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Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis

Signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang Xueping Wang Kenneth K.W.To Caimei Cui Min Luo Shaocong Wu Lamei Huang Kai Fu can pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu Fu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(Shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis.It remains elusive how CTCs evade immune surveillance and elimination by immune cells.In this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients.Moreover,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in vivo.Mechanistically,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response.Together,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关键词： CD45 metastasis prevention

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Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang can pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer therapy.They induce long-term tumor regression and overall survival benefit in many types of cancer.With the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for immunotherapy.Small molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively investigated.Monotherapy of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance.Here,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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Integrative transcriptome analysis identifies MYBL2 as a poor prognosis marker for osteosarcoma and a pan-cancer marker of immune infiltration

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Genes & Diseases 2024年第3期11卷 351-367页

作者： Xinzhu Quiu Hongbo He Hao Zeng Xiaopeng Tongg can Zhang Yupeng Liu Zhan Liao Qing Liu Department of Orthopaedics Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalChangshaHunan 410008China Department of Sports Medicine Research Center of Sports MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China

MYBL2(MYB proto-oncogene like 2)is an emerging prognostic marker for malignant tumors,and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated.We constructed a transcription factor activity profile of os-teosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression Omnibus.Subsequently,we calcu-lated the extent of MYBL2 activation in malignant proliferative osteoblasts.We also explored the association between MYBL2 and chemotherapy resistance in osteosarcoma.Furthermore,we systematically correlated MYBL2 with immunological signatures in the tumor microenviron-ment in pan-cancer,including immune cell infiltration,immune checkpoints,and tumor immu-notherapy prognosis.Finally,we developed and validated a risk score(MRGS),derived an osteosarcoma risk score nomogram based on MRGS,and tested its ability to predict prognosis.MYBL2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways.MYBL2 expres-sion positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell lines.pan-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived sup-pressor cells,Th2 cell infiltration,CD276,RELT gene expression,and tumor mutation burden.

关键词： Biomarker Immunecheckpoint MYBL2 Osteosarcoma pan-cancer

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Microbial Fertilizer: A Sustainable Strategy for Medicinal Plants Production

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Phyton-International Journal of Experimental Botany 2024年第6期93卷 1221-1236页

作者： Chuang Liu Jing Xie Hao Liu can Zhong Gen pan Shuihan Zhang Jian Jin Hunan Academy of Chinese Medicine Hunan University of Chinese MedicineChangsha410036China Institute of Chinese Medicine Resources Hunan Academy of Chinese MedicineChangsha410013China

Medicinal plants have aroused considerable interest as an alternative to chemical drugs due to the beneﬁcial effects of their active secondary metabolites.However,the extensive use of chemical fertilizers and pesticides in pursuit of yield has caused serious pollution to the environment,which is not conducive to sustainable devel-opment in theﬁeld of medicinal plants.Microbial fertilizers are a type of“green fertilizer”containing speciﬁc microorganisms that can improve the soil microbial structure,enhance plant resistance to biological and abiotic stresses,and increase the yield of medicinal plants.The root exudates of medicinal plants attract different micro-organisms to the rhizosphere,which then migrate further to the plant tissues.These microbes can increase the levels of soil nutrients,and improve the physical and chemical properties of soil through nitrogenﬁxation,and phosphorus and potassium solubilization.In addition,soil microbes can promote the synthesis of hormones that increase plant growth and the accumulation of active compounds,eventually improving the quality of med-icinal plants.In 2022,the total value of the global microbial fertilizer market was$4.6 billion and is estimated to reach$10.36 billion by 2030.In this review,we have summarized the types of microbial fertilizers,the coloniza-tion and migration of microorganisms to plant tissues,and the beneﬁcial effects of microbial fertilizers.In addi-tion,the prospects of developing microbial fertilizers and their application for medicinal plants have also been discussed.It aims to provide a reference for the rational application of microbial fertilizers in theﬁeld of med-icinal plants and the green and sustainable development of medicinal plant resources.

关键词： Microbial fertilizers market overview rhizosphere microorganisms endophytic bacteria beneﬁcial effects

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An Ultra-Compact Broadband Polarizing Beam Splitter Utilizing Hybrid Plasmonic Waveguide

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China Communications 2023年第6期20卷 49-59页

作者： Li Zhang Jiaqi Liu can pan Yatao Yang College of Electronics and Information Engineering Shenzhen UniversityShenzhen 518000China

Polarizing beam splitter has rather significant applications in polarization diversity circuits and polarization multiplexing systems.In this paper,we present an asymmetric polarizing beam splitter utilizing hybrid plasmonic waveguide.The special hybrid structure with a hybrid waveguide and a dielectric waveguide can limit the energy of TE and TM modes to a different layer.Therefore,we can achieve beam splitting by adjusting the corresponding parameters of the two waveguides.First,we studied the influences of different structure parameters on the real part of the effective mode refractive index of the two waveguides,and obtained a set of parameters that satisfy the condition of strong coupling of TM mode and weak coupling of TE mode.Then,the performance of our proposed polarizing beam splitter is evaluated numerically.The length of the coupling section is only 4.1μm,and the propagation loss of TM and TE modes is 0.0025 d B/μm and 0.0031 d B/μm respectively.Additionally,the extinction ratios of TM and TE modes are 10.62 d B and 12.55 d B,respectively.Particularly,the proposed device has excellent wavelength insensitivity.Over the entire C-band,the fluctuation of the whole normalized output power is less than 0.03.In short,our proposed asymmetric polarizing beam splitter features ultra-compactness,low propagation loss,and broad bandwidth,which would provide promising applications in polarization multiplexing system and polarization diversity circuits relevant to optical interconnection.

关键词： polarizing beam splitter hybrid plasmonic waveguide directional coupler polarization multiplexing systems

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A module based modeling framework for estimating lunar dust deposition due to human activities

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Chinese Journal of Aeronautics 2024年第2期37卷 501-510页

作者： Chunjian pan College of Automation Engineering Shanghai University of Electric PowerShanghai 200090China

Lunar dust is considered to be one of the top challenges for enabling humans to have extended stays on the moon.Human activities such as module landings and launches,walking,rover operation and construction activities will inevitably produce a significant amount of dust.Therefore,it is important to estimate the potential range and intensity of dust deposition caused by these activities to minimize dust accumulation over time and for maintenance planning and execution.A modular model that correlates the dust deposition distribution with initial mean dust particle velocity,its mean ejected angle and the total amount of ejected mass is developed for an elementary mechanical movement.This modular model is further employed to form a modeling framework to estimate dust deposition of a trajectory based activity of similar repeated movements such as the landing process of a lander,walking and rover operation.The model forms a unified modeling framework for different trajectory-based activities and is shown to predict consistent and physically meaningful ranges and intensities of dust deposition provided reliable data to calibrate the model parameters.

关键词： Lunar dust Dust deposition Lunar lander Lunar construction Model calibration

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Genome-wide association with transcriptomics reveals a shade-tolerance gene network in soybean

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The Crop Journal 2024年第1期12卷 232-243页

作者： Yanzhu Su Xiaoshuai Hao Weiying Zeng Zhenguang Lai Yongpeng pan can Wang Pengfei Guo Zhipeng Zhang Jianbo He Guangnan Xing Wubin Wang Jiaoping Zhang Zudong Sun Junyi Gai Soybean Research Institute/MARA National Center for Soybean Improvement MARA Key Laboratory of Biology and Genetic Improvement of Soybean/State Key Laboratory for Crop Genetics and Germplasm Enhancement/State Innovation Platform for Integrated Production and Education in Soybean Bio-breeding/Jiangsu Collaborative Innovation Center for Modern Crop Production Nanjing Agricultural UniversityNanjing 210095JiangsuChina Guangxi Academy of Agricultural Sciences Nanning 530007GuangxiChina

Shade tolerance is essential for soybeans in inter/relay cropping systems.A genome-wide association study(GWAS)integrated with transcriptome sequencing was performed to identify genes and construct a genetic network governing the trait in a set of recombinant inbred lines derived from two soybean parents with contrasting shade tolerance.An improved GWAS procedure,restricted two-stage multi-locus genome-wide association study based on gene/allele sequence markers(GASM-RTM-GWAS),identified 140 genes and their alleles associated with shade-tolerance index(STI),146 with relative pith cell length(RCL),and nine with both.Annotation of these genes by biological categories allowed the construction of a protein–protein interaction network by 187 genes,of which half were differentially expressed under shading and non-shading conditions as well as at different growth stages.From the identified genes,three ones jointly identified for both traits by both GWAS and transcriptome and two genes with maximum links were chosen as beginners for entrance into the network.Altogether,both STI and RCL gene systems worked for shade-tolerance with genes interacted each other,this confirmed that shadetolerance is regulated by more than single group of interacted genes,involving multiple biological functions as a gene network.

关键词： Soybean(Glycine max(L.)Merr.) Shade-tolerance Restricted two-stage multi-locus genomewide association study based on gene/allele sequence markers(GASM-RTM-GWAS) Shade-tolerance index(STI) Relative cell length(RCL) Transcriptome

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Aeroengine thrust estimation and embedded verification based on improved temporal convolutional network

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Chinese Journal of Aeronautics 2024年第1期37卷 106-117页

作者： Wanzhi MENG Zhuorui pan Sixin WEN pan QIN Ximing SUN Key Laboratory of Intelligent Control and Optimization for Industrial Equipment of Ministry of Education Dalian University of TechnologyDalian 116024China School of Control Science and Engineering Dalian University of TechnologyDalian 116024China

Thrust estimation is a significant part of aeroengine thrust control systems.The traditional estimation methods are either low in accuracy or large in computation.To further improve the estimation effect,a thrust estimator based on Multi-layer Residual Temporal Convolutional Network(M-RTCN)is proposed.To solve the problem of dead Rectified Linear Unit(ReLU),the proposed method uses the Gaussian Error Linear Unit(GELU)activation function instead of ReLU in residual block.Then the overall architecture of the multi-layer convolutional network is adjusted by using residual connections,so that the network thrust estimation effect and memory consumption are further improved.Moreover,the comparison with seven other methods shows that the proposed method has the advantages of higher estimation accuracy and faster convergence speed.Furthermore,six neural network models are deployed in the embedded controller of the micro-turbojet engine.The Hardware-in-the-Loop(HIL)testing results demonstrate the superiority of M-RTCN in terms of estimation accuracy,memory occupation and running time.Finally,an ignition verification is conducted to confirm the expected thrust estimation and real-time performance.

关键词： Thrust estimation Temporal convolutional network Embedded deployment Hardware-in-the-loop testing Ignition verification

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Cooperative Target Fencing of Multiple Vehicles for a General Target with Connectivity Preservation and Collision Avoidance

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Journal of Systems Science & Complexity 2024年第1期37卷 136-151页

作者： pan Zini CHEN Ben M Department of Mechanical and Automation Engineering The Chinese University of Hong KongHong KongChina

In this paper,the authors study the cooperative target-fencing problem for n-dimensional systems and a target with a general trajectory.Without using the velocity of the vehicles,a position feedback control law is proposed to fence the general target into the convex hull formed by the vehicles.Specifically,the dynamics of each vehicle is described by a double-integrator system.Two potential functions are designed to guarantee connectivity preservation of the communication network and collision avoidance among the vehicles.The proposed approach can deal with a target whose trajectory is any twice continuously differentiable function of time.The effectiveness of the result is verified by a numerical example.

关键词： Multi-agent systems networked systems target fencing

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Mechanisms of liver injuries caused by traditional Chinese medicines

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Hepatobiliary & pancreatic Diseases International 2024年第3期23卷 310-312页

作者： Shui-Fang Jin Qi pan Jin-Peng Zhou Xiao-Ping pan Intensive Care Unit The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou 310006China Institute of Liver Diseases College of Basic Medical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China The Second Clinical Medical College of Zhejiang Chinese Medical University Hangzhou 310056China

Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional Chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].

关键词： drugs tuberculosis TCM

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