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The Role of KDM2A and H3K36me2 Demethylation in Modulating MAPK Signaling During Neurodevelopment

Neuroscience Bulletin 2024年第8期40卷 1076-1092页

作者： Zongyao Ren Haiyan Tang Wendiao Zhang Minghui Guo Jingjie Cui Hua Wang Bin Xie Jing Yu Yonghao Chen Ming Zhang Cong Han Tianyao Chu Qiuman Liang Shunan Zhao Yingjie Huang Xuelian He Kefu Liu Chunyu Liu Chao Chen Center for medical genetics&Hunan Key laboratory of medical genetics School of Life Sciencesand Department of PsychiatryThe Second Xiangya HospitalCentral South UniversityChangsha 410028China national Clinical Research Center on Mental Disorders The Second Xiangya HospitalCentral South UniversityChangsha 410028China national Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410011China Furong laboratory Changsha 410000China Department of Psychiatry SUNY Upstate Medical UniversitySyracuseNY 13210USA Precision medical Center Wuhan Children's Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430014China Department of medical genetics Hunan Children's HospitalChangsha 410007China

Intellectual disability(ID)is a condition characterized by cognitive impairment and difficulties in adaptive *** our research,we identified two de novo mutations(c.955C>T and c.732C>A)at the KDM2A locus in individuals with varying degrees of *** addition,by using the Gene4Denovo database,we discovered five additional cases of de novo mutations in *** mutations we identified significantly decreased the expression of the KDM2A *** investigate the role of KDM2A in neural development,we used both 2D neural stem cell models and 3D cerebral *** findings demonstrated that the reduced expression of KDM2A impairs the proliferation of neural progenitor cells(NPCs),increases apoptosis,induces premature neuronal differentiation,and affects synapse *** ChIP-Seq analysis,we found that KDM2A exhibited binding to the transcription start site regions of genes involved in *** addition,the knockdown of KDM2A hindered H3K36me2 binding to the downstream regulatory elements of *** integrating ChIP-Seq and RNA-Seq data,we made a significant discovery of the core genes'remarkable enrichment in the MAPK signaling ***,this enrichment was specifically linked to the p38 MAPK ***,disease enrichment analysis linked the differentially-expressed genes identified from RNA-Seq of NPCs and cerebral organoids to neurodevelopmental disorders such as ID,autism spectrum disorder,and ***,our findings suggest that KDM2A plays a crucial role in regulating the H3K36me2 modification of downstream genes,thereby modulating the MAPK signaling pathway and potentially impacting early brain development.

关键词： Intellectual disability KDM2A Neurodevelopmental disorder Cerebral organoids

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Discovery of CCDC188 gene as a novel genetic target for human acephalic spermatozoa syndrome

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Protein & Cell 2024年第9期15卷 704-709页

作者： Jing Wang Hui-Juan Jin Yi Lu Zi-Han Wang Teng-Yan Li Lan Xia Hong-Jun Li Bin-Bin Wang Su-Ren Chen Department of medical genetics and Developmental Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Key laboratory of Cell Proliferation and Regulation Biology Ministry of EducationDepartment of BiologyCollege of Life SciencesBeijing Normal UniversityBeijing 100875China Graduate School Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Urology Peking Union Medical College HospitalBeijing 100005China Center for genetics National Research Institute of Family PlanningBeijing 100081China NHC Key laboratory of Reproductive Health Engineering Technology Research(NRIFP) Beijing 100081China

Dear Editor,Male infertility is a widespread health problem and affects approximately 6%–8%of the male population(Jiao et al.,2021).Acephalic spermatozoa syndrome(ASS),a rare but severe type of teratozoospermia,is ch... 详细信息

关键词： al. infertility finally

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EZH2 is a prognostic factor associated with tumor stemness and immune infiltration in skull base chordoma

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Genes & Diseases 2024年第5期11卷 85-87页

作者： Qian Liu Mingxuan Li Yujia Xiong Yutao Shen Tianshun Ma Tianhao Zhang Xiaohong R.Yang Yazhuo Zhang Jiwei Bai Beijing Neurosurgical Institute Capital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Division of Cancer Epidemiology and genetics National Cancer InstituteNIHDHHSBethesdaMD 20892USA

Enhancer of zeste homolog 2(EZH2),an epigenetic regulator that inhibits transcription primarily through trimethylation of Lys-27 in histone 3(H3K27me3),has been reported to play an important role in the regulation of cell cycle,autophagy,and apoptosis,and DNA damage repair.1 EZH2 is highly expressed in a variety of cancers including prostate cancer,breast cancer,and renal clear cell carcinoma,and is associated with adverse prognosis.1 Moreover,it has been reported that EZH2 might increase tumor stemness and metastasis capacity and inhibit antitumor immunity by affecting T cells,NK cells,macrophages,and immune checkpoints.2,3 However,the prognostic value and the mechanism of EZH2 have not been investigated in *** this study,RNA sequencing and whole genome sequencing data based on 48 skull base chordomas as well as immunohistochemistry of paraffin sections were analyzed to elucidate the role of EZH2 in skull base *** found copy number gain mediated high EZH2 expression is associated with tumor stemness,M2 macrophage infiltration,and adverse prognosis in ***,we demonstrated that EZH2 promotes the proliferation,migration,and invasion of chordoma cells in in vitro cell experiments.

关键词： EZH2 immunity invasion

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Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia

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Chinese medical Journal 2024年第8期137卷 980-989页

作者： Zhiyuan Fan Jing Zhou Yuan Tian Yu Qin Zhaojun Liu Liankun Gu Sanford M.Dawsey Wenqiang Wei Dajun Deng national Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key laboratory of Carcinogenesis and Translational Research(MOE/Beijing) Division of EtiologyPeking University Cancer Hospital and InstituteBeijing 100142China Division of Cancer Epidemiology and genetics National Cancer InstituteBethesdaMDUSA Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsu 211166China

Background:Somatic copy number variations(SCNVs)in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell ***,whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia(ESCdys)is *** study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate(m/M)***:This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of china(Ci County,Hebei Province;Yanting,Sichuan Province;Linzhou,Henan Province;Yangzhong,Jiangsu Province;and Feicheng,Shandong Province)from 2005 to *** DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients,and a quantitative polymerase chain reaction assay,P16-Light,was used to detect CDKN2A copy *** cumulative regression and progression rates of ESCdys were evaluated using competing risk ***:A total of 205 patients with baseline m/M ESCdys were *** proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts(18.8%[13/69]vs.35.0%[28/80]vs.51.8%[29/56],P<0.001).In the univariable competing risk analysis,the cumulative regression rate was statistically significantly lower(P=0.008),while the cumulative progression rate was higher(P=0.017)in ESCdys patients with CDKN2A deletion than in those without CDKN2A ***2A deletion was also an independent predictor of prognosis in ESCdys(P=0.004)in the multivariable ***:The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

关键词： Somatic copy number variations Esophageal squamous cell carcinoma Esophageal neoplasms Squamous intraepithelial lesions DNA copy number variations Prognosis Prospective study

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Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 307-323页

作者： Xufeng FU Hang HAN Hong YANG Bo XU Wenjie DAI Ling LIU Tiantian HE Xing DU Xiuying PEI Key laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China Key laboratory of Reproduction and genetics in Ningxia Ningxia Medical UniversityYinchuan 750004China

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain *** this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in ***,whole-body imaging found that PS-NPs accumulated in the testes of ***,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were *** oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were *** spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP *** phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by ***,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive *** study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

关键词： Polvstyrene nanoplastics(PS-NPs) Reproductive toxicity Ferroptosis Nuclear factor ervthroid 2-related factor 2(Nrf2)

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Haploids can be induced in knockout mutants of OsPLA1,but not OsDMP3 or OsDMP6,in rice

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The Crop Journal 2024年第1期12卷 213-221页

作者： Zongkai Liu Yu Zhong Xiaolong Qi Tai An Shuwei Guo Dong Wang Yuwen Wang Bin Feng Zuofeng Zhu Shaojiang Chen Chenxu Liu national Maize Improvement Center Engineering Research Center of Ministry of EducationChina Agricultural UniversityBeijing 100193China national Center for Evaluation of Agricultural Wild Plants(Rice) Department of Plant Genetics and BreedingChina Agricultural UniversityBeijing 100193China

Doubled haploid(DH)technology is an important tool in crop breeding because it can significantly accelerate the breeding ***1/MATL/NLD and ZmDMP are two key genes controlling haploid induction(HI)in maize,exhibiting a synergistic ***,it is unknown whether knock out of ZmDMP orthologs can stimulate HI in *** this study,a ZmPLA1 ortholog(OsPLA1)and two ZmDMP orthologs(OsDMP3 and OsDMP6)were identified in *** three genes encode plasma membrane-localized proteins and were highly expressed in mature *** of OsPLA1 in both Minghui 63 and Nipponbare resulted in reduced seed setting rate(SSR)and caused *** osdmp3,osdmp6 and the double mutant failed to trigger HI independently,nor increased the haploid induction rate(HIR)when combined with *** pollinations operations of QX654A with the ospla1 mutant significantly improve SSR,while reducing ***-seq profiling of mature ospla1 mutant anthers indicated that a large number of differentially expressed genes(DEGs)were enriched in redox homeostasis and lipid metabolic GO terms,plant hormone signal transduction,and MAPK signaling *** findings provide important insights towards construction of an efficient DH breeding technology and study of the molecular mechanism of HI in rice.

关键词： Doubled haploid breeding Haploid induction Mutation anlaysis Rice

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Weight change and all-cause and cause-specific mortality:A 25-year follow-up study

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Chinese medical Journal 2024年第10期137卷 1169-1178页

作者： Huan Yang Jianbing Wang Xiaokun Wang Wanyi Sun Chenyunhao Tong Jinhu Fan Youlin Qiao Christian *** Department of Cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Public Health Zhejiang University School of MedicineNational Clinical Research Center for Children’s HealthHangzhouZhejiang 310058China Metabolic Epidemiology Branch Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleMD 20850USA

Background:Whether the dynamic weight change is an independent risk factor for mortality remains *** study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial(NIT)***:Body weight of 21,028 healthy residents of Linxian,Henan province,aged 40-69 years was measured two times from 1986 to *** events were prospectively collected up to *** maintenance group(weight change<2 kg)or stable normal weight group was treated as the *** proportional hazard model was performed to calculate hazard ratios(HRs)and 95%confidence intervals(95%CIs)to estimate the risk of ***:A total of 21,028 subjects were included in the final *** with the weight maintenance group,subjects with weight loss≥2 kg had an increased risk of death from all-cause(HR_(All-cause)=1.14,95%CI:1.09-1.19,P<0.001),cancer(HR_(Cancer)=1.12,95%CI:1.03-1.21,P=0.009),and heart disease(HR_(Heart diseases)=1.21,95%CI:1.11-1.31,P<0.001),whereas subjects with weight gain≥5 kg had 11%(HR_(Cancer)=0.89,95%CI:0.79-0.99,P=0.033)lower risk of cancer mortality and 23%higher risk of stroke mortality(HR_(Stroke)=1.23,95%CI:1.12-1.34,P<0.001).For the change of weight status,both going from overweight to normal weight and becoming underweight within 5 years could increase the risk of total death(HR_(Overweight to normal)=1.18,95%CI:1.09-1.27;HR_(Becoming underweight)=1.35,95%CI:1.25-1.46)and cancer death(HR_(Overweight to normal)=1.20,95%CI:1.04-1.39;HR_(Becoming underweight)=1.44,95%CI:1.24-1.67),while stable overweight could increase the risk of total death(HR_(Stable overweight)=1.11,95%CI:1.05-1.17)and death from stroke(HR_(Stable overweight)=1.44,95%CI:1.33-1.56).Interaction effects were observed between age and weight change on cancer mortality,as well as between baseline BMI and weight change on all-cause,heart disease,and stroke mortality(all P_(

关键词： Weight change All-cause mortality Cancer Stroke Heart diseases Body mass index

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Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

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Journal of Animal Science and Biotechnology 2024年第1期15卷 53-67页

作者： Xiaoli Guo Qianqian Zhou Jiaming Jin Fangren Lan Chaoliang Wen Junying Li Ning Yang Congjiao Sun national Engineering laboratory for Animal Breeding and Key laboratory of Animal genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsChina Agricultural UniversityBeijing 100193China

Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying *** Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic *** The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol *** In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of ac

关键词： Acetylation Cholesterol metabolism Hepatic steatosis Laying hens Multiomics

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Promising dawn in tumor microenvironment therapy:engineering oral bacteria

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International Journal of Oral Science 2024年第2期16卷 208-224页

作者： Zifei Wang Wansu Sun Ruixue Hua Yuanyin Wang Yang Li Hengguo Zhang Key laboratory of Oral Diseases Research of Anhui Province College&Hospital of StomatologyAnhui Medical UniversityHefeiChina Department of Stomatology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina Department of genetics School of Life ScienceAnhui Medical UniversityHefeiChina

Despite decades of research,cancer continues to be a major global health *** human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via ***,the role of oral microbes in the development and progression of cancer has received increasing *** the same time,bioengineering technology and nanotechnology is growing rapidly,in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of *** engineered bacteria were transformed to achieve directed genetic reprogramming,selective functional reorganization and precise *** contrast to endotoxins produced by typical genetically modified bacteria,oral flora exhibits favorable biosafety *** outline the current cognitions upon oral microbes,engineered microbes and human cancers,related literatures were searched and reviewed based on the PubMed *** focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment,which involve in cancer occurrence and *** engineering oral bacteria can be a possible application of cancer therapy is worth consideration.A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.

关键词： prevention organs precise

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Revolutionary entrapment model of uniformly distributed swarm robots in morphogenetic formation

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Defence Technology（防务技术） 2024年第1期31卷 496-509页

作者： Chen Wang Zhaohui Shi Minqiang Gu Weicheng Luo Xiaomin Zhu Zhun Fan Shantou University ShantouGuangdongChina national University of Defense Technology ChangshaChina Key lab of Digital Signal and Image Processing of Guangdong Province China

This study proposes a method for uniformly revolving swarm robots to entrap multiple targets,which is based on a gene regulatory network,an adaptive decision mechanism,and an improved *** the gene regulatory network method,the robots can generate entrapping patterns according to the environmental input,including the positions of the targets and ***,an adaptive decision mechanism is proposed,allowing each robot to choose the most well-adapted capture point on the pattern,based on its *** robots employ an improved Vicsek-model to maneuver to the planned capture point smoothly,without colliding with other robots or *** proposed decision mechanism,combined with the improved Vicsek-model,can form a uniform entrapment shape and create a revolving effect around targets while entrapping *** study also enables swarm robots,with an adaptive pattern formation,to entrap multiple targets in complex *** robots can be deployed in the military field of unmanned aerial vehicles’(UAVs)entrapping multiple *** experiments demonstrate the feasibility and superiority of the proposed gene regulatory network method.

关键词： Swarm intelligence Revolutionary entrapment Flocking Robots Gene regulatory network Vicsek-model Entrapping multiple targets

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