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Neutrophil-sourced TNF in cancer:deciphering an intricate orchestrator of immunosuppressive communication in the tumor microenvironment

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3558-3560页

作者： Xinyuan Zhao Ye Lu Li Cui Stomatological Hospital School of StomatologySouthern Medical UniversityGuangzhou 510280 GuangdongChina Division of Oral Biology and Medicine School of DentistryUniversity of CaliforniaLos AngelesLos Angeles 90095 CAUSA

In a recent Cancer Discovery publication,Bianchi et al.unveil a crucial mechanism driving therapeutic resistance in pancreatic ductal adenocarcinoma(PDAC),orchestrated by cell-autonomous Cxcl1 and TNF from polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs).This insight provides fresh perspectives for surmounting such resistance in PDAC.1 PDAC represents a highly aggressive malignancy exhibiting substantial therapeutic resistance,attributable to factors such as intractable genomic aberrations,immunosuppression mediated by myeloid cells,and pro-inflammatory activation of cancerassociated fibroblasts.

关键词： cancer Cancer

PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c-Myc-mediated positive feedback loop

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Cancer Communications 2022年第10期42卷 987-1007页

作者： Xinyuan Zhao Dalong Shu Wenjuan Sun Shanshan Si Wei Ran Bing Guo Li Cui Department of Endodontics Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280P.R.China Department of Oral and Maxillofacial Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080P.R.China Department of Stomatology The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510630P.R.China Department of Oral Emergency Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280P.R.China Department of Dentistry The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080P.R.China Department of Oral and Maxillofacial Surgery Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280P.R.China Division of Oral Biology and Medicine School of DentistryUniversity of CaliforniaLos AngelesLos AngelesCalifornia 90095United States

Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molecular events regulating HNSCC tumorigenesis remain poorly understood.Therefore,uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC.In this study,we aimed to explore the role of pleckstrin-2(PLEK2)in regulating HNSCC tumorigenesis.Methods:The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort.In vitro and in vivo experiments,including cell proliferation,colony formation,Matrigel invasion,tumor sphere formation,ALDEFLUOR,Western blotting assays and xenograft mouse models,were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells.The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation,cycloheximide chase analysis,ubiquitination assays,chromatin immunoprecipitation-quantitative polymerase chain reaction,luciferase reporter assays and rescue experiments.Results:The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues,and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance.Additionally,PLEK2 was important for maintaining the proliferation,invasion,epithelial-mesenchymal transition,cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells.Mechanistically,PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7(FBXW7)with c-Myc,thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc.Moreover,the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells.c-M

关键词： c-Myc cancer stemness FBXW7 HNSCC PLEK2 positive feedback loop tumorigenesis ubiquitination-mediated degradation

Unified convergence analysis of a second-order method of multipliers for nonlinear conic programming

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Science China Mathematics 2022年第11期65卷 2397-2422页

作者： Liang Chen Junyuan Zhu Xinyuan Zhao School of Mathematics Hunan UniversityChangsha 410082China Hunan Provincial Key Laboratory of Intelligent Information Processing and Applied Mathematics Changsha 410082China School of Mathematics Beijing University of TechnologyBeijing 100124China

In this paper,we accomplish the unified convergence analysis of a second-order method of multipliers(i.e.,a second-order augmented Lagrangian method)for solving the conventional nonlinear conic optimization problems.Specifically,the algorithm that we investigate incorporates a specially designed nonsmooth(generalized)Newton step to furnish a second-order update rule for the multipliers.We first show in a unified fashion that under a few abstract assumptions,the proposed method is locally convergent and possesses a(nonasymptotic)superlinear convergence rate,even though the penalty parameter is fixed and/or the strict complementarity fails.Subsequently,we demonstrate that for the three typical scenarios,i.e.,the classic nonlinear programming,the nonlinear second-order cone programming and the nonlinear semidefinite programming,these abstract assumptions are nothing but exactly the implications of the iconic sufficient conditions that are assumed for establishing the Q-linear convergence rates of the method of multipliers without assuming the strict complementarity.

关键词： second-order method of multipliers augmented Lagrangian method convergence rate generalized Newton method second-order cone programming semidefinite programming

Global characterization of modifications to the charge isomers of IgG antibody

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Journal of Pharmaceutical Analysis 2022年第1期12卷 156-163页

作者： Xinling Cui Wei Mi Zhishang Hu Xiaoyu Li Bo Meng Xinyuan Zhao Xiaohong Qian Tao Zhu Wantao Ying State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingChina National Institute of Metrology Center for Advanced Measurement ScienceBeijingChina National Institute of Metrology Chemical Metrology&Analytical Science DivisionBeijingChina CanSino Bio Corporation Tianjin Key Laboratory of Recombinant Bacterial Recombination and Bacterial Vaccines TianjinChina

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

关键词： Antibody Charge isomers Mass spectrometry Posttranslational modification Glycopeptide

Building Indoor Dangerous Behavior Recognition Based on LSTM-GCN with Attention Mechanism

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Computer Modeling in Engineering & Sciences 2023年第11期137卷 1773-1788页

作者： Qingyue zhao Qiaoyu Gu Zhijun Gao Shipian Shao xinyuan Zhang School of Management Shenyang Jianzhu UniversityShenyang110168China School of Information and Communication Engineering North University of ChinaTaiyuan030051China School of Information and Control Engineering Shenyang Jianzhu UniversityShenyang110168China

Building indoor dangerous behavior recognition is a specific application in the field of abnormal human recognition.A human dangerous behavior recognition method based on LSTM-GCN with attention mechanism(GLA)model was proposed aiming at the problem that the existing human skeleton-based action recognition methods cannot fully extract the temporal and spatial features.The network connects GCN and LSTMnetwork in series,and inputs the skeleton sequence extracted by GCN that contains spatial information into the LSTM layer for time sequence feature extraction,which fully excavates the temporal and spatial features of the skeleton sequence.Finally,an attention layer is designed to enhance the features of key bone points,and Softmax is used to classify and identify dangerous behaviors.The dangerous behavior datasets are derived from NTU-RGB+D and Kinetics data sets.Experimental results show that the proposed method can effectively identify some dangerous behaviors in the building,and its accuracy is higher than those of other similar methods.

关键词： Human skeleton building indoor dangerous behaviors recognition graph convolution network long short term memory network attention mechanism

Growth substrates alter aboveground plant microbial and metabolic properties thereby influencing insect herbivore performance

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Science China(Life Sciences) 2023年第8期66卷 1728-1741页

作者： Jun Yuan Tao Wen Shengdie Yang Chao Zhang Mengli zhao Guoqing Niu Penghao Xie Xiaoyu Liu Xinyuan Zhao Qirong Shen T.Martijn Bezemer The Key Laboratory of Plant Immunity Jiangsu Provincial Key Lab for Organic Solid Waste UtilizationJiangsu Collaborative Innovation Center for Solid Organic WastesEducational Ministry Engineering Center of Resource-saving fertilizersNanjing Agricultural UniversityNanjing 210095China Institute of Biology Above-Belowground Interactions groupLeiden UniversityP.O.Box 95052300 RA LeidenThe Netherlands Department of Terrestrial Ecology Netherlands Institute of EcologyP.O.Box 506700 AB WageningenThe Netherlands

The gut microbiome of plant-eaters is affected by the food they eat,but it is currently unclear how the plant metabolome and microbiome are influenced by the substrate the plant grows in and how this subsequently impacts the feeding behavior and gut microbiomes of insect herbivores.Here,we use Plutella xylostella caterpillars and show that the larvae prefer leaves of cabbage plants growing in a vermiculite substrate to those from plants growing in conventional soil systems.From a plant metabolomics analysis,we identified 20 plant metabolites that were related to caterpillar feeding performance.In a bioassay,the effects of these plant metabolites on insects'feeding were tested.Nitrate and compounds enriched with leaves of soilless cultivation promoted the feeding of insects,while compounds enriched with leaves of plants growing in natural soil decreased feeding.Several microbial groups(e.g.,Sporolactobacillus,Haliangium)detected inside the plant correlated with caterpillar feeding performance and other microbial groups,such as Ramlibacter and Methylophilus,correlated with the gut microbiome.Our results highlight the role of growth substrates on the food metabolome and microbiome and on the feeding performance and the gut microbiome of plant feeders.It illustrates how belowground factors can influence the aboveground properties of plant-animal systems,which has important implications for plant growth and pest control.

关键词： cultivation pattern gut microbiome herbivory leaf microbiome leaf metabolome

Protein post-translational modification by lysine succinylation:Biochemistry,biological implications,and therapeutic opportunities

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Genes & Diseases 2023年第4期10卷 1242-1262页

作者： Guo zhao Junfeng Zhen xinyuan Liu Jinshuai Guo Duanduan Li Jianping Xie Longxiang Xie Institute of Biomedical Informatics Bioinformatics CenterHenan Provincial Engineering Center for Tumor Molecular MedicineSchool of Basic Medical SciencesHenan UniversityKaifengHenan 475004China State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area Key Laboratory of Eco-Environments in Three Gorges Reservoir RegionInstitute of Modern BiopharmaceuticalsMinistry of EducationSchool of Life SciencesSouthwest UniversityChongqing 400715China

Lysine succinylation(Ksuc)is a novel protein post-translational modification(PTM)wherein a succinyl group modifies a lysine residue.Ksuc leads to significant chemical and struc-tural changes to the modified protein.Recent studies have shown that Ksuc might play an important role in organism physiology and some pathophysiological processes,such as tumor-igenesis and metabolic diseases.To provide an understanding of the molecular mechanism and functions of Ksuc in different organisms,we reviewed the current literature about Ksuc,mainly summarizing the research advances in eukaryotes and prokaryotes based on both traditional study methods and site prediction tools.We also discussed inhibitors or activators associated with Ksuc that may contribute to proteomic studies and could be useful in future clinical prac-tice.A deeper understanding of Ksuc may shed new light on life science at the protein level and could lead to novel therapeutic strategies for various diseases.

关键词： Disease Eukaryotes Lysine succinylation Physiology Prokaryotes Protein post-translational modification

Cut-Vertex Independent Connectivity Maintaining Approach for Wireless Sensor and Actor Networks

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China Communications 2015年第S2期12卷 19-28页

作者： zhao xinyuan WANG Neng School of Computer Science and Technology Xinjiang Normal University Computer Science and Technology Department East China Normal University

In recent years, the development of wireless sensor networks(WSNs) has risen to a great interest in the Wireless Sensor and Actor Networks(WSANs), which consist of sensors and actors. Because actors have to collaborate with each other to perform tasks, it is vital to maintain the connectivity of actor network in WSANs. This paper proposes a 1-hop based cut-vertex independent connectivity maintaining approach(CIMA) to restore the broken connectivity caused by single actor failure. A balance is achieved in restoration overheads between all actors and individuals by bounding the maximum moveable distance of actor and determining a local optimal repair plan. The effectiveness of CIMA has been validated through simulation experiments.

关键词： actor failure connectivity restoration coordination cascaded

A systematic review of steel bridge deck pavement in China

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Journal of Road Engineering 2023年第1期3卷 1-15页

作者： Leilei Chen Xinyuan Zhao Zhendong Qian Jiaqi Li Intelligent Transportation System Research Center Southeast UniversityNanjing 211189China

As an important part of steel bridge deck,the engineering quality and service condition of steel bridge deck pavement(SBDP)directly affects the capacity and operational efficiency of the bridge.This paper reviews the history of the development of SBDP in China over the past 20 years from the exploration stage,rapid development stage and prosperity stage.The development and application of SBDP at different stages are discussed in terms of materials,structure,design,performance evaluation,maintenance and rehabilitation,respectively.The advantages and disadvantages of different pavement materials and structures,and the application of different research methods are summarized.The review shows that the improvement of pavement materials and structures and the development of new materials should be further studied on the multi-scale to enhance the durability of pavement materials,so as to extend the service life of pavements.The design method of SBDP related to the synergistic effect of vehicle,pavement and bridge should be established,and the design concept and method standard of rigid base pavement structure should be improved and formulate a complete design standard.In addition,multi-disease intelligent identification system and equipment should be studied to track the entire course of disease development in real time.And it is necessary to develop appropriate algorithms to select and classify the complex data of disease and maintenance history.

关键词： Steel bridge deck pavement Pavement material and structure Pavement design Service performance Maintenance and rehabilitation