In this paper, a whole field solution to finite internally cracked plates is derived by complex variable method, where the equations of equilibrium and compatibility, the single value condition of displacements and th...In this paper, a whole field solution to finite internally cracked plates is derived by complex variable method, where the equations of equilibrium and compatibility, the single value condition of displacements and the traction-free condition on crack surfaces are satisfied exactly. The stress intensity factors of finite plates with central crack or eccentric crack or cracks emanating from a hole are calculated by using minimum potential energy principle to treat the boundary conditions excluding those on crack surfaces. As an application of the method to engineering problems, the computation about a finite rivet joint stiffened plate with cracks emanating from a hole is also performed. The numerical results show that the method presented in this paper gives rapid convergence and is much time-saving in computations.展开更多
For the first time, this paper introduces Petri net theory to the domain of enterprise strategy management, puts forword a new way by using Petri net to analyse and describe the formulating process of enterprise merge...For the first time, this paper introduces Petri net theory to the domain of enterprise strategy management, puts forword a new way by using Petri net to analyse and describe the formulating process of enterprise merger and acquisition strategies, provides a clear and simple tool for supporting the management bureau of enterprise to make its merger and acquisition strategies.展开更多
Background: Most current approaches in forest science and practice require information about structure and growth of individual trees rather than- or in addition to- sum and mean values of growth and yield at forest s...Background: Most current approaches in forest science and practice require information about structure and growth of individual trees rather than- or in addition to- sum and mean values of growth and yield at forest stand level as provided by classic experimental designs. By inventing the wheel design, Nelder provided the possibility to turn to the individual tree as basic information unit. Such trials provide valuable insights into the dependency of growth on stand density at particular sites.Methods: Here, we present an extension of the original design and evaluation by Nelder.(i) We established Nelder wheels along an environmental gradient through Europe in atlantic climate in Belgium and Germany, Mediterranean climate in Italy, continental climate in Hungary as well as on high land climate in Mexico. Such disjunct Nelder wheels along an environmental gradient can be regarded and analysed as a two-factor design with the factors of site condition and stand density.(ii) We present an advanced statistical approach to evaluate density dependent growth dynamics of trees planted in form of the Nelder design, which considers spatio-temporal autocorrelation.(iii)We prove the usefulness of the methods in improving ecological theory concerning density related productivity,trade-offs between facilitation and competition, and allometric relations between size variables.Results: First evaluations based on remeasured Nelder wheels in oak(Quercus robur L.) show a size growth differentiation during the first observation period. In particular, height growth is accelerated under higher competition indicating facilitation effects. We detect furthermore a high variability in allometric relations.Conclusions: The proposed design, methods, and results are discussed regarding their impact on forest practice,model building, and ecological theory. We conclude that the extended Nelder approach is highly efficient in providing currently lacking individual tree level information.展开更多
The aim of this paper is to present the design and specifications of an integrated Delay Analysis Framework(DAF),which could be used to quantify the delay caused by the Risk Factors(RFs)in Oil and Gas Pipelines(OGPs)p...The aim of this paper is to present the design and specifications of an integrated Delay Analysis Framework(DAF),which could be used to quantify the delay caused by the Risk Factors(RFs)in Oil and Gas Pipelines(OGPs)projects in a simple and systematic way.The main inputs of the DAF are(i)the potential list of RFs in the projects and their impact levels on the projects and the estimated maximum and minimum duration of each task.Monte Carlo Simulation integrated within@Risk simulator was the key process algorithm that used to quantify the impact of delay caused by the associated RFs.The key output of the DAF is the amount of potential delay caused by RFs in the OGP project.The functionalities of the developed DAF were evaluated using a case study of newly developed OGP project,in the south of Iraq.It is found that the case study project might have delayed by 45 days if neglected the consideration of the RFs associated with the project at the construction stage.The paper concludes that identifying the associated RFs and analysing the potential delay in advance will help in reducing the construction delay and improving the effectiveness of the project delivery by taking suitable risk mitigation measures.展开更多
The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of ...The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of the ependymal surface of the adult mouse forebrain using whole mounts of lateral walls of lateral ventricles.We identified 12 different cell subtypes in the ependymal surface.Immunocytochemical analyses revealed that CD133^(+)multi-ciliated cells comprised 67.6%of ependymal cells,while the remaining 32.4%were CD133^(-).CD133^(+)ependymal cells can be further classified into FOXJ1^(+)/SOX2^(+)/ACTA2^(+)cells,FLT1^(+)/CD31^(+)/CLDN5^(+)endothelial-like cells,and PDGFRB^(+)/VTN^(+)/NG2^(+)pericyte-like cells,as well as endothelial-pericyte-like cells and Foxj1^(+)endothelial-like cells.CD133^(-)ependymal cells can be further divided into endothelial-like cells,Foxj1^(+)ependymal cells,Foxj1^(+)endothelial-like cells,pericyte-like cells,endothelial-pericyte-like cells,VIM^(+)cells,and cells negative for all of these markers.This comprehensive profiling confirms the heterogeneity of the ependymal surface in the adult mouse forebrain.Debate regarding whether adult ependymal cells contain neural stem cells has arisen because different researchers have examined different populations of ependymal cells.Our study provides a new perspective for investigation of clinical endogenous neural stem cells,ultimately paving the way for stem cell therapies in neurological diseases.展开更多
Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study...Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.展开更多
The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant ...The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.展开更多
If clinical research is to be relevant to real-world decision making it requires interventions that reflect usual practice.Observational studies may provide the best approach to defining this.Siting studies in the stu...If clinical research is to be relevant to real-world decision making it requires interventions that reflect usual practice.Observational studies may provide the best approach to defining this.Siting studies in the student clinics of acupuncture teaching institutions(ATIs).has potential benefits for the institutions as well as for researchers.This is the first such multi-centre study accredited ATIs展开更多
In this paper, we consider solving dense linear equations on Dawning1000 byusing matrix partitioning technique. Based on this partitioning of matrix, we give aparallel block LU decomposition method. The efficiency of ...In this paper, we consider solving dense linear equations on Dawning1000 byusing matrix partitioning technique. Based on this partitioning of matrix, we give aparallel block LU decomposition method. The efficiency of solving linear equationsby different ways is analysed. The numerical results are given on Dawning1000.By running our parallel program, the best speed up on 32 processors is over 25.展开更多
Analysing the heat states of transformers under DC bias requires careful consideration of their own structural and material characteristics.Although the 3D finite element method(FEM)is a reliable way of simulating all...Analysing the heat states of transformers under DC bias requires careful consideration of their own structural and material characteristics.Although the 3D finite element method(FEM)is a reliable way of simulating all the details of transformers,it may be time-consuming or have encountered convergence difficulties due to the complex internal structure of the transformer.To address the issues,this paper proposes a fast calculation model for estimating the top-oil temperature rise and the winding hotspot temperature rise of single-phase three-limb transformers under DC bias.This model is based on the coupling principle of electric circuits,magnetic circuits and thermal circuits,and it considers the winding loss and core loss of the transformer under DC bias as key factors linking electromagnetic and thermal effects.All the model parameters can be obtained from nameplate data and regular test data to ensure the method's engineering practicality.The results were compared with 3D FEM,demonstrating favourable performance in terms of computational speed and availability.展开更多
Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies...Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies of predominantly European ancestry,we performed a bidirectional two-sample Mendelian Randomization(MR)study to estimate causal effects of loneliness(N=487,647)and SI traits on IHD(N=184,305).SI traits included whether individuals lived alone,participated in various types of social activities,and how often they had contact with friends or family(N=459,830 to 461,369).A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators,including metabolic,behavioral and psychological factors.Results Loneliness increased IHD risk(OR=2.129;95%confidence interval[CI]:1.380 to 3.285),mediated by body fat percentage,waist-hip ratio,total cholesterol,and low-density lipoprotein cholesterol.For SI traits,only fewer social activities increased IHD risk(OR=1.815;95%CI:1.189 to 2.772),mediated by hypertension,high-density lipoprotein cholesterol,triglycerides,fasting insulin,and smoking cessation.No reverse causality of IHD with loneliness and SI was found.Conclusion These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD,with several mediators as prioritized targets for intervention.展开更多
In 1993,the World Bank released a global report on the efficacy of health promotion,introducing the disability-adjusted life years(DALY)as a novel indicator.The DALY,a composite metric incorporating temporal and quali...In 1993,the World Bank released a global report on the efficacy of health promotion,introducing the disability-adjusted life years(DALY)as a novel indicator.The DALY,a composite metric incorporating temporal and qualitative data,is grounded in preferences regarding disability status.This review delineates the algorithm used to calculate the value of the proposed DALY synthetic indicator and elucidates key methodological challenges associated with its application.In contrast to the quality-adjusted life years approach,derived from multi-attribute utility theory,the DALY stands as an independent synthetic indicator that adopts the assumptions of the Time Trade Off utility technique to define Disability Weights.Claiming to rely on no mathematical or economic theory,DALY users appear to have exempted themselves from verifying whether this indicator meets the classical properties required of all indicators,notably content validity,reliability,specificity,and sensitivity.The DALY concept emerged primarily to facilitate comparisons of the health impacts of various diseases globally within the framework of the Global Burden of Disease initiative,leading to numerous publications in international literature.Despite widespread adoption,the DALY synthetic indicator has prompted significant methodological concerns since its inception,manifesting in inconsistent and non-reproducible results.Given the substantial diffusion of the DALY indicator and its critical role in health impact assessments,a reassessment is warranted.This reconsideration is imperative for enhancing the robustness and reliability of public health decisionmaking processes.展开更多
Durable aggregates are essential for the stability and longevity of construction projects,and the Los Angeles Abrasion(LAA)value is a widely used indicator of aggregate durability.However,direct LAA testing is time-co...Durable aggregates are essential for the stability and longevity of construction projects,and the Los Angeles Abrasion(LAA)value is a widely used indicator of aggregate durability.However,direct LAA testing is time-consuming,costly,and requires specialized facilities.This study introduces a novel and efficient alternative by developing two hybrid machine learning models Artificial Neural Network integrated with Particle Swarm Optimization(ANN-PSO)and Artificial Neural Network combined with Teaching-Learning-Based Optimization(ANN-TLBO)for the first time to predict LAA values from petrographic characteristics of carbonate rocks.A total of 160 rock samples from 10 geological formations in Pakistan’s Salt Range were analyzed through petrographic examination and LAA testing.The predictive performance of the proposed models was compared with established techniques,including Multiple Linear Regression,Random Forest,Adaptive Boosting,Gradient Boosting,K-Nearest Neighbors,and Multilayer Perceptron.Results demonstrate that ANN-PSO significantly outperformed all other approaches,achieving an R^(2)of 0.9982,RMSE of 0.209,MAE of 0.159,and MAPE of 0.009.Model robustness was validated using Taylor plots,REC curves,and an external dataset.Sensitivity analysis identified quartz,calcite,and feldspar as the most influential factors affecting LAA prediction.The findings confirm that the ANN-PSO and ANN-TLBO models provide highly accurate,cost-effective,and practical alternatives to traditional LAA testing.This innovative approach advances rock mechanics and material assessment,offering engineers and geologists enhanced tools for aggregate selection and durability evaluation in infrastructure projects.展开更多
0 INTRODUCTION.The global availability of digital elevation model(DEM)data,such as 90-m Shuttle Radar Topography Mission(SRTM)DEM and 30-m Advanced Spaceborne Thermal Emission and Reflection Radiometer Global Digital ...0 INTRODUCTION.The global availability of digital elevation model(DEM)data,such as 90-m Shuttle Radar Topography Mission(SRTM)DEM and 30-m Advanced Spaceborne Thermal Emission and Reflection Radiometer Global Digital Elevation Model(ASTER GDEM),has been extensively utilized in morphotectonic analyses(e.g.,Wang et al.,2024;Cheng et al.,2018;Pérez-Pe?a et al.,2010;El Hamdouni et al.,2008).展开更多
Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characte...Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.展开更多
BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mech...BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mechanism remains unclear.Circular RNAs(circRNAs),which are formed from protein-coding genes,can sequester microRNAs or proteins,modulate transcription and interfere with splicing.Authoritative studies suggest that circRNAs may play an important role in myocardial I/R injury.AIM To explore the role and mechanism of circRNAs in myocardial I/R injury.METHODS We constructed a myocardial I/R injury model using ligation of the left anterior descending coronary artery,and evaluated the success of the validated model using triphenyltetrazolium chloride and hematoxylin-eosin staining.Then,left ventricular samples from different groups were selected for mRNA-sequence,and differential gene screening was performed on the obtained results.The differentially obtained mRNAs were divided into up-regulated and down-regulated according to their expression levels,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis were performed,respectively.Then,the obtained circRNA and microRNA(miRNA)were paired for analysis,and the binding sites of miRNA and mRNA were virtual screened.Finally,the obtained circRNA,miRNA and mRNA were constructed by ceRNA mutual most useful network.RESULTS We used an RNA sequencing array to investigate the expression signatures of circRNAs in myocardial I/R injury using three samples from the I/R group and three samples from the sham group.A total of 142 upregulated and 121 downregulated circRNAs were found to be differentially expressed(fold change≥2,P<0.05).GO and KEGG functional analyses of these circRNAs were performed.GO analysis revealed that these circRNAs were involved mainly in cellular and intracellular processes.KEGG analysis demonstrated that 6 of the top 20 pathways were correlated with cell apoptosis.Furthermore,a circRNA-miRNA coexpression network and ceRNA network based on these genes were constructed,revealing that mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 might be key regulators of myocardial I/R injury.CONCLUSION This research provides new insights into the mechanism of myocardial I/R,which mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 are expected to be new therapeutic targets for myocardial I/R injury.展开更多
文摘In this paper, a whole field solution to finite internally cracked plates is derived by complex variable method, where the equations of equilibrium and compatibility, the single value condition of displacements and the traction-free condition on crack surfaces are satisfied exactly. The stress intensity factors of finite plates with central crack or eccentric crack or cracks emanating from a hole are calculated by using minimum potential energy principle to treat the boundary conditions excluding those on crack surfaces. As an application of the method to engineering problems, the computation about a finite rivet joint stiffened plate with cracks emanating from a hole is also performed. The numerical results show that the method presented in this paper gives rapid convergence and is much time-saving in computations.
基金national Natural science Fundation of China. No.79570040
文摘For the first time, this paper introduces Petri net theory to the domain of enterprise strategy management, puts forword a new way by using Petri net to analyse and describe the formulating process of enterprise merger and acquisition strategies, provides a clear and simple tool for supporting the management bureau of enterprise to make its merger and acquisition strategies.
基金funding the project"Biodiversity,productivity,and C-sequestration of oak stands"(No.5102150)the Bavarian State Ministry for Nutrition,Agriculture and Forestry for permanent support of the project W 07"Long-term experimental plots for forest growth and yield research"(7831-23953-2014)
文摘Background: Most current approaches in forest science and practice require information about structure and growth of individual trees rather than- or in addition to- sum and mean values of growth and yield at forest stand level as provided by classic experimental designs. By inventing the wheel design, Nelder provided the possibility to turn to the individual tree as basic information unit. Such trials provide valuable insights into the dependency of growth on stand density at particular sites.Methods: Here, we present an extension of the original design and evaluation by Nelder.(i) We established Nelder wheels along an environmental gradient through Europe in atlantic climate in Belgium and Germany, Mediterranean climate in Italy, continental climate in Hungary as well as on high land climate in Mexico. Such disjunct Nelder wheels along an environmental gradient can be regarded and analysed as a two-factor design with the factors of site condition and stand density.(ii) We present an advanced statistical approach to evaluate density dependent growth dynamics of trees planted in form of the Nelder design, which considers spatio-temporal autocorrelation.(iii)We prove the usefulness of the methods in improving ecological theory concerning density related productivity,trade-offs between facilitation and competition, and allometric relations between size variables.Results: First evaluations based on remeasured Nelder wheels in oak(Quercus robur L.) show a size growth differentiation during the first observation period. In particular, height growth is accelerated under higher competition indicating facilitation effects. We detect furthermore a high variability in allometric relations.Conclusions: The proposed design, methods, and results are discussed regarding their impact on forest practice,model building, and ecological theory. We conclude that the extended Nelder approach is highly efficient in providing currently lacking individual tree level information.
文摘The aim of this paper is to present the design and specifications of an integrated Delay Analysis Framework(DAF),which could be used to quantify the delay caused by the Risk Factors(RFs)in Oil and Gas Pipelines(OGPs)projects in a simple and systematic way.The main inputs of the DAF are(i)the potential list of RFs in the projects and their impact levels on the projects and the estimated maximum and minimum duration of each task.Monte Carlo Simulation integrated within@Risk simulator was the key process algorithm that used to quantify the impact of delay caused by the associated RFs.The key output of the DAF is the amount of potential delay caused by RFs in the OGP project.The functionalities of the developed DAF were evaluated using a case study of newly developed OGP project,in the south of Iraq.It is found that the case study project might have delayed by 45 days if neglected the consideration of the RFs associated with the project at the construction stage.The paper concludes that identifying the associated RFs and analysing the potential delay in advance will help in reducing the construction delay and improving the effectiveness of the project delivery by taking suitable risk mitigation measures.
基金supported by the State Key Program of the National Natural Science Foundation of China,No.82030035(to YES)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai(to LZ).
文摘The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of the ependymal surface of the adult mouse forebrain using whole mounts of lateral walls of lateral ventricles.We identified 12 different cell subtypes in the ependymal surface.Immunocytochemical analyses revealed that CD133^(+)multi-ciliated cells comprised 67.6%of ependymal cells,while the remaining 32.4%were CD133^(-).CD133^(+)ependymal cells can be further classified into FOXJ1^(+)/SOX2^(+)/ACTA2^(+)cells,FLT1^(+)/CD31^(+)/CLDN5^(+)endothelial-like cells,and PDGFRB^(+)/VTN^(+)/NG2^(+)pericyte-like cells,as well as endothelial-pericyte-like cells and Foxj1^(+)endothelial-like cells.CD133^(-)ependymal cells can be further divided into endothelial-like cells,Foxj1^(+)ependymal cells,Foxj1^(+)endothelial-like cells,pericyte-like cells,endothelial-pericyte-like cells,VIM^(+)cells,and cells negative for all of these markers.This comprehensive profiling confirms the heterogeneity of the ependymal surface in the adult mouse forebrain.Debate regarding whether adult ependymal cells contain neural stem cells has arisen because different researchers have examined different populations of ependymal cells.Our study provides a new perspective for investigation of clinical endogenous neural stem cells,ultimately paving the way for stem cell therapies in neurological diseases.
基金supported by the National Natural Science Foundation of China,No.81972073(to HZ)a grant from the Taishan Scholars Program ofShandong Province-Young Taishan Scholars,No.tsqn201909197(to HZ)+1 种基金a grant from Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)a grant from Academic Expert International Innovation Summit,No.22JRRCRC00010(to SF).
文摘Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.
文摘The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.
文摘If clinical research is to be relevant to real-world decision making it requires interventions that reflect usual practice.Observational studies may provide the best approach to defining this.Siting studies in the student clinics of acupuncture teaching institutions(ATIs).has potential benefits for the institutions as well as for researchers.This is the first such multi-centre study accredited ATIs
文摘In this paper, we consider solving dense linear equations on Dawning1000 byusing matrix partitioning technique. Based on this partitioning of matrix, we give aparallel block LU decomposition method. The efficiency of solving linear equationsby different ways is analysed. The numerical results are given on Dawning1000.By running our parallel program, the best speed up on 32 processors is over 25.
基金supported by the National Natural Science Foundation of China Joint Fund Key Project(Grant U22B20118).
文摘Analysing the heat states of transformers under DC bias requires careful consideration of their own structural and material characteristics.Although the 3D finite element method(FEM)is a reliable way of simulating all the details of transformers,it may be time-consuming or have encountered convergence difficulties due to the complex internal structure of the transformer.To address the issues,this paper proposes a fast calculation model for estimating the top-oil temperature rise and the winding hotspot temperature rise of single-phase three-limb transformers under DC bias.This model is based on the coupling principle of electric circuits,magnetic circuits and thermal circuits,and it considers the winding loss and core loss of the transformer under DC bias as key factors linking electromagnetic and thermal effects.All the model parameters can be obtained from nameplate data and regular test data to ensure the method's engineering practicality.The results were compared with 3D FEM,demonstrating favourable performance in terms of computational speed and availability.
基金supported by the National Natural Science Foundation of China(82322059)the Chinese Academy of Medical·Sciences Innovation Fund for Medical Sciences(2021-I2M-1-010)+1 种基金the National Key Research and Development Program of China(2021YFC2500500)the National High Level Hospital Clinical Research Funding(2023-GSPRC-19).
文摘Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies of predominantly European ancestry,we performed a bidirectional two-sample Mendelian Randomization(MR)study to estimate causal effects of loneliness(N=487,647)and SI traits on IHD(N=184,305).SI traits included whether individuals lived alone,participated in various types of social activities,and how often they had contact with friends or family(N=459,830 to 461,369).A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators,including metabolic,behavioral and psychological factors.Results Loneliness increased IHD risk(OR=2.129;95%confidence interval[CI]:1.380 to 3.285),mediated by body fat percentage,waist-hip ratio,total cholesterol,and low-density lipoprotein cholesterol.For SI traits,only fewer social activities increased IHD risk(OR=1.815;95%CI:1.189 to 2.772),mediated by hypertension,high-density lipoprotein cholesterol,triglycerides,fasting insulin,and smoking cessation.No reverse causality of IHD with loneliness and SI was found.Conclusion These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD,with several mediators as prioritized targets for intervention.
文摘In 1993,the World Bank released a global report on the efficacy of health promotion,introducing the disability-adjusted life years(DALY)as a novel indicator.The DALY,a composite metric incorporating temporal and qualitative data,is grounded in preferences regarding disability status.This review delineates the algorithm used to calculate the value of the proposed DALY synthetic indicator and elucidates key methodological challenges associated with its application.In contrast to the quality-adjusted life years approach,derived from multi-attribute utility theory,the DALY stands as an independent synthetic indicator that adopts the assumptions of the Time Trade Off utility technique to define Disability Weights.Claiming to rely on no mathematical or economic theory,DALY users appear to have exempted themselves from verifying whether this indicator meets the classical properties required of all indicators,notably content validity,reliability,specificity,and sensitivity.The DALY concept emerged primarily to facilitate comparisons of the health impacts of various diseases globally within the framework of the Global Burden of Disease initiative,leading to numerous publications in international literature.Despite widespread adoption,the DALY synthetic indicator has prompted significant methodological concerns since its inception,manifesting in inconsistent and non-reproducible results.Given the substantial diffusion of the DALY indicator and its critical role in health impact assessments,a reassessment is warranted.This reconsideration is imperative for enhancing the robustness and reliability of public health decisionmaking processes.
文摘Durable aggregates are essential for the stability and longevity of construction projects,and the Los Angeles Abrasion(LAA)value is a widely used indicator of aggregate durability.However,direct LAA testing is time-consuming,costly,and requires specialized facilities.This study introduces a novel and efficient alternative by developing two hybrid machine learning models Artificial Neural Network integrated with Particle Swarm Optimization(ANN-PSO)and Artificial Neural Network combined with Teaching-Learning-Based Optimization(ANN-TLBO)for the first time to predict LAA values from petrographic characteristics of carbonate rocks.A total of 160 rock samples from 10 geological formations in Pakistan’s Salt Range were analyzed through petrographic examination and LAA testing.The predictive performance of the proposed models was compared with established techniques,including Multiple Linear Regression,Random Forest,Adaptive Boosting,Gradient Boosting,K-Nearest Neighbors,and Multilayer Perceptron.Results demonstrate that ANN-PSO significantly outperformed all other approaches,achieving an R^(2)of 0.9982,RMSE of 0.209,MAE of 0.159,and MAPE of 0.009.Model robustness was validated using Taylor plots,REC curves,and an external dataset.Sensitivity analysis identified quartz,calcite,and feldspar as the most influential factors affecting LAA prediction.The findings confirm that the ANN-PSO and ANN-TLBO models provide highly accurate,cost-effective,and practical alternatives to traditional LAA testing.This innovative approach advances rock mechanics and material assessment,offering engineers and geologists enhanced tools for aggregate selection and durability evaluation in infrastructure projects.
基金supported by the National Key Research and Development Project of China(No.2023YFC3007303)the Open Research Project of the Hubei Key Laboratory of Intelligent Geo-Information Processing(No.KLIGIP-2019B08)。
文摘0 INTRODUCTION.The global availability of digital elevation model(DEM)data,such as 90-m Shuttle Radar Topography Mission(SRTM)DEM and 30-m Advanced Spaceborne Thermal Emission and Reflection Radiometer Global Digital Elevation Model(ASTER GDEM),has been extensively utilized in morphotectonic analyses(e.g.,Wang et al.,2024;Cheng et al.,2018;Pérez-Pe?a et al.,2010;El Hamdouni et al.,2008).
基金The authors extend their appreciation to the Distinguished Scientist Fellowship program at King Saud University,Riyadh,Saudi Arabia,for funding this work through Research Supporting Project Number RSP2024R131.
文摘Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LQ23H020004The Medical and Health Research Project of Zhejiang province,No.2024KY983Basic Medical Health Technology Project of Wenzhou Science and Technology Bureau,No.Y20210818 and No.Y20210140.
文摘BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mechanism remains unclear.Circular RNAs(circRNAs),which are formed from protein-coding genes,can sequester microRNAs or proteins,modulate transcription and interfere with splicing.Authoritative studies suggest that circRNAs may play an important role in myocardial I/R injury.AIM To explore the role and mechanism of circRNAs in myocardial I/R injury.METHODS We constructed a myocardial I/R injury model using ligation of the left anterior descending coronary artery,and evaluated the success of the validated model using triphenyltetrazolium chloride and hematoxylin-eosin staining.Then,left ventricular samples from different groups were selected for mRNA-sequence,and differential gene screening was performed on the obtained results.The differentially obtained mRNAs were divided into up-regulated and down-regulated according to their expression levels,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis were performed,respectively.Then,the obtained circRNA and microRNA(miRNA)were paired for analysis,and the binding sites of miRNA and mRNA were virtual screened.Finally,the obtained circRNA,miRNA and mRNA were constructed by ceRNA mutual most useful network.RESULTS We used an RNA sequencing array to investigate the expression signatures of circRNAs in myocardial I/R injury using three samples from the I/R group and three samples from the sham group.A total of 142 upregulated and 121 downregulated circRNAs were found to be differentially expressed(fold change≥2,P<0.05).GO and KEGG functional analyses of these circRNAs were performed.GO analysis revealed that these circRNAs were involved mainly in cellular and intracellular processes.KEGG analysis demonstrated that 6 of the top 20 pathways were correlated with cell apoptosis.Furthermore,a circRNA-miRNA coexpression network and ceRNA network based on these genes were constructed,revealing that mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 might be key regulators of myocardial I/R injury.CONCLUSION This research provides new insights into the mechanism of myocardial I/R,which mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 are expected to be new therapeutic targets for myocardial I/R injury.
