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Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

Science China Life Sciences 2025年第01期 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei chen jiayun chen Ge Song Chuanbin Yang Yali Song Jigang Wang Department of Reproductive Medicine Dongguan Maternal and Child Health Care Hospital Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Reproductive Medicine Center Foshan Women and Children Hospital State Key Laboratory of Antiviral Drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

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Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1661-1676页

作者： Junhui chen Qian Zhang Jinan Guo Di Gu Jing Liu Piao Luo Yunmeng Bai jiayun chen Xinzhou Zhang Sheng Nie Chunbo chen Yulin Feng Jigang Wang National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine Jiangxi University of Chinese MedicineNanchang 330006China Department of Pulmonary and Critical Care Medicine Shenzhen Institute of Respiratory Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalFirst Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan UniversityShenzhen 518020China School of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Nephrology Nanfang Hospitalthe First Affiliated Hospital of Southern Medical UniversityGuangzhou 510515China Department of Critical Care Medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China State Key Laboratory for Quality Esurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Oncology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and *** natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or *** this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell *** results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer *** findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.

关键词： Rosmarinic acid Diabetic nephropathy scRNA sequencing Injury Oxidative stress Infiammation Proteomics

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Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening

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Acta Pharmaceutica Sinica B 2021年第1期11卷 222-236页

作者： Xiaofei chen Yunlong Wu Chun chen Yanqiu Gu Chunyan Zhu Suping Wang jiayun chen Lei Zhang Lei Lv Guoqing Zhang Yongfang Yuan Yifeng Chai Mingshe Zhu Caisheng Wu School of Pharmacy Naval Medical UniversityShanghai 200433China Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiamen 361102China Department of Pharmacy Shanghai Ninth People’s HospitalShanghai Jiao Tong UniversityShanghai 201999China Department of Pharmacy Shanghai Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200438China MassDefect Technologies PrincetonNJ 08540USA

Lianhuaqingwen(LHQW)capsule,a herb medicine product,has been clinically proved to be effective in coronavirus disease 2019(COVID-19)pneumonia ***,human exposure to LHQW components and their pharmacological effects remain largely ***,this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological *** of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach,leading to detection of 132 LHQW prototype and metabolite components,which were absorbed via the gastrointestinal tract and formed via biotransformation in human,*** with data from screening by comprehensive 2 D angiotensin-converting enzyme 2(ACE2)biochromatography,8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic *** show that rhein,forsythoside A,forsythoside I,neochlorogenic acid and its isomers exhibited high inhibitory effect on *** the first time,this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to *** also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines.

关键词： Lianhuaqingwen capsule PATBS COVID-19 ACE2 Biochromatography Comprehensive 2D analysis In vivo exposure Surface plasma response Molecular docking

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Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid

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Journal of Pharmaceutical Analysis 2022年第6期12卷 839-851页

作者： Xiaojuan Jiang Yihua Lin Yunlong Wu Caixia Yuan Xuli Lang jiayun chen Chunyan Zhu Xinyi Yang Yu Huang Hao Wang Caisheng Wu Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cell Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiamenFujian361102China Department of Respiratory and Critical Care Medicine The Third Clinical Medical CollegeFujian Medical UniversityFuzhou350122China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Xiamen UniversityXiamenFujian361003China Laboratory of Pharmacology/Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China School of Pharmacy Ningxia Medical UniversityYinchuan750004China School of Pharmacy Minzu University of ChinaBeijing100081China Key Laboratory of Ethnomedicine(Minzu University of China) Ministry of EducationBeijing100081China Institute of National Security Minzu University of ChinaBeijing100081China

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of ***,the pharmacological components of GC for pneumonia treatment are rarely *** An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many ***,GAHJ was selected as a compound preparation for the study of GC in the treatment of *** conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three *** the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in *** analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective *** experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in *** following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and ***,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

关键词： Glycyrrhizae Radix et Rhizoma Pneumonia Active components Inducible nitric oxide synthase Glycyrrhetinic acid

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Chemical proteomic profling with photoaffinity labeling strategy identifies antimalarial targets of artemisinin

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Chinese Chemical Letters 2023年第12期34卷 460-465页

作者： Peng Gao jiayun chen Peng Sun Jianyou Wang Huan Tang Fei Xia Liwei Gu Huimin Zhang chen Wang Yin Kwan Wong Yinhua Zhu chengchao Xu Jigang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Pharmaceutical College Henan UniversityKaifeng 475004China Shandong Academy of Chinese Medicine Ji'nan 250014China Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Afiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China

Present research on the antimalarial mechanisms of artemisinin(ART)is mainly focused on covalent drug binding targets alkylated by free radicals,while non-covalent binding targets have rarely been ***,we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical *** results demonstrated that ART can bind to par-asite proteins by both covalent and non-covalent modification,and these may jointly contribute to the antimalarial *** work enriches the research on the antimalarial targets of ART,and provides a new perspective for further exploring the antimalarial mechanism of ART.

关键词： Artemisinin Antimalarial Chemical proteomic Target identification Photoaffinity probe

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Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

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Journal of Pharmaceutical Analysis 2023年第7期13卷 817-829页

作者： jiayun chen Xueling He Yunmeng Bai Jing Liu Yin Kwan Wong Lulin Xie Qian Zhang Piao Luo Peng Gao Liwei Gu Qiuyan Guo Guangqing cheng chen Wang Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdong518020China

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ *** on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain *** study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental *** scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during *** could restore neutrophils’chemotaxis and immune function in the septic *** inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during *** also promoted the differentiation and activity of splenic B cells in mice with *** results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the ***,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

关键词： Artesunate Sepsis Single-cell RNA sequencing Immunomodulatory activity

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Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

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Journal of Pharmaceutical Analysis 2023年第8期13卷 908-925页

作者： Qiuyan Guo Jiangpeng Wu Qixin Wang Yuwen Huang Lin chen Jie Gong Maobo Du Guangqing cheng Tianming Lu Minghong Zhao Yuan Zhao Chong Qiu Fei Xia Junzhe Zhang jiayun chen Feng Qiu Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China School of Chinese Materia Medica and State Key Laboratory of Component-Based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin301617China Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China College of Food Science and Engineering Institute of OceanBohai UniversityJinzhouLiaoning121013China State Key Laboratory of Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenGuangdong518033China

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii *** been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune ***,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing *** present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)*** TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total *** the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate *** analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling ***,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

关键词： Tripterygium glycosides tablet Acute liver injury scRNA-seq

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Investigation on the Copper Content of Matte Smelting Slag in Peirce-Smith Converter

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Journal of University of Science and Technology Beijing 2001年第3期8卷 177-181页

作者： Chunlin chen, jiayun Zhang, Meng Bai, Shoukun Wei Metallurgy School, University of Science & Technology Beijing, Beijing 100083, China Guixi Smelter, Jiangxi Copper Co. Ltd., Jiangxi 335424, China Univ Sci & Technol Beijing Met Sch Beijing 100083 Peoples R China Jiangxi Copper Co Ltd Guixi Smelter Jiangxi 335424 Peoples R China

The copper contents and its existing forms in the slags during the slag-making stage of Peirce-Smith converters in Guixi Smelter, Jiangxi Province, China have been investigated. The investigation was based on plant trials with the corresponding thermodynamic calculations and kinetic considerations. From the plant data, the total copper content in the slags was in the range of 2% to 8% (mass fraction). The mechanical entrainment of matte drops has been found to be the main cause of the copper loss. The suspension index, defined as the ratio of the mass fraction of copper in suspended matte drops in the slag to that in bulk of the matte phase, has been adopted to quantify the matte entrainment. The values of this parameter estimated in this work have been found mainly within a range of 2.5%-8.0%. The Fe3O4 content in the slag has been estimated to be the most important factor, among others, influencing the separation of slag with matte and, consequently, the copper loss from the slag.

关键词： Peirce-Smith converter copper content molten slag

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Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2300-2314页

作者： Piao Luo Dandan Liu Qian Zhang Fan Yang Yin-Kwan Wong Fei Xia Junzhe Zhang jiayun chen Ya Tian Chuanbin Yang Lingyun Dai Han-Ming Shen Jigang Wang Artemisinin Research Center Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Central People’s Hospital of Zhanjiang Zhanjiang 524037China Department of Urology the Second Clinical Medical CollegeJinan University(Shenzhen People’s Hospital)Shenzhen 518020China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Faculty of Health Sciences University of MacaoTaipaMacao 999078China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron-and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species(ROS) and inducing ferroptosis in activated hepatic stellate cells(HSCs). By using activity-based protein profiling(ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay(CETSA), we show that celastrol directly binds to peroxiredoxins(PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6,through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1(HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2,PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

关键词： Celastrol Ferroptosis Peroxiredoxin HO-1 Hepatic fibrosis ABPP Anti-oxidant Reactive oxygen species

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Thermodynamic Study on Process in Copper Converters (The Copper-making Stage)

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International Journal of Minerals,Metallurgy and Materials 2000年第3期14卷 184-188页

作者： Chunlin chen, jiayun Zhang, Tuping Zhou, Shoukun Wei, Xingxiang Lu2), Meng Bai, Jinhong Jiang ( Metallurgy School, University of Science and Technology Beijing, Beijing 100083, China Guixi Smelter, Jiangxi, 335424) Metallurgy School University of Science and Technology Beijing Beijing 100083 China Guixi Smelter Jiangxi 335424 China

Theoretical calculations were based on thermodynamic equilibrium in the multi-component and multi-phase system with heat and mass balance as well as the oxygen efficiency to take account for the effects of process kinetics. The variations of temperature, mass fractions of dissolved oxygen and sulfur in blister copper, partial pressures for O2, S2, SO2 in gas phase for the copper-making stage were calculated. The model predicted temperature, time of blowing as well as mass of the blister copper at end points for 6 heats showed a fairly good agreements with corresponding plant data. The calculated content of 0.065% and content of 0.87% in blister copper were both at reasonable levels. Compared with the so called Goto model, the present model has very much improved process description of copper-making stage as well as the prediction of end points for a copper converter by introducing the oxygen efficiency.

关键词： Peirce-Smith copper converter thermodynamic model copper-making stage

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