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p53 and its isoforms in DNA double-stranded break repair

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第6期20卷 457-466页

作者： Yu-xi ZHANG Wen-ya PAN Jun CHEN moe key laboratory of biosystems homeostasis&protection and Innovation Center for Cell Signaling Network College of Life SciencesZhejiang University

DNA double-stranded break(DSB)is one of the most catastrophic damages of genotoxic *** repair of DNA DSBs results in the loss of genetic information,mutation,and the generation of harmful genomic rearrangements,which predisposes an organism to immunodeficiency,neurological damage,and *** tumor repressor p53 plays a key role in DNA damage response,and has been found to be mutated in 50%of human cancer.p53,p63,and p73 are three members of the p53 gene *** discoveries have shown that human p53 gene encodes at least 12 *** p53 members and isoforms play various roles in orchestrating DNA damage response to maintain genomic *** review briefly explores the functions of p53 and its isoforms in DNA DSB repair.

关键词： p53 p53 isoform DNA double-stranded break repair Cell death

Rodent abundance triggered switch between the relative mutualism and predation in a rodent-seed system of the subtropical island forest

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Integrative Zoology 2021年第1期16卷 109-119页

作者： Di ZENG Tinghao JIN Yuhao ZHAO Chuan YAN Zhibin ZHANG Ping DING moe key laboratory of biosystems homeostasis&protection College of Life SciencesZhejiang UniversityHangzhouZhejiangChina State key laboratory of Integrated Management of Pest Insects and Rodents in Agriculture Institute of ZoologyChinese Academy of Sciences(CAS)BeijingChina Institute of Innovation Ecology Lanzhou UniversityLanzhouGansuChina

Density-dependent non-monotonic species interactions are important in maintaining ecosystem stability and function,but empirical evidences are still ***,as both seed dispersers and seed predators,have dual effects on plant regeneration and may result in non-monotonic rodent-plant *** to the non-monotonic models,the relative positive or negative effects of rodents on seedling establishment can be measured based on the positive or negative association of seedling recruitment rate and rodent *** this study,we investigated the fates of acorns of Quercus serrata by tracking tagged seeds on 21 fragmented subtropical islands in the Thousand Island Lake,*** found that the proportion of germinated seeds of all released seeds showed a dome-shaped association with rodent abundance per *** proportion of removed seeds and cached seeds showed a saturated-and a weak dome-shaped association with rodent abundance per seed,*** results demonstrated a clear empirical evidence that rodent abundance per seed triggered a switch between the relative mutualism and predation in a rodent-seed *** study implied that the observed non-monotonic interactions between plants and animals may play a significant role in maintaining biodiversity and ecosystem *** appeal for more investigations of the complex non-monotonic interactions in various ecosystems.

关键词： ecological non-monotonicity plant-animal interaction relative mutualism or predation rodent abundance per seed

C176-loaded and phosphatidylserine-modified nanoparticles treat retinal neovascularization by promoting M2 macrophage polarization

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Bioactive Materials 2024年第9期39卷 392-405页

作者： An Shao Lulu Jin Yanni Ge Ziqiang Ye Mingyu Xu Yifan Zhou Yingyu Li Linyan Wang Pinglong Xu Kai Jin Zhengwei Mao Juan Ye Eye Center The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009China moe key laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027China moe key laboratory of biosystems homeostasis&protection and Zhejiang Provincial key laboratory of Cancer Molecular Cell Biology Life Sciences InstituteZhejiang UniversityHangzhou310030China

Retinal neovascularization(RNV),a typical pathological manifestation involved in most neovascular diseases,causes retinal detachment,vision loss,and ultimately irreversible *** intravitreal injections of anti-VEGF drugs were developed against RNV,with limitations of incomplete responses and adverse ***,a new treatment with a better curative effect and more prolonged dosage is ***,we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176,appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization.C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal *** biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated“eat me”signal,which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically.A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy *** conclusion,these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.

关键词： Retinal neovascularization Macrophage polarization cGAS-STING pathway Nanocarrier

Haploinsufficiency of A20 (HA20): updates on the genetics, phenotype, pathogenesis and treatment

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World Journal of Pediatrics 2020年第6期16卷 575-584页

作者： Mei-Ping Yu Xi-Sheng Xu Qing Zhou Natalie Deuitch Mei-Ping Lu Department of Rheumatology Immunology and Allergy.Children's Hospital Zhejiang University School of MedicineHangzhou 310052China moe key laboratory of biosystems homeostasis&protection Life Sciences Institute.Zhejiang UniversityHangzhouChina Genetics Department Stanford UniversityCaliforniaUSA

Background A20,a protein encoded by the tumor necrosis factor alpha-induced protein 3 gene(TNFAIP3),plays a vital role in the negative regulation of inflammation and ***-of-function mutation in TNFAIP3 leads to a new described autoinflammatory disease-haploinsufficiency of A20(HA20).Since HA20 was first described in 2016,a number of new cases have been described in this literature,however,the disease and its pathogenesis are poorly *** review seeks to improve clinical recognition of this disorder,and promote both earlier diagnosis and initiation of targeted therapies to improve patients’*** We reviewed 26 papers about A20 and HA20,and we summarized genetic variants and clinical manifestations of a total of 61 reported patients from 26 families identified to have a genetic diagnosis of germline pathogenic variants in TNFAIP3/***,we discussed the pathogenesis and treatment of *** A total of 24 pathogenic variants of A20 had been *** was significant clinical heterogeneity,even among those with the same variants in *** to receiving a molecular diagnosis of HA20,patients had been diagnosed with Behcet's disease,rheumatoid arthritis,rheumatic fever,juvenile idiopathic arthritis,systemic lupus erythematosus,and even adult-onset Stills'*** patients with HA20 that presented with inflammatory signatures in NF-kB signaling were mostly responsive to *** HA20 is a monogenic autoinflammatory disease with highly variable clinical *** extensive heterogeneity makes it difficult to set a clinical diagnostic criteria,and genetic sequencing is necessary for a definitive diagnosis of HA20.

关键词： Autoinflammatory disease HA20 NF-κB signaling TNFAIP3 Treatment

A diet-induced type 2 diabetes model in Drosophila

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Science China(Life Sciences) 2021年第2期64卷 326-329页

作者： Danping Chen Jie Yang Zhengyun Xiao Sicong Zhou Liming Wang moe key laboratory of biosystems homeostasis&protection and Innovation Center for Cell Signaling Network Life Sciences InstituteZhejiang UniversityHangzhou 310058China Institute of Insect Science College of Agriculture and BiotechnologyZhejiang UniversityHangzhou 310058China

Dear *** 2 diabetes has become a global *** is a disease characterized by insulin resistance and relative insulin deficiency,resulting in hyperglycemia and various physiological and metabolic *** genetic risk factors,inappropriate life styles,such as lack of physical activity and imbalanced diet,also contribute to the development of type 2diabetes in human(Jia et al.,2019).Animal models of type 2diabetes are of great value to understand its underlying mechanisms as well as to develop and evaluate potential diagnostic and therapeutic options(Kleinert et al.,2018).

关键词： al. diabetes Animal

Fragmentation for selection: how the deleterious mt DNA is removed in the female germline

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Science Bulletin 2019年第22期64卷 1646-1648页

作者： Chao Tong moe key laboratory for biosystems homeostasis & protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University The Second Affiliated Hospital School of Medicine Zhejiang University

Mitochondria are the energy factories and metabolic centers of cells,and their malfunction can lead to multiple human *** highly dynamic organelles,mitochondria undergo frequent fission and fusion processes[1].The fusion process enables the exchange of inner materials between individual *** materials from healthy mitochondria could potentially compensate for the defects found in the defective *** processes not only increase the mitochondrial number but also separate the damaged parts of mitochondria from the healthy ones,thus,facilitating the elimination of the defective mitochondria through a process known as *** fusion leads to extra connections and branching of the mitochondria,whereas extra fission results in fragmentation of *** fusion and fission processes are differently tuned in various tissues to adapt to different physiological requirements[2].

关键词： removed branching elimination

PARP1-DNA co-condensation:the driver of broken DNA repair

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2351-2353页

作者： Xiang Wei Fangfang Zhou Long Zhang Life Sciences Institute The Second Affiliated Hospital of the Zhejiang University School of MedicineThe MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell BiologyZhejiang UniversityHangzhouChina The First Affiliated Hospital the Institutes of Biology and Medical SciencesSuzhou Medical CollegeSoochow UniversitySuzhouJiangsu 215123China

A recent study published by Simon Alberti1 in Cell has revealed that DNA double-strand break(DSB)sites that prevent the disjunction of broken DNA ends are formed through poly(ADPribose)(PAR)polymerase 1(PARP1)-DNA co-condensation.1(Fig.1).Here,a comprehensive and novel model was provided for the ordered assembly of PARP1-DNA condensates,which can rationally make clear broken DNA end synapses and how repair effectors are recruited to repair DSB.

关键词： PARP1 repair rational

Caenorhabditis elegans homologue of Fam210 is required for oogenesis and reproduction

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Journal of Genetics and Genomics 2020年第11期47卷 694-704页

作者： Jing Kang Hengda Zhou Fengxiu Sun Yongtian Chen Jianzhi Zhao Wei-Jun Yang Suhong Xu Caiyong Chen moe key laboratory of biosystems homeostasis and protection College of Life SciencesZhejiang UniversityHangzhou 310058China Center for Stem Cell and Regenerative Medicine and Department of Cardiology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China

Mitochondria are the central hub for many metabolic processes,including the citric acid cycle,oxidative phosphorylation,and fatty acid *** studies have identified a new mitochondrial protein family,Fam210,that regulates bone metabolism and red cell development in *** model organism Caenorhabditis elegans has a Fam210 gene,y56a3a.22,but it lacks both bones and red blood *** this study,we report that Y56A3A.22 plays a crucial role in regulating mitochondrial protein homeostasis and *** nematode y56a3a.22 is expressed in various tissues,including the intestine,muscle,hypodermis,and germline,and its encoded protein is predominantly localized in mitochondria.y56a3a.22 deletion mutants are sterile owing to impaired *** of Y56A3A.22 induced mitochondrial unfolded protein response(UPRmt),which is mediated through the ATFS-1-dependent pathway,in tissues such as the intestine,germline,hypodermis,and vulval *** further show that infertility and UPRmt induces by Y56A3A.22 deficiency are not attributed to systemic iron ***,our study reveals an important role of Y56A3A.22 in regulating mitochondrial protein homeostasis and oogenesis and provides a new genetic tool for exploring the mechanisms regulating mitochondrial metabolism and reproduction as well as the fundamental role of the Fam210 family.

关键词： Oogenesis Iron metabolism Mitochondrial protein homeostasis Ferritin Reproduction C.elegans

High-resolution spatiotemporal mapping:a comprehensive view of eukaryotic cell cycle proteome dynamics

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2354-2356页

作者： Jing Zou Ziran Qin Long Zhang Life Sciences Institute Second Affiliated Hospital of the Zhejiang University School of MedicineThe MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell BiologyZhejiang UniversityHangzhouZhejiangChina The moe Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors The First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangChina Cancer Center Zhejiang UniversityHangzhouZhejiangChina

In a recent study published in Cell,Litsios et *** a highresolution spatiotemporal map of the eukaryotic cell cycle proteome.1 They identified proteome-level changes in both abundance and spatial distribution throughout the cell cycle and provided a valuable resource for future exploration into the global proteome dynamics that drive cell cycle progression(https://***/cellcycle).

关键词： al. cycle dynamics