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Direct technetium-99m labeling of anti-hepatoma monoclonal antibody fragment:a radioimmunoconjugate for hepatocellular carcinoma imaging

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World Journal of Gastroenterology 2000年第3期6卷 348-352页

作者： Hui Jie Bian zhi nan chen Jing Lan Deng Cell Engineering Research Center Basic Medical.DepartmentFourth Military Medical UniversityXi’an 710032Shaanxi ProvinceChina Department of Clinical Nuclear Medicine Xijing HospitalXi’an 710033Shaanxi ProvinceChina

AIM To directly radiolabel an anti-hepatomamAb fragment HAb18 F（ab’）2 with 99mTc bystannous-reduced method,and assess thestability,biodistribution and radioimmun-oimaging（RⅡ）.METHODS Immunoreactive fraction wasdetermined according to Lindmo’s ***’s reagent was used to determine thenumber of thiols in the reduced F（ab’）2.Labelingefficiency and homogeneity were measured bypaper chromatography,sodium dodecylsulphatepolyacrylamide gel electrophoresis（SDS-PAGE）and *** assay involvedthe incubation of aliquots of labeled antibody inethylenediaminetetraacetate（ EDTA ）and L-cysteine（L-cys）solutions with different molarratio at 37℃ for 1h,*** vivo utilized nude mice bearing humanhepatocellular carcinoma（HHCC）xenograftswith gamma camera imaging and tissuebiodistribution studies at regular *** The labeling procedure was finishedwithin 1.5 h compared with the'pretinning'method which would take at least *** vitrostudies demonstrated that the radiolabeled mAbfragment was homogeneous and retained *** studies indicatedthat 99mTc-labeled HAb18 F（ab’）2 in EDTA is morestable than in *** and biodistribution showed a significant tumor uptake at 24 h post-injection of 99mTc-labeled HAb18 F（ab’）2.Theblood,kidney,liver and tumor uptakes at 24hwere 0.56±0.09,56.45±11.36,1.43±0.27 and6.57±3.01（%ID/g）,*** 99mTc-HAb18 F（ab’）2 conjugateprepared by this direct method appears to be aneffective way to detect hepatoma in nude micemodel.

关键词： antibody monoclonal antibody fragments technetium-99m hepatocellular carcinoma liver neoplasms radioimmunoimaging

CD147 deficiency in T cells prevents thymic involution by inhibiting the EMT process in TECs in the presence of TGFβ

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Cellular & Molecular Immunology 2021年第1期18卷 171-181页

作者： Ruo chen Ke Wang Zhuan Feng Ming-Yang Zhang Jiao Wu Jie-Jie Geng zhi-nan chen Department of Cell Biology College of Life Science and TechnologyJinan UniversityGuangdongChina National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityShaanxiChina

Thymic involution during aging is a major cause of decreased T-cell production and reduced ***,we show that the loss of CD147 on T cells prevents thymic senescence,resulting in slowed shrinkage of the thymus with age and increased production of naive T *** phenotype is the result of slowing of the epithelial-mesenchymal transition(EMT)process in thymic epithelial cells(TECs),which eventually leads to reduced adipocyte *** an in vitro coculture system,we found that TGFβ is an important factor in the EMT process in TECs and that it can reduce the expression of E-cadherin through p-5mad2/FoxC2 ***,CD147 on T cells can accelerate the decline in E-cadherin expression by interacting with Annexin A2 on *** the presence of TGFβ,Annexin A2 and E-cadherin colocalize on ***,CD147 on T cells competitively binds to Annexin A2 on TECs,leading to the isolation of ***,the isolated E-cadherin is easily phosphorylated by phosphorylated Src kinase,the phosphorylation of which was induced by TGFβ,and finally,p-E-cadherin is ***,in the thymus,the interaction between T ceils and TECs contributes to thymic involution with *** this study,we illuminate the mechanism underlying the triggering of the EMT process in TECs and show that inhibiting TGFβ and/or CD147 may serve as a strategy to hinder age-related thymic involution.

关键词： CD147 TGFβ thymic involution EMT

Modified Therapeutic Antibodies: Improving Efficacy

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Engineering 2021年第11期7卷 1529-1540页

作者： Ji-Min Dai Xue-Qin Zhang Jing-Yao Dai Xiang-Min Yang zhi-nan chen Department of Cell Biology National Translational Science Center for Molecular MedicineState Key Laboratory of Cancer BiologyThe Fourth Military Medical UniversityXi’an 710032China Department of Hepatobiliary Surgery Chinese PLA General HospitalBeijing 100853China Department of Hepatobiliary Surgery Air Force Medical CenterBeijing 100142China

The prosperity of the biotherapeutics market reflects the feasibility and effectiveness of therapeutic antibodies for the treatment of cancers,inflammatory disorders,and refractory *** drawbacks emerge in clinical trials and practice,such as impeded binding,reduced effector functions,and frequent adverse reactions,modifications of therapeutic antibodies are unprecedently burgeoning in research and development(R&D).These modifications include:①modified glycosylation;②fragment of crystallizable domain(Fc)amino acid alterations;③cross-isotype or cross-subclass exchanges;④antibody–drug conjugates(ADCs);⑤single chain of variable region fragment(scFv)for chimeric antigen receptor T(CAR-T)cells;and⑥bispecific antibodies(bsAbs)in order to promote binding affinity,half-life in circulation,effectiveness toward target cells and,ultimately,to achieve overall improved *** many achievements have been made around the world in the past decades,China has been playing an active role in this realm,with its great demand for biotherapeutics with R&D *** review recapitulates the international progress that has been achieved with modified therapeutic antibodies,and then focuses on that of China in an independent section.

关键词： Therapeutic antibody Modification Efficacy Antigen Antibody-drug conjugate Bispecific antibody

Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis

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Journal of Pharmaceutical Analysis 2023年第10期13卷 1135-1152页

作者： Jia-Jia Zhang Chang-Geng Song Miao Wang Gai-Qin Zhang Bin Wang Xi chen Peng Lin Yu-Meng Zhu zhi-Chuan Sun Ya-Zhou Wang Jian-Li Jiang Ling Li Xiang-Min Yang zhi-nan chen National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi'an710032China Department of Neurology Xijing HospitalFourth Military Medical UniversityXi'an710032China Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education College of Chemistry and Materials ScienceNorthwest UniversityXi'an710032China Department of Neurosurgery Xi'an Daxing HospitalXi'an710032China Department of Neurobiology and Institute of Neurosciences Collaborative Innovation Center for Brain ScienceSchool of Basic MedicineFourth Military Medical UniversityXi'an710032China

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of *** the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine *** the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular *** successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial *** of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/b-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based *** mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of *** established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic *** blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/b-arrestin2 ***,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alleviated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine ***,intrathecal electroporation of silencing short hairpin RNA illustrated that the in v

关键词： Morphine tolerance Mu-opioid receptor Endocytosis Monoclonal antibody Physical dependence

CD147 regulates antitumor CD8^(+)T-cell responses to facilitate tumor-immune escape

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Cellular & Molecular Immunology 2021年第8期18卷 1995-2009页

作者： Yatong chen Jing Xu Xiaodong Wu Hui Yao Zhou Yan Ting Guo Wenjing Wang Peixiao Wang Yu Li Xiangmin Yang Hao Li Huijie Bian zhi-nan chen National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical University710032Xi’anChina Medical Research Center Southern University of Science and Technology Hospital518055ShenzhenChina Center of Anesthesiology&Operation Chinese PLA General Hospital100853BeijingChina Department of Radiation Oncology First Peoples’Hospital of ChangzhouThird Affiliated Hospital of Soochow University213000ChangzhouChina Department of Gastroenterology Henan Children’s Hospital450018ZhengzhouChina

Negative regulation of antitumor T-cell-immune responses facilitates tumor-immune ***,we show that deletion of CD147,a type I transmembrane molecule,in T cells,strongly limits in vivo tumor growth of mouse melanoma and lung cancer in a CD8^(+)T-cell-dependent *** mouse tumor models,CD147 expression was upregulated on CD8^(+)tumor-infiltrating lymphocytes(TILs),and CD147 was coexpressed with two immune-checkpoint molecules,Tim-3 and *** publicly available gene-profiling data for CD8^(+)TILs in tumor biopsies from metastatic melanoma patients showed a higher level of CD147 expression in exhausted CD8^(+)TILs than in other subsets of CD8^(+)TILs,along with expression of PD-1 and ***,CD147 deletion increased the abundance of TILs,cytotoxic effector function of CD8^(+)T cells,and frequency of PD-1^(+)CD8^(+)TILs,and partly reversed the dysfunctional status of PD-1^(+)Tim-3^(+)CD8^(+)*** cytotoxic transcription factors Runx3 and T-bet mediation enhanced antitumor responses by CD147^(-/-)CD8^(+)T ***,CD147 deletion in T cells increased the frequency of TRM-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor *** of tumor tissue samples from patients with non-small-cell lung cancer showed negative correlations between CD147 expression on CD8^(+)TILs and the abundance of CD8^(+)TILs,histological grade of the tumor tissue samples,and survival of patients with advanced ***,we found a novel function of CD147 as a negative regulator of antitumor responses mediated by CD8^(+)TILs and identified CD147 as a potential target for cancer immunotherapy.

关键词： CD147 CD8+T cells Anti-tumor immunity

CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis

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Cellular & Molecular Immunology 2021年第12期18卷 2618-2631页

作者： JieJie Geng Ruo chen Feng-fan Yang Peng Lin Yu-meng Zhu Xianghui Fu Ke Wang Zhuan Feng Jiao Wu Hai Zhang Qi-jing Li zhi-nan chen Ping Zhu Department of Clinical Immunology Xijing HospitalFourth Military Medical UniversityXi’anP.R.China National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi’anP.R.China Department of Immunology Duke University Medical CenterDurhamNCUSA

Regulatory T cell(Treg)stability is necessary for the proper control of immune activity and tissue ***,it remains unclear whether Treg stability must be continually reinforced or is established during development under physiological ***3 has been characterized as a central mediator of the genetic program that governs Treg ***,we demonstrate that to maintain Foxp3 protein expression,Tregs require cell-to-cell contact,which is mediated by the CD147-CD98 *** Tregs are produced,CD147,which is expressed on their surface,is stimulated by CD98,which is widely expressed in the physiological *** a result,CD147’s intracellular domain binds to CDK2 and retains it near the membrane,leading to Foxp3 dephosphorylation and the prevention of Foxp3 *** addition,the optimal distribution of Foxp3+Tregs under both pathological and physiological conditions depends on CD98 ***,our study provides direct evidence that Foxp3-dependent Treg stability is reinforced in the periphery by the interaction between CD147 and CD98 in the surrounding *** importantly,Tregs with high CD147 expression effectively inhibit inflammatory responses and maintain Foxp3 stability,which has guiding significance for the application of Tregs in immunotherapy.

关键词： Treg Stability CD147 CD98 CDK2 Immune therapy

Notably Accelerated nano-Bainite Transformation via Increasing Undissolved Carbides Content on GCr15Si1Mo Bearing Steel

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Acta Metallurgica Sinica(English Letters) 2024年第4期37卷 703-712页

作者： Yan-Hui Wang Hua-Qiang Sun Wen-Jing Feng Lei-Jie Zhao Xiang chen Qing-An chen Hai-Tao Sun Jian-Jun Wang zhi-nan Yang Key Laboratory of Intelligent Industrial Equipment Technology of Hebei Province School of Mechanical and Equipment EngineeringHebei University of EngineeringHandan056038China Collaborative Innovation Center for Modern Equipment Manufacturing of Jinan New Area Hebei University of EngineeringHandan056038China School of Materials Science and Engineering Tsinghua UniversityBeijing100084China Avic Shang da Superalloys Company Limited Xingtai054800China National Engineering Research Center for Equipment and Technology of Cold Strip Rolling Yanshan UniversityQinhuangdao066004China

In this study, a high-carbon nano-bainitic GCr15Si1Mo bearing steel was investigated. Specifically, the effects of content and size of undissolved carbides on the microstructure and transformation kinetics of nano-bainite were analyzed. The results demonstrated that after prolonged austempering at low temperatures, the mixed microstructure composed of nano-bainite (NB), undissolved carbides (UC), and retained austenite (RA) was obtained in GCr15SiMo steel. When the experimental steel was austenitized at 900 ℃, the undissolved carbides gradually dissolved until reaching a stable state with increasing holding time. Furthermore, at the same austempering temperature, despite different volume fractions of undissolved carbides in the substrate, the volume fractions of nano-bainite in the final microstructures remained essentially the same. Moreover, the higher the content of undissolved carbides in steel, the faster the transformation rate of nano-bainite and the shorter the total transformation time.

关键词： nano-bainite Undissolved carbides Bainitic transformation kinetics Carbon concentration

Prediction of contact resistance of electrical contact wear using different machine learning algorithms

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Friction 2024年第6期12卷 1250-1271页

作者： Zhen-bing CAI Chun-lin LI Lei YOU Xu-dong chen Li-ping HE Zhong-qing CAO zhi-nan ZHANG Tribology Research Institute Southwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Mechanical System and Vibration Shanghai Jiao Tong UniversityShanghai 200240China

H62 brass material is one of the important materials in the process of electrical energy transmission and signal transmission,and has excellent performance in all *** the wear behavior of electrical contact pairs is particularly complex when they are in service,we evaluated the effects of load,sliding velocity,displacement amplitude,current intensity,and surface roughness on the changes in contact *** learning(ML)algorithms were used to predict the electrical contact performance of different factors after wear to determine the correlation between different factors and contact *** forest(RF),support vector regression(SVR)and BP neural network(BPNN)algorithms were used to establish RF,SVR and BPNN models,respectively,and the experimental data were trained and *** was proved that BP neural network model could better predict the stable mean resistance of H62 brass alloy after *** analysis shows that the load and current have great influence on the predicted electrical contact *** wear behavior of electrical contacts is influenced by factors such as load,sliding speed,displacement amplitude,current intensity,and surface roughness during *** learning algorithms can predict the electrical contact performance after wear caused by these *** results indicate that an increase in load,current,and surface roughness leads to a decrease in stable mean resistance,while an increase in displacement amplitude and frequency results in an increase in stable mean resistance,leading to a decline in electrical contact *** reduce testing time and costs and quickly obtain the electrical contact performance of H62 brass alloy after wear caused by different factors,three algorithms(random forest(RF),support vector regression(SVR),and BP neural network(BPNN))were used to train and test experimental results,resulting in a machine learning model suitable for predicting the stable mean

关键词： electrical contact wear contact resistance machine learning(ML) neural network

Design and Application of an S-band Fast Radio Bursts Search Pipeline for the nanshan 26 m Radio Telescope

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Research in Astronomy and Astrophysics 2024年第7期24卷 111-117页

作者： Yan-Ling Liu Mao-Zheng chen Jian Li Jian-Ping Yuan Rai Yuen zhi-Yong Liu Hao Yan Wen-Long Du nan-nan Zhai Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Xinjiang Key Laboratory of Microwave Technology Urumqi 830011China University of Chinese Academy of Sciences Beijing 100049China

Fast radio bursts(FRBs)are among the most studied radio transients in astrophysics,but their origin and radiation mechanism are still *** is a challenge to search for FRB events in a huge amount of observational data with high speed and high *** the rapid advancement of the FRB research process,FRB searching has changed from archive data mining to either long-term monitoring of the repeating FRBs or all-sky surveys with specialized ***,establishing a highly efficient and high quality FRB search pipeline is the primary task in FRB *** learning techniques provide new ideas for FRB search *** have detected radio bursts from FRB 20201124A in the L-band observational data of the nanshan 26 m radio telescope(NSRT-26m)using the constructed deep learning based search pipeline named dispersed dynamic spectra search(DDSS).Afterwards,we further retrained the deep learning model and applied the DDSS framework to S-band *** this paper,we present the FRB observation system and search pipeline using the S-band *** carried out search experiments,and successfully detected the radio bursts from the magnetar SGR J1935+2145and FRB *** experimental results show that the search pipeline can complete the search efficiently and output the search results with high accuracy.

关键词： radio continuum general-methods data analysis-methods observational