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N-glycosylation of Wnt3 regulates the progression of hepatocellular carcinoma by affecting Wnt/β-catenin signal pathway

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2769-2780页

作者： Xin-Zhan Zhang Xiao-Chuan Mo Zhu-Ting Wang Rong Sun Da-Quan Sun Department of Biochemistry and Molecular Biology&research center for Basic medical Sciences Guizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina

BACKGROUND Wnt/FZD-mediated signaling pathways are activated in more than 90%of hepatocellular carcinoma(HCC)cell *** a well-known secretory glycoprotein,Wnt3 can interact with FZD receptors on the cell surface,thereby activating the Wnt/β-catenin signaling ***,the N-glycosylation modification site of Wnt3 and the effect of this modification on the biological function of the protein are still *** To investigate the effect of Wnt3 N-glycosylation on the biological function of HCC *** Site-directed mutagenesis was used to verify the Wnt3 N-glycosylation sites,actinomycin D treatment was used to detect the stability of Wnt3 after site-directed mutation,the binding of the N-glycosylation site-directed mutant Wnt3 to FZD7 was observed by laser confocal microscopy,and the effects of the N-glycosylation site-directed mutation of Wnt3 on the Wnt/β-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function *** Wnt3 has two N-glycosylation-modified sites(Asn90 and Asn301);when a single site at amino acid 301 is mutated,the stability of Wnt3 is weakened;the binding ability of Wnt3 to FZD7 decreases when both sites are mutated simultaneously;and the level of proteins related to the Wnt/β-catenin signaling pathway is *** proliferation,migration and invasion are also weakened in the case of single 301 site and double-site *** These results indicate that by inhibiting the N-glycosylation of Wnt3,the proliferation,migration,invasion and colony formation abilities of liver cancer cells can be weakened,which might provide new therapeutic strategies for clinical liver cancer in the future.

关键词： Wnt3 N-glycosylation Hepatocellular carcinoma Liver cancer Wnt/β-catenin FZD7

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Macrophages in cardiovascular diseases:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2598-2641页

作者： Runkai Chen Hongrui Zhang Botao Tang Yukun Luo Yufei Yang Xin Zhong Sifei Chen Xinjie Xu Shengkang Huang Canzhao Liu Department of Cardiology Laboratory of Heart CenterHeart CenterTranslational Medicine Research CenterZhujiang HospitalSouthern Medical University253 Industrial AvenueGuangzhou 510280China State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

The immune response holds a pivotal role in cardiovascular disease *** multifunctional cells of the innate immune system,macrophages play an essential role in initial inflammatory response that occurs following cardiovascular injury,thereby inducing subsequent damage while also facilitating ***,the diverse phenotypes and phenotypic alterations of macrophages strongly associate with distinct types and severity of cardiovascular diseases,including coronary heart disease,valvular disease,myocarditis,cardiomyopathy,heart failure,atherosclerosis and aneurysm,which underscores the importance of investigating macrophage regulatory mechanisms within the context of specific ***,recent strides in single-cell sequencing technologies have revealed macrophage heterogeneity,cell–cell interactions,and downstream mechanisms of therapeutic targets at a higher resolution,which brings new perspectives into macrophage-mediated mechanisms and potential therapeutic targets in cardiovascular ***,myocardial fibrosis,a prevalent characteristic in most cardiac diseases,remains a formidable clinical challenge,necessitating a profound investigation into the impact of macrophages on myocardial fibrosis within the context of cardiac *** this review,we systematically summarize the diverse phenotypic and functional plasticity of macrophages in regulatory mechanisms of cardiovascular diseases and unprecedented insights introduced by singlecell sequencing technologies,with a focus on different causes and characteristics of diseases,especially the relationship between inflammation and fibrosis in cardiac diseases(myocardial infarction,pressure overload,myocarditis,dilated cardiomyopathy,diabetic cardiomyopathy and cardiac aging)and the relationship between inflammation and vascular injury in vascular diseases(atherosclerosis and aneurysm).Finally,we also highlight the preclinical/clinical macrophage targeting strategies and translational

关键词： diseases cardiovascular therapeutic

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In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes

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Stroke & Vascular Neurology 2024年第1期9卷 8-17,I0001-I0033页

作者： Yu Tian Mengxing Wang Yuesong Pan Xia Meng Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina National center for Neurological Diseases BeijingChina Advanced Innovation center for Human Brain Protection Capital Medical UniversityBeijingChina China National Clinical research center for Neurological Diseases BeijingChina

Introduction It remains unclear whether enlarged perivascular spaces(EPVS)predict poor clinical outcomes in patients with acute ischaemic stroke(AIS)or transient ischaemic attack(TIA).Method Data were obtained from the Third China National Stroke Registry *** estimated EPVS in basal ganglia(BG)and centrum semiovale(CSO)using a semiquantified scale(Grade from 0 to 4).Using Cox and logistic regression analyses,the associations of EPVS with 3-month and 1-year adverse outcomes(including recurrent stroke,ischaemic stroke,haemorrhagic stroke,combined vascular event,disability and mortality)were *** analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion(SAO)were *** Among 12603 patients with AIS/TIA,median age was 61.7±11.6 years,and 68.2%were *** adjusting for all potential confounders,frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke(HR 0.71,95%CI 0.55 to 0.92,p=0.01)but an increased risk of haemorrhagic stroke(HR 1.99,95%CI 1.11 to 3.58,p=0.02)at 1 year after AIS/TIA,compared with none-to-mild *** with frequent-to-severe CSO-EPVS had a decreased risk of disability(OR 0.76,95%CI 0.62 to 0.92,p=0.004)and all-cause death(HR 0.55,95%CI 0.31 to 0.98,p=0.04)within 3-month but not 1-year follow-ups,compared with those with none-to-mild *** analyses showed that both BG-EPVS(HR 0.43,95%CI 0.21 to 0.87,p=0.02)and CSO-EPVS(HR 0.58,95%CI 0.35 to 0.95,p=0.03)were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year *** BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 ***,caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

关键词： patients haemorrhagic prevention

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Prediction of the burden of road traffic injuries in Iran by 2030: Prevalence, death,and disability-adjusted life years

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Chinese Journal of Traumatology 2024年第4期27卷 242-248页

作者： Mozhgan Seif Sedigheh Edalat Ali Majidpour Azad Shirazi Somayeh Alipouri Mohsen Bayati Non-communicable Diseases research center Department of EpidemiologySchool of HealthShiraz University of Medical SciencesShirazIran Health Human Resources research center School of Health Management and Information SciencesShiraz University of Medical SciencesShirazIran Health Policy research center Institute of HealthShiraz University of Medical SciencesShirazIran

Purpose:Road traffic accidents pose a global challenge with substantial human and economic *** a high incidence of road traffic injuries,leading to a significant burden on *** studyaims to predict the future burden of road traffic injuries in Iran until 2030,providing valuable insights forpolicy-making and interventions to improve road safety and reduce the associated human and ***:This analytical study utilized time series models,specifically autoregressive integrated movingaverage(ARIMA)and artificial neural networks(ANNs),to predict the burden of road traffic accidents byanalyzing past data to identify patterns and trends in Iran until *** required data related toprevalence,death,and disability-adjusted life years(DALYs)rates were collected from the Institute forHealth Metrics and Evaluation database and analyzed using R software and relevant modeling andstatistical analysis ***:Both prediction models,ARIMA and ANNs indicate that the prevalence rates(per 100,000)of allroad traffic injuries,except for motorcyclist road injuries which have an almost flat trend,remaining ataround 430,increase by *** on estimations of both models,the rates of death and DALYs due tomotor vehicle and pedestrian road traffic injuries *** motor vehicle road injuries,estimatedtrends decrease to approximately 520 DALYs and 10 ***,for pedestrian road injuries these ratesreached approximately 300 DALYs and 6 deaths,according to the *** cyclists and other roadtraffic injuries,the predicted DALY rates by the ANN model increase to almost 50 and 8,while predictionsconducted by the ARIMA model show a static trend,remaining at 40 and approximately ***,these rates for the prediction of death rate by the ANN model increased to 0.6 and 0.1,while predictionsconducted by the ARIMA model show a static trend,remaining at 0.43 and *** to the ANNmodel,the predicted rates of DALY and death for m

关键词： Accidents Traffic Accident prevention Motorcycles Road injury Forecasting

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Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

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Oncology research 2024年第1期32卷 101-125页

作者： ROGHAYEH GHORBANI MAHMOUD GHARBAVI ALI SHARAFI ELHAM RISMANI HAMED REZAEEJAM YOUSEF MORTAZAVI BEHROOZ JOHARI Department of medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Nanotechnology research center Ahvaz Jundishapur University of Medical SciencesAhvazIran Zanjan Pharmaceutical Biotechnology research center Zanjan University of Medical SciencesZanjanIran Department of Pharmaceutical Biotechnology School of PharmacyZanjan University of Medical SciencesZanjanIran Molecular Medicine Department Biotechnology Research CenterPasteur Institute of IranPasteur AvenueTehranIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer *** decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics *** were loaded on the synthesized Se@BSA@Chi-MTX *** physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis ***,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell *** results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,*** results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of *** results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/*** ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic *** targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the *** results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP *** nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

关键词： Chemoradiotherapy Combination therapy Decoy oligodeoxynucleotides Myc transcription factor Selenium nanoparticle Prostate cancer

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Molecular packing tuning via chlorinated end group enables efficient binary organic solar cells over 18.5%

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Carbon Energy 2024年第3期6卷 196-203页

作者： Yafeng Li Zhenyu Chen Xingzheng Yan Ziyi Ge Zhejiang Business Technology Institute NingboZhejiangChina Zhejiang Engineering research center for Energy Optoelectronic Materials and devices Ningbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboZhejiangChina center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijingChina

Designing novel nonfullerene acceptors(NFAs)is of vital importance for the development of organic solar cells(OSC).Modification on the side chain and end group are two powerful tools to construct efficient ***,based on the high-performance L8BO,we selected 3-ethylheptyl to substitute the inner chain of 2-ethylhexyl,obtaining the backbone of *** we introduced different halogen atoms of fluorine and chlorine on 2-(3-oxo-2,3-dihydro-1Hinden-1-ylidene)malononitrile end group(EG)to construct efficient NFAs named BON3-F and BON3-Cl,*** donor D18 was chosen to combine with two novel NFAs to construct OSC ***,D18:BON3-Cl-based device shows a remarkable power conversion efficiency(PCE)of 18.57%,with a high open-circuit voltage(V_(OC))of 0.907 V and an excellent fill factor(FF)of 80.44%,which is one of the highest binary PCE of devices based on D18 as the ***,BON3-F-based device shows a relatively lower PCE of 17.79%with a decreased FF of 79.05%.The better photovoltaic performance is mainly attributed to the red-shifted absorption,higher electron and hole mobilities,reduced charge recombination,and enhanced molecular packing in the D18:BON3-Cl ***,we performed stability tests on two binary systems;the D18:BON3-Cl and D18:BON3-F devices maintain 88.1%and 85.5%of their initial efficiencies after 169 h of storage at 85°C in an N2-filled glove box,*** work demonstrates the importance of selecting halogen atoms on EG and provides an efficient binary system of D18:BON3-Cl for further improvement of PCE.

关键词： binary organic solar cell chlorinated end group molecular packing

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Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 75-81,I0047-I0052页

作者： Xiaoling Liao Shuo Feng Yicong Wang Yuesong Pan Weiqi Chen Hui Qu Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research center for Neurological Diseases Beijing TiantanHospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina National center for Neurological Diseases BeijingChina Advanced Innovation center for Human Brain Protection Capital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment ***,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic ***,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains *** To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin *** Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in *** patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to *** primary endpoint is a new stroke or END within 90 *** primary safety endpoint is severe or moderate bleeding within 90 *** The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with *** registration number NCT05310968.

关键词： Aspirin regimen centre

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New‑Generation Ferroelectric AlScN Materials

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Nano-Micro Letters 2024年第11期16卷 88-118页

作者： Yalong Zhang Qiuxiang Zhu Bobo Tian Chungang Duan Key Laboratory of Polar Materials and devices Ministry of EducationShanghai Center of Brain‑Inspired Intelligent Materials and DevicesDepartment of ElectronicsEast China Normal UniversityShanghai 200241People’s Republic of China Collaborative Innovation center of Extreme Optics Shanxi UniversityTaiyuan 030006ShanxiPeople’s Republic of China

Ferroelectrics have great potential in the field of nonvolatile memory due to programmable polarization states by external electric field in nonvolatile ***,complementary metal oxide semiconductor compatibility and uniformity of ferroelectric performance after size scaling have always been two thorny issues hindering practical application of ferroelectric memory *** emerging ferroelectricity of wurtzite structure nitride offers opportunities to circumvent the *** review covers the mechanism of ferroelectricity and domain dynamics in ferroelectric AlScN *** performance optimization of AlScN films grown by different techniques is summarized and their applications for memories and emerging in-memory computing are ***,the challenges and perspectives regarding the commercial avenue of ferroelectric AlScN are discussed.

关键词： AlScN Ferroelectrics Nonvolatile memory In-memory computing

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Targeting proprotein convertase subtilisin/kexin type 9(PCSK9):from bench to bedside

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Signal Transduction and Targeted Therapy 2024年第2期9卷 509-557页

作者： Xuhui Bao Yongjun Liang Hanman Chang Tianji Cai Baijie Feng Konstantin Gordon Yuekun Zhu Hailian Shi Yundong He Liyi Xie Institute of Therapeutic Cancer Vaccines Fudan University Pudong Medical CenterShanghaiChina Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghaiChina Department of Oncology Fudan University Pudong Medical CenterShanghaiChina center for Clinical research Fudan University Pudong Medical CenterShanghaiChina Clinical research center for Cell-based Immunotherapy Fudan UniversityShanghaiChina Department of Pathology Duke University Medical CenterDurhamNCUSA center for medical research and Innovation Fudan University Pudong Medical CenterShanghaiChina Institute for Food Safety and Health Illinois Institute of TechnologyChicagoILUSA Department of Sociology University of MacaoTaipaMacaoChina medical Institute Peoples’Friendship University of RussiaMoscowRussia A.Tsyb medical Radiological research center ObninskRussia Department of Colorectal Surgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineZhangjiang Hi-tech ParkShanghaiChina Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina

Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,*** exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular *** also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient *** advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular *** therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular ***,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer *** review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer *** conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms acr

关键词： PCSK9 metabolism convert

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Cross-Project Software Defect Prediction Based on SMOTE and Deep Canonical Correlation Analysis

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Computers, Materials & Continua 2024年第2期78卷 1687-1711页

作者： Xin Fan Shuqing Zhang Kaisheng Wu Wei Zheng Yu Ge School of Software Nanchang Hangkong UniversityNanchang330063China Software testing and Evaluation center Nanchang Hangkong UniversityNanchang330063China

Cross-Project Defect Prediction(CPDP)is a method that utilizes historical data from other source projects to train predictive models for defect prediction in the target ***,existing CPDP methods only consider linear correlations between features(indicators)of the source and target *** models are not capable of evaluating non-linear correlations between features when they exist,for example,when there are differences in data distributions between the source and target *** a result,the performance of such CPDP models is *** this paper,this paper proposes a novel CPDP method based on Synthetic Minority Oversampling Technique(SMOTE)and Deep Canonical Correlation Analysis(DCCA),referred to as *** Correlation Analysis(CCA)is employed to address the issue of non-linear correlations between features of the source and target projects.S-DCCA extends CCA by incorporating the MlpNet model for feature extraction from the *** redundant features are then eliminated by maximizing the correlated feature subset using the CCA loss ***,cross-project defect prediction is achieved through the application of the SMOTE data sampling *** Under Curve(AUC)and F1 scores(F1)are used as evaluation *** paper conducted experiments on 27 projects from four public datasets to validate the proposed *** results demonstrate that,on average,our method outperforms all baseline approaches by at least 1.2%in AUC and 5.5%in F1 *** indicates that the proposed method exhibits favorable performance characteristics.

关键词： Cross-project defect prediction deep canonical correlation analysis feature similarity

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