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MicroRNA-30a inhibits cell proliferation in a sepsis-induced acute kidney injury model by targeting the YAP-TEAD complex

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Journal of Intensive Medicine 2024年第2期4卷 231-239页

作者： Junfeng su Ying Wang Jing Xie long Chen Xinxin Lin Jiandong Lin Xiongjian xiao Department of General Intensive Care Unit The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Critical Care Medicine The First Affiliated HospitalFujian Medical UniversityFuzhouChina Department of Critical Care Medicine National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouChina

Background Acute kidney injury(AKI)is a primary feature of renal complications in patients with sepsis.MicroRNA(miRNA/miR)-30a is an essential regulator of cardiovascular diseases,tumors,phagocytosis,and other physical processes,but whether it participates in sepsis-induced AKI(sepsis-AKI)is unknown.We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI.Methods The classical cecal ligation and puncture(CLP)method and lipopolysaccharide(LPS)-induced Human Kidney 2(HK-2)cells were used to establish in vivo and in vitro sepsis-AKI models.Specific pathogen-free and mature male Sprague-Dawley(SD)rats,aged 6–8 weeks(weight 200–250 g),were randomly divided into five-time phase subgroups.Fluid resuscitation with 30 mL/kg 37°C saline was administered after the operation,without antibiotics.Formalin-fixed,paraffin-embedded kidney sections were stained with hematoxylin and eosin.SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors,and compared with untreated normal controls.RNA,protein,and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),western blot,and cell counting kit-8 methods.A Dual-Luciferase Assay Kit(Promega)was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics.Results Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h(Psue 3 h after the operation in rats(P<0.05),and gradually decreased 6 h,12 h,and 24 h after CLP.Levels of miR-30a-5p and miR-30a-3p were significantly down-regulated at 3 h after LPS treatment(P<0.05),and gradually decreased in HK-2 cells.One hour after LPS(10µg/mL)treatment,TNF-αand IL-1βlevels in HK-2 cells were significantly up-

关键词： MicroRNA-30a TEAD1 YAP-TEAD complex Sepsis Acute kidney injury

Numerical study of the influence of the atmospheric pressure on the thermal environment in the passenger cabin

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Building Simulation 2024年第2期17卷 253-265页

作者： Xin su Yu Guo Zhengwei long Yi Cao Tianjin Key Lab.of Indoor Air Environmental Quality Control School of Environmental Science and EngineeringTianjin UniversityTianjin300072China Shanghai Aircraft Design and Research Institute Jinke RoadPudong DistrictShanghai201210China

The cabin air pressure remains lower than the horizontal atmospheric pressure when the airplane is in flight.Air pressure is one of the parameters that must be taken into consideration while studying the thermal environment of an airplane cabin.There are still no reference values for aircraft cabins despite the fact that numerous studies on low pressure heat transfer have demonstrated the connection between convective heat transfer coefficient(CHTC)and air pressure.In this paper,a correction method for CHTC under low pressure conditions was established by using the dummy heat dissipation in the low-pressure cabin experiment.On this basis,a thermal environment simulation model was developed,then was applied to the simulation of a seven-row aircraft cabin containing 42 passengers,and the CHTC and heat loss of dummy surface in the cabin were obtained.Finally,the results of PMV calculated by using heat dissipation and air parameters at sampling points were compared.The results show that the modified CHTC can accurately reflect the cabin thermal environment under low pressure conditions,and the correction of CHTC can be realized by adjusting the turbulent Prandtl number,which is nonlinear correlated with the pressure.The simulation results of the thermal environment in the seven-row cabin show that the CHTC changes by about 42%before and after modification.The air pressure decreases during take-off,which reduces the average CHTC of the crew surface from 5.09 W/(m^(2)·K)to 4.56 W/(m^(2)·K),but the air temperature rises by about 0.2°C as a whole.The deviation of PMV results calculated by using simulated heat loss data and using air parameters of measuring points in space is up to 0.5,but the latter is representative for calculating the thermal comfort level of the whole cabin.

关键词： low pressure aircraft cabin simulation heat dissipation convective heat transfer coefficient

Less pressure contributes to gravity-driven membrane ultrafiltration with greater performance:Enhanced driving efficiency and reduced disinfection by-products formation potential

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Journal of Environmental Sciences 2024年第3期137卷 407-419页

作者： xiaoting Wu Yufei Li Zhaoyang su long Tian Muhammad Saboor Siddique Wenzheng Yu Colleges of Forestry Northeast Forestry UniversityHarbin 150040China State Key Laboratory of Environmental Aquatic Chemistry Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China

Gravity-driven membrane(GDM)systems have been well developed previously;however,impacts of driving(i.e.,transmembrane)pressure on their performance received little attention,which may infuence GDM performance.In this study,we evaluated 4 GDM systems via altering the transmembrane pressure from 50 mbar to 150 mbar with 2 groups,treating surface water in Beijing,China.Results showed that less driving pressure was more favorable.Specifically,compared to groups(150 mbar),groups under a pressure of 50 mbar were found to have greater normalized permeability and lower total resistance.During the whole operation period,the quality of effuents was gradually improved.For example,the removal efficiency of UV254was significantly improved;particularly,under low driving pressure,the removal efficiency of UV254in PES GDM system increased by 11.91%,as compared to the corresponding system under high driving pressure.This observation was consistent with the reduction on disinfection by-products(DBPs)formation potential;groups under 50 mbar achieved better DBPs potential control,indicating the advantages of lower driving pressure.Biofilms were analyzed and responsible for these differences,and distinct distributions of bacteria communities of two GDM systems under 50 and 150 mbar may be responsible for various humic-like substances removal efficiency.Overall,GDM systems under less pressure should be considered and expected to provide suggestions on the design of GDM systems in real applications.

关键词： Ultrafiltration Gravity driven operation Membrane fouling Biofilms Disinfection by-products

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Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou School of Traditional Chinese Medicine Beijing University of Chinese Medicine

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol(LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor(LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9(PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

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Oncology Research 2024年第7期32卷 1197-1207页

作者： ANGUO WU JIAO YAN TING su CHI FENG XIN long YIRU PAN RUPEI YE TIAN XIA HANAN long JIANMING WU XIULI xiao Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou646000China The Department of Pathology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China The Department of Pathology Mianyang Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaMianyang621000China The Department of Pathology Yongchuan Hospital of Chongqing Medical UniversityChongqing402160China School of Basic Medical Sciences Southwest Medical UniversityLuzhou646000China School of Clinical Medical Sciences Southwest Medical UniversityLuzhou646000China

Breast cancer,a predominant global health issue,requires ongoing exploration of new therapeutic strategies.Palbociclib(PAL),a well-known cyclin-dependent kinase(CDK)inhibitor,plays a critical role in breast cancer treatment.While its efﬁcacy is recognized,the interplay between PAL and cellular autophagy,particularly in the context of the RAF/MEK/ERK signaling pathway,remains insufﬁciently explored.This study investigates PAL’s inhibitory effects on breast cancer using both in vitro(MCF7 and MDA-MB-468 cells)and in vivo(tumor-bearing nude mice)models.Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib(TRA),an MEK inhibitor,our research seeks to address the challenge of PAL-induced drug resistance.Ourﬁndings reveal that PAL signiﬁcantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells.However,PAL also induces protective autophagy,potentially leading to drug resistance via the RAF/MEK/ERK pathway activation.Introducing TRA effectively neutralized this autophagy,enhancing PAL’s anti-tumor efﬁcacy.A combination of PAL and TRA synergistically reduced cell viability and proliferation,and in vivo studies showed notable tumor size reduction.In conclusion,the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance,offering a new horizon in breast cancer treatment.

关键词： Palbociclib Trametinib Protective autophagy RAF/MEK/ERK MCF7 MDA-MB-468

Identification of high oxygen-consuming substances in stormwater drainage systems illicitly connected with sewage system

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Journal of Environmental Sciences 2024年第4期138卷 132-140页

作者： Chen Xu Zuxin Xu Wenhai Chu Shanshan Wu Rong xiao Lei su State Key Laboratory of Pollution Control and Resource Reuse College of Environmental Science and EngineeringTongji UniversityShanghai 200092China Ministry of Education Key Laboratory of Yangtze River Water Environment Tongji UniversityShanghai 200092China Guangzhou Resource Environmental Protection Technology Co. Ltd.Guangzhou 510030China

The dissolved oxygen content in water is an important indicator for assessing the quality of the water environment,and maintaining a certain amount of dissolved oxygen is essential for the healthy development of the ecological environment.When a water body is anoxic,the activity of anaerobic microorganisms increases and organic matter is decomposed to produce a large number of blackening and odorizing substances,resulting in black and odorous water bodies,which is a very common and typical phenomenon in China.Presently,there is still a relatively universal occurrence of illicitly connected stormwater and sewage pipes in the urban drainage pipe network in China,which makes oxygen-consuming substances be directly discharged into rivers through stormwater pipes and consume the dissolved oxygen in the water bodies,resulting in an oxygen deficiency of the water.This induces seasonal or year-round black and stink phenomena in urban rivers.Hence,identifying high oxygen-consuming substances,which lays the foundation for the subsequent removal of oxygen-consuming substances,is essential.Through a series of comparisons of water quality indicators and analysis of organic characteristics,it was found that the oxygen consumption capacity of domestic sewage was higher than that of industrial wastewater in the selected area of this study,and the oxygen-consuming substances of domestic sewage were small molecular amino acids.By comparing 20 conventional free amino acids,it was found that seven of them consumed oxygen easily,and compared with chemical oxygen consumption,biological oxygen consumption was in a leading position.

关键词： Urban drainage system Oxygen-consuming substances Domestic sewage Amino acid

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Association of complement components with risk of colorectal cancer:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2168-2180页

作者： xiao-Lin Zhu Lu Zhang su-Xia Qi Department of Gastroenterology Qingdao Municipal HospitalQingdao 266071Shandong ProvinceChina Department of Medical Administration Qingdao Municipal HospitalQingdao 266071Shandong ProvinceChina

BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the relationship between complement components and CRC risk and clinical characteristics.METHODS Searches were conducted in PubMed,the Cochrane Library,and the China National Knowledge Infrastructure database until June 1,2023.We included cohort studies encompassing participants aged≥18 years,investigating the association between complement components and CRC.The studies were of moderate quality or above,as determined by the Agency for Healthcare Research and Quality.The meta-analysis employed fixed-effects or random-effects models based on the I^(2)test,utilizing risk ratio(RR)and their corresponding 95%confidence interval(CI)for outcomes.Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity.REsuLTS Data from 15 studies,comprising 1631 participants that met the inclusion criteria,were included in the meta-analysis.Our findings indicated that protein levels of cluster of differentiation 46(CD46)(RR=3.66,95%CI:1.75-7.64,Psults demonstrated notable heterogeneity,subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies.CONCLUSION Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC,emphasi

关键词： Complement components Colorectal cancer Lymph node metastasis Systematic review Meta-analysis

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients

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World Journal of Diabetes 2024年第5期15卷 898-913页

作者： su-su Feng Si-Jing Wang Lin Guo Pan-Pan Ma xiao-long Ye Ming-Lin Pan Bo Hang Jian-Hua Mao Antoine M Snijders Yi-Bing Lu Da-Fa Ding Department of Endocrinology The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011Jiangsu ProvinceChina Biological Systems and Engineering Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720United States

BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.METHODS A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and NAFLD.External validation encompassed 172 participants.NAFLD patients were divided based on liver fibrosis scores.The analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.REsuLTS Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific BAs.In UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative correlation.Levels ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in NAFLD.The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.

关键词： Bile acid Non-alcoholic fatty liver disease Type 2 diabetes mellitus Unsaturated fatty acid

Global,regional and national burdens of bipolar disorders in adolescents and young adults:a trend analysis from 1990 to 2019

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General Psychiatry 2024年第1期37卷 122-132页

作者： Yunxi Zhong Yifan Chen xiaoying su Meiqi Wang Qixiu Li Ziming Shao long sun Centre for Health Management and Policy Research School of Public HealthCheeloo College of MedicineShandong UniversityJinanShandongChina National Health Commission of China(NHC)Key Laboratory of Health Economics and Policy Research Shandong UniversityJinanShandongChina nstitute of Health and Elderly Care Shandong UniversityJinanShandongChina

Background Bipolar disorder is identified as a cause of severe damage to the physical,psychological and social functioning of adolescents and young adults.Aims The aim of this study is to ascertain the trends in the burden of bipolar disorder among individuals aged 10-24 years at global,regional and national levels from 1990 to 2019.Methods The data analysed in this study were from the Global Burden of Diseases 2019.The numbers,rates per 100000 population,average annual percentage changes(AAPCs)of incidence,prevalence and years lived with disability(YLDs)of bipolar disorder are reported at the global,regional and national levels among individuals aged 10-24 years.Global trends by age,sex and Social Development Index(SDI)were further analysed.Results Globally,the incidence of bipolar disorder among adolescents and young adults increased from 79.21 per 100000 population(95%uncertainty interval(Ul):58.13 to 105.15)in 1990 to 84.97 per 100000 population(95%Ul:61.73 to 113.46)in 2019,AAPC 0.24(95%confidence interval(Cl):0.22 to 0.26).In the past three decades,there has been an increase in incidence,prevalence and YLDs in both males and females.The largest increase in incidence between 1990 and 2019 was observed in those aged 20-24 years old from 51.76 per 100000 population(95%Ul:26.81 to 87.20)in 1990 to 58.37 per 100000 population(95%UI:30.39 to 98.55)in 2019;AAPC 0.42(95%Cl:0.38 to 0.47).By the SDI quintile,the largest increase in incidence was observed in the middle SDl;however,the high SDI countries had the highest incidence.Regionally,the largest increase in incidence was observed in southern Latin America.At the national level,the most pronounced increase in the incidence was in Greenland.Conclusions The global increase in incidence among adolescents and young adults between 1990 and 2019 indicates that strategies to improve their mental health still need to be emphasised.

关键词： adolescent bipolar young