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Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

Cancer Biology & Medicine 2024年第4期21卷 331-346页

作者： Shuangcheng Li tianci Wang Xinghui Xiao Xiaodong Zheng Haoyu Sun Rui Sun Hongdi Ma zhigang tian Xiaohu Zheng Hefei National Research Center for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Immunology University of Science and Technology of ChinaHefei 230027China Hefei TG ImmunoPharma Corporation Limited Hefei 230601China Research Unit of NK Cell Study Chinese Academy of Medical SciencesBeijing 100864China Key Laboratory of Quantitative Synthetic Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

关键词： NK cell CD300A phosphatidylserine immune checkpoint hematologic malignancy

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Bayesian inference-based wear prediction method for plain bearings under stationary mixed-friction conditions

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Friction 2024年第6期12卷 1272-1282页

作者： Florian KÖNIG Florian WIRSING Georg JACOBS Rui HE zhigang tian Ming J.ZUO Institute for Machine Elements and Systems Engineering RWTH Aachen UniversityAachen 52062Germany Department of Mechanical Engineering University of AlbertaEdmonton T6G1H9Canada Qingdao International Academician Park Research Institute Qingdao 266000China

This study introduces a method to predict the remaining useful life(RUL)of plain bearings operating under stationary,wear-critical conditions.In this method,the transient wear data of a coupled elastohydrodynamic lubrication(mixed-EHL)and wear simulation approach is used to parametrize a statistical,linear degradation model.The method incorporates Bayesian inference to update the linear degradation model throughout the runtime and thereby consider the transient,system-dependent wear progression within the RUL prediction.A case study is used to show the suitability of the proposed method.The results show that the method can be applied to three distinct types of post-wearing-in behavior:wearing-in with subsequent hydrodynamic,stationary wear,and progressive wear operation.While hydrodynamic operation leads to an infinite lifetime,the method is successfully applied to predict RUL in cases with stationary and progressive wear.

关键词： plain bearings wear modeling remaining useful life prediction Bayesian inference

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Preparation, Crystallization and Mechanical Properties of Potassium Aluminosilicate Glass-ceramics

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Journal of Wuhan University of Technology(Materials Science) 2024年第3期39卷 587-595页

作者：郑伟宏黄猛 GAO Zipeng ZHANG Hang YUAN Jian tian Peijing PENG zhigang State Key Laboratory of Silicate Materials for Architectures Wuhan University of TechnologyWuhan 430070China Shahe Research Institute of Glass Technology Shahe 054100China

In this study,transparent K_(2)O-Al_(2)O_(3)-SiO_(2)(KAS)glass-ceramics with leucite as the main crystalline phase were prepared by melting-quench method and two-step heat treatment.The effects of SiO_(2)/Al_(2)O_(3) ratio and heat treatment on crystallization and mechanical properties were studied.The crystallization kinetics and X-Ray Diffraction(XRD)results showed that SiO_(2)/Al_(2)O_(3) ratio and heat treatment system had a direct impact on the crystallization behavior of potassium aluminosilicate glass-ceramics.When heat-treated at 680℃/2 h and 780℃/1 h,cracks generated on the surface of the sample with the addition of SiO_(2)/Al_(2)O_(3)=4.8(in mol)due to the huge difference in the coefficient of thermal expansion between glass matrix and surface.When the addition of SiO_(2)/Al_(2)O_(3)(in mol)was 4,the sample with leucite as the main crystalline phase showed an excellent fracture toughness(1.46 MPa·m^(0.5))after the heat treatment of 680℃/2 h and 780℃/5 h.And there was a phase transformation from kaliophilite to leucite.The crystalline phases of the sample heat-treated at 680℃/8 h and 780℃/1 h were leucite and kaliophilite,which resulted in the visible light transmittance of 63%and the fracture toughness of 0.91 MPa·m^(0.5).Furthermore,after the heat treatment of 680℃/2 h and 780℃/5 h,the main crystalline phase of the sample with SiO_(2)/Al_(2)O_(3)=3.2(in mol)was still kaliophilite.Because leucite only grows on the surface of the sample and is hard to grow inward,it is hard to achieve the bulk crystallization of leucite in the sample with SiO_(2)/Al_(2)O_(3)=3.2(in mol).

关键词： leucite glass-ceramic kaliophilite crystallization kinetics

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U-Pb zircon ages and petrogeochemistry and tectonic implications of gabbro and granite in southwest Lahad Datu area of Sabah, Malaysia

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Acta Oceanologica Sinica 2024年第2期43卷 94-110页

作者： zhigang Zhao Wu Tang Shixiang Liu Huafeng Tang Pujun Wang Zhiwen tian China National Offshore Oil Corporation(CNOOC)Research Institute Co. Ltd.Beijing 100028China College of Earth Sciences Jilin UniversityChangchun 130061China

The southwest Lahad Datu felsic rocks were previously thought to have formed in the late Triassic as part of the microcontinental crystalline basement.Based on U-Pb ages,geochemistry,and the Hfisotopes of zircon from the southeastern Sabah gabbro and granite,in this study,the tectonic properties of the Sabah area during the Triassic were investigated.The weighted average U-Pb zircon ages of the gabbro and granite samples were determined to be(230.9±2.5)Ma and(207.1±3.3)Ma,respectively.The granite had SiO_(2) contents of 66.54%-79.47%,low TiO_(2) contents of 0.08%-0.3%,Al_(2)O_(3) contents of 10.97%-16.22%,Na_(2)O contents of 5.91 %-6.39%,and low K_(2)O contents of 0.15%-0.65%.The chondrite-normalized rare earth element(REE) patterns exhibit light REE enrichment,with right-sloping curves.The primitive mantle-normalized trace element spider diagrams exhibit Th,U,La,Sr,and Zr enrichment and Nb,Ta,P and Ti depletions,i.e.,the geochemical characteristics of typical island arc igneous rocks.The tectonic discriminant diagram indicates that the granite is a volcanic arc granite.The Hf isotopic an alysis of gabbro zircon revealed that the zircons have ε_(Hf)(t)values of 12.08-16.24(mean of 14.32) and two-stage model ages(t_(DM2)) of 223-491 Ma(mean of 347 Ma).This indicates that the diagenetic magma of the gabbro was mainly derived from melting of newly formed crustal materials.The ophiolite in southeast Sabah has existed since the early Late Triassic.The crystalline basement granite in southeastern S abah was emplaced lasted from late Triassic to early Cretaceous.Based on previous studies and global plate reconstruction models,it is speculated that the southeastern Sabah granite may have been formed in an island arc setting,i.e.,where the oceanic crust of the Paleo-Tethys Ocean collided with the oceanic crust of the Panthalassa Ocean.

关键词： Sabah early late Triassic ophiolite granite tectonic properties

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Profile of Dr. zhigang tian

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Science China(Life Sciences) 2018年第12期61卷 1474-1476页

作者： tian, zhigang Univ Sci & Technol China Hefei Anhui Peoples R China Chinese Acad Sci Inst Immunol Beijing Peoples R China Chinese Acad Sci Key Lab Innate Immun & Chron Dis Beijing Peoples R China USTC Med Ctr Hefei Anhui Peoples R China USTC Sch Life Sci Hefei Anhui Peoples R China

Dr.zhigang tian's laboratory is credited with seminal discoveries regarding basic knowledge and clinical study of natural killer(NK)cells,particularly liver-resident NK cells, cytokine-producing NK cell subsets,and NK cell-based immunotherapy.Dr.tian has made outstanding contributions in the field of NK cell research,and was elected as a member of the Chinese Academy of Engineering in 2017.

关键词： tian's laboratory the Chinese Academy

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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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Oncology Research 2024年第6期32卷 1109-1118页

作者： zhigang XIA MENGYAO tian YUCAI CHENG WENFANG YI ZEFAN DU tianWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN Pediatric Hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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A Blockchain-Based Access Control Scheme for Reputation Value Attributes of the Internet of Things

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Computers, Materials & Continua 2024年第1期78卷 1297-1310页

作者： Hongliang tian Junyuan tian College of Electrical Engineering Northeast Electric Power UniversityJilin132012China

The Internet of Things(IoT)access controlmechanism may encounter security issues such as single point of failure and data tampering.To address these issues,a blockchain-based IoT reputation value attribute access control scheme is proposed.Firstly,writing the reputation value as an attribute into the access control policy,and then deploying the access control policy in the smart contract of the blockchain system can enable the system to provide more fine-grained access control;Secondly,storing a large amount of resources fromthe Internet of Things in Inter Planetary File System(IPFS)to improve system throughput;Finally,map resource access operations to qualification tokens to improve the performance of the access control system.Complete simulation experiments based on the Hyperledger Fabric platform.Fromthe simulation experimental results,it can be seen that the access control system can achieve more fine-grained and dynamic access control while maintaining high throughput and low time delay,providing sufficient reliability and security for access control of IoT devices.

关键词： Blockchain IoT access control Hyperledger Fabric

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Holistic Service-Based Architecture for Space-Air-Ground Integrated Network for 5G-Advanced and Beyond

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China Communications 2022年第1期19卷 14-28页

作者： Xiaoyun Wang Tao Sun Xiaodong Duan Dan Wang Yongjing Li Ming Zhao zhigang tian China Mobile Communications Group Cor. Ltd.Beijing 100053China China Mobile Research Institute Beijing 100053China Tsinghua University Beijing 100084China

The Service-based Architecture(SBA) is one of the key innovations of 5G architecture that leverage modularized, self-contained and independent services to provide flexible and cloud-native 5G network. In this paper, SBA for Space-Air-Ground Integrated Network(SAGIN) is investigated to enable the 5G integration deployment. This paper proposes a novel Holistic Service-based Architecture(H-SBA)for SAGIN of 5G-Advanced and beyond, i.e., 6G. The H-SBA introduces the concept of end-to-end servicebased architecture design. The "Network Function Service", introduced in 5G SBA, is extended from Control Plane to User Plane, from core network to access network. Based on H-SBA, the new generation of protocol design is proposed, which proposes to use IETF QUIC and SRv6 to substitute 5G HTTP/2.0 and GTP-U. Testing results show that new protocols can achieve low latency and high throughput, making them promising candidate for H-SBA.

关键词： holistic service-based architecture SBA 5G-advanced evolution space-air-ground integrated architecture 6G architecture

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Innate lymphocytes:pathogenesis and therapeutic targets of liver diseases and cancer

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Cellular & Molecular Immunology 2021年第1期18卷 57-72页

作者： Yongyan Chen zhigang tian Hefei National Laboratory for Physical Sciences at Microscale the CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Institute of Immunology University of Science and Technology of ChinaHefeiChina

The liver is a lymphoid organ with unique immunological properties,particularly,its predominant innate immune system.The balance between immune tolerance and immune activity is critical to liver physiological functions and is responsible for the sensitivity of this organ to numerous diseases,including hepatotropic virus infection,alcoholic liver disease,nonalcoholic fatty liver disease,autoimmune liver disease,and liver cancer,which are major health problems globally.In the past decade,with the discovery of liver-resident natural killer cells,the importance of innate lymphocytes with tissue residency has gradually become the focus of research.In this review,we address the current knowledge regarding hepatic innate lymphocytes with unique characteristics,including NK cells,ILC1/2/3s,NKT cells,γδ T cells,and MAIT cells,and their potential roles in liver homeostasis maintenance and the progression of liver diseases and cancer.A better understanding of the immunopathogenesis of hepatic innate lymphocytes will be helpful for proposing effective treatments for liver diseases and cancer.

关键词： Innate lymphocyte Liver disease Liver cancer Innate lymphoid cell Innate-like T lymphocyte

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Robust adaptive radar beamforming based on iterative training sample selection using kurtosis of generalized inner product statistics

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Journal of Systems Engineering and Electronics 2024年第1期35卷 24-30页

作者： tian Jing ZHANG Wei School of Information and Electronics Beijing Institute of TechnologyBeijing 100081China National Key Laboratory of Electromagnetic Space Security Chengdu 610036China

In engineering application,there is only one adaptive weights estimated by most of traditional early warning radars for adaptive interference suppression in a pulse reputation interval(PRI).Therefore,if the training samples used to calculate the weight vector does not contain the jamming,then the jamming cannot be removed by adaptive spatial filtering.If the weight vector is constantly updated in the range dimension,the training data may contain target echo signals,resulting in signal cancellation effect.To cope with the situation that the training samples are contaminated by target signal,an iterative training sample selection method based on non-homogeneous detector(NHD)is proposed in this paper for updating the weight vector in entire range dimension.The principle is presented,and the validity is proven by simulation results.

关键词： adaptive radar beamforming training sample selection non-homogeneous detector electronic jamming jamming suppression

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