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A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells(TCR-T cells)against hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2215-2230页

作者： Wei Zhu Zhiming zhang Jinzhang Chen Xiaolan Chen Lei Huang xiaoyong zhang Xuan Huang Na Ma Weikang Xu Xuan Yi Xinyu Lu Xin Fu Siwei Li Guoheng Mo Yiyue Wang Guosheng Yuan Mengya Zang Qi Li Xiaotao Jiang Yajing He Sha Wu Yukai He Yongyin Li Jinlin Hou State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Institute of Cellular Medicine Newcastle University Medical SchoolNewcastleUK Department of Pathology The First People’s Hospital of FoshanFoshanChina Dermatology Hospital Southern Medical UniversityGuangzhouChina Department of Immunology School of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhouChina Key Laboratory of Proteomics of Guangdong Province Demonstration Center for Experimental Education of Basic Medical Sciences of ChinaGuangzhouChina Medical College of Georgia Augusta University112015th StreetAugustaGAUSA

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma(HCC)are urgently needed.The common cytokine receptorγchain(γc)family cytokines such as IL-2,IL-7,IL-15 and IL-21 play fundamental roles in T cell development,differentiation and effector phases.This study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell therapy.The antitumor function of AFP-specific T cell receptor-engineered T cells(TCR-T)was augmented by exogenous IL-21 in vitro and in vivo.IL-21 enhanced proliferation capacity,promoted memory differentiation,downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation.A novel engineered IL-21 receptor was established,and TCR-T armed with the novel engineered IL-21 receptors(IL-21R-TCR-T)showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ligand.IL-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in vivo.IL-21R-TCR-T exhibited a less differentiated,exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen stimulation.The novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic utilization.The novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

关键词： hepatocellular TCR utilize

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Investigation of the seismic behavior of grouted sandy gravel foundations using shaking table tests

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Frontiers of Structural and Civil Engineering 2022年第9期16卷 1196-1211页

作者： Tiancheng WANG Yu LIANG xiaoyong zhang Zhihuan RUAN Guoxiong MEI Key Laboratory of Disaster Prevention and Structural Safety of Ministry of Education College of Civil Engineering and ArchitectureGuangxi UniversityNanning 530004China Ocean College Zhejiang UniversityZhoushan 316021China

Sandy gravel foundations exhibit non-linear dynamic behavior when subjected to strong ground motions,which can have amplification effects on superstructures and can reveal insufficient lateral resistance of foundations.Grouting methods can be used to improve the seismic performance of natural sandy gravel foundations.The strength and stiffness of grouted sandy gravel foundations are different from those of natural foundations,which have unknown earthquake resistance.Few studies have investigated the seismic behavior of sandy gravel foundations before and after grouting.In this study,two shaking table tests were performed to evaluate the effect of grouting reinforcement on seismic performance.The natural frequency,acceleration amplification effect,lateral displacement,and vertical settlement of the non-grouted and grouted sandy gravel foundations were measured and compared.Additionally,the dynamic stress-strain relationships of the two foundations were obtained by a linear inversion method to evaluate the seismic energy dissipation.The test results indicated that the acceleration amplification,lateral displacement amplitude,and vertical settlement of the grouted sandy gravel foundation were lower than that of the non-grouted foundation under low-intensity earthquakes.However,a contrasting result was observed under high-intensity earthquakes.This demonstrated that different grouting reinforcement strategies are required for different sandy gravel foundations.In addition,the dynamic stress-strain relationship of the two foundations exhibited two different energy dissipation mechanisms.The results provide insights relating to the development of foundations for relevant engineering sites and to the dynamic behavior of grouted foundations prior to investigating soil-structure interaction problems.

关键词： sandy gravel foundation grouting-treated reinforcement shaking table test seismic behavior

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Noncanonical NF-κB Signaling Pathway in Liver Diseases

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 81-89页

作者： Qianhui Chen Xinyu Lu xiaoyong zhang State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina Hepatology Unit Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdongChina

The noncanonical NF-κB signaling pathway is an important branch of NF-κB signaling.It is involved in regulating multiple important biological processes,including inflammation and host immune response.A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase(NIK),which activates the downstream kinase IKKαto process p100 to p52,thereby forming the RelB/p52 heterodimer to initiate the expression of target genes.Currently,many specific inhibitors and monoclonal antibodies targeting or triggering this pathway are being developed and tested for various diseases,including cancers,autoimmune diseases,and virus infection.Given that aberrant activation of the noncanonical NF-κB pathway is frequently observed in various liver diseases,targeting this pathway may be a promising therapeutic strategy to alleviate liver inflammation.Moreover,activation of this pathway may contribute to the antiviral immune response and promote the clearance of persistent hepatotropic virus infection.Here,we review the role of the noncanonical NF-κB pathway in the occurrence and development of different liver diseases,and discuss the potency and application of modulating the noncanonical NF-κB pathway for treatment of these liver diseases.

关键词： Noncanonical NF-κB pathway NF-κB-inducing kinase Liver inflammation Immune responses Liver diseases

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Targeting cIAPs,a New Option for Functional Cure of Chronic Hepatitis B Infection?

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Virologica Sinica 2018年第5期33卷 459-461页

作者： Hongyan Liu Jinlin Hou xiaoyong zhang State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious Diseases Nanfang HospitalSouthern Medical University

Hepatitis B virus (HBV)infection causes a wide spectrum of liver diseases in more than 240million people worldwide (Ott et al.2012).Patients with chronic hepatitis B (CHB)may progress to HBV-related end-stage liver di... 详细信息

关键词： Chronic Hepatitis B Infection cIAPs

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基于自校准机制的时空采样图卷积行为识别模型

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工程科学学报 2024年第3期46卷 480-490页

作者：曹毅吴伟官张小勇夏宇高清源江南大学机械工程学院无锡214122 江南大学江苏省食品制造装备重点实验室无锡214122

针对现有行为识别算法忽视时空信息上下文的依赖关系和缺乏多层次感受野的特征提取问题,本文提出一种基于自校准机制的时空采样图卷积网络行为识别模型.首先,介绍ST-GCN和3D-GCN、Transformer和自注意力机制的工作原理,并分析了3D-GCN和... 详细信息

针对现有行为识别算法忽视时空信息上下文的依赖关系和缺乏多层次感受野的特征提取问题,本文提出一种基于自校准机制的时空采样图卷积网络行为识别模型.首先,介绍ST-GCN和3D-GCN、Transformer和自注意力机制的工作原理,并分析了3D-GCN和Transformer不能有效进行时空上下文建模;其次,为有效进行时空上下文建模而提出了一种时空采样图卷积网络,其以时序连续多帧作为时空采样将全局动作分为多个子动作,通过非局部网络计算单一节点与采样频率帧内所有节点的相关性来建立局部跨时空依赖关系,并通过结合非局部网络和时域卷积计算单个采样子动作与全局子动作的相关性以此来建立全局跨时空依赖关系;然后,为了有效地增强多层次的感受野来捕获更具判别力的时域特征,提出了一种时域自校准卷积网络在两个不同的尺度时空中分别进行卷积并特征融合:一种是原始比例尺度的时空,另一种是使用下采样具有较小比例尺度的潜在时空;再者,结合时空采样图卷积网络和时域自校准网络构建基于自校准机制的时空采样图卷积网络行为识别模型,在多流网络下进行端到端的训练.最后,基于NTU-RGB+D和NTU-RGB+D120骨架动作数据集开展了骨架行为识别的相关实验研究,研究结果表明该行为识别模型具有高效的时空特征提取能力以及优秀的性能.

关键词：行为识别时空采样图卷积时空上下文时域自校准多流网络

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Revealing the Distribution of Aggregation-Induced Emission Nanoparticles via Dual-Modality Imaging with Fluorescence and Mass Spectrometry

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Research 2021年第1期2021卷 826-834页

作者： Liucheng Mao Yuming Jiang Hui Ouyang Yulin Feng Ruoxin Li xiaoyong zhang Zongxiu Nie Yen Wei The Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology(Ministry of Education) Department of ChemistryTsinghua UniversityBeijing 100084China Beijing National Laboratory for Molecular Sciences Key Laboratory of Analytical Chemistry for Living BiosystemsInstitute of ChemistryChinese Academy of SciencesBeijing 100190China State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment Jiangxi University of Traditional Chinese MedicineNanchang 330006China Department of Chemistry Nanchang University999 Xuefu AvenueNanchang 330031China

Aggregation-induced emission nanoparticles(AIE NPs)are widely used in the biomedical field.However,understanding the biological process of AIE NPs via fluorescence imaging is challenging because of the strong background and poor penetration depth.Herein,we present a novel dual-modality imaging strategy that combines fluorescence imaging and label-free laser desorption/ionization mass spectrometry imaging(LDI MSI)to map and quantify the biodistribution of AIE NPs(TPAFN-F127 NPs)by monitoring the intrinsic photoluminescence and mass spectrometry signal of the AIE molecule.We discovered that TPAFN-F127 NPs were predominantly distributed in the liver and spleen,and most gradually excreted from the body after 5 days.The accumulation and retention of TPAFN-F127 NPs in tumor sites were also confirmed in a tumor-bearing mouse model.As a proof of concept,the suborgan distribution of TPAFN-F127 NPs in the spleen was visualized by LDI MSI,and the results revealed that TPAFN-F127 NPs were mainly distributed in the red pulp of the spleen with extremely high concentrations within the marginal zone.The in vivo toxicity test demonstrated that TPAFN-F127 NPs are nontoxic for a long-term exposure.This dual-modality imaging strategy provides some insights into the fine distribution of AIE NPs and might also be extended to other polymeric NPs to evaluate their distribution and drug release behaviors in vivo.

关键词： spleen distribution retention

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Vertical characteristics and source identification of PM_(10) in Tianjin

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Journal of Environmental Sciences 2012年第1期24卷 112-115页

作者： Zhimei Xiao Jianhui Wu Suqin Han Yufen zhang Hong Xu xiaoyong zhang Guoliang Shi Yinchang Feng State Environmental Protection Key Laboratory of Urban Ambient Air Particulate Matter Pollution Prevention and Control College of Environmental Science and Engineering Nankai University Tianjin 300071 China Tianjin Meteorological Administration Tianjin 300071 China

Ambient PM 10 （particulate matter with a diameter less than 10μm） concentrations were measured on a 255 meter tower in Tianjin,China.The samples were collected at four vertical levels （10,40,120 and 220 m）.Vertical characteristics for PM 10 samples were studied.The results showed that the concentrations of PM 10 and constituent species had a negative correlation with the sampling height.The highest concentrations of PM 10 and species were obtained at the 10 m level,and the lowest concentrations were measured at the 220 m level.For the fractions of species to total mass,SO 4 2- and NO 3- had higher values （fraction） at greater height;while Ca had a higher fraction at lower height.Possible source categories for the PM 10 ambient dataset were identified by the principal component analysis method.The possible source categories included crustal dust,vehicles,cement dust,and incineration as well as secondary sulfate and nitrate sources.Analysis of meteorological factors on PM 10 concentrations indicated that wind speed and inversion may be the main factors contributing to different concentrations of PM 10 at different heights.

关键词： vertical characteristic PM 10 sources principal component analysis

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Phylogenetic diversity and bioactivity of culturable deepsea-derived fungi from Okinawa Trough

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Journal of Oceanology and Limnology 2021年第3期39卷 892-902页

作者： xiaoyong zhang Yiyang LI Zonghe YU Xiao LIANG Shuhua QI Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation College of Marine SciencesSouth China Agricultural UniversityGuangzhou 510642China Key Laboratory of Tropical Marine Bio-resources and Ecology/RNAM Center for Marine Microbiology/Guangdong Key Laboratory of Marine Material Medical South China sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) Guangzhou 511458China

Deep-sea sediments are now recognized as a home for rich and largely microbial community.Recently,it has been believed in an increasing number of studies that bacteria could be abundant in deepsea sediments of many types;however,fungi in deep-sea sediments remain relatively unknown.The phylogenetic diversity and bioactivity of culturable deep-sea-derived fungi from Okinawa Trough sediments were investigated in traditional method combined with fungal identification of molecular biology in this study.A total of 76 isolates belonged to 15 fungal taxa were recovered in a harsh condition of low nutrient and low temperature,indicating that the fungal communities in deep-sea sediments from Okinawa Trough were relatively abundant and diversified.Aspergillus,Cladosporium,and Penicillium were the dominant fungal genera,while Mycosphaerella,Purpureocillium,and Schizophyllum were relatively rare in the deep-sea sediments from Okinawa Trough.Among the six genera recovered,Mycosphaerella was firstly recovered from deep-sea sediments in this study.Moreover,about 75%of the extracts from the 15 fungal representative isolates displayed distinct bioactivity against at least one indicator bacterium or marine macrofouler,emphasizing the potentials of these deep-sea-derived fungi from Okinawa Trough as producers of bioactive metabolites.Notably,isolates Cladosporium oxysporum SCSIO z001 and Penicillium citrinum SCSIO z049 displayed a wide spectrum of bioactivities,isolates Cladosporium cladosporioides SCSIO z015,Cladosporium sphaerospermum SCSIO z030,and Penicillium verruculosum SCSIO z007 exhibited a strong anti-bacterial-growth activity,and isolate Penicillium chrysogenum SCSIO z062 displayed a strong anti-larval-settlement activity.These results suggest that these isolates deserved further study as potential sources of novel bioactive metabolites.

关键词： deep-sea-derived fungi phylogenetic diversity bioactivity Okinawa Trough hydrothermal vents

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基于常时微动的单结构面危岩体损伤识别实验

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工程科学学报 2024年第4期46卷 589-599页

作者：吴志祥谢谟文张晓勇张磊王建慧陈新北京科技大学土木与资源工程学院北京100083 北京市水科学技术研究院北京100048

危岩体的动力学参数能够表征危岩体与基岩之间结构面的损伤,实际工程中人工激励危岩体较为困难,因此,如何根据场地常时微动特征识别危岩体动力学参数仍是亟需解决的问题.本文将常时微动激励下的危岩体振动问题归为欠阻尼条件单自由度结... 详细信息

危岩体的动力学参数能够表征危岩体与基岩之间结构面的损伤,实际工程中人工激励危岩体较为困难,因此,如何根据场地常时微动特征识别危岩体动力学参数仍是亟需解决的问题.本文将常时微动激励下的危岩体振动问题归为欠阻尼条件单自由度结构受迫振动问题,将危岩体频谱幅值与基岩频谱幅值之比作为相对幅值谱,通过相对幅值K>1的最大峰值点对应的频率得到危岩体的一阶固有频率.以宏观裂缝控制型危岩体(悬臂式和错断式危岩体)及微观裂隙控制型危岩体(滑移式危岩体)为研究对象,通过模型实验验证了常时微动条件下测量危岩体一阶固有频率的可行性,通过切割裂缝模拟悬臂式危岩体和错断式危岩体结构面损伤弱化,发现随着损伤程度加剧,一阶固有频率呈明显下降趋势;通过水溶胶冻结融化模拟滑移式危岩体结构面损伤弱化,随着损伤程度加剧,其一阶固有频率无明显变化,高频段的重心频率发生明显变化.实验结果表明对于宏观裂缝控制型危岩体结构面损伤可通过危岩体的一阶固有频率进行识别,对于微观裂隙控制型危岩体结构面损伤可通过危岩体高频段的重心频率变化进行识别,将两者综合起来对危岩体结构面损伤进行识别将更加有效.

关键词：单结构面危岩体损伤识别常时微动相对幅值动力特征

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Analysis of crystallographic orientation and morphology of microstructure during hot working for an alpha/beta titanium alloy

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Journal of Materials Science & Technology 2020年第24期59卷 1-13页

作者： Jianwei Xu Weidong Zeng Dadi Zhou Wei Chen Shengtong He xiaoyong zhang State Key Laboratory of Solidification Processing School of Materials Science and EngineeringNorthwestern Polytechnical UniversityXi’an710072China Defense Technoloies Innovation Center of Precision Forging and Ring Rolling School of Materials Science and EngineeringNorthwestern Polytechnical UniversityXi’an710072China State Key Laboratory of Powder Metallurgy Central South UniversityChangsha410083China

This work focuses on analysis of microstructure morphology and crystallographic orientation for Ti-17 alloy during hot working.The results show that alpha phase and beta phase influence each other and there is a coordinate deformation between them.The non-uniform deformation is observed under small deformation conditions.The observing area can be divided into small deformation zone(area L)and large deformation zone(area H).Both alpha and beta phases remain the initial morphology,and they have better capability of coordinate deformation in area L,while coordinate capability is weak in area H in which alpha phase is globularized.Correspondingly,the Burgers orientation relations are well preserved in area L,but the orientation relations are more or less destroyed in area H.Dynamic recovery is the main mechanism of beta phase evolution when height reduction is lower.By contrast,the continuous dynamic recrystallization(CDRX)of beta phase gradually dominates the deformation pattern as the deformation increases.An uniformly globularized alpha structure is obtained under large deformation condition.The unsynchronized rotation of alpha phase aroundpole occurs during deformation,which leads to the uniform crystal structure inside the same alpha lamellae.This process is an important step of globularization of the lamellar structure.

关键词： Ti-17 alloy Hot working Microstructure evolution Crystallographic orientation

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