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Acta Pharmaceutica Sinica B 2024年第4期14卷 1592-1604页

作者： Yuanjin Zhang Junze Huang Shengbo Huang Jie Liu Luyao Deng Chenmeizi Liang Yuanqing Guo Bingyi Yao Xin Wang Changning Maternity and infant Health Hospital and School of Life Sciences Shanghai Key Laboratory of Regulatory BiologyEast China Normal UniversityShanghai 200241China

Organic anion-transporting polypeptides IB1(OATPIB1)plays a crucial role in the transport of ***,there are too few animal models related to OATPIB1,especially humanized animal *** this study,the human SLCOIB1 cDNA was inserted into the second exon of the rat Slcolb2 gene using CRISPR/Cas9 *** characteristics of statins were conducted in wild-type(WT),humanized OATPIB1(hOATPIB1),and OATPIB2 knockout(OATPIB2 KO)rats,*** results showed that human OATPIB1 was successfully expressed in rat liver and exhibited transport ***,the pharmacokinetic results revealed that OATPIB1 exhibited varying uptake levels of pivastatin,rosuvastatin,and fluvastatin,leading to different levels of exposure within the *** results were consistent with those obtained from in vitro experiments using overexpressed cell *** conclusion,we established a novel humanized SLCOIBI transgenic rat model to assess the role of human OATPIB1 in the uptake of different *** different uptake mediated by OATPIB1 may be an important reason for the different efficacy of *** hOATPIB1 rat is a promising model for improving the prediction of human drug transport.

关键词： CRISPR/Cas9 Drug transport Drug disposition Geneediting Humanized rat model OATP1B1 SLCO1B1 Statins

Glucagon-like peptide 1 agonists are potentially useful drugs for treating metabolic dysfunction-associated steatotic liver disease

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World Journal of Gastroenterology 2024年第30期30卷 3541-3547页

作者： Maurizio Soresi Lydia Giannitrapani Department of Health Promotion Sciences Maternal and Infant CareInternal Medicine and Medical Specialties(PROMISE)University of PalermoPalermo 90127Italy

In this editorial,we comment on Yin et al’s recently published Letter to the *** particular,we focus on the potential use of glucagon-like peptide 1 receptor agonists(GLP-1RAs)alone,but even more so in combination therapy,as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease(MASLD),the new definition of an old condition,non-alcoholic fatty liver disease,which aims to better define the spectrum of steatotic *** is well known that GLP-1RAs,having shown outstanding performance in fat loss,weight loss,and improvement of insulin resistance,could play a role in protecting the liver from progressive *** clinical trials have shown that,among GLP-1RAs,semaglutide is a safe,well-studied therapeutic choice for MASLD patients;however,most studies demonstrate that,while semaglutide can reduce steatosis,including steatohepatitis histological signs(in terms of inflammatory cell infiltration and hepatocyte ballooning),it does not improve *** of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the *** particular,GLP-1RAs associated with antifibrotic drug therapy,dual glucose-dependent insulinotropic polypeptide(GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis,liver biochemistry,and non-invasive fibrosis tests than ***,although to date there are no definitive indications from international drug agencies,there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD,one that will certainly include the use of GLP-1RAs as combination therapy.

关键词： Non-alcoholic fatty liver disease Glucagon-like peptide 1 Semaglutide Liver fibrosis Therapy

Effect of SARS-CoV-2 infection in early pregnancy on placental development

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Science China(Life Sciences) 2024年第3期67卷 622-625页

作者： Shanru Yi Liping Wang Mengting Wang Wei Hong Ben Xu Xiaoying He Mengtian Yang Zhiping Wu Beiying Wang Guang Yang Shijun Shen Xinyu Cui Ruixue Wang Kai Wang Hong Wang Xiaocui Li Shaorong Gao Cizhong Jiang Jiayu Chen Clinical and Translation research Center of Shanghai First Maternity and infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Frontier Science Center for Stem cell research Tongji UniversityShanghai 200092China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai 201204China

Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have ... 详细信息

关键词： pregnancy fetal Effect

Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy

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Protein & Cell 2024年第6期15卷 460-473页

作者： Chenxiang Xi Zihui Yan Dandan Bai Yalin Zhang Beiying Wang Xiaoxiao Han Li Wu Xiaohui Shi Zhiyi Hu Ming Tang Zhongqu Su Yingdong Liu Binya Liu Jiqing Yin Hong Wang Xiaocui Li Yanping Zhang Shaorong Gao Wenqiang Liu Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Jiaxing Maternity and Child Health Care Hospital Jiaxing 314050China

The current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)remains a threat to pregnant ***,the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly ***,we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early *** to control placentas,SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks ***,subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal ***,the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second *** study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.

关键词： fetal alterations pregnancy

Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science China(Life Sciences) 2024年第10期67卷 2132-2148页

作者： Mengting Wang Liping Wang Yanxin Huang Zhibin Qiao Shanru Yi Weina Zhang Jing Wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and Translational research Center of Shanghai First Maternity and infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Tenth People’s Hospital School of MedicineTongji UniversityShanghai 200072China Frontier Science Center for Stem Cell research Tongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Shanghai Institute of Stem Cell research and Clinical Translation Shanghai 200120China

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription,the epigenome and ***,previous studies using knockdown(KD)or knockout(KO)models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles,as well as compensatory effects among TET family members,which has made the understanding of the enzymatic role of TET not accurate *** solve this problem,we successfully generated mice catalytically inactive for specific Tet members(Tetm/m).We observed that,compared with the reported KO mice,mutant mice exhibited distinct developmental defects,including growth retardation,sex imbalance,infertility,and perinatal ***,Tetm/mmouse embryonic stem cells(mESCs)were successfully established but entered an impaired developmental program,demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA ***,Tet3,traditionally considered less critical for m ESCs due to its lower expression level,had a significant impact on the global hydroxymethylation,gene expression,and differentiation potential of ***,there were common regulatory regions between Tet1 and Tet3 in pluripotency *** summary,our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

infant feces-derived Bifidobacterium breve CCFM1078 inhibits the occurrence of rheumatoid cachexia by IRS1/PI3K/Akt signaling pathway

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Food Science and Human Wellness 2024年

作者： Bowen Li Mengfan Ding Chen Chi Guoxun Shi Xiaoming Liu Jianxin Zhao Paul Ross Catherine Stanton Wei Chen Bo Yang State Key Laboratory of Food Science and Resources， Jiangnan University School of Food Science and Technology， Jiangnan University Department of Rheumatology， Jiangnan University Medical Center International Joint research Center for Probiotics & Gut Health， Jiangnan University APC Microbiome Ireland， University College Cork Teagasc Food research centre National Engineering research Center for Functional Food， Jiangnan University

This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia （RC）. Twenty-four female Wistar rats were assigned to three groups: CON group （normal saline by gavage）， CIA group （collagen-induced arthritis， normal saline by gavage）， and CCFM1078 group (collagen-induced arthritis， 3×109CFU/rat/day B breve CCFM1078 gavage). The results demonstrated that B. breve CCFM1078 not only improved skeletal muscle function in CIA rats， but also modulated the gut microbiota， skeletal muscle metabolism and hormone levels， reduced inflammation in the knee joint and skeletal muscles， decreased activity of the NF-κB inflammatory signaling pathway， enhanced the IRS1/PI3K/Akt signaling pathway， promoted skeletal muscle differentiation， and maintained skeletal muscle fiber diameter， consequently slowing down the progression of RC. These findings suggested that B. breve CCFM1078 may have a beneficial role as part of a dietary intervention for RC， enhancing overall therapeutic effects.

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Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

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Protein & Cell 2024年第7期15卷 530-546页

作者： Tao Chen Yiliang Xu Xiaocui Xu Jianzhang Wang Zhiruo Qiu Yayuan Yu Xiaohong Jiang Wanqi Shao Dandan Bai Mingzhu Wang Shuyan Mei Tao Cheng Li Wu Shaorong Gao Xuan Che Department of Obstetrics and Gynecology Affiliated Women and Children Hospital of Jiaxing UniversityJiaxing 314000China Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Animal Bioengineering and Disease Prevention of Shandong Province College of Animal Science and TechnologyShandong Agricultural UniversityTaian 271018China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310013China Postgraduate training base Alliance of Wenzhou Medical University Wenzhou Medical UniversityWenzhou 325035China Jiaxing University Master Degree Cultivation Base Zhejiang Chinese Medical UniversityHangzhou 310053China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyClinical and Translational Research CenterShanghai First Maternity and Infant HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

Adenomyosis is a poorly understood gynecological disorder lacking effective *** persists regarding“invagination”and“metaplasia”*** endometrial-myometrial junction(EMJ)connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis,but its in-depth study is just *** single-cell RNA sequencing and spatial profiling,we mapped transcriptional alterations across eutopic endometrium,lesions,and *** lesions,we identified unique epithelial(LGR5+)and invasive stromal(PKIB+)subpopulations,along with WFDC1+progenitor cells,supporting a complex interplay between“invagination”and“metaplasia”theories of ***,we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin ***-cell communication differed markedly between ectopic and eutopic endometrium,with aberrant signaling in lesions involving pleiotrophin,TWEAK,and WNT *** study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified,dysfunctional signaling,and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.

关键词： adenomyosis single-cell RNA sequencing spatial transcriptomics endometrial-myometrial junction progenitor cells

Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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Science China(Life Sciences) 2024年第5期67卷 958-969页

作者： Kang Chen Wenju Liu Jiang Zhu Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Lan Kang Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell research Tongji UniversityShanghai 200092China Clinical and Translation research Center of Shanghai First Maternity&infant Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains *** existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ***,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor *** with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor *** H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII ***,we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo *** study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

关键词： ZGA lncRNA MuERV-L

Transcriptome Dynamics and Cell Dialogs Between Oocytes and Granulosa Cells in Mouse Follicle Development

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 93-106页

作者： Wenju Liu Chuan Chen Yawei Gao Xinyu Cui Yuhan Zhang Liang Gu Yuanlin He Jing Li Shaorong Gao Rui Gao Cizhong Jiang Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Clinical and Translational research Center of Shanghai First Maternity and infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell research Tongji UniversityShanghai 200092China Department of Epidemiology and Biostatistics Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjing 210029China

The development and maturation of follicles is a sophisticated and multistage *** dynamic gene expression of oocytes and their surrounding somatic cells and the dialogs between these cells are critical to this *** this study,we accurately classified the oocyte and follicle development into nine stages and profiled the gene expression of mouse oocytes and their surrounding granulosa cells and cumulus *** clustering of the transcriptomes showed the trajectories of two distinct development courses of oocytes and their surrounding somatic *** expression changes precipitously increased at Type 4 stage and drastically dropped afterward within both oocytes and granulosa ***,the number of differentially expressed genes between oocytes and granulosa cells dramatically increased at Type 4 stage,most of which persistently passed on to the later ***,cell communications within and between oocytes and granulosa cells became active from Type 4 stage *** dialogs connected oocytes and granulosa cells in both unidirectional and bidirectional ***2/3,TGFBR2/3,INHBA/B,and ACVR1/1B/2B of TGF-βsignaling pathway functioned in the follicle *** signaling pathway regulated the development of granulosa ***,many maternally DNA methylation-or H3K27me3-imprinted genes remained active in granulosa cells but silent in oocytes during ***,Type 4 stage is the key turning point when significant transcription changes diverge the fate of oocytes and granulosa cells,and the cell dialogs become active to assure follicle *** findings shed new insights on the transcriptome dynamics and cell dialogs facilitating the development and maturation of oocytes and follicles.

关键词： Folliculogenesis Oocyte Granulosa cell Transcriptome Cell dialog

Lipidomic remodeling during mammalian preimplantation embryonic development

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Life Metabolism 2024年第2期3卷 3-5页

作者： Qingran Kong Shaorong Gao Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouZhejiang 325035China Clinical and Translational research Center of Shanghai First Maternity and infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

The dynamic changes in lipids during early embryonic development in mammals have not yet been comprehensively investi*** a recent paper published in Nature Cell Biology,Zhang et *** the dynamic lipid landscapes during preimplantation embryonic development in mice and *** highlight the crucial role of lipid unsaturation in regulating embryogenesis.

关键词： Lipid al. lipids