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Temperature regulates negative supercoils to modulate meiotic crossovers and chromosome organization

Science China Life Sciences 2024年

作者： Yingjin Tan Taicong Tan Shuxian Zhang Bo Li Beiyi Chen Xu Zhou Ying Wang Xiao Yang Binyuan Zhai Qilai Huang Liangran Zhang Shunxin Wang Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences (No.2021RU001) Advanced Medical Research Institute Shandong University State Key Laboratory of Reproductive Medicine and Offspring Health Center for Reproductive Medicine Institute of Women Children and Reproductive Health Shandong University Shandong Provincial Key Laboratory of Animal cell and Developmental biology School of Life Sciences Shandong University center for cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance Biology College of Life Sciences Shandong Normal University National Research center for Assisted Reproductive Technology and Reproductive Genetics Shandong University Key Laboratory of Reproductive Endocrinology (Shandong University) Ministry of Education Shandong Technology Innovation center for Reproductive Health Shandong Provincial Clinical Research center for Reproductive Health Shandong Key Laboratory of Reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical University

Crossover recombination is a hallmark of meiosis that holds the paternal and maternal chromosomes(homologs) together for their faithful segregation, while promoting genetic diversity of the progeny. The pattern of crossover is mainly controlled by the architecture of the meiotic chromosomes. Environmental factors, especially temperature, also play an important role in modulating crossovers. However, it is unclear how temperature affects crossovers. Here, we examined the distribution of budding yeast axis components(Red1, Hop1, and Rec8)and the crossover-associated Zip3 foci in detail at different temperatures, and found that both increased and decreased temperatures result in shorter meiotic chromosome axes and more crossovers. Further investigations showed that temperature changes coordinately enhanced the hyperabundant accumulation of Hop1 and Red1 on chromosomes and the number of Zip3 foci. Most importantly, temperature-induced changes in the distribution of axis proteins and Zip3 foci depend on changes in DNA negative supercoils. These results suggest that yeast meiosis senses temperature changes by increasing the level of negative supercoils to increase crossovers and modulate chromosome organization. These findings provide a new perspective on understanding the effect and mechanism of temperature on meiotic recombination and chromosome organization, with important implications for evolution and breeding.

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Colorectal cancer:Recent advances in management and treatment

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World Journal of Clinical Oncology 2024年第9期15卷 1136-1156页

作者： Hiba Fadlallah Jad El Masri Hiam Fakhereddine Joe Youssef Chrystelle Chemaly Samer Doughan Wassim Abou-Kheir Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon Department of Surgery American University of Beirut Medical CenterBeirut 1107-2020Lebanon

Colorectal cancer(CRC)is the third most common cancer worldwide,and the second most common cause of cancer-related *** 2020,the estimated number of deaths due to CRC was approximately 930000,accounting for 10%of all cancer deaths ***,there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and *** management strategies for CRC include surgical procedures for resectable cases,and radiotherapy,chemotherapy,and immunotherapy,in addition to their combination,for non-resectable *** these options,CRC remains incurable in 50%of ***,significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated,leading to the availability of new drugs and therapeutic *** review summarizes the most recent therapeutic approaches for CRC,with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC.

关键词： Colorectal cancer Treatment Surgery Chemotherapy Targeted therapy Immunotherapy

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Going only half the way:cell cycle exit after the G1 restriction point

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Signal Transduction and Targeted Therapy 2024年第1期9卷 1-2页

作者： Lisa Muller Tony Gutschner Mechthild Hatzfeld Department of Pathobiochemistry Institute of Molecular MedicineMartin Luther University Halle-WittenbergCharles Tanford Protein Research CenterHalleGermany Department of RNA biology and Pathogenesis Institute of Molecular MedicineMartin Luther University Halle-WittenbergCharles Tanford Protein Research CenterHalleGermany

In a recent article published in Nature,James *** et *** that cyclin A2 levels determine whether cells will make an entrance into mitosis or whether cells will leave the cell cycle after having passed the G1/restriction(R)-point implicating that the decision is fully reversible(Fig.1).This ground-breaking study could impact future approaches for cancer treatment by targeting the mitotic clock.

关键词： point cycle

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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6

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Science Bulletin 2024年第2期69卷 173-178页

作者： Siyuan Jiang Xiaoqi Han Tihui Liu Ying He Zidong Zhao Tongfeng Liu Shuwen Cheng Jihang Zhang Liqiang Duan Yajuan Liu Tianyou Cheng Yong Liu Qinong Ye Shan Gao Zhongda Hospital Medical SchoolAdvanced Institute for Life and HealthSoutheast UniversityNanjing 20096China Medical School of Guizhou University Guiyang 550025China Shanxi Academy of Advanced Research and Innovation Taiyuan 030032China Zhongda Hospital School of Life Sciences and TechnologyAdvanced Institute for Life and HealthSoutheast UniversityNanjing 210096China Nanjing University Medical School Nanjing 210046China Hubei Key Laboratory of cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430072China Department of Medical Molecular biology Beijing Institute of BiotechnologyCollaborative Innovation Center for Cancer MedicineBeijing 100850China

Endocytosis is a crucial cellular process that takes up cargos by enclosing them in membrane-bound vesicles,and transports cargos to different parts of the cell,such as the lysosomes[1].Endocytosis is classified into several mechanistically and morphologically pathways,including clathrin-mediated endocytosis(CME)and caveolae-mediated endocytosis(CavME)[1,2].

关键词： endocytosis cargo uptake

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An orally-available monovalent SMAC mimetic compound as a broad-spectrum antiviral

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Protein & cell 2024年第1期15卷 69-75页

作者： Miao Mei Maria_Antonietta Impagnatiello Jun Jiao Ulrich Reiser Ulrike Tontsch-Grunt Ju Zhang Paul Nicklin Bingke Yu Yu Wang Yuan He Xu Tan Tsinghua-Peking center for Life Sciences Beijing Advanced Innovation Center for Structural BiologyBeijing Frontier Research Center for Biological StructureMOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologySchool of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China Chinese Institutes for Medical Research Beijing 100069China Boehringer Ingelheim RCV GmbH&Co KG ViennaAustria College of Life Sciences and Oceanography Shenzhen UniversityShenzhen 518060China Research Beyond Borders Boehringer IngelheimBiberach an der RissGermany Research Beyond Borders Boehringer IngelheimShanghai 200120China

DearEditor,The coronavirus disease 2019(COVID-19)pandemic caused great global morbidity and mortality concurrent with astronomical socioeconomic damages and *** now,the culpable pathogen,SARS-CoV-2,has infected over 6 hundred million people resulting in more than 6 million deaths worldwide(WHO SARSCoV-2 cases).There is an urgent need for rapid development of effective and affordable therapeutics for COVID-19 patients.

关键词： mortality spectrum compound

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Finding my way: The role of dirigent proteins in lignin assembly

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Molecular Plant 2024年第2期17卷 230-232页

作者： Dyoni M.Oliveira Igor Cesarino Department of Plant Biotechnology and Bioinformatics Ghent University9052 GhentBelgium VIB center for Plant Systems biology 9052 GhentBelgium Departamento de Botanica Instituto de BiocienciasUniversidade de Sao PauloRua do Matao277Sao Paulo 05508-090Brazil Synthetic and Systems biology center InovaUSPAvenida Professor Lucio Martins Rodrigues370SaoPaulo 05508-020Brazil

Lignin emerged around 450 million years ago in early tracheophytes and played a pivotal role in the colonization of terrestrial ecosystems by *** aromatic biopolymer provides mechanical strength to supportive tissues and hydrophobicity to water-transporting vasculature and acts as a physical barrier against herbivores and pathogens(Renault et al.,2019).The deposition of lignin in cell walls for proper cellular functionalization involves several molecular steps,including the tight regulation of tissue-or cell-type-specific expression of lignin biosynthetic genes,the biosynthesis of distinct lignin monomers and their transportation to the apoplast,and the polymerization of monomer radicals to produce tissue-or cell-type-dependent polymers with distinct physico-chemical properties.

关键词： properties. lignin walls

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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 *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** 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 ***,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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Root-derived long-distance signals trigger ABA synthesis and enhance drought resistance in Arabidopsis

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Journal of Genetics and Genomics 2024年第7期51卷 749-761页

作者： Qian-Qian Liu Jin-Qiu Xia Jie Wu Yi Han Gui-Quan Zhang Ping-Xia Zhao Cheng-Bin Xiang Division of Life Sciences and Medicine Division of Molecular&Cell BiophysicsHefei National Science Center for Interdisciplinary Sciences at the MicroscaleUniversity of Science and Technology of ChinaThe Innovation Academy of Seed DesignChinese Academy of SciencesHefeiAnhui 230027China College of Life Sciences Anhui Agricultural UniversityHefeiAnhui 230036China College of Agronomy South China Agricultural UniversityGuangzhouGuangdong 510642China School of biology and Basic Medical Sciences Soochow UniversitySuzhouJiangsu 215123China

Vascular plants have evolved intricate long-distance signaling mechanisms to cope with environmental stress,with reactive oxygen species(ROS)emerging as pivotal systemic signals in plant stress ***,the exact role of ROS as root-to-shoot signals in the drought response has not been *** this study,we reveal that compared with wild-type plants,ferric reductase defective 3(frd3)mutants exhibit enhanced drought resistance concomitant with elevated NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3(NCED3)transcript levels and abscisic acid(ABA)contents in leaves as well as increased hydrogen peroxide(H_(2)O_(2))levels in roots and *** experiments distinctly illustrate that drought resistance can be conferred by the frd3 rootstock regardless of the scion genotype,indicating that long-distance signals originating from frd3 roots promote an increase in ABA levels in ***,the drought resistance conferred by the frd3 mutant rootstock is weakened by the CAT2-overexpressing scion,suggesting that H_(2)O_(2)may be involved in long-distance ***,the results of comparative transcriptome and proteome analyses support the drought resistance phenotype of the frd3 *** together,our findings substantiate the notion that frd3 root-derived long-distance signals trigger ABA synthesis in leaves and enhance drought resistance,providing new evidence for root-to-shoot long-distance signaling in the drought response of plants.

关键词： frd3 Drought resistance Root-to-shoot long-distance signals Reactive oxygen species(ROS) H_(2)O_(2) Iron ABA

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Neoantigen cancer vaccines:a new star on the horizon

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Cancer biology & Medicine 2024年第4期21卷 274-311页

作者： Xiaoling Li Jian You Liping Hong Weijiang Liu Peng Guo Xishan Hao cell Biotechnology Laboratory Tianjin Cancer Hospital Airport HospitalTianjin 300308China National Clinical Research center for Cancer Tianjin 300060China Haihe Laboratory of Synthetic biology Tianjin 300090China Department of Thoracic Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China Department of Thoracic Oncology Surgery Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Tianjin Medical University Cancer Institute&Hospital Tianjin 300060China

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer *** of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal *** neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint *** made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of ***,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents *** review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

关键词： Immunotherapy neoantigen cancer vaccine solid tumors high-throughput sequencing bioinformatics PDOs AI HLA TCR

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