking analysis demonstrated that the domains of key proteins could bind THSG more effectively,with no difference in

关键词： THSG breast cancer full-length transcriptome sequencing alternative splicing

2型糖尿病模型大鼠口服司美格鲁肽胶囊的药效学与药动学研究

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中国药理学与毒理学杂志 2024年第8期38卷 604-609页

作者：秦红倩王夏怡张枢李小川许卉杨雪超孙健民烟台大学药学院山东烟台264000 澳门科技大学医学部药学院中国澳门999078 桂林医学院药学院广西桂林541199

目的研究2型糖尿病大鼠ig给予司美格鲁肽(Sem)胶囊的药效学与药动学。方法将雄性SD大鼠分为正常对照组、2型糖尿病模型组及模型+Sem胶囊0.839,1.678和2.517 mg·kg^(-1)组。采用高糖高脂饮食喂养结合ip给予链脲佐菌素(STZ)诱导2型糖尿... 详细信息

目的研究2型糖尿病大鼠ig给予司美格鲁肽(Sem)胶囊的药效学与药动学。方法将雄性SD大鼠分为正常对照组、2型糖尿病模型组及模型+Sem胶囊0.839,1.678和2.517 mg·kg^(-1)组。采用高糖高脂饮食喂养结合ip给予链脲佐菌素(STZ)诱导2型糖尿病大鼠模型。给予STZ 7 d后,模型+Sem胶囊组空腹ig给予Sem胶囊,每天1次,连续给药14 d。定期检测各组大鼠体重、空腹血糖(FBG)和糖化血红蛋白(HbA1c)水平。连续给药结束后不同时间点采集模型+Sem胶囊0.839,1.678和2.517 mg·kg^(-1)组大鼠血浆,采用液相色谱-串联质谱法测定血浆中Sem的含量,绘制浓度-时间曲线,用WinNonlin非房室模型拟合主要药动学参数。结果与模型组相比,模型+Sem胶囊各剂量组大鼠体重在Sem胶囊干预7和14 d后均明显下降(P2.517 mg·kg^(-1)组大鼠FBG和HbA1c水平在Sem胶囊干预14 d后无显著差异,提示其FBG和HbA1c水平基本恢复到正常水平。药动学结果表明,大鼠ig给予Sem胶囊0.839,1.678和2.517 mg·kg^(-1)14 d后Sem在血浆中的消除半衰期(t1/2)分别为7.40±1.34,7.48±0.33和(8.23±0.90)h;达峰浓度(Cmax)分别为18±9,81±23和(256±53)μg·L-1;达峰时间(Tmax)分别为0.06±0.13,1.56±0.88和(1.50±1.00)h;曲线下面积(AUC0-t)分别为158±76,858±310和(3795±1539)μg·h·L-1;蓄积指数(RAC)分别为1.12±0.05,1.12±0.01和1.15±0.04。结论Sem胶囊ig给药可有效降低2型糖尿病模型大鼠体重、FBG和HbA1c水平,具有降糖减重的作用。连续给药14 d后,Sem胶囊在0.839~2.517 mg·kg^(-1)剂量范围内Sem在大鼠体内无蓄积,暴露量随剂量增加而增大。

关键词：司美格鲁肽胰高血糖素样肽1受体激动剂 2型糖尿病药动学药效学

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稀花八角枫的化学成分研究

中国中药杂志 2024年第3期49卷 735-743页

作者：金倩倩杨婷朱敏汇张美秦汪洋潘洁王永林李勇军贵州医科大学民族药与中药开发应用教育部工程研究中心/省部共建药用植物功效与利用国家重点实验室贵州贵阳550004 贵州医科大学贵州省药物制剂重点实验室贵州贵阳550004 贵州医科大学药学院贵州贵阳550004

对稀花八角枫70%乙醇提取物化学成分进行研究。采用D-101大孔树脂、硅胶、Sephadex LH-20等柱色谱技术对稀花八角枫70%乙醇提取物的化学成分进行分离纯化,从中分离鉴定出19个化合物,分别为4-环己烯-1α,2α,3α-三醇-1-O-β-D-葡萄糖苷... 详细信息

对稀花八角枫70%乙醇提取物化学成分进行研究。采用D-101大孔树脂、硅胶、Sephadex LH-20等柱色谱技术对稀花八角枫70%乙醇提取物的化学成分进行分离纯化,从中分离鉴定出19个化合物,分别为4-环己烯-1α,2α,3α-三醇-1-O-β-D-葡萄糖苷(1)、1β,4α,6α,13-tetrahydroxy-eudesm-11(12)-ene(2)、蔗糖(3)、1′-O-benzyl-α-L-rhamnopyranosyl-(1″→6′)-β-D-glucopyranoside(4)、双(2-乙基己基)苯-1,2-二羧酸酯(5)、(Z)-10-二十碳烯酸(6)、di-O-methylcrenatin(7)、甲基-α-D-呋喃果糖苷(8)、β-胡萝卜苷(9)、丁香酸(10)、香草酸(11)、二十八烷醇(12)、isoarborinol(13),2,7-dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthalenecarboxylate(14)、香草醛(15)、松柏醛(16)、9(11)-去氢麦角甾醇过氧化物(17)、5α,8α-过氧-(22E,24R)-麦角甾-6,22-二烯-3β-醇(18)、β-谷甾醇(19)。其中化合物1和2为新化合物,化合物5~11、13、15~18为首次从八角枫属中分离得到。通过脂多糖(LPS)诱导的RAW264.7巨噬细胞炎症模型对化合物1进行了抗炎活性测定,结果显示,化合物1对LPS诱导的RAW264.7细胞NO生成具有一定的抑制作用,其抑制率为54.57%。

关键词：稀花八角枫化学成分分离鉴定

Genetic diversity and phylogenetic analysis of EG95 sequences of Echinococcus granulosus:Implications for EG95 vaccine application

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Asian Pacific Journal of Tropical Medicine 2017年第5期10卷 497-500页

作者： Wei pan De-Sheng Chen Yun-Juan Lu hui-Wen xu Wen-Ting hao Ya-Wen zhang Su-ping qin Kui-yang Zheng Ren-Xian Tang Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyLaboratory of Infection and ImmunityXuzhou Medical University Department of Clinical Medicine Xuzhou Medical University

Objective:To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus(E. granulosus). Methods:We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1(DNASTAR Inc.,Madison,WI),and the phylogenetic analysis was performed by using MEGA5.1(CEMI,Tempe,AZ,USA). In addition,linear and conformational epitopes were analysed,including secondary structure,NXT/S glycosylation,fibronectin type ecoⅢ(Fnndary Ⅲ) domain and glycosylphosphatidylinositol anchor signal(GPIanchor). The s structure was predicted by PSIPRED method. Results:Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence,X90928. However,EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates,respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine,X90928,and they belonged to Subgroup 1. However,in comparison to X90928,several amino acid mutations occurred in most isolates besides oncosphere,which potentially altered the immunodominant linear epitopes,glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. Conclusions:This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates,and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.

关键词： Echinococcus granulosus Cystic echinococcosis EG95 Vaccine Genetic diversity

CEPC Technical Design Report

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Radiation Detection Technology and Methods 2024年第1期8卷 I0003-I0016,1-1091页

作者： Waleed Abdallah Tiago Carlos Adorno de Freitas Konstantin Afanaciev Shakeel Ahmad Ijaz Ahmed Xiaocong Ai Abid Aleem Wolfgang Altmannshofer Fabio Alves Weiming An Rui An Daniele Paolo Anderle Stefan Antusch Yasuo Arai Andrej Arbuzov Abdesslam Arhrib Mustafa Ashry Sha Bai Yu Bai yang Bai Vipul Bairathi Csaba Balazs Philip Bambade Yong Ban Tripamo Bandyopadhyay Shou-Shan Bao Desmond P.Barber Ayse Bat Varvara Batozskaya Subash Chandra Behera Alexander Belyaev Michele Bertucci Xiao-Jun Bi Yuanjie Bi Tianjian Bian Fabrizio Bianchi Thomas Biekotter Michela Biglietti Shalva Bilanishvili Deng Binglin Denis Bodrov Anton Bogomyagkov Serge Bondarenko Stewart Boogert Maarten Boonekamp Marcello Borri Angelo Bosotti Vincent Boudry Mohammed Boukidi Igor Boyko Ivanka Bozovic Giuseppe Bozzi Jean-Claude Brient Anastasiia Budzinskaya Masroor Bukhari Vladimir Bytev Giacomo Cacciapaglia Hua Cai Wenyong Cai Wujun Cai Yijian Cai Yizhou Cai Yuchen Cai haiying Cai Huacheng Cai Lorenzo Calibbi Junsong Cang Guofu Cao Jianshe Cao Antoine Chance xuejun Chang Yue Chang Zhe Chang Xinyuan Chang Wei Chao Auttakit Chatrabhuti Yimin Che Yuzhi Che Bin Chen Danping Chen Fuqing Chen Fusan Chen Gang Chen Guoming Chen Hua-Xing Chen huirun Chen Jinhui Chen Ji-Yuan Chen Kai Chen Mali Chen Mingjun Chen Mingshui Chen Ning Chen Shanhong Chen Shanzhen Chen Shao-Long Chen Shaomin Chen Shiqiang Chen Tianlu Chen Wei Chen Xiang Chen Xiaoyu Chen Xin Chen xun Chen xurong Chen Ye Chen Ying Chen Yukai Chen Zelin Chen Zilin Chen Gang Chen Boping Chen Chunhui Chen Hok Chuen Cheng Huajie Cheng Shan Cheng Tongguang Cheng Yunlong Chi Pietro Chimenti Wen Han Chiu Guk Cho Ming-Chung Chu Xiaotong Chu Ziliang Chu Guglielmo Coloretti Andreas Crivellin Hanhua Cui Xiaohao Cui Zhaoyuan Cui Brunella D'Anzi Ling-Yun Dai Xinchen Dai xuwen Dai Antonio De Maria Nicola De Filippis Christophe De La Taille Francesca De Mori Chiara De Sio Elisa Del Core Shuangxue Deng Wei-Tian Deng Zhi Deng Ziyan Deng Bhupal Dev Tang Dewen Biagio Di Micco Ran Ding Siqin Dingl Yadong Ding haiyi Dong Jianin AGH University of Science and Technology Faculty of Physics and Applied Computer ScienceKrakow Anhui University HefeiAnhui Applied Physics Department Federal Urdu University of ArtsScience and TechnologyIslamabad Banaras Hindu University Institute of ScienceVaranasi Bandirma Onyedi Eylul University Bandirma Beihang University Beijing Beijing Computational Science Research Center Beijing Beijing Conveyi LTD Beijing Beijing Glass Research Institute Co. LtdBeijing Beijing Institute of Technology Beijing Beijing Normal University Beijing Brown University ProvidenceRI Budker Institute of Nuclear Physics Novosibirsk Cadi Ayyad University Laboratory of Fundamental and Applied PhysicsPolydisciplinary FacultyMarrakech Cairo University Giza Center for Theory and Computation National Tsing Hua UniversityHsinchu Central China Normal University WuhanHubei Central South University ChangshaHunan Centro de Fisica Teorica de Particulas Universidade Tecnica de LisboaLisboa Chengdu KaitengSifang Digital Radio&TV Equipment Co. LtdChengduSichuan China academy of engineering physics MianyangSichuan China building materials academy Beijing China Center of Advanced Science and Technology Beijing China Institute of Atomic Energy Beijing China Jiliang University HangzhouZhejiang China Nuclear Instrument CO. LTDBeijing China University of Geosciences Beijing China University of Geosciences WuhanHubei China University of Mining and Technology XuzhouJiangsu China West Normal University NanchongSichuan Chongqing University Department of PhysicsChongqing Chulalongkorn University Bangkok City University of Hong Kong Department of PhysicsHong Kong Cockcroft Institute Daresbury Cornell University IthacaNY CPPM(AMU/IPhU&CNRS/INP) Marseille Dalian Minzu University DalianLiaoning Dalian University of Technology Department of PhysicsDalian Deutsches Elektronen-Synchrotron DESY Hamburg Dzhelepov Laboratory of Nuclear Problems of Joint Institute for Nuclear Research(DLNP JINR) Dubna East China University Of Science And Technol

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international *** complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs *** its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs *** the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of *** Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering ***,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection *** is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 *** commencement of experiments and data collection could potentially be initiated in the mid-2030s.

关键词： initiated exceeding precise

USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID

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Signal Transduction and Targeted Therapy 2022年第2期7卷 451-465页

作者： Yuewen Luo Xiantao zhang Ran Chen Rong Li yang Liu Junsong zhang qin liu Meijun Si Jun Liu Bolin Wu xuemei Wang Shijian Wu Yiwen zhang xu zhang Deyin Guo Xin He Ting pan hui zhang Institute of Human Virology Key Laboratory of Tropical Disease Control of Ministry of EducationGuangdong Engineering Research Center for Antimicrobial Agent and ImmunotechnologyZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China School of Medicine Sun Yat-sen UniversityGuangzhou/Shenzhen 510080China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhouChina Guangdong Provincial People’s Hospital Guangdong Academy of Medical SciencesGuangzhouGuangdongChina Guanghua School of Stomatology Hospital of StomatologySun Yat-sen UniversityGuangdong Provincial Key Laboratory of StomatologyGuangzhou 510060 GuangdongChina National Guangzhou Laboratory Bio-IslandGuangzhouGuangdong 510320China

Activation-induced cytidine deaminase(AID)initiates class-switch recombination and somatic hypermutation(SHM)in antibody *** expression and activity are tightly controlled by various ***,it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it ***,we demonstrated that a deubiquitinase USP10,which specifically stabilizes nuclear AID protein,can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS ***,the signals from BCR and TLR1/2 synergistically promoted this *** deficiency of USP10 in B cells significantly decreased AID protein levels,subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)or human immunodeficiency virus type 1(HIV-1)nanoparticle ***,we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID *** manipulation could be used for the development of vaccines and adjuvants.

关键词： USP10 vaccines ubiquitin