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

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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 *** 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 *** 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 ***,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 ***,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular *** differences can be explained by the differential expression pattern of the transcription factor ***,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

HepG2.2.15-derived exosomes facilitate the activation and fibrosis of hepatic stellate cells

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World Journal of Gastroenterology 2024年第19期30卷 2553-2563页

作者： Yang Gao Li Li Sheng-Ning Zhang Yuan-Yi Mang Xi-Bing Zhang shi-ming Feng Department of Hepatobiliary Pancreatic and Vascular Surgery The Affiliated Calmette Hospital of Kunming Medical University and The First Hospital of KunmingKunming 650011Yunnan ProvinceChina

BACKGROUND The role of exosomes derived from HepG2.2.15 cells,which express hepatitis B virus(HBV)-related proteins,in triggering the activation of LX2 liver stellate cells and promoting liver fibrosis and cell proliferation remains *** focus was on comprehending the relationship and influence of differentially expressed microRNAs(DE-miRNAs)within these *** To elucidate the effect of exosomes derived from HepG2.2.15 cells on the activation of hepatic stellate cell(HSC)LX2 and the progression of liver *** Exosomes from HepG2.2.15 cells,which express HBV-related proteins,were isolated from parental HepG2 and WRL68 *** blotting was used to confirm the presence of the exosomal marker protein *** activation of HSCs was assessed using oil red staining,whereas DiI staining facilitated the observation of exosomal uptake by LX2 ***,we evaluated LX2 cell proliferation and fibrosis marker expression using 5-ethynyl-2′-deoxyuracil staining and western blotting,***-miRNAs were analyzed using *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were used to annotate the target genes of *** Exosomes from HepG2.2.15 cells were found to induced activation and enhanced proliferation and fibrosis in LX2 cells.A total of 27 miRNAs were differentially expressed in exosomes from HepG2.2.15 *** analysis indicated that these DE-miRNA target genes were associated with cell differentiation,intracellular signal transduction,negative regulation of apoptosis,extracellular exosomes,and RNA *** pathway analysis highlighted ubiquitin-mediated proteolysis,the MAPK signaling pathway,viral carcinogenesis,and the toll-like receptor signaling pathway,among others,as enriched in these *** These findings suggest that exosomes from HepG2.2.15 cells play a substantial role in the activation,proliferation,and fibrosis of LX2 cells and that DE-miRNAs within these exos

关键词： Hepatic stellate cells Liver fibrosis Exosomes Small RNA sequencing HepG2.2.15

Two H3K36 methyltransferases differentially associate with transcriptional activity and enrichment of facultative heterochromatin in rice blast fungus

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aBIOTECH 2024年第1期5卷 1-16页

作者： Mengting Xu Ziyue Sun Huanbin shi Jiangnan yue Xiaohui Xiong Zhongling Wu Yanjun Kou Zeng Tao Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insects Institute of BiotechnologyZhejiang UniversityHangzhou 310058China State Key Lab of Rice Biology and Breeding China National Rice Research InstituteHangzhou 310021China

Di-and tri-methylation of lysine 36 on histone H3(H3K36me2/3)is catalysed by histone methyltransferase Set2,which plays an essential role in transcriptional *** there is a single H3K36 methyltransferase in yeast and higher eukaryotes,two H3K36 methyltransferases,Ash1 and Set2,were present in many filamentous ***,their roles in H3K36 methylation and transcriptional regulation remained *** with methods of RNA-seq and ChIP-seq,we revealed that both Ash1 and Set2 are redundantly required for the full H3K36me2/3 activity in Magnaporthe oryzae,which causes the devastating worldwide rice blast ***1 and Set2 distinguish genomic H3K36me2/3-marked regions and are differentially associated with repressed and activated transcription,***,Ash1-catalysed H3K36me2 was co-localized with H3K27me3 at the chromatin,and Ash1 was required for the enrichment and transcriptional silencing of H3K27me3-occupied *** the different roles of Ash1 and Set2,in H3K36me2/3 enrichment and transcriptional regulation on the stress-responsive genes,they differentially respond to various stresses in ***,we reveal a novel mechanism by which two H3K36 methyltransferases catalyze H3K36me2/3 that differentially associate with transcriptional activities and contribute to enrichment of facultative heterochromatin in eukaryotes.

关键词： Ash1 Facultative heterochromatin H3K36me2/3 Magnaporthe oryzae Set2 Transcriptional regulation

Participant Heterogeneity of Systemic Scleroderma Interventional Trials Worldwide

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International Journal of Dermatology and Venereology 2024年第2期7卷 99-107页

作者： Li-Qing shi shi-Hang Zhou Ping-Lang Ruan Bo Zhang yue Xin Cheng Zhao Xu Yao Jing-Ru Tian Qian-Jin Lu Hospital for Skin Diseases(Institute of Dermatology) Chinese Academy of Medical Sciences and Peking Union Medical CollegeNanjingJiangsu 210042China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases Chinese Academy of Medical SciencesNanjingJiangsu 210042China Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs NanjingJiangsu 210042China Department of Dermatology Hunan Key Laboratory of Medical Epigenomicsthe Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

Objective:Heterogeneity of participants in clinical trials distorts intervention ***,factors associated with participant heterogeneity in randomized clinical trials(RCTs)focusing on systemic sclerosis(SSc)are not *** conducted this systematic review to establish normative standards for future research and help develop management ***:Three databases and 4 registries were searched to identify characteristics of SSc RCTs across different *** of bias was assessed by the Cochrane Collaboration’s tool and logistic regression was performed to calculate crude and adjusted odds ***:In total,261 trials met our inclusion *** quality of SSc RCTs worldwide was relatively poor,with no trend of improvement in recent years,and only 12.2%were ranked as having a low risk of *** with a low risk of bias as well as single-center,single-country,or open-label trials tended to have better participant adherence than trials with a high risk of bias and multiple-center,multiple-country,or double-blind ***,trial registration and primary outcome definition contributed to high *** income was also relevant;participant adherence in high-income countries,but not in upper-and lower-middle-income countries,was significantly altered by different ***:Overall,the risk of bias,national income,and trial design may lead to participant heterogeneity of SSc RCTs and ultimately confound the general clinical utility of the *** with a rigorous design and transparent conduction protocol are crucial for obtaining unbiased data that can serve as a reference and for maintaining the fundamental repeatability of SSc RCTs.

关键词： systemic sclerosis randomized clinical trials heterogeneity participant adherence national income risk of bias

Seasonal compensation implied no weakening of the land carbon sink in the Northern Hemisphere under the 2015/2016 El Niño

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Science China Earth Sciences 2024年第1期67卷 281-294页

作者： Fangzhong shi Xiuchen WU Xiaoyan LI Philippe CIAIS Hongyan LIU Chao yue Yuting YANG Shulei ZHANG Shushi PENG Yi YIN Benjamin POULTER Deliang CHEN State Key Laboratory of Earth Surface Processes and Resource Ecology Beijing Normal UniversityBeijing 100875China Faculty of Geographical Science Beijing Normal UniversityBeijing 100875China Key Laboratory of Tibetan Plateau Land Surface Processes and Ecological Conservation Qinghai Normal UniversityXining 810016China Research and Development Center for Watershed Environmental Eco-Engineering Beijing Normal University(Zhuhai)Zhuhai 519085China Laboratoire des Sciences du Climat et de l’Environnement(LSCE) CEA-CNRS-UVSQUMR821291191Gif-sur-YvetteFrance College of Urban and Environmental Science MOE Laboratory for Earth Surface ProcessesPeking UniversityBeijing 100871China State Key Laboratory of Hydroscience and Engineering Department of Hydraulic EngineeringTsinghua UniversityBeijing 100084China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) School of Atmospheric SciencesSun Yat-sen UniversityGuangzhou 510275China California Institute of Technology PasadenaCA 91125USA Biospheric Sciences Laboratory NASA Goddard Space Flight CenterGreenbeltMaryland 20771USA Regional Climate Group Department of Earth SciencesUniversity of GothenburgGothenburg SE-40530Sweden

The recurrent extreme El Niño events are commonly linked to reduced vegetation growth and the land carbon sink over many but discrete regions of the Northern Hemisphere(NH).However,we reported here a pervasive and continuous vegetation greening and no weakened land carbon sink in the maturation phase of the 2015/2016 El Niño event over the NH(mainly in the extra-tropics),based on multiple evidences from remote sensing observations,global ecosystem model simulations and atmospheric CO_(2)*** discovered a significant compensation effect of the enhanced vegetation growth in spring on subsequent summer/autumn vegetation growth that sustained vegetation greening and led to a slight increase in the land carbon sink over the spring and summer of 2015(average increases of 23.34%and 0.63%in net ecosystem exchange from two independent datasets relative to a 5-years average before the El Niño event,respectively)and spring of 2016(6.82%),especially in the extra-tropics of the NH,where the water supply during the pre-growing-season(November of the previous year to March of the current year)had a positive *** seasonal compensation effect was much stronger than that in 1997 and 1998 and significantly alleviated the adverse impacts of the 2015/2016 El Niño event on vegetation growth during its maturation *** legacy effect of water supply during the pre-growing-season on subsequent vegetation growth lasted up to approximately six *** findings highlight the role of seasonal compensation effects on mediating the land carbon sink in response to episodic extreme El Niño events.

关键词： El Niño Seasonal compensation effect Vegetation greening Land carbon sink Net ecosystem exchange Legacy effect

Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library

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Journal of Pharmaceutical Analysis 2024年第5期14卷 722-732页

作者： shi-Qi Wang Xun Zhao Li-Jun Zhang yue-Mei Zhao Lei Chen Jin-Lin Zhang Bao-Cheng Wang Sheng Tang Tom Yuan Yaozuo Yuan Mei Zhang Hian Kee Lee Hai-Wei shi Jiangsu Institute for Food and Drug Control Nanjing210019China School of Pharmacy China Pharmaceutical UniversityNanjing211112China School of Pharmacy Nanjing University of Chinese MedicineNanjing210046China Chinese Pharmacopoeia Commission Beijing100061China Nanjing Well Pharmaceutical Group Co. Ltd.Nanjing210018China School of Environmental and Chemical Engineering Jiangsu University of Science and TechnologyZhenjiangJiangsu212003China University of Massachusetts Amherst Amherst01003USA Department of Chemistry National University of SingaporeSingapore117543Singapore

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual *** similar structures and polarities of PS20 components make accurate separation,identification,and quantification *** this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple *** separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD *** polysorbate compound database and library were expanded over 7-time compared to the commercial *** method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process ***-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different *** method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to ***-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

关键词： Polysorbate 20 Component Database Discrimination Degradation

Subsurface multi-physical characterization of mountain excavation and city construction in loess plateau with a fiber-optic sensing system

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第8期16卷 2935-2946页

作者： Jie Liu Bin shi Kai Gu Meng-Ya Sun Jun-Cheng Yao He-ming Han School of Earth Sciences and Engineering Nanjing UniversityNanjingJiangsu210023China Frontiers Science Center for Critical Earth Material Cycling Nanjing UniversityNanjing210023China School of Earth Sciences and Engineering Hohai UniversityNanjing210098China

Mountain excavation and city construction(MECC)projects being launched in the Loess Plateau in China involve the creation of large-scale artificial *** the subsurface evolution characteristics of the artificial land is essential,yet ***,we use an improved fiber-optic monitoring system for its subsurface multi-physical *** system enables us to gather spatiotemporal distribution of various parameters,including strata deformation,temperature,and ***’an New District was selected as a case study to conduct refined in-situ monitoring through a 77 m-deep borehole and a 30 m-long *** reveal that the ground settlement involves both the deformation of the filling loess and the underlying intact ***,the filling loess exhibits a stronger creep capability compared to underlying intact *** deformation along the profile is unevenly distributed,with a positive correlation with soil *** accumulation has been observed at the interface between the filling loess and the underlying intact loess,leading to a significant ***,the temperature and moisture in the filling loess have reached a new equilibrium state,with their depths influenced by atmospheric conditions measuring at 31 m and 26 m,*** refined investigation allows us to identify critical layers that matter the sustainable development of newly created urban areas,and provide improved insights into the evolution mechanisms of land creation.

关键词： Mountain excavation and city construction Fiber-optic monitoring Multi-physical characterization Compacted loess

Dynamic interwell connectivity analysis of multi-layer waterflooding reservoirs based on an improved graph neural network

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Petroleum Science 2024年第2期21卷 1062-1080页

作者： Zhao-Qin Huang Zhao-Xu Wang Hui-Fang Hu shi-ming Zhang Yong-Xing Liang Qi Guo Jun Yao School of Petroleum Engineering China University of Petroleum(East China)Qingdao266580ShandongChina Exploration and Development Research Institute Shengli OilfieldSINOPECDongying257015ShandongChina

The analysis of interwell connectivity plays an important role in the formulation of oilfield development plans and the description of residual oil distribution. In fact, sandstone reservoirs in China's onshore oilfields generally have the characteristics of thin and many layers, so multi-layer joint production is usually adopted. It remains a challenge to ensure the accuracy of splitting and dynamic connectivity in each layer of the injection-production wells with limited field data. The three-dimensional well pattern of multi-layer reservoir and the relationship between injection-production wells can be equivalent to a directional heterogeneous graph. In this paper, an improved graph neural network is proposed to construct an interacting process mimics the real interwell flow regularity. In detail, this method is used to split injection and production rates by combining permeability, porosity and effective thickness, and to invert the dynamic connectivity in each layer of the injection-production wells by attention *** on the material balance and physical information, the overall connectivity from the injection wells,through the water injection layers to the production layers and the output of final production wells is established. Meanwhile, the change of well pattern caused by perforation, plugging and switching of wells at different times is achieved by updated graph structure in spatial and temporal ways. The effectiveness of the method is verified by a combination of reservoir numerical simulation examples and field example. The method corresponds to the actual situation of the reservoir, has wide adaptability and low cost, has good practical value, and provides a reference for adjusting the injection-production relationship of the reservoir and the development of the remaining oil.

关键词： Graph neural network Dynamic interwell connectivity Production-injection splitting Attention mechanism Multi-layer reservoir

Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

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Cancer Biology & Medicine 2024年第7期21卷 636-650页

作者： ming Bai Yao Lu Chunmei shi Jianwei Yang Wei Li Xianli Yin Chenghui Huang Lin Shen Liangzhi Xie Yi Ba Department of GI Medical Oncology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin Key Laboratory of Digestive CancerTianjin 300060China Fujian Medical University Union Hospital Fuzhou 350001China Fujian Provincial Cancer Hospital Fuzhou 350014China Cancer Center The First Hospital of Jilin UniversityChangchun 130021China Department of Medical Oncology Gastroenterology and Urology Hunan Cancer HospitalAffiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of Oncology The Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Bejing)Peking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering Research Center of Protein and Antibody Sinocelltech Ltd.Bejing 100176China Department of Cancer Center Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100010China

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical *** with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and *** primary endpoints were the objective response rate(ORR)and *** secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,*** ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,*** treatment-related adverse events(TRAEs)were ***,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination ***:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety *** head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration ***04229537).

关键词： Colorectal cancer SCT-I10A SCT200 epidermal growth factor receptor programmed cell death 1