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Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

Protein & Cell 2024年第5期15卷 364-384页

作者： Huifen lu Ying Jing chen Zhang Shuai Ma Weiqi Zhang Daoyuan Huang Bin Zhang Yuesheng Zuo Yingying Qin Guang-Hui Liu yang Yu Jing qu Si Wang Advanced Innovation center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration CASBeijing 100101China China national center for Bioinformation Beijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish center for Education and research Beijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell research center Peking UniversityThird HospitalBeijing 100191China center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of Education National Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium Beijing 100101China

The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of ***,the molecular basis of ovarian aging in higher vertebrates remains poorly ***,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate *** a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian ***,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2.Metallothionein 2.highly expressing spot(MT2.(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ***,with advanced age,a subpopulation of MT2.(high)accumulates,likely disseminating and amplifying the senescent signal *** study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

关键词： spatial transcriptome primate ovary aging senescence inflammation

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Expression and functional analysis of the rice plasma-membrane intrinsic protein gene family

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Cell research 2006年第3期16卷 277-286页

作者： Lei Guo~1 Zi Yi Wang~1 Hong Lin~1 Wei Er Cui~1 Jun chen~1 Meihua Liu~1 Zhang Liang chen~(1,2. Li Jia qu~(1,2. Hongya Gu~(1,{2. Peking-Yale Joint {2. center for Plant Molecular Genetics and AgroBiotechnology,national Laboratoryfor Protein Engineering and Plant Genetic Engineering,College of Life Sciences,Peking University,beijing 100871,China 2.The national Plant Gene {2. center,beijing 100101,China Peking-Yale Joint research center for Plant Molecular Genetics and AgroBiotechnology National Laboratory for Protein Engineering and Plant Genetic Engineering College of Life Sciences Peking University Beijing China The national Plant Gene research {2. Beijing China

Plasma membrane intrinsic proteins (PIPs) are a subfamily of aquaporins that enable fast and controlled translocationof water across the *** this study,we systematically identified and cloned ten PIP genes from *** on thesimilarity of the amino acid sequences they encoded,these rice PIP genes were classified into two groups and designatedas OsPIPI-1 to OsPIP1-3 and OsPIP2.1 to OsPIP2.7 following the nomenclature of PIP genes in ***-PCR analysis identified three root-specific and one leaf-specific OsPIP ***,the expression profile ofeach OsPIP gene in response to salt,drought and ABA treatment was examined in *** on transgenic plantsover-expressing of either OsPIP1 (OsPIPI-1) or OsPIP2.(OsPIP2.2. in wild-type Arabidopsis,showed enhanced toler-ance to salt (100 mM of NaCl) and drought (2.0 mM of mannitol),but not to salt treatment of higher concentration (150mM of NaCl).Taken together,these data suggest a distinct role of each OsPIP gene in response to different stresses,andshould add a new layer to the understanding of the physiological function of rice PIP genes.

关键词： aquaporins PIP quantitative RT-PCR Oryza sativa organ-specific

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Arabidopsis AtBECLIN 1/AtAtg6/AtVps30 is essential for pollen germination and plant development

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Cell research 2007年第3期17卷 249-263页

作者： Genji Qin~1 Zhiqiang Ma~1 Li Zhang~1 Shufan Xing~1 Xianhui Hou~1 Jie Deng~1 Jingjing Liu~1 Zhangliang chen~(1,2. Li-Jia qu~(1,2. Hongya Gu~(1,2. ~1national Laboratory for Protein Engineering and Plant Genetic Engineering,Peking- Yale Joint {2. center for Plant Molecular Genetics and AgroBiotechnology,College of Life Sciences,Peking University,beijing 100871,China ~2.he national Plant Gene {2. center (beijing),beijing 100101,China national Laboratory for Protein Engineering and Plant Genetic Engineering Peking-Yale Joint Research Center for Plant Molecular Genetics and AgroBiotechnology College of Life Sciences Peking University Beijing 100871 China The national Plant Gene research {2. (beijing) Beijing 100101 China

Pollen germination on the surtace ot compatible stigmatic tissues is an essential step tor plant *** wereport that the Arabidopsis mutant bcl1 is male sterile as a result of the failure of pollen *** show that the bcl1mutant allele cannot be transmitted by male gametophytes and no homozygous bcl1 mutants were *** ofpollen developmental stages indicates that the bcl1 mutation affects pollen germination but not pollen ***-lar analysis demonstrates that the failure of pollen germination was caused by the disruption of AtBECLIN ***1 is expressed predominantly in mature pollen and encodes a protein with significant homology to Beclin1/Atg6/Vps30required for the processes of autophagy and vacuolar protein sorting(VPS)in *** also show that AtBECLIN 1 isrequired for normal plant development,and that genes related to autophagy,VPS and the glycosylphosphatidylinositolanchor system,were affected by the deficiency of AtBECLIN 1.

关键词： Arabidopsis thaliana AtBECLIN 1 pollen germination plant normal development

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Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

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Food Science and Human Wellness 2024年第3期13卷 1390-1401页

作者： Ting Liu Si chen Yunhe qu lujuan Zheng Xiaoxuan yang Shuhan Men Yuanning Wang Hanrui Ma Yifa Zhou Yuying Fan Engineering research center of Glycoconjugates Ministry of EducationJilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural DrugsSchool of Life SciencesNortheast Normal UniversityChangchun 130024China

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-*** pancreatic islets and enhancing insulin secretion has been therapeutic *** is the main type of polysaccharide from natural mushroom,which has potential medicinal ***,the antidiabetic property of mannogalactoglucan in T1DM has not been fully *** this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of *** and investigated the potential therapeutic value of AAMP-N in *** demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM ***-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in *** that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2.) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2.VAMP2..Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

关键词： Mannogalactoglucan Mushroom Pancreatic islets Insulin secretion Insulin synthesis Unfolded protein response(UPR) Type 1 diabetes mellitus(T1DM)

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Nickel-Catalyzed Regiodivergent Acylzincation of Styrenes with Organozincs and CO

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Chinese Journal of Chemistry 2024年第6期42卷 599-604页

作者： chenglong Wang Ning Liu Xianqing Wu Jingping qu Yifeng chen Key Laboratory for Advanced Materials and Joint International research Laboratory of Precision Chemistry and Molecular Engineering Feringa Nobel Prize Scientist Joint Research CenterFrontiers Science Center for Materiobiology and Dynamic ChemistrySchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghai200237 China Dedicated to the Special Issue of C1 Chemistry.

Transition metal-catalyzed carbometallation of unsaturated hydrocarbons constitutes one of the most efficient synthetic methodologies for the construction of C—C ***,the incorporation of organometallic reagent with the CO gas as a nucleophilic acyl synthon could enable the acylmetallation reaction,which greatly increases the horizon of carbometallation ***,we report a nickel-catalyzed regiodivergent acylzincation of o-cyano cinnamate ester and o-cyano styrene,in which the cyano moiety intramolecularly captures zinc intermediates to trigger the tandem cyclization *** protocol features mild conditions,broad substrate scope and excellent functional group tolerance,thus affording a diverse array of highly functionalized carbocyclic compounds.

关键词： Carbonylation Carbometallation Styrene Nickel Cyclization

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Timing and Spectral Analysis of the Black Hole X-Ray Binary MAXI J1803-2.8 with Insight-HXMT Data

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research in Astronomy and Astrophysics 2024年第6期24卷 209-224页

作者： Ying-chen Xu Jin-lu qu MMéndez Rui-Can Ma Long Ji Liang Zhang Yue Huang Qing-Cui Bu Li-Ming Song Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100049China Kapteyn Astronomical Institute University of GroningenP.O.BOX 8009700 AV GroningenThe Netherlands Dongguan Neutron Science center Dongguan 523808China School of Physics and Astronomy Sun Yat-Sen UniversityZhuhai 519082China Institut für Astronomie und Astrophysik Kepler Center for Astro and Particle PhysicsEberhard Karls UniversitätSand 1D-72076 TübingenGermany

We present a comprehensive analysis of the 2.2. outburst of MAXI J1803–2.8 utilizing observations of the Insight-Hard X-ray Modulation Telescope(Insight-HXMT)spanning from the low hard state to the high soft *** the Insight-HXMT data set,compared to the previous work,we identify a more prolonged presence of typeC quasi-periodic oscillations(QPOs)with centroid frequencies ranging from~0.16 to 6.3 Hz,which present correlations with the hardness ratio and the photon index of the Comptonized *** QPO frequencies less than~2.Hz,the QPO phase lags are hard(photons of 10–19 keV arrive later than those of 1–4 keV),while at higher frequencies,the lags become soft at and above~4 ***,the spectra in all Insight-HXMT observations consist of a multi-color blackbody component and a Comptonized component,as commonly observed in classical black hole X-ray *** analyze state transitions and the evolution of accretion geometry in this *** fitted inner disk radius increases abnormally during the low hard state,hypothesized to result from the corona condensing onto the inner ***,two significant drops in flux are observed during the soft intermediate state,maybe implying changes in the corona/jet and the disk,respectively.

关键词： X-rays:binaries accretion accretion disks stars:black holes

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A First-principles Study on the Adhesion Strength,Interfacial Stability,and Electronic Properties of Mg/Mg_(2.Y Interface

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Acta Metallurgica Sinica(English Letters) 2024年第3期37卷 537-550页

作者： Yunxuan Zhou wenjun Tian quan Dong Hailian Wang Jun Tan Xianhua chen Kaihong Zheng Fusheng Pan College of Materials Science and Engineering National Engineering Research Center for Magnesium AlloysChongqing UniversityChongqing 400044China State Key Laboratory of Mechanical Transmission Chongqing UniversityChongqing 400044China Institute of New Materials Guangdong Academy of SciencesGuangzhou 510650China

The interfacial microstructures and configurations directly affect the comprehensive properties of the composites,but their interfacial adhesion mechanism is complicated to expound by experimental *** this work,based on the stacking sequence of the Mg/Mg_(2.Y interface models,nine different Mg/Mg_(2.Y interface configurations with top site,bridge site,and hollow site(HCP)under Mg1,Mg_(2.,and Y terminations were successfully constructed and systematically explored by first-principles *** results showed that the Mg_(2.Y(0001)surface with Y termination is the most stable when the yttrium chemical potential()is less than-1.09 eV;otherwise,Mg_(2.Y(0001)surface with Mg1 termination is the most *** seven-layer Mg(0001)and eleven-layer Mg_(2.Y(0001)slabs are employed to reflect the bulk-like interior ***,the Mg(0001)/Mg_(2.Y(0001)with the Y-HCP stacking has the largest interface thermodynamic stability with the value of 2.383 J/m^(2. in all interface configurations owing to its largest work of *** addition,the interfacial energy of Y-HCP stacking is significantly smaller than those of Mg1-HCP when is approximately less than-0.55 eV,showing that it is more *** thermodynamic stability of Mg/Mg_(2.Y with Y-HCP is due to Mg-Y chemical bonds formed between Mg and Y ***,the Mg/Mg_(2.Y interfaces are strong interfaces based on the Griffith fracture theory.

关键词： Mg/Mg_(2.Y interface Interface stability Work of adhesion Electronic structure First-principles calculations

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Disruption of phytoene desaturase gene results in albino and dwarf phenotypes in Arabidopsis by impairing chlorophyll, carotenoid, and gibberellin biosynthesis

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Cell research 2007年第5期17卷 471-482页

作者： Genji Qin1 Hongya Gu1,2.Ligeng Ma1,3 Yiben Peng1 Xing Wang Deng1,3 Zhangliang chen1 Li-Jia qu1,2. 1 Peking-Yale Joint center for Plant Molecular Genetics and Agrobiotechnology, {2. Laboratory for Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, beijing 100871, China 2.The {2. Plant Gene research center (beijing), beijing 100101, China 3 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven Connecticut 62.2.-8104, USA Peking-Yale Joint center for Plant Molecular Genetics and Agrobiotechnology National Laboratory for Protein Engineering and Plant Genetic Engineering College of Life Sciences Peking University Beijing China The national Plant Gene research {2. (beijing) Beijing China Department of Molecular Cellular and Developmental Biology Yale University New Haven Connecticut USA

Carotenoids play an important role in many physiological processes in plants and the phytoene desaturase gene （PDS3）encodes one of the important enzymes in the carotenoid biosynthesis pathway. Here we report the identification andanalysis of a T-DNA insertion mutant of PDS3 gene. Functional complementation confirmed that both the albino anddwarf phenotypes of the pds3 mutant resulted from functional disruption of the PDS3 gene. Chloroplast development wasarrested at the proplastid stage in the pds3 mutant. Further analysis showed that high level of phytoene was accumulatedin the pds3 mutant. Addition of exogenous GA3could partially rescue the dwarf phenotype, suggesting that the dwarfphenotype of the pds3 mutant might be due to GA deficiency. Microarray and RT-PCR analysis showed that disruptingPDS3 gene resulted in gene expression changes involved in at least 2. metabolic pathways, including the inhibition ofmany genes in carotenoid, chlorophyll, and GA biosynthesis pathways. Our data suggest that the accumulated phytoenein the pds3 mutant might play an important role in certain negative feedbacks to affect gene expression of diverse cel-lular pathways.

关键词： Arabidopsis thaliana phytoene desaturase albino dwarf microarray analysis

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Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

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Zoological research 2024年第1期45卷 108-124页

作者： Huanpeng lu Jinwei Chai Zijian Xu Jiena Wu Songzhe He Hang Liao Peng Huang Xiaowen Huang Xi chen Haishan Jiang Shaogang qu Xueqing Xu Department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong-Hong Kong-Macao Greater Bay Area center for Brain Science and Brain-Inspired Intelligence GuangzhouGuangdong 510515China Key Laboratory of Mental Health of the Ministry of Education Southern Medical UniversityGuangzhouGuangdong 510515China Department of Dermatology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Neurology Ganzhou Hospital-Nanfang HospitalSouthern Medical UniversityGanzhouJiangxi 341001China

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its *** peptides may thus present therapeutic potential for *** this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for *** vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant *** the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2.3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2.related factor 2.Nrf2.pathway *** focal adhesion kinase(FAK)and p38 were also identified as regulatory *** the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated *** the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative *** findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

关键词： Cath-KP Peptide Parkinson’s disease Oxidative stress Neuroprotection

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Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1726-1741页

作者： Yanjiang Xing yangfeng Hou Tianfei Fan Ran Gao Xiaohang Feng Bolun Li Junling Pang wenjun Guo Ting Shu Jinqiu Li Jie yang Qilong Mao Ya luo Xianmei Qi Peiran yang Chaoyang Liang Hongmei Zhao Wenhui chen Jing Wang chen Wang State Key Laboratory of Respiratory Health and Multimorbidity Institute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005China Department of lung Transplantation National Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina–Japan Friendship HospitalInstitute of Respiratory MedicineChinese Academy of Medical SciencesBeijing 100029China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300051China The State Key Laboratory of Complex Severeand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100005China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610044China

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

关键词： Phosphodiesterase 4B Pulmonary hypertension Endothelial-to-mesenchymal transition

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