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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 life.The balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of OA.Currently,there is a lack of effective therapeutic strategies for OA treatment.With 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 regulators.Supported by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA therapy.This 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 treatment.Moreover,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

Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants

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Chronic Diseases and Translational Medicine 2024年第2期10卷 118-129页

作者： Huan Zhang yuxi chen Peng Xu Dan Liu Naqiong Wu Laiyuan Wang Xingbo Mo Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Department of EpidemiologySchool of Public HealthMedical College of Soochow UniversitySuzhouJiangsuChina Cardiometabolic Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Cardiovascular Epidemiology&Department of Epidemiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina MOE Key Laboratory of Geriatric Diseases and Immunology School of Public HealthCenter for Genetic Epidemiology and GenomicsMedical College of Soochow UniversitySuzhouJiangsuChina

Background Genome-wide association studies(GWAS)have identified more than a thousand loci for blood pressure(BP).Functional genes in these loci are cell-type specific.The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms(RNAm-SNPs).Methods Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium,we identified associations between RNAm-SNPs and BP.The association between RNAm-SNPs,gene expression,and BP were examined.Results A total of 355 RNAm-SNPs related to m6A,m1A,m5C,m7G,and A-to-I modification were associated with BP.The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway.The BP GWAS signals were significantly enriched with m6A-SNPs,highlighting the potential functional relevance of m6A in physiological processes influencing BP.Notably,m6A-SNPs in CYP11B1,PDE3B,HDAC7,ACE,SLC4A7,PDE1A,FRK,MTHFR,NPPA,CACNA1D,and HDAC9 were identified.Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected.RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection(AD)cases and controls.In scRNA-seq study,we identified ARID5A,HLA-DPB1,HLA-DRA,IRF1,LINC01091,MCL1,MLF1,MLXIPL,NAA16,NADK,RERG,SRM,and USP53 as differential expression genes for AD in aortic cells.Conclusion The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs,gene expression,and BP.The identified BP-associated genes in aortic cells were associated with AD.

关键词： aortic dissection blood pressure genome-wide association study RNA modification single-cell

Comprehensive analyses of the proteome and ubiquitome revealed mechanism of high temperature accelerating petal abscission in tree peony

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Horticultural Plant Journal 2024年第1期10卷 205-222页

作者： Chunying Liu Ziqi Liu Yanchao Yuan yuxi Zhang Yifu Fang Junqiang chen Shupeng Gai Key Laboratory of Plant Biotechnology in Shandong Province College of Life SciencesQingdao Agricultural UniversityQingdaoShandong 266109China Shandong Academy of Forestry JinanShandong 250014China

Tree peony(Paeonia suffruticosa Andrews)is a well-known ornamental plant with high economic value,but the short fluorescence is a key obstacle to its ornamental value and industry development.High temperature accelerates flower senescence and abscission,but the associated mechanisms are poorly understood.In this study,the tandem mass tag(TMT)proteome and label-free quantitative ubiquitome from tree peony cut flowers treated with 20℃for 0 h(RT0),20℃or 28℃for 60 h(RT60 or HT60)were examined based on morphological observation,respectively.Totally,6970 proteins and 1545 lysine ubiquitinated(Kub)sites in 844 proteins were identified.Hydrophilic residues(such as glutamate and aspartate)neighboring the Kub sites were in preference,and 36.01%of the Kub sites were located on the protein surface.The differentially expressed proteins(DEPs)and Kub-DEPs in HT60 vs RT60 were mainly enriched in ribosomal protein,protein biosynthesis,secondary metabolites biosynthesis,flavonoid metabolism,carbohydrate catabolism,and auxin biosynthesis and signaling revealed by GO and KEGG analysis,accompanying the increase of endogenous abscisic acid(ABA)accumulation and decrease of endogenous indoleacetic acid(IAA)level.Additionally,the expression patterns of six enzymes(SAMS,ACO,YUC,CHS,ANS and PFK)putatively with Kub modifications were analyzed by proteome and real-time quantitative RT-PCR.The cell-free degradation assays showed PsSAMS and PsACO proteins could be degraded via the 26 S proteasome system in tree peony flowers.Finally,a working model was proposed for the acceleration of flower senescence and abscission by high temperature.In summary,all results contributed to understanding the mechanism of flower senescence induced by high temperature and prolonging fluorescence in tree peony.

关键词： Tree peony Proteome Ubiquitome High temperature Flower senescence

CmMYB3-like negatively regulates anthocyanin biosynthesis and flower color formation during the post-flowering stage in Chrysanthemum morifolium

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Horticultural Plant Journal 2024年第1期10卷 194-204页

作者： Lijie Zhou Shenhui Liu Yiguang Wang yuxi Wang Aiping Song Jiafu Jiang Sumei chen Zhiyong Guan Fadi chen State Key Laboratory of Crop Genetics and Germplasm Enhancement The Key Laboratory of LandscapingMinistry of Agriculture and Rural AffairsCollege of HorticultureNanjing Agricultural UniversityNanjingJiangsu 210095China

Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulation decreases during the post-flowering stage still unclear,which greatly restricts design of molecular breeding in chrysanthemum.Here,a chrysanthemum SG7 R2R3 MYB transcription factor(TF),CmMYB3-like,was identified to have a function in regulating anthocyanin biosynthesis during the post-flowering stage.Quantitative real time PCR(qRT-PCR)assays showed that the expression of CmMYB3-like was gradually downregulated when anthocyanin content increased during the flowering stage and was significantly upregulated during the post-flowering stage.Genetic transformation of chrysanthemum and dual-luciferase assays in N.benthamiana leaves showed that CmMYB3-like suppressed anthocyanin accumulation by inhibiting the transcription of CmCHS and CmANS directly and that of CmF3H indirectly.However,overexpression or suppression of CmMYB3-like did not affect the biosynthesis of flavones or flavonols.Genetic transformation of chrysanthemum revealed that the overexpression of CmMYB3-like inhibited anthocyanin accumulation,but its suppression prevented the decrease in anthocyanin accumulation during the post-flowering stage.Our results revealed a crucial role of CmMYB3-like in regulating the color of petals during the post-flowering stage and provided a target gene for molecular design breeding to improve the postharvest quality of chrysanthemum.

关键词： Post-flowering stage Color fading Anthocyanins CmMYB3-like Chrysanthemum Molecular breeding

Synthesis of atomically dispersed cationic nickel-confined mesoporous ZSM-48(ANMZ-48)directed by metal complexes in amphiphilic molecules

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Science China Chemistry 2024年第1期67卷 343-350页

作者： Yu chen Quanzheng Deng Yiru Mao yuxi Fang Zhihua Cao Honggen Peng Shunai Che Lu Han School of Chemical Science and Engineering Tongji UniversityShanghai 200092China School of Chemistry and Chemical Engineering Nanchang UniversityNanchang 330031China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Resources and Environment Nanchang UniversityNanchang 330031China State Key Laboratory of Metal Matrix Composites Shanghai Key Laboratory for Molecular Engineering of Chiral DrugsShanghai Jiao Tong UniversityShanghai 200240China

The synthesis of mesoporous zeolite-anchored atomically dispersed metal catalysts(ADCs)is a considerable challenge in chemistry and materials science.Here we report the synthesis of atomically dispersed cationic nickel-confined mesoporous ZSM-48(ANMZ-48)by in situ hydrothermal reaction employing a designed tri-functional metal complex template,by which the triquaternary ammonium groups in the hydrophilic region direct the formation of ZSM-48 zeolite;the aromatic groups in the hydrophobic tail generate the mesopores through π-π stacking;and the complexes formed by nickel ions coordinated with terpyridyl groups generate atomically dispersed Ni2+confined in zeolite frameworks due to the strong sintering resistance generated by the strong coordination interaction.The ANMZ-48 is consisting of stacking of sheet-like ZSM-48 domains connected by multiply crystal twinning sharing the common(011)plane,generating abundant of imbedded mesopores with the uniform thickness of~2.4 nm and with the width of 10-50 nm.The excellent catalytic activity and stability of ANMZ-48 were also reflected in the dry reforming of methane(DRM)reaction.

关键词： atomically dispersed catalyst mesoporous zeolite ZSM-48 in situ hydrothermal synthesis the dry reforming of methane reaction

Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei chen Zheyue Shu Longxian Lv yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive disorder.Herein,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut mycobiome.As liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse models.The metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC group.The abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in HCC.Based on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were depleted.The increased abundance of C.albicans and depletion of S.cerevisiae may be hallmarks of the progression of liver cirrhosis to early HCC.Moreover,the administration of C.albicans and S.cerevisiae in the LC-HCC progression could accelerate or retard the progression of HCC.Therefore,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

Long-term in vivo chimeric cells tracking in non-human primate

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Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang Xiang Luo Shaoxing Dai yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical Research Kunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

Pan-genome analysis reveals a highly plastic genome and extensive secreted protein polymorphism in Puccinia striformis f.sp.tritici

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Journal of Genetics and Genomics 2024年第5期51卷 574-577页

作者： Jierong Wang yuxi Peng Yiwen Xu Zhiru Li Gangming Zhan Zhensheng Kang Jing Zhao College of Plant Protection Northwest A&F UniversityYanglingShaanxi 712100China State Key Laboratory of Crop Stress Biology for Arid Areas Northwest A&F UniversityYanglingShaanxi 712100China College of Life Science Northwest A&F UniversityYanglingShaanxi 712100China

The obligate biotrophic basidiomycete fungus Puccinia striformis f.***.tritici(Pst)is the causative agent of wheat stripe(yellow)rust,a disease that results in severe damage to global wheat production(chen and Kang,2017).This pathogen has a mixed reproductive mode encompassing both asexual and sexual reproduction.The asexual stage is accomplished by reinfecting wheat with urediniospores,while the sexual cycle involves five different spore types and two phylogenetically unrelated plant hosts wheat,which is the primary host,and barberry,which is the alternate host(Zhao et al.,2016).This extremely complex lifecycle facilitates large genetic variation among Pst populations,which is conducive to the emergence of new virulent races that can overcome wheat resistance genes,resulting in epidemics(chen and Kang,2017).Secreted effector proteins,the key virulence factors in fungal pathogens,can not only suppress plant immune systems but also trigger host immune responses following recognition by plant receptors(Toruno et al.,2016).

关键词： Puccinia overcome wheat

Polyphenol components in black chokeberry(Aronia melanocarpa)as clinically proven diseases control factors——an overview

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Food Science and Human Wellness 2024年第3期13卷 1152-1167页

作者： Ningxuan Gao Chi Shu Yuehua Wang Jinlong Tian yuxi Lang chenyu Jin Xingyue Cui Hanqian Jiang Shi’an Liu Zhiying Li Wei chen Hao Xu Bin Li Department of Food Science College of FoodShenyang Agricultural UniversityShenyang 110161China Department of Food Science and Nutrition College of Biosystems Engineering and Food ScienceZhejiang UniversityHangzhou 310058China Chaoyang Beihe Food Co. Ltd.Chaoyang 122100China

The black chokeberry is rich in polyphenols,including flavonoids with anthocyanins,flavanols and lavonols as the main components and a variety of phenolic acids represented by chlorogenic acid.Because of these polyphenols,black chokeberry has the effect of preventing and adjuvant therapy diseases.This study summarized the current research results on the types and contents of functional components in black chokeberry,and analyzed their digestion,absorption and metabolism in human body.On this basis,the disease control functions that have been proved effective in clinical research were reviewed and analyzed.These studies showed that black chokeberry have good prevention and adjuvant therapy effects on hyperlipidemia,hypertension,diabetes and inflammation.Because there are different functional components in black chokeberry,its prevention and treatment of the same disease can come from multiple pathways,which provides a more reliable effectiveness for the disease control of different populations.

关键词： Black chokeberry Hyperlipidemia Hypertension Diabetes Inflammation

Soxllb regulates the migration and fate determination of Müller glia-derived progenitors during retina regeneration in zebrafish

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Neural Regeneration Research 2023年第2期18卷 445-450页

作者： Kaida Song Zihao Lin Lining Cao Bowen Lu yuxi chen Shuqiang Zhang Jianfeng Lu Hui Xu Key Lab of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Shanghai YangZhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center) Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina

The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 homolog,regulates the migration and fate determination of Müller glia-derived progenitors(MGPCs)in an adult zebrafish model of mechanical retinal injury.Following a stab injury,the expression of Sox11 b was induced in proliferating MGPCs in the retina.Sox11 b knockdown did not affect MGPC formation at 4 days post-injury,although the nuclear morphology and subsequent radial migration of MGPCs were alte red.At 7 days post-injury,Sox11 b knockdown res ulted in an increased proportion of MGPCs in the inner retina and a decreased propo rtion of MGPCs in the outer nuclear layer,compared with controls.Furthermore,Sox11 b knockdown led to reduced photoreceptor regeneration,while it increased the numbe rs of newborn amacrines and retinal ganglion cells.Finally,quantitative polymerase chain reaction analysis revealed that Sox11 b regulated the expression of Notch signaling components in the retina,and Notch inhibition partially recapitulated the Sox11 b knockdown phenotype,indicating that Notch signaling functions downstream of Sox11 b.Our findings imply that Sox11 b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish,which may have critical im plications for future explorations of retinal repair in mammals.

关键词： cell migration fate determination Müllerglia Müller glia-derived progenitor Notch signaling photoreceptor retina regeneration Sox11 transcription factor zebrafish