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Signal Transduction and Targeted Therapy 2024年第1期9卷 10-11页

作者： Anna Brichkina Roman Suezov Magdalena Huber institute of systems immunology Member of the German Center for Lung Research(DZL)Philipps University of Marburg35043 MarburgGermany

In a recent article published in Cancer Discovery,Guirguis et al.demonstrated that enzymatic inhibitors of the m6 A methyltransferase METTL3 induced a formation of immunostimulatory doublestranded mRNAs(dsRNAs)in cancer cells,which triggered a profound tumor-cell-intrinsic interferon response leading to an enhanced antigen presentation and thereby increased killing of tumor cells by cytotoxic CD8+T-lymphocytes.The inhibition of METTL3 synergized with anti-PD1 immunotherapy,highlighting its potential for improving cancer treatment.

关键词： PD1 immunity

Novel insights into regulation of butyrophilin molecules:critical components of cancer immunosurveillance by yo T cells

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Cellular & Molecular immunology 2024年第4期21卷 409-411页

作者： Dieter Kabelitz institute of immunology University of KielKielGermany

Members of the butyrophilin(BTN)family of transmembrane molecules play an important role in the activation of humanγδT cells.In recent years,it has been discovered that BTN3A1 and BTN2A1 are indispensable in this process,but other members like BTN3A2 and BTN3A3 are also required.So far,very little is known about the transcriptional and post-translational regulation of BTN expression.

关键词： expression. insight critical

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： Jun Zhou Jiaqi Liu Bingjing Wang Nan Li Juan Liu Yanmei Han Xuetao Cao institute of immunology Zhejiang University School of MedicineHangzhou 310058China National Key Laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China Department of immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China institute of immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against infection.The cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains elusive.Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense.Here we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell apoptosis.Eosinophil-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)infection.Mechanistically,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon L.m.infection in vitro.Furthermore,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of L.m.infection in vivo.Adoptive transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory responses.Together,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against L.m.infection.Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen

Virus-like nanoparticle vaccines for inducing long-lasting immunity against infectious diseases

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National Science Review 2024年第4期11卷 13-15页

作者： Yi-Nan Zhang Sarah Auclair Jiang Zhu Department of Integrative Structural and Computational Biology The Scripps Research Institute Department of immunology and Microbiology The Scripps Research Institute

Prophylactic vaccines that can generate long-lasting protective immune responses are needed for many infectious diseases. Efficient vaccination requires vaccine antigens to be retained and presented to B cells in lymp...

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The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao Department of immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou institute of systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier Research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life Sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate defense.However,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still unknown.We used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil mobilization.ALKBH5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic mice.In addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type littermates.During bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human neutrophils.Mechanistically,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in neutrophils.The RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected neutrophils.Considering these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrophils is a potential target for treating bacteria

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

Unveiling the early stage evolution of local atomic structures in the crystallization process of a metallic glass

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Chinese Physics B 2024年第3期33卷 58-64页

作者：马琳杨晓东杨锋周鑫嘉武振伟 institute of Nonequilibrium systems School of Systems ScienceBeijing Normal UniversityBeijing 100875China

The early stage evolution of local atomic structures in a multicomponent metallic glass during its crystallization process has been investigated via molecular dynamics simulation.It is found that the initial thermal stability and earliest stage evolution of the local atomic clusters show no strong correlation with their initial short-range orders,and this leads to an observation of a novel symmetry convergence phenomenon,which can be understood as an atomic structure manifestation of the ergodicity.Furthermore,in our system we have quantitatively proved that the crucial factor for the thermal stability against crystallization exhibited by the metallic glass is not the total amount of icosahedral clusters,but the degree of global connectivity among them.

关键词： metallic glass crystallization molecular dynamics simulation local atomic clusters

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A novel non-intrusive load monitoring technique using semi-supervised deep learning framework for smart grid

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Building Simulation 2024年第3期17卷 441-457页

作者： Mohammad Kaosain Akbar Manar Amayri Nizar Bouguila Concordia institute for Information systems Engineering Concordia UniversityMontrealCanada

Non-intrusive load monitoring(NILM)is a technique which extracts individual appliance consumption and operation state change information from the aggregate power consumption made by a single residential or commercial unit.NILM plays a pivotal role in modernizing building energy management by disaggregating total energy consumption into individual appliance-level insights.This enables informed decision-making,energy optimization,and cost reduction.However,NILM encounters substantial challenges like signal noise,data availability,and data privacy concerns,necessitating advanced algorithms and robust methodologies to ensure accurate and secure energy disaggregation in real-world scenarios.Deep learning techniques have recently shown some promising results in NILM research,but training these neural networks requires significant labeled data.Obtaining initial sets of labeled data for the research by installing smart meters at the end of consumers’appliances is laborious and expensive and exposes users to severe privacy risks.It is also important to mention that most NILM research uses empirical observations instead of proper mathematical approaches to obtain the threshold value for determining appliance operation states(On/Off)from their respective energy consumption value.This paper proposes a novel semi-supervised multilabel deep learning technique based on temporal convolutional network(TCN)and long short-term memory(LSTM)for classifying appliance operation states from labeled and unlabeled data.The two thresholding techniques,namely Middle-Point Thresholding and Variance-Sensitive Thresholding,which are needed to derive the threshold values for determining appliance operation states,are also compared thoroughly.The superiority of the proposed model,along with finding the appliance states through the Middle-Point Thresholding method,is demonstrated through 15%improved overall improved F1micro score and almost 26%improved Hamming loss,F1 and Specificity score for the performance of individual appliance when compared

关键词： semi-supervised learning non-intrusive load monitoring middle-point thresholding deep learning TCN LSTM

Classification of knowledge graph completeness measurement techniques

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Journal of systems Engineering and Electronics 2024年第1期35卷 154-162页

作者： ZHANG Ying XIAO Gang institute of systems Engineering Academy of Military SciencesBeijing 100107China

At present,although knowledge graphs have been widely used in various fields such as recommendation systems,question and answer systems,and intelligent search,there are always quality problems such as knowledge omissions and errors.Quality assessment and control,as an important means to ensure the quality of knowledge,can make the applications based on knowledge graphs more complete and more accurate by reasonably assessing the knowledge graphs and fixing and improving the quality problems at the same time.Therefore,as an indispensable part of the knowledge graph construction process,the results of quality assessment and control determine the usefulness of the knowledge graph.Among them,the assessment and enhancement of completeness,as an important part of the assessment and control phase,determine whether the knowledge graph can fully reflect objective phenomena and reveal potential connections among entities.In this paper,we review specific techniques of completeness assessment and classify completeness assessment techniques in terms of closed world assumptions,open world assumptions,and partial completeness assumptions.The purpose of this paper is to further promote the development of knowledge graph quality control and to lay the foundation for subsequent research on the completeness assessment of knowledge graphs by reviewing and classifying completeness assessment techniques.

关键词： quality assessment completeness assessment closed world assumptions open world assumption partial completeness assumption

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Emergence of machine language: towards symbolic intelligence with neural networks

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National Science Review 2024年第4期11卷 27-30页

作者： Yuqi Wang Xu-Yao Zhang Cheng-Lin Liu Tieniu Tan Zhaoxiang Zhang State Key Laboratory of Multimodal Artificial Intelligence systems Institute of AutomationChinese Academy of Sciences

Representation learning is a core issue in artificial intelligence (AI). Currently,there exists a disparity in the choice of representation between humans and machines. Humans rely on discrete language for communicati...

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Nutritional competition within tumor microenvironment dictates anti-tumor immunity

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National Science Review 2024年第2期11卷 98-100页

作者： Yankang Fei Xuetao Cao Juan Liu National Key Laboratory of Immunity and Inflammation Institute of Immunology Naval Medical University Department of immunology Chinese Academy of Medical Sciences institute of immunology College of Life Sciences Nankai University

The crosstalk between metabolism and immunity has emerged as an essential regulator of tumor immune escape, and targeting immunometabolic pathways holds great potential for cancer immunotherapy [1]. Abnormal metabolic...

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