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ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader

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Protein & Cell 2024年第7期15卷 493-511页

作者： Chuanle Wang Yan Huang Yue Yang Ruofei Li Yingying Li Hongxin Qiu Jiali Wu Guang Shi Wenbin Ma Zhou Songyang MOE Key Laboratory of gene Function and regulation State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy AgingSchool of LifesciencesSun Yat-sen UniversityGuangzhou 510275China department of Oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510275China department of Nephrology The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China

Telomeres are specialized structures at the ends of linear chromosomes that protect genome *** telomeric repeat-containing RNA(TERRA)that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called *** tumor cells,R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres(ALT)*** R-loops can cause stalled replication forks and telomere ***,how R-loops are recognized and regulated,particularly at telomeres,is not well *** discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous *** out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage *** addition,ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT *** the proximity-dependent biotin identification(BioID)technology,we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases,including ***,ILF3 may aid in the resolution of telomeric R-loops through its interaction with *** findings suggest that ILF3 may function as a reader of telomeric R-loops,helping to prevent abnormal homologous recombination and maintain telomere homeostasis.

关键词： ILF3 RNA:DNA hybrids telomeric R-loops homologous recombination telomeric DNA damage responses

Current therapies for osteoarthritis and prospects of CRISPR-based genome,epigenome,and RNA editing in osteoarthritis treatment

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Journal of genetics and Genomics 2024年第2期51卷 159-183页

作者： Yuxi Chen Xiao Luo Rui Kang Kaixin Cui Jianping Ou Xiya Zhang Puping Liang MOE Key Laboratory of gene Function and regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China Center for Reproductive Medicine The Third Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhouGuangdong 510630China

Osteoarthritis(OA)is one of the most common degenerative joint diseases worldwide,causing pain,disability,and decreased quality of *** balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of ***,there is a lack of effective therapeutic strategies for OA *** the development of CRISPR-based genome,epigenome,and RNA editing tools,OA treatment has been improved by targeting genetic risk factors,activating chondrogenic elements,and modulating inflammatory *** by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA *** review summarizes CRISPR-based genome,epigenome,and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA ***,in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.

关键词： Osteoarthritis Genome editing Epigenone editing RNA editing

TaMYB72 directly activates the expression of TaFT to promote heading and enhance grain yield traits in wheat(Triticum aestivum L.)

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Journal of Integrative Plant Biology 2024年第7期66卷 1266-1269页

作者： Lifen Wu Zhencheng Xie Danping Li Yaoyu Chen Chuan Xia Xiuying Kong Xu Liu Lichao Zhang State Key Laboratory of Crop gene Resources and Breeding Institute of Crop Sciencesthe Chinese Academy of Agricultural SciencesBeijing 100081China State Key Laboratory of North China Crop Improvement and regulation Hebei Sub‐Center for National Maize Improvement CenterCollege of AgronomyHebei Agricultural UniversityBaoding 071001China

Wheat(Triticum aestivum L.)is a staple food for approximately half the global *** the population continues to grow,the demand for high-yielding varieties is increasing(Zorb et al.,2018).Higher yields can be achieved by increasing the number and weight of grains produced and by optimizing heading dates to maximize production in local environments(Sakuma and Schnurbusch,2020).

关键词： heading Wheat yielding

Roles of cancer-associated fibroblast functional heterogeneity in shaping the lymphatic metastatic landscape:new insights and therapeutic strategies

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Cancer Biology & Medicine 2024年第6期21卷 445-450页

作者： Hanhao Zheng Daiyin Liu Zhicong Liu Mingjie An Yuming Luo Changhao Chen Tianxin Lin department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510003China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and gene regulation Sun Yat-sen Memorial HospitalState Key Laboratory of Oncology in South ChinaGuangzhou 510003China department of general Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510003China

Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of cancer dissemination,and a critical indicator of cancer progression and worsening prognosis1. The occurrence of LN metastasis indicates that the tumor has invaded the lymphatic system.

关键词： metastasis lymphatic landscape

CsRAXs negatively regulate leaf size and fruiting ability through auxin glycosylation in cucumber

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Journal of Integrative Plant Biology 2024年第5期66卷 1024-1037页

作者： Jiacai Chen Liu Liu Guangxin Chen Shaoyun Wang Ye Liu Zeqin Zhang Hongfei Li Liming Wang Zhaoyang Zhou Jianyu Zhao Xiaolan Zhang Beijing Key Laboratory of Growth and Developmental regulation for Protected Vegetable Crops Department of Vegetable SciencesBeijing key Laboratoy of Growtn and Developmental Regul China Agricultural UniversityBeijing 100193China

Leaves are the main photosynthesis organ that directly determines crop yield and *** the regulatory mechanism of leaf development is crucial for food security and ecosystem ***,we identified the novel function of R2R3-MYB transcription factors CsRAXs in regulating cucumber leaf size and fruiting ***5 single mutant exhibited enlarged leaf size and stem diameter,and Csrax1/2/5 triple mutant displayed further enlargement *** of CsRAX1 or CsRAX5 gave rise to smaller leaf and thinner *** fruiting ability of Csrax1/2/5 plants was significantly enhanced,while that of CsRAX5 overexpression lines was greatly ***,cell number and free auxin level were elevated in mutant plants while decreased in overexpression *** data indicated that CsRAX1/5 directly promoted the expression of auxin glucosyltransferase gene ***,our data suggested that CsRAXs function as repressors for leaf size development by promoting auxin glycosylation to decrease free auxin level and cell division in *** findings provide new gene targets for cucumber breeding with increased leaf size and crop yield.

关键词： auxin glycosylation CsRAXs CsUGT74E2 fruiting ability leaf size

Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3467-3482页

作者： Zhan-Li Chen Chen Xie Wei Zeng Rui-Qi Huang Jin-E Yang Jin-Yu Liu Ya-Jing Chen Shi-Mei Zhuang MOE Key Laboratory of gene Function and regulation Guangdong Province Key Laboratory of Pharmaceutical Functional GenesSchool of Life SciencesState Key Laboratory of Oncology in Southern ChinaSun Yat-sen UniversityGuangzhouPR China Key Laboratory of Liver Disease of Guangdong Province The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630PR China

Mitotic catastrophe(MC),which occurs under dysregulated mitosis,represents a fascinating tactic to specifically eradicate tumor *** pyroptosis can be a death form of MC remains ***-mediated protein degradation is crucial for ***(BTZ),which inhibits the 20S catalytic particle of proteasome,is approved to treat multiple myeloma and mantle cell lymphoma,but not solid tumors due to primary *** date,whether and how proteasome inhibitor affected the fates of cells in M-phase remains ***,we show that BTZ treatment,or silencing of PSMC5,a subunit of 19S regulatory particle of proteasome,causes G2-and M-phase arrest,multi-polar spindle formation,and consequent caspase-3/GSDME-mediated pyroptosis in M-phase(designated as mitotic pyroptosis).Further investigations reveal that inhibitor of WEE1/PKMYT1(PD0166285),but not inhibitor of ATR,CHK1 or CHK2,abrogates the BTZ-induced G2-phase arrest,thus exacerbates the BTZ-induced mitotic arrest and *** BTZ and PD0166285 treatment(named BP-Combo)selectively kills various types of solid tumor cells,and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 *** using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment,and no obvious toxicity is observed in BP-Combo-treated *** findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase,characterize pyroptosis as a new death form of mitotic catastrophe,and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells.

关键词： proteasome inhibiting catastrophe

Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance

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Science China(Life Sciences) 2024年第1期67卷 19-40页

作者： Jing Cai Xiaoding Xu Phei Er Saw Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and gene regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Nanhai Translational Innovation Center of Precision Immunology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityFoshan 528200China

A potential reason for the failure of tumor therapies is treatment *** to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and *** major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,*** studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell *** ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor ***,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback ***,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor *** also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.

关键词： ferroptosis cancer therapy therapy resistance nanoinducers

The bHLH transcription factor CsPIF4 positively regulates high temperature-induced hypocotyl elongation in cucumber

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Horticultural Plant Journal 2024年第5期10卷 1187-1197页

作者： Jing Nie Yu Jiang Lijun Lv Yuzi Shi Peiyu Chen Qian Zhang Xiaolei Sui Beijing Key Laboratory of Growth and Developmental regulation for Protected Vegetable Crops College of HorticultureChina Agricultural UniversityBeijing 100193China

High temperature-induced hypocotyl elongation is a typical thermomorphogenesis trait that may significantly affect early seedling growth and subsequent crop *** ambient temperature and endogenous auxin are two critical factors that regulate hypocotyl ***,the mechanism of temperature and auxin integration in horticultural plants remains poorly *** this study,the roles of the basic helix-loop-helix transcription factor CsPIF4 in regulating auxin biosynthesis genes and the auxin content in the hypocotyl of cucumber(Cucumis sativus L.)seedlings under high temperature were ***-PCR and in situ hybridization analysis revealed that expression of CsPIF4 was enhanced in the epidermis and vascular bundles in the hypocotyl of cucumber seedlings in response to high ***-PCR and HPLC analysis showed that CsPIF4 positively regulated transcription of the auxin biosynthesis gene CsYUC8 and the auxin content in the hypocotyl under high temperature(35℃).The CRISPR/Cas9-mediated knockout of CsPIF4 resulted in a shorter hypocotyl compared with that of the wild type,together with decreased expression of CsYUC8 and lower auxin content in response to high ***,biochemical assays showed that CsPIF4 could bind directly to the G-box motif of the CsYUC8 promoter and thereby activate CsYUC8 *** findings provide insight into the molecular mechanism of high temperature-mediated hypocotyl elongation in cucumber.

关键词： Cucumber Hypocotyl elongation High temperature CsPIF4 Auxin

Rationally construction of atomic-precise interfacial charge transfer channel and strong build-in electric field in nanocluster-based Zscheme heterojunctions with enhanced photocatalytic hydrogen production

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Nano Research 2024年第6期17卷 5002-5010页

作者： Qingtao Zhu Honglei Shen Chao Han Liu Huang Yanting Zhou Yuanxin Du Xi Kang Manzhou Zhu department of Materials Science and Engineering Centre for Atomic Engineering of Advanced MaterialsKey Laboratory of Structure and Functional Regulation of Hybrid Materials of Ministry of EducationKey Laboratory of Functional Inorganic Material Chemistry of Anhui ProvinceAnhui UniversityHefei 230601China

The lack of effective charge transfer driving force and channel limits the electron directional migration in nanoclusters(NC)-based heterostructures,resulting in poor photocatalytic ***,a Z-scheme NC-based heterojunction(Pt1Ag28-BTT/CoP,BTT=1,3,5-benzenetrithiol)with strong internal electric field is constructed via interfacial Co-S bond,which exhibits an absolutely superiority in photocatalytic performance with 24.89 mmol·h^(−1)·g−1 H_(2)production rate,25.77%apparent quantum yield at 420 nm,and~100%activity retention in stability,compared with Pt1Ag28-BDT/CoP(BDT=1,3-benzenedithiol),Ag29-BDT/CoP,and *** enhanced catalytic performance is contributed by the dual modulation strategy of inner core and outer shell of NC,wherein,the center Pt single atom doping regulates the band structure of NC to match well with CoP,builds internal electric field,and then drives photogenerated electrons steering;the accurate surface S modification promotes the formation of Co-S atomic-precise interface channel for further high-efficient Z-scheme charge directional *** work opens a new avenue for designing NC-based heterojunction with matchable band structure and valid interfacial charge transfer.

关键词： atomically precise metal nanocluster Z-scheme heterojunction interfacial charge transfer build-in electric field photocatalytic hydrogen production