Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning

Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).

Weighted gene co-expression network analysis reveals similarities and differences of molecular features between dilated and ischemic cardiomyopathies

Cardiomyopathies represent the most common clinical and genetic heterogeneous group of diseases that affect the heart function.Though progress has been made to elucidate the process,molecular mechanisms of different classes of cardiomyopathies remain elusive.This paper aims to describe the similarities and differences in molecular features of dilated cardiomyopathy(DCM)and ischemic cardiomyopathy(ICM).We firstly detected the co-expressed modules using the weighted gene co-expression network analysis(WGCNA).Significant modules associated with DCM/ICM were identified by the Pearson correlation coefficient(PCC)between the modules and the phenotype of DCM/ICM.The differentially expressed genes in the modules were selected to perform functional enrichment.The potential transcription factors(TFs)prediction was conducted for transcription regulation of hub genes.Apoptosis and cardiac conduction were perturbed in DCM and ICM,respectively.TFs demonstrated that the biomarkers and the transcription regulations in DCM and ICM were different,which helps make more accurate discrimination between them at molecular levels.In conclusion,comprehensive analyses of the molecular features may advance our understanding of DCM and ICM causes and progression.Thus,this understanding may promote the development of innovative diagnoses and treatments.

Identification of key genes underlying clinical features of hepatocellular carcinoma based on weighted gene co‑expression network analysis and bioinformatics analysis

Objective: To identify module genes that are closely related to clinical features of hepatocellular carcinoma (HCC) by weighted gene co‑expression network analysis, and to provide a reference for early clinical diagnosis and treatment. Methods: GSE84598 chip data were downloaded from the GEO database, and module genes closely related to the clinical features of HCC were extracted by comprehensive weighted gene co‑expression network analysis. Hub genes were identified through protein interaction network analysis by the maximum clique centrality (MCC) algorithm;Finally, the expression of hub genes was validated by TCGA database and the Kaplan Meier plotter online database was used to evaluate the prognostic relationship between hub genes and HCC patients. Results: By comparing the gene expression data between HCC tissue samples and normal liver tissue samples, a total of 6 262 differentially expressed genes were obtained, of which 2 207 were upregulated and 4 055 were downregulated. Weighted gene co‑expression network analysis was applied to identify 120 genes of key modules. By intersecting with the differentially expressed genes, 115 candidate hub genes were obtained. The results of enrichment analysis showed that the candidate hub genes were closely related to cell mitosis, p53 signaling pathway and so on. Further application of the MCC algorithm to the protein interaction network of 115 candidate hub genes identified five hub genes, namely NUF2, RRM2, UBE2C, CDC20 and MAD2L1. Validation of hub genes by TCGA database revealed that all five hub genes were significantly upregulated in HCC tissues compared to normal liver tissues;Moreover, survival analysis revealed that high expression of hub genes was closely associated with poor prognosis in HCC patients. Conclusions: This study identifies five hub genes by combining multiple databases, which may provide directions for the clinical diagnosis and treatment of HCC.

Network Analysis of Road Traffic Crash and Rescue Operations in Federal Capital City

Abuja is witnessing an upsurge of victims from Road Traffic Crash (RTC) which is mostly due to the attendant rapid increase in the volume of vehicles, traffic jams, bad driving, over speeding, insufficient road signs and bad conditions of vehicles that ply the roads. The problem is compounded by a lack of early emergency response. Geographic Information System (GIS) based travel time model was applied in the street network analysis to identify RTC black spots that are outside the close reach of Federal Road Safety Commission (FRSC) rescue points/health facilities in Federal Capital City (FCC). Five minutes, Ten minutes and Fifteen minutes travel times were used as the impedance factor. Remote Sensing and GIS techniques were used to carry out network analysis. This was achieved by conducting the closest facility operation in the ArcGIS network analyst extension using the time of travel from each FRSC zebra point location to the RTC black spot zones/health facility. The results were presented on road network maps and bar graphs. The areas where quick response and medical facilities are insufficient were identified. It was concluded that the available health centres can sufficiently service RTC black spots in FCC, but the FRSC zebra points are insufficient which renders rescue operations inefficient and thereby exposes RTC victims to more danger. In order to ensure that there is sufficient coverage for response times, it was suggested that additional zebra points be created.

Structural Characteristics and Influencing Factors of Carbon Emission Spatial Association Network:A Case Study of Yangtze River Delta City Cluster,China

City cluster is an effective platform for encouraging regionally coordinated development.Coordinated reduction of carbon emissions within city cluster via the spatial association network between cities can help coordinate the regional carbon emission management,realize sustainable development,and assist China in achieving the carbon peaking and carbon neutrality goals.This paper applies the improved gravity model and social network analysis(SNA)to the study of spatial correlation of carbon emissions in city clusters and analyzes the structural characteristics of the spatial correlation network of carbon emissions in the Yangtze River Delta(YRD)city cluster in China and its influencing factors.The results demonstrate that:1)the spatial association of carbon emissions in the YRD city cluster exhibits a typical and complex multi-threaded network structure.The network association number and density show an upward trend,indicating closer spatial association between cities,but their values remain generally low.Meanwhile,the network hierarchy and network efficiency show a downward trend but remain high.2)The spatial association network of carbon emissions in the YRD city cluster shows an obvious‘core-edge’distribution pattern.The network is centered around Shanghai,Suzhou and Wuxi,all of which play the role of‘bridges’,while cities such as Zhoushan,Ma'anshan,Tongling and other cities characterized by the remote location,single transportation mode or lower economic level are positioned at the edge of the network.3)Geographic proximity,varying levels of economic development,different industrial structures,degrees of urbanization,levels of technological innovation,energy intensities and environmental regulation are important influencing factors on the spatial association of within the YRD city cluster.Finally,policy implications are provided from four aspects:government macro-control and market mechanism guidance,structural characteristics of the‘core-edge’network,reconfiguration and optimization of the spatial layout of the YRD city cluster,and the application of advanced technologies.

Trends and hotspots in gastrointestinal neoplasms risk assessment: A bibliometric analysis from 1984 to 2022

BACKGROUND Gastrointestinal neoplasm(GN)significantly impact the global cancer burden and mortality,necessitating early detection and treatment.Understanding the evolution and current state of research in this field is vital.AIM To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research,focusing on key contributors,institutions,and thematic evolution.METHODS This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the"bibliometrix"R package,VOSviewer,and CiteSpace.The analysis focused on the distribution of publications,contributions by institutions and countries,and trends in keywords.The methods included data synthesis,network analysis,and visualization of international collaboration networks.RESULTS This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration.It highlights the United States'critical role in advancing this field,with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute.The last five years,substantial advancements have been made,representing nearly 45%of the examined literature.Publication rates have dramatically increased,from 20 articles in 2002 to 112 in 2022,reflecting intensified research efforts.This study underscores a growing trend toward interdisciplinary and international collaboration,with the Journal of Clinical Oncology standing out as a key publication outlet.This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks.CONCLUSION This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis.This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy,ultimately enhancing worldwide patient care.

Network Analysis of Research Project Members in Grant-in-Aid for Scientific Research in Japan

The researcher network that appeared in research projects funded by the Japanese government was analyzed. Several static and dynamic network analysis methods were applied to the data for 20 years to explore the fine structure of the researcher’s network for grants. Our analysis shows that the long-term trend of researchers’ group sizes has become smaller, particularly rapidly decreasing in recent years. Some findings on researcher behavior in joining a project have also been reported.

Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis

BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

Exploring the molecular mechanism of Suoquan pill in the treatment of diabetic kidney disease based on network pharmacology,molecular docking,in vitro experiment

Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.

Identify the signature genes for diagnose of uveal melanoma by weight gene co-expression network analysis

AIM: To identify and understand the relationship between co-expression pattern and clinic traits in uveal melanoma, weighted gene co-expression network analysis(WGCNA) is applied to investigate the gene expression levels and patient clinic features. Uveal melanoma is the most common primary eye tumor in adults. Although many studies have identified some important genes and pathways that were relevant to progress of uveal melanoma, the relationship between co-expression and clinic traits in systems level of uveal melanoma is unclear yet. We employ WGCNA to investigate the relationship underlying molecular and phenotype in this study.METHODS: Gene expression profile of uveal melanoma and patient clinic traits were collected from the Gene Expression Omnibus(GEO) database. The gene co-expression is calculated by WGCNA that is the R package software. The package is used to analyze the correlation between pairs of expression levels of genes.The function of the genes were annotated by gene ontology(GO).RESULTS: In this study, we identified four co-expression modules significantly correlated with clinictraits. Module blue positively correlated with radiotherapy treatment. Module purple positively correlates with tumor location(sclera) and negatively correlates with patient age. Module red positively correlates with sclera and negatively correlates with thickness of tumor. Module black positively correlates with the largest tumor diameter(LTD). Additionally, we identified the hug gene(top connectivity with other genes) in each module. The hub gene RPS15 A, PTGDS, CD53 and MSI2 might play a vital role in progress of uveal melanoma.CONCLUSION: From WGCNA analysis and hub gene calculation, we identified RPS15 A, PTGDS, CD53 and MSI2 might be target or diagnosis for uveal melanoma.

Identification of key genes involved in axon regeneration and Wallerian degeneration by weighted gene co-expression network analysis

Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration.Therefore,investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system.In this study,we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury.We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments,respectively.Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration,while the differentially expressed genes in distal modules promoted neurodegeneration.Next,we constructed hub gene networks for selected modules and identified a key hub gene,Kif22,which was up-regulated in both nerve segments.In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway.Collectively,our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments,and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration.All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University,China(approval No.S20210322-008)on March 22,2021.

A spillover network analysis of the global crude oil market:Evidence from the post-financial crisis era

The frequent occurrence of geopolitical crises in the post-financial crisis era is driving the rethinking behind whether the global crude oil market is still a highly connected"great pool".Using the spillover network model suggested by Baruník and Krehlík(2018),and the daily data of 31 global crude oil markets from 2009 to 2019,this study examines the return and volatility spillover effects and their timevarying behavior in six crude oil market segments at different timescales.The findings indicate that heterogeneity exists in the co-movements between global crude oil markets in the post-financial crisis era.In the medium term,both return and volatility spillover effects are not significant,which makes the diversified portfolio strategy useful.Prices in the Europe and Central Asian regions take the lead in return spillovers.In contrast,Asia-Pacific regional prices contribute the most in terms of volatility spillovers.Long-term volatility spillovers increase sharply when confronted with oil-related events in the postfinancial crisis era.Therefore,policymakers should take effective measures to prevent any large-scale risk transmission in the long run.

Analysis of PROFIBUS-DP Network Delay and Its Influence on the Performance of Control Systems

This paper analyzes PROFIBUS-DP network delay in detail and presents the calculational formula of its maximum time-delay, which is significant to the research of PROFIBUS-DP. At the same time, the paper puts forward a method of simplifying the network induced time-varying indeterminate system according to the features of the network. Through the analysis of a pump-control-motor system which is composed of PROFIBUS-DP network, it illustrates the network＇s influence on the performance of control systems. This method helps to design and analyze the network＇s influence on the performance of control systems, which is of considerable practical value in a time when network control systern is widely used.

Weighted Gene Co-expression Network Analysis of Gene Modules for the Prognosis of Esophageal Cancer

Esophageal cancer is a common malignant tumor, whose pathogenesis and prognosis factors are not fully understood. This study aimed to discover the gene clusters that have similar functions and can be used to predict the prognosis of esophageal cancer. The matched microarray and RNA sequencing data of 185 patients with esophageal cancer were downloaded from The Cancer Genome Atlas(TCGA), and gene co-expression networks were built without distinguishing between squamous carcinoma and adenocarcinoma. The result showed that 12 modules were associated with one or more survival data such as recurrence status, recurrence time, vital status or vital time. Furthermore, survival analysis showed that 5 out of the 12 modules were related to progression-free survival(PFS) or overall survival(OS). As the most important module, the midnight blue module with 82 genes was related to PFS, apart from the patient age, tumor grade, primary treatment success, and duration of smoking and tumor histological type. Gene ontology enrichment analysis revealed that 'glycoprotein binding' was the top enriched function of midnight blue module genes. Additionally, the blue module was the exclusive gene clusters related to OS. Platelet activating factor receptor(PTAFR) and feline Gardner-Rasheed(FGR) were the top hub genes in both modeling datasets and the STRING protein interaction database. In conclusion, our study provides novel insights into the prognosis-associated genes and screens out candidate biomarkers for esophageal cancer.

Network analysis using organizational risk analyzer

The tool system of the organizational risk analyzer (ORA) to study the network of East Turkistan terrorists is selected. The model of the relationships among its personnel, knowledge, resources and task entities is represented by the meta-matrix in ORA, with which to analyze the risks and vulnerabilities of organizational structure quantitatively, and obtain the last vulnerabilities and risks of the organization. Case study in this system shows that it should be a shortcut to destroy effectively the network of terrorists by recognizing the caucus persons of the terrorism organization for the first and eliminating them when strikes the terror organization. It is vital to ensure effective use of the resources and control the risks of terrorist attacks.

Identification of Prognostic Genes for Colon Cancer through Gene Coexpression Network Analysis

Objective:The present study was aimed to identify novel key genes,prognostic biomarkers and molecular pathways implicated in tumorigenesis of colon cancer.Methods:The microarray data GSE41328 containing 10 colon cancer samples and 10 adjacent normal tissues was analyzed to identify 4763 differentially expressed genes.Meanwhile,another microarray data GSE17536 was performed for weighted gene co-expression network analysis(WGCNA).Results:In present study,12 co-expressed gene modules associated with tumor progression were identified for further studies.The red module showed the highest association with pathological stage by Pearson's correlation analysis.Functional enrichment analysis revealed that genes in red module focused on cell division,cell proliferation,cell cycle and metabolic related pathway.Then,a total of 26 key hub genes were identified,and GEPIA database was subsequently selected for validation.Holliday junction-recognizing protein(HJURP)and cell division cycle 25 homolog C(CDC25C)were identified as effective prognosis biomarkers,which were all detrimental to prognosis.Gene set enrichment analyses(GSEA)found the two hub genes were enriched in“oocyte meiosis”,“oocyte maturation that are progesterone-mediated”,“p53 signaling pathway”,and“cell cycle”.Furthermore,the immunohistochemistry and western blotting showed that HJURP was highly expressed in colon cancer tissue.Conclusion:HJURP was identified as a key gene associated with colon cancer progression and prognosis by WGCNA,which might influence the prognosis by regulating cell cycle pathways.

Network analysis and spatial agglomeration of China’s high-speed rail: A dual network approach

China has the largest high-speed railway(HSR) system in the world, and it has gradually reshaped the urban network.The HSR system can be represented as different types of networks in terms of the nodes and various relationships(i.e.,linkages) between them. In this paper, we first introduce a general dual network model, including a physical network(PN)and a logical network(LN) to provide a comparative analysis for China’s high-speed rail network via complex network theory. The PN represents a layout of stations and rail tracks, and forms the basis for operating all trains. The LN is a network composed of the origin and destination stations of each high-speed train and the train flows between them. China’s high-speed railway(CHSR) has different topological structures and link strengths for PN in comparison with the LN. In the study, the community detection is used to analyze China’s high-speed rail networks and several communities are found to be similar to the layout of planned urban agglomerations in China. Furthermore, the hierarchies of urban agglomerations are different from each other according to the strength of inter-regional interaction and intra-regional interaction, which are respectively related to location and spatial development strategies. Moreover, a case study of the Yangtze River Delta shows that the hub stations have different resource divisions and are major contributors to the gap between train departure and arrival flows.

Global Collaboration in Artificial Intelligence:Bibliometrics and Network Analysis from 1985 to 2019

Purpose:This study aims to explore the trend and status of international collaboration in the field of artificial intelligence(AI)and to understand the hot topics,core groups,and major collaboration patterns in global AI research.Design/methodology/approach:We selected 38,224 papers in the field of AI from 1985 to 2019 in the core collection database of Web of Science(WoS)and studied international collaboration from the perspectives of authors,institutions,and countries through bibliometric analysis and social network analysis.Findings:The bibliometric results show that in the field of AI,the number of published papers is increasing every year,and 84.8%of them are cooperative papers.Collaboration with more than three authors,collaboration between two countries and collaboration within institutions are the three main levels of collaboration patterns.Through social network analysis,this study found that the US,the UK,France,and Spain led global collaboration research in the field of AI at the country level,while Vietnam,Saudi Arabia,and United Arab Emirates had a high degree of international participation.Collaboration at the institution level reflects obvious regional and economic characteristics.There are the Developing Countries Institution Collaboration Group led by Iran,China,and Vietnam,as well as the Developed Countries Institution Collaboration Group led by the US,Canada,the UK.Also,the Chinese Academy of Sciences(China)plays an important,pivotal role in connecting the these institutional collaboration groups.Research limitations:First,participant contributions in international collaboration may have varied,but in our research they are viewed equally when building collaboration networks.Second,although the edge weight in the collaboration network is considered,it is only used to help reduce the network and does not reflect the strength of collaboration.Practical implications:The findings fill the current shortage of research on international collaboration in AI.They will help inform scientists and policy makers about the future of AI research.Originality/value:This work is the longest to date regarding international collaboration in the field of AI.This research explores the evolution,future trends,and major collaboration patterns of international collaboration in the field of AI over the past 35 years.It also reveals the leading countries,core groups,and characteristics of collaboration in the field of AI.

Identification of Potential Therapeutic Targets of Alzheimer's Disease By Weighted Gene Co-Expression Network Analysis

Objective Alzheimer's disease(AD)is the most common cause of dementia.The pathophysiology of the disease mostly remains unearthed,thereby challenging drug development for AD.This study aims to screen high throughput gene expression data using weighted co-expression network analysis(WGCNA)to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus(GEO)database.Normalization,quality control,filtration,and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules.Furthermore,the correlation coefiidents between the modules and clinical traits were computed to identify the key modules.Gene ontology and pathway enrichment analyses were performed on the key module genes.The STRING database was used to construct the protein-protein interaction(PPI)networks,which were further analyzed by Cytoscape app(MCODE).Finally,validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules,among which 6 modules were identified as the key module relating to AD occurrence.These key modules are primarily involved in chemical synaptic transmission(G0:0007268),the tricarboxylic acid(TCA)cycle and respiratory electron transport(R-HSA-1428517).WDR47,OXCT1,C3orfl4,ATP6V1A,SLC25A14,NAPB were found as the hub genes and their expression were validated by external datasets.Conclusions Through modules co-expression network analyses and PPI network analyses,we identified the hub genes of AD,including WDR47,0XCT1,C3orfl4i ATP6V1A,SLC25A14 and NAPB.Among them,three hub genes(ATP6V1A,SLC25A14,OXCT1)might contribute to AD pathogenesis through pathway of TCA cycle.

Evaluation and optimization analysis of high-speed rail network structure in Northeast China under the background of northeast revitalization

The construction of high-speed rail(HSR)network has promoted the social-economic ties of cities,accelerated the compression of time and space,and changed the pattern of regional development.In this paper,with the adoption of the operation frequency data of HSR from 12306 website,and based on the HSR connection strength model and social network analysis model,as well as according to the HSR connection strength,HSR network density,centrality,agglomeration subgroup,and other indicators,we analyzed the characteristics of HSR network structure in Northeast China.Results show that the number of HSR cities in Northeast China is small,cities in HSR network generally exhibit weak connectivity,and the existence of HSR network marginalizes cities such as Ulanhot,Baicheng,and Songyuan,which significantly reduce the overall network connectivity of Northeast China.The overall centrality of HSR network in Northeast China is characterized by“one axis,four edges”;specifically,the one axis is located in Harbin-Dalian transportation line and the four edges are located on both sides of the main axis of Harbin-Dalian transportation line.Eight agglomeration subgroups(four double city subgroups and four multi city subgroups)have formed in Northeast China.The core status of Shenyang in HSR network is improved significantly,and“one axis and two wings”HSR network in Liaoning Province is improved significantly.With the gradual expansion of Chaoyang-Fuxin,Dandong-Benxi,and Jilin-Yanji branch networks,the“point axis”HSR network mode in Northeast China has gradually developed and matured.In the future,it is recommended to rely on eight agglomerating subgroups to encrypt HSR network structure,create secondary node central cities,and gradually build a new pattern of opening up in Northeast China.