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Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity

Science China(Life Sciences) 2024年第1期67卷 51-66页

作者： Yonghui jiang Xueying Gao Yue Liu Xueqi Yan Huangcong Shi Rusong Zhao zi-jiang chen Fei Gao Han Zhao Shigang Zhao Center for Reproductive Medicine Shandong UniversityJinan 250012China Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250012China Shandong Key Laboratory of Reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250012China Shandong Provincial Clinical Research Center for Reproductive Health Jinan 250012China National Research Center of Assisted Reproductive Technology and Reproductive Genetics Shandong UniversityJinan 250012China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215000China Center for reproductive medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics Shanghai 200127China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of ScienceBeijing 100101China

Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly documented.In this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial cells.Furthermore,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.

关键词： obesity ovarian microenvironment snRNA-seq Stereo-seq Foxo1

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Allelic reprogramming of chromatin states in human early embryos

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National Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai Han Zhao zi-jiang chen jiang Liu Keliang Wu Center for Reproductive Medicine Shandong University CAS Key Laboratory of Genome Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of Chinese Academy of Sciences CUHK-SDU Joint Laboratory on Reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong Key Laboratory of Reproductive Endocrinology of the Ministry of Education Shandong University Center for Reproductive Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse embryos.The allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early embryos.Collectively, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K27me3 chromatin accessibility

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Profile of Dr. zi-jiang chen

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Science China(Life Sciences) 2020年第6期63卷 845-848页

作者： chen, zi-jiang

Dr. chen received her bachelor-equivelent medical education at School of Medicine Shandong University (previously the Shandong Medical College), and got her MD–Ph D in1989 majoring in Obstetrics and Gynecology. As the youngest professor in the school’s history, Dr. chen joined the faculty of School of Medicine Shandong University.

关键词： Nat Profile of Dr zi-jiang chen

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DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation

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Science China Life Sciences 2024年第8期 1620-1634页

作者： Yunde Dou Rusong Zhao Han Wu Zhiheng Yu Changjian Yin Jie Yang Chaoyan Yang Xiaohua Luan Yixiao cheng Tao Huang Yuehong Bian Shan Han Yuqing Zhang Xin Xu zi-jiang chen Han Zhao Shigang Zhao National Research Center for Assisted Reproductive Technology and Reproductive Genetics Shandong University The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Nanjing Medical University Gusu School Nanjing Medical University Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory Institute of Women Guangdong Second Provincial General Hospital Reproductive Medicine Center Guangdong Second Provincial General Hospital Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences (No.2021RU001) Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics Center for Reproductive Medicine Renji Hospital School of Medicine Shanghai Jiao Tong University Children and Reproductive Health Shandong University State Key Laboratory of Reproductive Medicine and Offspring Health Key laboratory of Reproductive Endocrinology of Ministry of Education Shandong University Shandong Key Laboratory of Reproductive Medicine Shandong University Shandong Provincial Clinical Research Center for Reproductive Health

Polycystic ovary syndrome(PCOS) is a complex disorder.Genome-wide association studies(GWAS) have identified several genes associated with this condition,including DENND1A.DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport.However,the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly understood.In this study,we investigated DENND1A expression in ovarian granulosa cells(GCs)from PCOS patients and its correlation with hormones.Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases,which was positively correlated with testosterone levels.To further explore the functional implications of DENND1A,we generated a transgenic mouse model overexpressing Dennd1a(TG mice).These TG mice exhibited subfertility,irregular estrous cycles,and increased testosterone production following PMSG stimulation.Additionally,the TG mice displayed diminished responsiveness to FSH,characterized by smaller ovary size,less well-developed follicles,and abnormal expressions of FSH-priming genes.Mechanistically,we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor(FSHR),promoting its internalization and inhibiting recycling.These findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms,thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.

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Controllable chemical redox reactions to couple microbial degradation for organic contaminated sites remediation:A review

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Journal of Environmental Sciences 2024年第5期139卷 428-445页

作者： Bin chen jiang Xu Lizhong Zhu College of Environmental and Resource Sciences Zhejiang UniversityHangzhou 310058China Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control Zhejiang UniversityHangzhou 310058China Zhejiang Agriculture&Forest University Lin'an 311300China

Global environmental concern over organic contaminated sites has been progressively conspicuous during the process of urbanization and industrial restructuring.While traditional physical or chemical remediation technologies may significantly destroy the soil structure and function,coupling moderate chemical degradation with microbial remediation becomes a potential way for the green,economic,and efficient remediation of contaminated sites.Hence,this work systematically elucidates why and how to couple chemical technology with microbial remediation,mainly focused on the controllable redox reactions of organic contaminants.The rational design of materials structure,selective generation of reactive oxygen species,and estimation of degradation pathway are described for chemical oxidation.Meanwhile,current progress on efficient and selective reductions of organic contaminants(i.e.,dechlorination,defluorination,-NO_(2) reduction)is introduced.Combined with the microbial remediation of contaminated sites,several consideration factors of how to couple chemical and microbial remediation are proposed based on both fundamental and practical points of view.This review will advance the understanding and development of chemical-microbial coupled remediation for organic contaminated sites.

关键词： Soil remediation Groundwater remediation Rational design Reactive species Environmental nanotechnology

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Observation of accurately designed bound states in the continuum in momentum space

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Photonics Research 2024年第4期12卷 638-647页

作者： JIAJU WU JINGGUANG chen XIN QI ZHIWEI GUO JIAJUN WANG FENG WU YONG SUN YUNHUI LI HAITAO jiang LEI SHI JIAN zi HONG chen MOE Key Laboratory of Advanced Micro-Structured Materials School of Physics Science and EngineeringTongji UniversityShanghai 200092China State Key Laboratory of Surface Physics Key Laboratory of Micro-and Nano-Photonic Structures(Ministry of Education)and Department of PhysicsFudan UniversityShanghai 200433China School of Optoelectronic Engineering Guangdong Polytechnic Normal UniversityGuangzhou 510665China

Bound states in the continuum(BICs)in artificial photonic structures have received considerable attention since they offer unique methods for the extreme field localization and enhancement of light-matter interactions.Usually,the symmetry-protected BICs are located at high symmetric points,while the positions of accidental BICs achieved by tuning the parameters will appear at some points in momentum space.Up to now,to accurately design the position of the accidental BIC in momentum space is still a challenge.Here,we theoretically and experimentally demonstrate an accurately designed accidental BIC in a two-coupled-oscillator system consisting of bilayer gratings,where the optical response of each grating can be described by a single resonator model.By changing the interlayer distance between the gratings to tune the propagation phase shift related to wave vectors,the position of the accidental BIC can be arbitrarily controlled in momentum space.Moreover,we present a general method and rigorous numerical analyses for extracting the polarization vector fields to observe the topological properties of BICs from the polarization-resolved transmission spectra.Finally,an application of the highly efficient second harmonic generation assisted by quasi-BIC is demonstrated.Our work provides a straightforward strategy for manipulating BICs and studying their topological properties in momentum space.

关键词： polarization tuning resonator

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Chain Dynamics Heterogeneity in Plasticized Poly(vinyl butyral)(PVB) as Elucidated by Solid-State NMR

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Chinese Journal of Polymer Science 2024年第1期42卷 113-124,I0010页

作者： Jing Lv Xu chen zi-Shuo Wu Ya-Hui Li Wei chen National Synchrotron Radiation Laboratory Anhui Provincial Engineering Laboratory of Advanced Functional Polymer FilmCAS Key Laboratory of Soft Matter ChemistryUniversity of Scienceand Technology of ChinaHefei 230026China

The chain dynamics heterogeneity of the poly(vinyl butyral)(PVB) plasticized by triethylene glycol bis(2-ethylhexa noate)(TEG-EH) was investigated by various solid-state NMR techniques.The plasticized PVB shows two domains in distinct molecular dynamics differences,namely,rigid and soft domains,where the latter is the plasticizer-rich domain.The time domain low field NMR was first used to investigate the dynamics heterogeneity of the plasticized PVB,and the results show the decreasing activated energy of components in the soft domain of plasticized PVB(E_a=20.2 kJ/mol) as compared with that of the pristine one(E_a=24.3 kJ/mol).Detailed dynamics heterogeneity was obtained by high-field NMR with site-specific features.The quadrupole-echo ~2H-NMR was adopted to elucidate the dynamics heterogeneity of the vinyl alcohol(VA) units,where only the hydroxyl group of VA is deuterated.The ~1H-^(13)C WISE NMR spectra show that there is not much difference in the mobility of the VB unit in PVB with and without plasticizer,whereas the glass transition temperature differed by approximately 53℃.This is further supported by Torchia's T_1 relaxation measurements.The origin of such an unusual phenomenon is attributed to the critical role of the remaining VA(~22%) in the soft domain,where the VA units locally aggregate through hydrogen bonding.Also,the existence of a mobility gradient in the VB unit has been demonstrated.Moreover,the mobility difference for VB with different stereo-geometry(meso or racemic conformation) is observed for the first time.This indicates the importance of modulating the ratio of meso over racemic VB for controlling the macroscopic perfo rmance of PVB.

关键词： Poly(vinyl butyral) Dynamics heterogeneity Plasticizer Solid state NMR

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Ruxolitinib improves the inflammatory microenvironment,restores glutamate homeostasis,and promotes functional recovery after spinal cord injury

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Neural Regeneration Research 2024年第11期19卷 2499-2512页

作者： jiang Cao Xiao Yu Jingcheng Liu Jiaju Fu Binyu Wang Chaoqin Wu Sheng Zhang Hongtao chen zi Wang Yinyang Xu Tao Sui Jie Chang Xiaojian Cao Department of Orthopedics The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Trauma Surgery Subei People’s Hospital of JiangsuClinical Medical College of Yangzhou UniversityYangzhouJiangsu ProvinceChina Department of Orthopedics Zhongda HospitalSoutheast UniversityNanjingJiangsu ProvinceChina Department of Orthopedic Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.

关键词： astrocytes EAAT2 excitotoxicity glutamate homeostasis JAK-STAT pathway locomotor function neurotoxicity ruxolitinib spinal cord injury transcriptome analysis

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Pig H3K4me3,H3K27ac,and gene expression profiles reveal reproductive tissue-specific activity of transposable elements

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Zoological Research 2024年第1期45卷 138-151页

作者： Tao jiang Zhi-Min Zhou zi-Qi Ling Qing Zhang Zhong-zi Wu Jia-Wen Yang Si-Yu Yang Bin Yang Lu-Sheng Huang National Key Laboratory of Pig Genetic Improvement and Germplasm Innovation Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Regulatory sequences and transposable elements(TEs)account for a large proportion of the genomic sequences of species;however,their roles in gene transcription,especially tissue-specific expression,remain largely unknown.Pigs serve as an excellent animal model for studying genomic sequence biology due to the extensive diversity among their wild and domesticated populations.Here,we conducted an integrated analysis using H3K27ac ChIP-seq,H3K4me3 ChIP-seq,and RNA-seq data from 10 different tissues of seven fetuses and eight closely related adult pigs.We aimed to annotate the regulatory elements and TEs to elucidate their associations with histone modifications and mRNA expression across different tissues and developmental stages.Based on correlation analysis between mRNA expression and H3K27ac and H3K4me3 peak activity,results indicated that H3K27ac exhibited stronger associations with gene expression than H3K4me3.Furthermore,1.45%of TEs overlapped with either the H3K27ac or H3K4me3 peaks,with the majority displaying tissue-specific activity.Notably,a TE subfamily(LTR4C_SS),containing binding motifs for SIX1 and SIX4,showed specific enrichment in the H3K27ac peaks of the adult and fetal ovaries.RNA-seq analysis also revealed widespread expression of TEs in the exons or promoters of genes,including 4688 TE-containing transcripts with distinct development stage-specific and tissue-specific expression.Of note,1967 TE-containing transcripts were enriched in the testes.We identified a long terminal repeat(LTR),MLT1F1,acting as a testis-specific alternative promoter in SRPK2(a cell cycle-related protein kinase)in our pig dataset.This element was also conserved in humans and mice,suggesting either an ancient integration of TEs in genes specifically expressed in the testes or parallel evolutionary patterns.Collectively,our findings demonstrate that TEs are deeply embedded in the genome and exhibit important tissue-specific biological functions,particularly in the reproductive organs.

关键词： Transposable elements Porcine Histone modification Alternative promoter TE-containing transcript

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Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance

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Cancer Communications 2024年第2期44卷 205-225页

作者： chen Ming-Kun chen zi-Xian Cai Mao-Ping chen Hong chen Zhuang-Fei Zhao Shan-Chao Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhouGuangdongP.R.China The Third Clinical College Southern Medical UniversityGuangzhouGuangdongP.R.China Luoyang Key Laboratory of Organic Functional Molecules College of Food and DrugLuoyang Normal UniversityLuoyangHenanP.R.China Department of Urology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malig-nant tumor cells remain significant clinical challenges.However,there are only few effective methods to address these issues.Extracellular vesicles(EVs),actively secreted by cells,play a crucial role in intercellular information transmis-sion and cargo transportation.Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects.Nevertheless,there is an urgent need for further improvements in the isolation and purification of EVs,surface modification techniques,drug assem-bly processes,and precise recognition of tumor cells for targeted drug delivery purposes.In this review,we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance,and current challenges asso-ciated with engineered EVs are also discussed.This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

关键词： drug delivery drug resistance extracellular vesicles nanoparticles

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