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New insight into the role of exosomes in idiopathic membrane nephropathy

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BIOCELL 2024年第1期48卷 21-32页

作者： JIANHONG LIU KAI HE HAN wang XIAOHONG CHENG Department of Nephrology Shaanxi Provincial Hospital of Traditional Chinese MedicineXian710000China School of BasicMedical Sciences and State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese MedicineChengdu611137China Department of Pathophysiology West China College of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu610041China

Exosomes,nanoscale extracellular vesicles(EVs)derived from the invagination of the endosomal membrane,are secreted by a majority of cell *** carriers of DNA,mRNA,proteins,and microRNAs,exosomes are implicated in regulating biological activities under physiological and pathological ***-derived exosomes,which vary in origin and function,may either contribute to the pathogenesis of disease or represent a potential therapeutic *** nephropathy(MN),an autoimmune kidney disease characterized by glomerular damage,is a predominant cause of nephrotic ***,MN,especially idiopathic membranous nephropathy(IMN),often results in end-stage renal disease(ESRD),affecting approximately 30%of patients and posing a considerable economic challenge to healthcare *** substantial research,therapeutic options remain ineffective at halting IMN progression,underscoring the urgent need for innovative *** evidence has implicated exosomes in IMN’s pathophysiology;Providing a fresh perspective for the discovery of novel biomarkers and therapeutic *** review aims to scrutinize recent developments in exosome-related mechanisms in IMN and evaluate their potential as promising therapeutic targets and diagnostic biomarkers,with the hope of catalyzing further investigations into the utility of exosomes in MN,particularly IMN,ultimately contributing to improved patient outcomes in these challenging disease settings.

关键词： Exosomes Biomarkers Membranous nephropathy Therapeutic targets

Clinical significance,molecular characterization,and immune microenvironment analysis of coagulation-related genes in clear cell renal cell carcinoma

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Cancer Innovation 2024年第1期3卷 29-49页

作者： Weihao Chen Xupeng Zhao Yongliang Lu Hanfeng wang Xiyou wang Yi wang Chen Liang Zhuomin Jia Wei Ma Department of Urology The Third Medical Center of PLA General HospitalBeijingChina School of Medicine Nankai UniversityTianjinChina Medical Service Department The PLA General HospitalBeijingChina Senior Department of Otolaryngology-Head&Neck Surgery The Sixth Medical Center of PLA General HospitalBeijingChina

Background:Numerous studies have revealed a tight connection between tumor development and the coagulation ***,the effects of coagulation on the prognosis and tumor microenvironment(TME)of clear cell renal cell carcinoma(ccRCC)remain poorly ***:We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation ***quently,we examined variations in the overall survival(OS),genomic profiles,and TME characteristics between these *** develop a prognostic coagulation-related risk score(CRRS)model,we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression *** also created a nomogram to aid in the clinical application of the risk score,evaluating the relationships between the CRRS and the immune microenvironment,responsiveness to immunotherapy,and targeted *** clinical significance of PLAUR and its biological function in ccRCC were also further ***:There were significant differences in clinical features,prognostic stratification,genomic variation,and TME characteristics between the two coagulation-related *** established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC *** variations in survival outcomes were observed between the high-and low-risk *** nomogram was proficient in predicting the 1-,3-,and 5-year ***,the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ***,we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient *** knockdown notably inhibited ccRCC cell proliferation and ***:Our data suggested that CRRS may be employed as a reliable predictive biomarker that can pro

关键词： clear cell renal cell carcinoma coagulation immunotherapy risk score tumor immune microenvironment

Kaempferol ameliorated levodopa-induced dyskinesia in experimental rats: A role of brain monoamines, cFOS, FosB, Parkin, Pdyn, TH, and p-JNK

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BIOCELL 2024年第3期48卷 513-523页

作者： PEI QIN MIAO LIU XIN wang JIANHUA MA Geriatrics Department Chengde Central HospitalChengde067000China

Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are *** reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinﬂ*** is anotherﬂavonoid bearing these ***:To evaluate neuroprotective activity of kaempferol in dyskinetic ***:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 *** were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor *** administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in ***,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with ***:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.

关键词： AIMs cFOS Kaempferol Levodopa-induced dyskinesia Pdyn

A reinforcement learning approach to vehicle coordination for structured advanced air mobility

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Green Energy and Intelligent Transportation 2024年第2期3卷 20-37页

作者： Sabrullah Deniz Yufei Wu Yang Shi Zhenbo wang Department of Mechanical Aerospaceand Biomedical EngineeringThe University of TennesseeKnoxvilleTN37996USA

Advanced Air Mobility(AAM)has emerged as a pioneering concept designed to optimize the efficacy and ecological sustainability of air *** core objective is to provide highly automated air transportation services for passengers or cargo,operating at low altitudes within urban,suburban,and rural *** seeks to enhance the efficiency and environmental viability of the aviation sector by revolutionizing the way air travel is *** a complex aviation environment,traffic management and control are essential technologies for safe and effective AAM *** of the most difficult obstacles in the envisioned AAM systems is vehicle coordination at merging points and *** escalating demand for air mobility services,particularly within urban areas,poses significant complexities to the execution of such *** this study,we propose a novel multi-agent reinforcement learning(MARL)approach to efficiently manage high-density AAM operations in structured *** approach provides effective guidance to AAM vehicles,ensuring conflict avoidance,mitigating traffic congestion,reducing travel time,and maintaining safe ***,intelligent learning-based algorithms are developed to provide speed guidance for each AAM vehicle,ensuring secure merging into air corridors and safe passage through *** validate the effectiveness of our proposed model,we conduct training and evaluation using BlueSky,an open-source air traffic control simulation *** the simulation of thousands of aircraft and the integration of real-world data,our study demonstrates the promising potential of MARL in enabling safe and efficient AAM *** simulation results validate the efficacy of our approach and its ability to achieve the desired outcomes.

关键词： Advanced Air Mobility(AAM) Urban Air Mobility(UAM) Air Traffic Control(ATC) Multi-Agent Reinforcement Learning(MARL)

Metal-N_(4)model single‐atom catalyst with electroneutral quadri‐pyridine macrocyclic ligand for CO_(2)electroreduction

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Carbon Energy 2024年第8期6卷 122-133页

作者： Jian‐Zhao Peng Yin‐Long Li Yao‐Ti Cheng Fu‐Zhi Li Bo Cao Qing wang Xian Yue Guo‐Tao Lai Yang‐Gang wang Jun Gu Department of Chemistry Southern University of Science and TechnologyShenzhenGuangdongChina Institute for Catalysis Hokkaido UniversitySapporoJapan

Metal–N–C single‐atom catalysts,mostly prepared from pyrolysis of metalorganic precursors,are widely used in heterogeneous *** metal sites with diverse local structures coexist in this type of material and it is challenging to characterize the local structure,a reliable structure–property relationship is difficult to *** macrocyclic complexes adsorbed on carbon support are well‐defined models to mimic the singleatom ***–N_(4)site with four electroneutral pyridine‐type ligands embedded in a graphene layer is the most commonly proposed structure of the active site of single‐atom catalysts,but its molecular counterpart has not been *** this work,we synthesized the conjugated macrocyclic complexes with a metal center(Co,Fe,or Ni)coordinated with four electroneutral pyridinic ligands as model catalysts for CO_(2)*** comparison,the complexes with anionic quadri‐pyridine macrocyclic ligand were also *** Co complex with the electroneutral ligand expressed a turnover frequency of CO formation more than an order of magnitude higher than that of the Co complex with the anionic *** ab initio molecular dynamics simulations based on the well‐defined structures of the model catalysts indicate that the Co complex with the electroneutral ligand possesses a stronger ability to mediate electron transfer from carbon to CO_(2).

关键词： ab initio molecular dynamics CO_(2)reduction electrocatalysis model catalyst single‐atom catalyst

COL4A2 enhances thyroid cancer cell proliferation through the AKT pathway

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Oncology Research 2024年第9期32卷 1467-1478页

作者： LIANG HE WEI HAN KAI YUE XUDONG wang Department of Maxillofacial and Otorhinolaryngological Oncology Tianjin Medical University Cancer Institute and HospitalKey Laboratory of Basic and Translational Medicine on Head&Neck Cancer(Tianjin)Key Laboratory of Cancer Prevention and TherapyTianjin Cancer InstituteNational Clinical Research Center for CancerTianjin300060China Department of Thyroid&Breast Surgery Luoyang Central HospitalLuoyang471000China Department of Otorhinolaryngological Surgery Zhengzhou Central HospitalZhengzhou450000China

Objectives:Thyroid cancer(THCA)is the most common malignant tumor in endocrine system and the incidence has been increasing *** the number of patients dying from THCA has also gradually risen because the incidence continues to increase,so the mechanisms related to effective targets is necessary to improve the *** study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer(THCA)cell proliferation and the associated ***:Bioinformatics analysis revealed that COL4A2 was closely associated with cancer ***4A2 expression in THCA tissues was analyzed using immunohistochemistry,and survival information was determined via Kaplan-Meier *** expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot *** formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity,*** of COL4A2 was identified by Gene set enrichment analysis(GSEA).The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse ***:Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of *** patients with high COL4A2 expression had shorter recurrence-free *** of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and *** use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell *** use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse ***:COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA.

关键词： Thyroid cancer(THCA) Proliferation COL4A2 AKT pathway Biomarker cancer progression

Intra-arterial tenecteplase during thrombectomy for acute stroke(BRETIS-TNK II):rationale and design

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Stroke & Vascular Neurology 2024年第1期9卷 59-65页

作者： Zi-Ai Zhao Jing Qiu Wei Li Thanh Nguyen Shouchun wang Huaizhang Shi Ming Wei Feng wang Di Li Hui-Sheng Chen Department of Neurology General Hospital of Northern Theater CommandShenyangLiaoning ProvinceChina Neurology RadiologyBoston Medical CenterBostonMassachusettsUSA Department of Neurology First Affiliated Hospital of Jilin UniversityChangchunJilinChina Department of Neurosurgery First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Department of Neurosurgery Tianjin Huanhu HospitalTianjinTianjinChina Department of Interventional Therapy First Affiliated Hospital of Dalian Medical UniversityDalianChina Neurological Intervention Department Dalian Municipal Central HospitalDalianLiaoningChina

Background Our recent pilot study suggests intra-arterial tenecteplase(TNK)during the first pass of endovascular treatment(EVT)seems safe,may increase first-pass reperfusion and good outcome in acute ischaemic stroke(AIS)patients with large-vessel occlusion(LVO).Aims To determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom *** size estimates A maximum of 380 patients are required to test the superiority hypothesis with 80%power according to a two-side 0.05 level of significance,stratified by age,gender,baseline systolic blood pressure,prestroke modified Rankin Scale(mRS),baseline National Institute of Health stroke scale,baseline ASPECTS,time from onset to groin puncture,intravenous thrombolysis before EVT,stroke territory and stroke *** Intra-arterial TNK during thrombectomy for acute stroke(BRETIS-TNK II)study is a prospective,randomised,adaptive enrichment,open-label,blinded end point,multicentre *** AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:*** experimental group will be treated with intra-arterial infusion of TNK during *** control group will be treated with standard *** The primary end point is a favourable outcome,defined as an mRS score of 0–2 at 90 *** primary safety end point is symptomatic intracranial haemorrhage within 48 hours,which is defined as an increase in the National Institutes of Health Stroke Scale score of≥4 points as a result of the intracranial *** The results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.

关键词： rational stratified TNK

A Novel Method for Aging Prediction of Railway Catenary Based on Improved Kalman Filter

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Structural Durability & Health Monitoring 2024年第1期18卷 73-90页

作者： Jie Li Rongwen wang Yongtao Hu Jinjun Li School of Electrical Engineering and Automation Henan Institute of TechnologyXinxiang453003China Technology Center Sichuan Injet Electric Co.Ltd.Deyang618000China Embedded System Research Institute Xinxiang Engineering Research Center for Intelligent Condition Monitoring of MachineryXinxiang453003China

The aging prediction of railway catenary is of profound significance for ensuring the regular operation of electrified ***,in real-world scenarios,accurate predictions are challenging due to various *** paper addresses this challenge by proposing a novel method for predicting the aging of railway catenary based on an improved Kalman filter(KF).The proposed method focuses on modifying the priori state estimate covariance and measurement error covariance of the KF to enhance accuracy in complex *** comparing the optimal displacement value with the theoretically calculated value based on the thermal expansion effect of metals,it becomes possible to ascertain the aging status of the *** improve prediction accuracy,a railway catenary aging prediction model is constructed by integrating the Takagi-Sugeno(T-S)fuzzy neural network(FNN)and *** this model,an adaptive training method is introduced,allowing the FNN to use fewer fuzzy *** inputs of the model include time,temperature,and historical displacement,while the output is the predicted ***,the KF is enhanced by modifying its prior state estimate covariance and measurement error *** modifications contribute to more accurate ***,a low-power experimental platform based on FPGA is implemented to verify the effectiveness of the proposed *** test results demonstrate that the proposed method outperforms the compared method,showcasing its superior performance.

关键词： Railway catenary Takagi-Sugeno fuzzy neural network Kalman filter aging prediction

Research on Flexible Job Shop Scheduling Based on Improved Two-Layer Optimization Algorithm

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Computers, Materials & Continua 2024年第1期78卷 811-843页

作者： Qinhui Liu Laizheng Zhu Zhijie Gao Jilong wang Jiang Li College of Mechanical and Electrical Engineering Harbin Engineering UniversityHarbin150001China

To improve the productivity,the resource utilization and reduce the production cost of flexible job shops,this paper designs an improved two-layer optimization algorithm for the dual-resource scheduling optimization problem of flexible job shop considering workpiece ***,a mathematical model is established to minimize the maximum completion ***,an improved two-layer optimization algorithm is designed:the outer layer algorithm uses an improved PSO(Particle Swarm Optimization)to solve the workpiece batching problem,and the inner layer algorithm uses an improved GA(Genetic Algorithm)to solve the dual-resource scheduling ***,a rescheduling method is designed to solve the task disturbance problem,represented by machine failures,occurring in the workshop production ***,the superiority and effectiveness of the improved two-layer optimization algorithm are verified by two typical *** case results show that the improved two-layer optimization algorithm increases the average productivity by 7.44% compared to the ordinary two-layer optimization *** setting the different numbers of AGVs(Automated Guided Vehicles)and analyzing the impact on the production cycle of the whole order,this paper uses two indicators,the maximum completion time decreasing rate and the average AGV load time,to obtain the optimal number of AGVs,which saves the cost of production while ensuring the production *** research combines the solved problem with the real production process,which improves the productivity and reduces the production cost of the flexible job shop,and provides new ideas for the subsequent research.

关键词： Dual resource scheduling workpiece batching rescheduling particle swarm optimization genetic algorithm