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GRK2-YAP signaling is implicated in pulmonary arterial hypertension development

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中华医学杂志(英文版) 2024年第7期137卷 846-858页

作者： Ye Peng Deng Yunfei Gu Yue Liu Pengfei Luo jie Pu jiangqin chen jingyu Huang Yu Wang Nanping ji yong chen Shaoliang Wuxi People’s Hospital Wuxi jiangsu 300247 Institute of Vascular Medicine The Chinese University of Hong Kong Hongkong 999077 Health Science Center East China Normal University Shanghai 200241 School of Pharmacy Division of Cardiovascular Molecular Laboratory jiangsu 210004 Third Clinical College Nanjing Medical University Nanjing jiangsu 210006 China Division of Cardiovascular Laboratory Nanjing First Hospital Division of Pulmonary Surgery

Background: Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods: GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specificGrk2-knockout mice (Grk2?SM22), and littermate controls (Grk2flox/flox) were grouped into control and hypoxia mice (n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels ofGrk2 and Yes-associated protein (YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays.Results: The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated inGrk2?SM22 mice compared with littermate controls. The amelioration of PH inGrk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling.In vitro study further confirmed thatGRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression ofGRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferat

关键词： Pulmonary arterial hypertension GRK2 YAP Pulmonary artery smooth muscle cell Hypoxia

Four Triterpene Oligoglycosides from the seeds of Aesculus Chinensis

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Chinese Chemical Letters 1999年第4期10卷 291-294页

作者： jing ZHAO Xiu Wei YANG Yu Xin CUI Xue Hui LIU Shu Yan LIU Hong Ying ZHI ji yong chen Fa Bing ZHU Yun Li XUE and Dian Bo LIU (National Laboratory of Natural and Biomimetic Drugs, Beijing Medical University ,Beijing 1 00083)(Yantai Luye Pharmaceutical Natl. Lab. Nat. and Biomimetic Drugs Beijing Medical University Beijing 100083 China Yantai Luye Pharmaceutical Co. Ltd. 43 Yingbin Road Yantai Shandong 264001 China

A pair of novel geometrically isomeric triterpenoid saponins named escins IVa and IVb, together with known escins Ia and Ib. were isolated from the seeds of Aesculus chinensis. Their structures were determined on the ... 详细信息

关键词： Aesculus chinensis hippocastanaceae escins Ia Ib IVa Ivb X-ray analysis

The Role of Adipose Tissue-derived Exosomes in Chronic Metabolic Disorders

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Current Medical Science 2024年第3期44卷 463-474页

作者： Rui HE yong chen Division of Endocrinology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Laboratory of Endocrinology & Metabolism Key Laboratory of Vascular Aging of the Ministry of EducationTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Branch of National Clinical Research Center for Metabolic Diseases Wuhan430030China

Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body metabolism.Exosomes are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms.However,the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated.In this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders.Moreover,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.

关键词： exosome adipose tissue obesity diabetes chronic metabolic disorder miRNA

Review of Iron-Based Catalysts for Carbon Dioxide Fischer-Tropsch Synthesis

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Transactions of Tianjin University 2024年第2期30卷 178-197页

作者： ji-Yue jia Yu-Ling Shan yong-Xiao Tuo Hao Yan Xiang Feng De chen State Key Laboratory of Heavy Oil Processing China University of PetroleumQingdao 266580China College of Chemical Engineering Qingdao University of Science and TechnologyQingdao 266042China Department of Chemical Engineering Norwegian University of Science and Technology7491 TrondheimNorway

Capturing and utilizing CO_(2)from the production process is the key to solving the excessive CO_(2)emission problem. CO_(2)hydrogenation with green hydrogen to produce olefins is an effective and promising way to utilize CO_(2)and produce valuable chemicals. The olefins can be produced by CO_(2)hydrogenation through two routes, i.e., CO_(2)-FTS (carbon dioxide Fischer- Tropsch synthesis) and MeOH (methanol-mediated), among which CO_(2)-FTS has significant advantages over MeOH in practical applications due to its relatively high CO_(2)conversion and low energy consumption potentials. However, the CO_(2)-FTS faces challenges of difficult CO_(2)activation and low olefins selectivity. Iron-based catalysts are promising for CO_(2)-FTS due to their dual functionality of catalyzing RWGS and CO-FTS reactions. This review summarizes the recent progress on iron-based catalysts for CO_(2)hydrogenation via the FTS route and analyzes the catalyst optimization from the perspectives of additives, active sites, and reaction mechanisms. Furthermore, we also outline principles and challenges for rational design of high-performance CO_(2)-FTS catalysts.

关键词： CO_(2)hydrogenation Olefins CO_(2)-FTS Iron-based catalysts

Research on the influences of motion characteristics of jetting projectile charge under water

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Defence Technology（防务技术） 2024年第3期33卷 411-425页

作者： Xing chen yong-gang Lu Institute of Systems Engineering China Academy of Engineering PhysicsMianyang 621900SichuanChina

Shaped charge warhead is important for enhancing the damage performance of underwater weapons.This paper used finite element analysis software and based on JPC water penetration experiments to examine the influence of liner parameters(wall thickness,material),charge aspect ratio,and stand-off distance on the movement characteristics of JPC in water.The findings reveal that the head diameter of the JPC increases and experiences significant erosion after entering the water,the effective length of the JPC in water undergoes two distinct phases:a growth phase and a decrease phase,with the velocity of the JPC decaying exponentially.Increasing the liner thickness,stand-off distance and the charge aspect ratio can improve the erosion resistance and the velocity retention capacity of the JPC.The optimal ranges for liner thickness and stand-off distance are 0.0363D_(k) to 0.0545D_(k)(D_(k) is the charge diameter),the stand-off distance should be within 1.0D_(k).After the charge aspect ratio higher than 1.25,the charge structure exerts minimal influence the movement characteristics of the JPC in water.Material density plays a crucial role in the velocity decay pattern of the JPC during penetration.JPC with higher densities exhibit superior velocity retention capabilities in water,with the velocity decay pattern converging if the densities are similar.Consequently,copper,tantalum and tungsten liners are deemed appropriate for underwater shaped charge warhead.Finally,the results will provide an important reference for the design of underwater shaped charge warhead.

关键词： JPC Movement characteristics Underwater penetration Numerical simulation

Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 4-13页

作者： ji-Yao Sheng Zi-Fan Meng Qiao Li yong-Sheng Yang Department of Hepatobiliary and Pancreatic Surgery the Second Hospital of Jilin UniversityChangchun 130041China jilin Engineering Laboratory for Translational Medicine of Hepatobiliary and Pancreatic Diseases the Second Hospital of Jilin UniversityChangchun 130041China

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://***/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

关键词： Cirrhotic portal hypertension Target drug Primary prevention Bleeding

Detection and analysis of serum bile acid profile in patients with colonic polyps

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World Journal of Clinical Cases 2024年第13期12卷 2160-2172页

作者： Xin ji Hong chen School of Medicine Southeast UniversityNanjing 210009Jiangsu ProvinceChina Department of Gastroenterology Zhongda Hospital Southeast UniversityNanjing 210009Jiangsu ProvinceChina

BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationship between the serum BA profile and colonic polyps.AIM To study the serum BA profile detection results of patients with colonic polyps,and analyze the correlation between BA and colonic polyps.METHODS From January 1,2022,to June 1,2023,204 patients with colonic polyps who were diagnosed and treated at Zhongda Hospital Southeast University were chosen as the study subjects,and 135 non-polyp people who underwent physical examination were chosen as the control group.Gathering all patients'clinical information,typical biochemical indicators,and BA profile.RESULTS Compared with the control group,the serum levels of taurocholic acid,glycocholic acid,glycochenodeoxycholic acid,and taurochenodeoxycholic acid in the colonic polyp group were significantly higher than those in the control group,while the content of deoxycholic acid(DCA)was lower than that in the control group(P<0.05).When colonic polyps were analyzed as subgroups,it was shown that there was a strong correlation between changes in the BA profile and polyp diameter,location,morphology,pathological kind,etc.CONCLUSION The serum BA profile showed significant changes in patients with colonic polyps,with a significant increase in primary conjugated BA content and a decrease in secondary free bile acid DCA content.There is a certain correlation between primary free BA and pathological parameters of polyps.

关键词： Serum Bile acid profile Colonic polyps Bile acid metabolism

Physics-Informed Neural Networks with Two Weighted Loss Function Methods for Interactions of Two-Dimensional Oceanic Internal Solitary Waves

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Journal of Systems Science & Complexity 2024年第2期37卷 545-566页

作者： SUN Junchao chen yong TANG Xiaoyan School of Mathematical Sciences Key Laboratory of Mathematics and Engineering Applications(Ministry of Education)&Shanghai Key Laboratory of PMMPEast China Normal UniversityShanghai 200241China College of Mathematics and Systems Science Shandong University of Science and TechnologyQingdao 266590China

The multiple patterns of internal solitary wave interactions(ISWI)are a complex oceanic phenomenon.Satellite remote sensing techniques indirectly detect these ISWI,but do not provide information on their detailed structure and dynamics.Recently,the authors considered a three-layer fluid with shear flow and developed a(2+1)Kadomtsev-Petviashvili(KP)model that is capable of describing five types of oceanic ISWI,including O-type,P-type,TO-type,TP-type,and Y-shaped.Deep learning models,particularly physics-informed neural networks(PINN),are widely used in the field of fluids and internal solitary waves.However,the authors find that the amplitude of internal solitary waves is much smaller than the wavelength and the ISWI occur at relatively large spatial scales,and these characteristics lead to an imbalance in the loss function of the PINN model.To solve this problem,the authors introduce two weighted loss function methods,the fixed weighing and the adaptive weighting methods,to improve the PINN model.This successfully simulated the detailed structure and dynamics of ISWI,with simulation results corresponding to the satellite images.In particular,the adaptive weighting method can automatically update the weights of different terms in the loss function and outperforms the fixed weighting method in terms of generalization ability.

关键词： Internal solitary wave interactions KP equation PINN method weighted loss function method

Pyrolysis Empirical Modeling of Polyester Glass Fiber Reinforced Plastics Using Sestak-Berggren Model Method

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Journal of Thermal Science 2024年第2期33卷 725-738页

作者： NAN Wei ji Wenhui YUAN Yanping YUAN Zhongyuan SUN yong School of Mechanical Engineering Southwest Jiaotong UniversityChengdu610031China CRRC Changchun Railway Vehicles Co. LtdChangchun130062China

Polyester Glass Fiber Reinforced Plastic(Polyester GFRP),a thermosetting plastic comprised of glass fiber and polyester polymer compounds,is extensively utilized in high-speed trains.Unraveling its pyrolysis mechanism is crucial as it significantly influences the combustion characteristics and fire safety aspects.Currently,kinetic research on polyester GFRP primarily focuses on employing the Coats-Redfern method to derive a theoretical kinetic model.However,the pyrolysis process of polyester GFRP is complex and the aforementioned theoretical model fails to accurately describe the pyrolysis mechanism.Therefore,this study seeks to utilize the Sestak and Berggren(SB) model as a methodological approach to reveal the complex reaction mechanism during the pyrolysis process.Based on thermogravimetric analysis,the entire pyrolysis process of polyester GFRP is divided into two primary stages.Furthermore,model-free methods are employed to ascertain the activation energy and pre-exponential factor.The results show that the fitted empirical models of the two main pyrolysis stages are f(α)=(1-α)^(1.47)[-ln(1-α)]^(1.50) and f(α)=(1-α)^(1.77)[-ln(1-α)]^(1.72),respectively.The predicted results are in good agreement with experimental data under different heating rates,which indicates that the empirical model can sufficiently describe the pyrolysis process of polyester GFRP.

关键词： polyester GFRP model-fitting methods empirical models pyrolysis