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Antigenic Peptide Loading into Major Histocompatibility Complex Class I Is Driven by the Substrate N-Terminus

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CCS Chemistry 2022年第3期4卷 910-925页

作者： Mengna Lin Honglin Xu Yi Shi Lin-Tai Da Key Laboratory of System Biomedicine(Ministry of Education) Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghai 200240 Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersShanghai Jiao Tong UniversityShanghai 200030

Major histocompatibility complex class I(MHC-I),a key element of the acquired immune system,plays essential roles in activating CD8^(+)T cells by recognizing intracellular antigens derived from pathogens and cancer.Assembly of MHC-I and antigen peptides is critical for the antigen presentation on the cell surface.However,the structural dynamics of antigenic peptide loading into MHC-I,at atomistic resolution,is still elusive.Here,by constructing a Markov state model(MSM)based onlarge scale all-atommolecular dynamics(MDs)simulations with an aggregated simulation time∼24μs,we reveal the detailed molecular mechanism underlying the peptide-loading dynamics into MHC-I and identify the key intermediates with associated thermodynamic/kinetic properties.Furthermore,we examine how the chaperone tapasin-binding protein related(TAPBPR)participates in promoting the peptide loading,and the results show that TAPBPR,by binding to the F pocket,allosterically modulates the structures of the distant pocket B,resulting in formation of a peptide-receptive conformation ideal for accommodating the incoming peptide N-terminus.This study provides fundamental structural insights for the peptide loading into MHC-I in both chaperone uncatalyzed and catalyzed contexts.

关键词： antigenic peptide MHC-I molecule loading molecular dynamics simulations Markov state model

Environmental Information-Aided Electromagnetic Propagation Testbed for Maritime Communication

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China Communications 2023年第3期20卷 302-315页

作者： Ting Zhou Yuzhen Wang Bilian xu Tianheng xu Xiaoming Tao honglin Hu Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai 201210China School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of ScienceBeijing 100049China School of Microelectronics Shanghai UniversityShanghai 200444China Department of Electronic Engineering Tsinghua UniversityBeijing 100084China

Maritime channel modeling can be affected by some key time-varying environmental factors.The ducting effect is one of the thorniest factors since it causes anomalous propagation enhancement and severe co-channel interference.Moreover,the atmospheric attenuation is much more severe in the ocean environment,resulting in shorter coverage distance and more link outage.In this paper,we propose an environmental information-aided electromagnetic propagation testbed.It is based on complex refractivity estimation and improved parabolic equation propagation model,taking into account both ducting effect and atmospheric attenuation.A large-scale temporal and spatial propagation measurement was conducted with meteorological acquisition.We consider practical path loss and ducting conditions to verify the testbed feasibility in these long-distance radio links.The simulation results are in good agreement with the measured data,which further reveal the basic temporal and spatial distribution of ducting effect at 3.5 GHz band.

关键词： broadband maritime communication maritime channel ducting effect electromagnetic propagation testbed propagation measurement atmospheric attenuation path loss

A dual-specific CRISPR-Cas nanosystem for precision therapeutic editing of liver disorders

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3198-3201页

作者： Xiaojie xu honglin Tang Jjiajing Guo Huhu Xin Yuan Ping College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Department of Medical Oncology Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310058China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou 311121China

Dear Editor,The most common liver disorders,such as acute liver injury and liver fbrosis,can induce acute or chronic inflammatory responses,which in turn gradually promote the development and progres-sion of the disor... 详细信息

关键词： acute liver disorders

CAMSAP3-dependent microtubule dynamics regulates Golgi assembly in epithelial cells

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Journal of Genetics and Genomics 2017年第1期44卷 39-49页

作者： Jing Wang Honglin Xu Yuqiang Jiang Mikiko Takahashi Masatoshi Takeichi Wenxiang Meng State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences No.19A Yuquan RoadBeijing 100049China Faculty of Pharmaceutical Sciences Teikyo Heisei University4-21-2 NakanoNakano-kuTokyo 164-8530Japan RIKEN Center for Developmental Biology 2-2-3 Chuo-kuKobe 650-0047Japan

The Golgi assembly pattern varies among cell types. In fibroblast cells, the Golgi apparatus concentrates around the centrosome that radiates microtubules; whereas in epithelial cells, whose microtubules are mainly noncentrosomal, the Golgi apparatus accumulates around the nucleus independently of centrosome. Little is known about the mechanisms behind such cell wpe-specific Golgi and microtubule organization. Here, we show that the microtubule minus-end binding protein Nezha/CAMSAP3 （calmodulin-regulated spectrin-associated protein 3） plays a role in translocation of Golgi vesicles in epithelial cells. This function of CAMSAP3 is supported by CG-NAP （centrosome and Golgi localized PKN- associated protein） through their binding. Depletion of either one of these proteins similarly induces fragmentation of Golgi membranes. Furthermore, we find that stathmin-dependent microtubule dynamics is graded along the radial axis of ceils with highest activity at the perinuclear region, and inhibition of this gradient disrupts perinuclear distribution of the Golgi apparatus. We propose that the assembly of the Golgi apparatus in epithelial cells is induced by a multi-step process, which includes CAMSAP3-dependent Golgi vesicle clustering and graded microtubule dynamics.

关键词： CG-NAP Nezha/CAMSAP3 Golgi Noncentrosomal micfotubules Stathmin

A deep-learning-based workflow to deal with the defocusing problem in high-throughput experiments

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Bioactive Materials 2022年第5期7卷 218-229页

作者： Yunfan xue honglin Qian xu Li Jing Wang Kefeng Ren Jian Ji MOE Key Laboratory of Macromolecule Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027PR China

The increasing throughput of experiments in biomaterials research makes automatic techniques more and more necessary.Among all the characterization methods,microscopy makes fundamental contributions to biomaterials science where precisely focused images are the basis of related research.Although automatic focusing has been widely applied in all kinds of microscopes,defocused images can still be acquired now and then due to factors including background noises of materials and mechanical errors.Herein,we present a deep-learning-based method for the automatic sorting and reconstruction of defocused cell images.First,the defocusing problem is illustrated on a high-throughput cell microarray.Then,a comprehensive dataset of phase-contrast images captured from varied conditions containing multiple cell types,magnifications,and substrate materials is prepared to establish and test our method.We obtain high accuracy of over 0.993 on the dataset using a simple network architecture that requires less than half of the training time compared with the classical ResNetV2 architecture.Moreover,the subcellular-level reconstruction of heavily defocused cell images is achieved with another architecture.The applicability of the established workflow in practice is finally demonstrated on the high-throughput cell microarray.The intelligent workflow does not require a priori knowledge of focusing algorithms,possessing widespread application value in cell experiments concerning high-throughput or time-lapse imaging.

关键词： High-throughput Deep learning Cell imaging Refocusing Microscopy

Programmable Oligonucleotide-Peptide Complexes:Synthesis and Applications

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Chemical Research in Chinese Universities 2022年第4期38卷 856-865页

作者： xu Min ZHOU Baomei DING Yan DU Shanshan SU Mengke LIU honglin China Light Industry Key Laboratory of Meat Microbial Control and Utilization School of Food and Biological EngineeringHefei University of TechnologyHefei230009P.R.China First Affiliated Hospital of Anhui Medical University Hefei230000P.R.China

Nucleic acids form biological blueprint and polypeptides assist life activities,both of which are indispensable to organisms.Recently,oligonucleotide-peptide complexes(OPCs)have shown great potential in biomedicine,material chemistry and other fields due to their considerable stability and programmability.It remains a huge challenge to stably and facilely constructing OPCs that also limits the wide applications.This tutorial review first summarizes the synthesis strategies of OPC conjugation and the corresponding characteristics in detail,then gives examples of the applications of OPCs,and finally presents a prospective overview on challenges and future perspectives of OPCs.This review aims to help researchers understand the current situation and challenges in this field,thereby furthering interests in developing novel OPC synthesis techniques.

关键词： Oligonucleotide Peptide Complex

Experimental study on the controlling factors of frictional coefficient for lost circulation control and formation damage prevention in deep fractured tight reservoir

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Petroleum 2022年第3期8卷 352-362页

作者： Chengyuan xu honglin Zhang Mingming Zhu Yili Kang Xiaopeng Yan Jingyi Zhang Yingrui Bai State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Southwest Petroleum UniversityChengduChina School of Petroleum Engineering China University of Petroleum(East China)QingdaoChina Changqing Drilling Branch CNPC Chuanqing Drilling Engineering Co.Ltd.Xi'an 710000China

Working fluids loss is a major contributor to low productivity during production process of fractured tight reservoirs.Lost circulation control effect directly related to the tribological behavior between fracture surface and lost circulation materials(LCMs).In this study,the friction coefficient(FC)was investigated using typical clastic rocks and LCMs by considering multiple effect factors divided into external condition and internal condition.The results show that normal load had a relatively high effect on sliding model.A positive correlation was observed between FC and asperities heights.FC decreased induced by particle size degradation of rigid LCMs.Elastic LCMs manifested higher FC compared with rigid LCMs.Under the lubrication condition by working fluid,FC of rigid LCMs was mainly controlled by their surface wettability.FC of organic LCMs is more sensitive to high temperature aging than inorganic LCMs.Fracture plugging experiments show that LCMs optimized based on the research results can effectively improve the efficiency and strength of fracture plugging.

关键词： Fractured tight reservoirs Lost circulation control Friction coefficient Lost circulation materials

Research on cross-chain and interoperability for blockchain system

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The Journal of China Universities of Posts and Telecommunications 2021年第5期28卷 1-17,26页

作者： Li Ming Qiu honglin xu Quanqing Song Wenpeng Liu Baixiang Shanghai Key Laboratory of Intelligent Information Processing Fudan UniversityShanghai 200433China School of Computer Science Fudan UniversityShanghai 200433China China Electronics Standardization Institute Beijing 100007China Ant Group Hangzhou 310063China

At present, there is an urgent need for blockchain interoperability technology to realize interconnection between various blockchains, data communication and value transfer between blockchains, so as to break the ‘value silo’ phenomenon of each blockchain. Firstly, it lists what people understand about the concept of interoperability. Secondly, it gives the key technical issues of cross-chain, including cross-chain mechanism, interoperability, eventual consistency, and universality. Then, the implementation of each cross-chain key technology is analyzed, including Hash-locking, two-way peg, notary schemes, relay chain scheme, cross-chain protocol, and global identity system. Immediately after that, five typical cross-chain systems are introduced and comparative analysis is made. In addition, two examples of cross-chain programmability and their analysis are given. Finally, the current state of cross-chain technology is summarized from two aspects: key technology implementation and cross-chain application enforcement. The cross-chain technology as a whole has formed a centralized fixed mechanism, as well as a trend of modular design, and some of the solutions to mature applications were established in the relevant standards organizations, and the cross-chain technology architecture tends to be unified, which is expected to accelerate the evolution of the open cross-chain network that supports the real needs of the interconnection of all chains.

关键词： blockchain distributed ledger technology cross-chain interoperability Hash-locking notary relay multi-chain

Design,synthesis and SAR study of 2-aminopyridine derivatives as potent and selective JAK2 inhibitors

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Chinese Chemical Letters 2022年第6期33卷 2969-2974页

作者： Dandan Liu Huan Ge Fangling xu Yufang xu Wenjun Liu honglin Li Lili Zhu Yanyan Diao Zhenjiang Zhao Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghai 200237China Research and Development Department Jiangzhong Pharmaceutical Co.Ltd.Nanchang 330096China

The abnormal activation of JAK2 kinase is closely related to the occurrence and progression of myeloproliferative neoplasms(MPNs).At present,there is still an obvious unmet medical need for selective JAK2 inhibitors in clinic.In this paper,a class of 2-aminopyridine derivatives as potent and selective JAK2 inhibitors was obtained by combining drug design,synthesis and structure-activity relationship studies based on the previously identified lead Crizotinib.Among them,21 b exhibited high inhibitory activity against JAK2 with an IC_(50)of 9 nmol/L,moreover,it showed 276-and 184-fold selectivity over JAK1 and JAK3,respectively.Besides,21 b had a significant antiproliferative activity against HEL cells,and also inhibited the phosphorylation of JAK2 and its down-stream signaling pathway.These results indicated that2-aminopyridine compound 21 b had the potential to be developed as a selective JAK2 inhibitor for further study.

关键词： JAK2 Selectivity Inhibitors Cancer Structure-activity relationships