The prognostic and immunological impacts of DCX expression:a pan-cancer analysis

Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)

The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.

A pan-cancer analysis of the biological function and clinical value of BTLA in tumors

B and T-lymphocyte attenuator(BTLA)plays an immunosuppressive role by inhibiting T-and B-cell functions.BTLA is associated with a variety of diseases,especially cancer immunity.However,the function of BTLA in various cancers and its clinical prognostic value have still not been comprehensively analyzed.This study aimed to identify the relationship between BTLA and cancer from the perspectives of differences in BTLA expression,its clinical value,immune infiltration,and the correlation with immune-related genes in various cancers.Data regarding mRNA expression,miRNA expression,lncRNA expression,and clinical data of patients of 33 existing cancers were collected from the TCGA database.Target miRNA of BTLA and the lncRNA that interacts with the target miRNA were obtained from the StarBase database.Based on bioinformatics analysis methods,the relationship between various types of cancers and BTLA was thoroughly investigated,and a competing endogenous RNA network of BTLA,target miRNA,and interacting lncRNA was constructed.The Kaplan-Meier(KM)prognostic analysis of BTLA and target miRNA(has-miR-137)in various types of cancers was completed using the KM plotter.BTLA expression varied in different cancers,with statistical significance in nine cancer types.KM plotter to analyze the overall survival(OS)and regression-free survival prognosis of cancer patients revealed that the BTLA expression was statistically different in the OS of 11 types of cancers out of 21 types of cancers;the OS of 8 type of cancers was also statistically different.Correlation analysis of tumor immune genes revealed a positive correlation of BTLA expression with immunosuppressive gene(CTLA4 and PDCD1)expression.Gene Set Enrichment Analysis showed that BTLA and its co-expressed genes mainly act through biological processes and pathways,including immune response regulation,cell surface receptor signaling pathway,antigen binding,antigen receptor-mediated signaling pathway,and leukocyte migration.BTLA has the potential as a prognostic marker for CLL,COAD,NSCLC,and OV and a diagnostic marker for CLL,COAD,and KIRC.BTLA has a close and complex relationship with the occurrence and development of tumors,and cancer immunotherapy for BTLA is worthy of further analysis.

A pan-cancer analysis identifies SOAT1 as an immunological and prognostic biomarker

Sterol o-acyltransferase1(SOAT1)is an enzyme that regulates lipid metabolism.Nevertheless,the predictive value of SOAT1 regarding immune responses in cancer is not fully understood.Herein,we aimed to expound the predictive value and the potential biological functions of SOAT1 in pan-cancer.Raw data related to SOAT1 expression in 33 different types of cancer were acquired from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.SOAT1 expression was significantly increased in most cancers and showed a distinct correlation with prognosis.This enhanced expression of the SOAT1 gene was confirmed by evaluating SOAT1 protein expression using tissue microarrays.In addition,we found significant positive associations between SOAT1 expression levels and infiltrating immune cells,including T cells,neutrophils,and macrophages.Moreover,the co-expression analysis between SOAT1 and immune genes showed that many immune-related genes were increased with enhanced SOAT1 expression.A gene set enrichment analysis(GSEA)revealed that the expression of SOAT1 correlated with the tumor microenvironment,adaptive immune response,interferon signaling,and cytokine signaling.These findings indicate that SOAT1 is a potential candidate marker for predicting prognosis and a promising target for tumor immunotherapy in cancers.

Pan-cancer analysis of positive regulatory domain-containing 16 in human tumors

Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multiple types of cancer by pan cancer analyses.Methods:UALCAN and TIMER2 database were utilized to evaluate PRDM16 expression in cancer patients.Gene Expression Profiling Interactive Analysis was employed to analyze the overall survival and disease-free survival across all The Cancer Genome Atlas Program tumors.Using the cBioPortal tool,we analyzed the mutation features of PRDM16 for the The Cancer Genome Atlas Program tumors,then utilized the Encyclopedia of RNA Interactomes database to predict the miRNA-mRNA relationships associated with the PRDM16 for all tumors.Results:The expression level of PRDM16 in the tumor tissues is lower than that in the normal tissues.Interesting,the high expression of PRDM16 has a positive effect on the prognosis of kidney clear cell carcinoma and lung adenocarcinoma,but not conducive to the prognosis of most cancers.In multiple cancer types,the expression of PRDM16 was significantly positively correlated with immune infiltration of cancer-associated fibroblasts.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated that PRDM16 may be related to transcriptional misregulation pathway in cancer.We identified potential miRNAs that play regulatory roles of PRDM16 in kidney clear cell carcinoma and lung adenocarcinoma.Conclusion:PRDM16 is expressed in different cancers,it can be used as a biomarker for prognosis of pan-cancer and is associated with immune infiltration.

Comprehensive analysis of the expression and prognosis for APOE in malignancies: A pan-cancer analysis

Apolipoprotein E(APOE),a gene identified as one of the strongest genetic factors contributing to the risk determinant of developing late-onset Alzheimer’s disease(AD),may also contribute to the risk of cancer.However,no pan-cancer analysis has been conducted specifically for the APOE gene.In this study,we investigated the oncogenic role of the APOE gene across cancers by GEO(Gene Expression Omnibus)and TCGA(The Cancer Genome Atlas).Based on the available data,we found that most cancer types overexpress APOE,and clear associations exist between the expression level of APOE and prognosis in tumor patients.The expression of APOE also correlates with certain gender-associated tumors including,ovarian cancer,uterine carcinosarcoma,and breast cancer.However,there is a significant negative association between cancer-associatedfibroblast infiltration levels and the expression level of APOE in testicular germ cell tumors.Moreover,acute inflammatory response and protein-activation cascade-associated functions play an important role in the functional mechanisms of APOE.The present pan-cancer analysis of APOE shows that the protein phosphorylation,DNA methylation,and genetic alterations of APOE have a significant clinical relevance for survival prognosis and immune cell infiltration.This novel pan-cancer study outlines the current understanding of APOE oncogenic roles across thirty-three cancers and highlights the complex association between AD and cancers.

GFPT2 pan-cancer analysis and its prognostic and tumor microenvironment associations

Objective Glutamine fructose-6-phosphate transaminase 2(GFPT2)is involved in a wide range of biological functions in human cancer.However,few studies have comprehensively analyzed the correlation between GFPT2 and different cancer prognoses and tumor microenvironments(TMEs).Methods We evaluated the expression level and prognostic value of GFPT2 using updated public databases and multiple comprehensive bioinformatics analysis methods and explored the relationship between GFPT2 expression and immune infiltration,immune neoantigens,tumor mutational burden(TMB),and microsatellite instability in pan-cancer.Results GFPT2 was highly expressed in five cancers.GFPT2 expression correlates with the prognosis of several cancers from The Cancer Genome Atlas(TCGA)and is significantly associated with stromal and immune scores in pan-cancer.High GFPT2 expression in BLCA,BRCA,and CHOL was positively correlated with the infiltration of immune cells,such as B-cells,CD4+T,CD8+T cells,dendritic cells,neutrophils,and macrophages.Conclusion High GFPT2 expression may modify the outcomes of patients with BLCA,BRCA,or CHOL cancers by increasing immune cell infiltration.These findings may provide insights for further investigation into GFPT2 as a potential target in pan-cancer.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Pan-cancer analysis of DNA epigenetic modifications by hydrophilic interaction liquid chromatography-tandem mass spectrometry

Accumulating evidence in recent years indicates that DNA methylation(5-methyl-2-deoxycytidine,5-mdC) and hydroxymethylation(5-hydroxymethyl-2-deoxycytidine, 5-hmd C) have been implicated in various biological processes, and the aberrations of these DNA cytosine modifications is tightly associated with cancer. N6-methyl-2-deoxyadenosine(m~6dA), as a newly discovered epigenetic modification in genome of mammals, has been demonstrated to play vital regulatory roles in tumorigenesis. However, the content information of m~6dA in human tumor tissues is still limited and pan-cancer analysis of these DNA epigenetic modifications is lacked. Herein, we developed a sensitive and robust stable isotopediluted hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS) method for accurate quantification of m~6dA, 5-mdC and 5-hmdC in genomic DNA from 82 pairs of human tumor tissues and matched tumor-adjacent normal tissues. The types of tumors included esophagus cancer, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, stromal tumor and colorectal cancer.Compared to the normal tissues, we revealed the level of m6dA was increased in tumor tissues of esophagus cancer, lung cancer and liver cancer, whereas the level of m~6dA was diminished in tumor tissues of pancreatic cancer and gastric cancer;while the contents of 5-mdC and 5-hmdC exhibited significant decrease in tumor tissues of most types of cancer. It is worth noting that we revealed, for the first time,the content of genomic m~6dA in pancreatic cancer, stromal tumor and colorectal cancer. The significant changes of these DNA epigenetic modifications indicate they may serve as indicators of cancers. In addition, this study will benefit for better understanding of the regulatory roles of these DNA epigenetic modifications in cancers.

Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors

Background:The molecular mechanisms driving tumorigenesis have continually been the focus of researchers.Cuproplasia is defined as copper-dependent cell growth and proliferation,including its primary and secondary roles in tumor formation and proliferation through signaling pathways.In this study,we analyzed the differences in the expression of cuproplasia-associated genes(CAGs)in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication.Methods:Raw data from 11,057 cancer samples were acquired from multiple databases.Pan-cancer analysis was conducted to analyze the CAG expression,single-nucleotide variants,copy number variants,methylation signatures,and genomic signatures of micro RNA(miRNA)-messenger RNA(mRNA)interactions.The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs.Using single-sample Gene Set Enrichment Analysis(ssGSEA)and Immune Cell Abundance Identifier database,immune cell infiltration was analyzed with the ssGSEA score as the standard.Results:Aberrantly expressed CAGs were found in multiple cancers.The frequency of single-nucleotide variations in CAGs ranged from 1%to 54%among different cancers.Furthermore,the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers.ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma,while the converse was true for MT1A and MT2A.In addition,we established cuproplasia scores and demonstrated their strong correlation with patient prognosis,immunotherapy responsiveness,and disease progression(P<0.05).Finally,we identified potential candidate drugs by matching gene targets with existing drugs.Conclusions:This study reports the genomic characterization and clinical features of CAGs in pan-cancers.It helps clarify the relationship between CAGs and tumorigenesis,and may be helpful in the development of biomarkers and new therapeutic agents.

Pan-Cancer dissection of ORAI1:prognostic implications and immune landscapecorrelation

Background:The ORAI1 gene,central to store-operated calcium entry(SOCE),is increasingly recognized for its pivotal role in cancer progression and patient prognosis across a broad spectrum of malignancies.Despite its critical involvement in calcium signaling pathways that are essential for cellular functions such as proliferation,migration,and apoptosis,the comprehensive impacts of ORAI1 within the tumor microenvironment(TME)and its modulation across various cancers have not been fully elucidated.Methods:We conducted a pan-cancer analysis leveraging data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)to assess ORAI1 expression.Differential expression analyses were performed,complemented by correlative studies with tumor mutation burden(TMB),microsatellite instability(MSI),immune infiltration,and key biological processes and pathways.Results:Our results demonstrate that ORAI1 is consistently upregulated in a range of cancer types,associated with aggressive tumor characteristics and poor patient outcomes.Significantly,ORAI1 upregulation correlates with increased tumor mutation burden(TMB)and microsatellite instability(MSI),markers of genomic instability that are predictive of response to immunotherapy,underscoring its potential utility in clinical stratification and treatment decision-making.ORAI1's influence extended to the immune landscape,showing associations with immune cell infiltration and both immunosuppressive and immunostimulatory gene sets,thereby affecting the TME and possibly the efficacy of immunotherapeutic interventions.Conclusions:The multifaceted nature of ORAI1's involvement in cancer pathophysiology positions it as a prospective biomarker and therapeutic target.Its expression dynamics and correlative significance with prognostic and immune regulatory elements underscore its potential in guiding therapeutic strategies and improving clinical outcomes.This study lays a foundation for future research,aiming to leverage ORAI1's biological significance in cancer prognosis and therapy optimization.

Deciphering the role of FSCN family genes in cancer:a pan-cancer bioinformatics study

Background:The Fascin(FSCN)family,comprising actin-bundling proteins,plays vital roles in cytoskeletal reorganization and cell migration.FSCN1,FSCN2,and FSCN3 are implicated in cancer progression through cell motility,invasion,and metastasis.However,their specific contributions across different cancer types remain unclear.Methods:We conducted a pan-cancer bioinformatics analysis of FSCN genes using data from The Cancer Genome Atlas.This included differential expression patterns,copy number variations(CNVs),mutations,methylation status,and correlations with tumor mutational burden,microsatellite instability,and immune checkpoint molecule expression.Differential expression was analyzed using DESeq2,while CNV and mutation analyses utilized GISTIC2.0 and MuTect2.Methylation data were assessed using the Illumina Human Methylation 450K BeadChip.Results:FSCN1 and FSCN2 showed significant differential expression in multiple cancers,often correlating with poor prognosis.FSCN3 exhibited less variability but a protective role in certain contexts.CNV analysis indicated frequent gene gains in FSCN genes,correlating with increased expression.FSCN3 had a higher mutation rate,suggesting genetic instability.Methylation analysis showed hypomethylation of FSCN1 and FSCN2 in tumors compared to normal tissues,whereas FSCN3 had minor changes.Significant associations were found between FSCN gene expression and tumor mutational burden,microsatellite instability,and immune checkpoint molecules,suggesting their involvement in tumor immunogenicity and the immune microenvironment.Conclusions:This pan-cancer analysis highlights the multifaceted roles of FSCN genes in cancer biology,emphasizing their potential as biomarkers and therapeutic targets.FSCN1 and FSCN2 are associated with poor prognosis and aggressive phenotypes,while FSCN3 shows protective roles in specific contexts.These findings offer new avenues for cancer diagnosis and treatment,particularly in personalized medicine.Future studies should validate these findings and explore the underlying mechanisms to fully harness the clinical potential of FSCN family proteins in oncology.

Associations of PGK1 promoter hypomethylation and PGK1-mediated PDHK1 phosphorylation with cancer stage and prognosis:a TCGA pan-cancer analysis

Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the clini-cal significance of PGK1 expression and function in cancer progression is unclear.Here,we investigated the relation-ship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation.Methods:We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets.Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation,we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types.Results:The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types,respectively.In breast carcinoma,elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis.Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival(OS)in cancers of the breast,liver,lung,stomach,and esophagus and with advanced TNM stage in breast and esophageal cancers.PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver,lung,and stomach cancer.Conclusions:The elevated expression,promoter hypomethylation,and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer.PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.

Pan-cancer analysis of long non-coding RNA NEAT1 in various cancers

Changes in the abundance and activity of long non-coding RNAs(lncRNAs)have an important impact on the development of cancer.The nuclear paraspeckle assembly transcript 1(NEAT1)has been reported to be overexpressed in many types of cancer since its discovery.However,inconsistencies exist as NEAT1 can also function as a tumor suppressor in certain types of cancer,such as acute promyelocytic leukemia.Here we systematically describe our current understanding of NEAT1 in tumor initiation and progression.First,we analyzed the expression patterns of NEAT1 in various normal tissues and malignant cancers using data from public data portals,the Genotype-Tissue Expression Project(GTEx)and the Cancer Genome Atlas(TCGA),together with recent progress in the study of NEAT1 in various types of cancer.Second,we discussed the functions and mechanisms of NEAT1 in modulating tumor activity.Then,the upstream transcription factors and downstream microRNA targets of NEAT1 in the transcription cascade of cancers were also summarized.These data highlight the emerging role of NEAT1 in tumorigenesis,and present promising targetable pathways and clinical opportunities for tumor prevention and classifications.

Pan-cancer analysis identifies RNA helicase DDX1 as a prognostic marker

The DEAD-box RNA helicase(DDX)family plays a critical role in the growth and development of multiple organisms.DDX1 is involved in mRNA/rRNA processing and mature,virus replication and transcription,hormone metabolism,tumo-rigenesis,and tumor development.However,how DDX1 functions in various cancers remains unclear.Here,we explored the potential oncogenic roles of DDX1 across 33 tumors with The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases.DDX1 is highly expressed in breast cancer(BRCA),cholangiocarcinoma(CHOL),and colon adenocarcinoma(COAD),but it is lowly expressed in renal cancers,including kidney renal clear cell carcinoma(KIRC),kidney chromophobe(KICH),and kidney renal papillary cell carcinoma(KIRP).Low expression of DDX1 in KIRC is cor-related with a good prognosis of overall survival(OS)and disease-free survival(DFS).Highly expressed DDX1 is linked to a poor prognosis of OS for adrenocortical carcinoma(ACC),bladder urothelial carcinoma(BLCA),KICH,and liver hepatocellular carcinoma(LIHC).Also,the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer(OV)but decreased in KIRC.Immune infiltration analysis exhibited that DDX1 expression affected CD8+T cells,and it was significantly associated with MSI(microsatellite instability),TMB(tumor mutational burden),and ICT(immune checkpoint blockade therapy)in tumors.In addition,the depletion of DDX1 dramatically affected the cell viability of human tumor-derived cell lines.DDX1 could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database.Thus,our pan-cancer analysis revealed that DDX1 had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.

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).

Social-ecological perspective on the suicidal behaviour factors of early adolescents in China:a network analysis

Background In early adolescence,youth are highly prone to suicidal behaviours.Identifying modifiable risk factors during this critical phase is a priority to inform effective suicide prevention strategies.Aims To explore the risk and protective factors of suicidal behaviours(ie,suicidal ideation,plans and attempts)in early adolescence in China using a social-ecological perspective.Methods Using data from the cross-sectional project‘Healthy and Risky Behaviours Among Middle School Students in Anhui Province,China',stratified random cluster sampling was used to select 5724 middle school students who had completed self-report questionnaires in November 2020.Network analysis was employed to examine the correlates of suicidal ideation,plans and attempts at four levels,namely individual(sex,academic performance,serious physical llness/disability,history of self-harm,depression,impulsivity,sleep problems,resilience),family(family economic status,relationship with mother,relationship with father,family violence,childhood abuse,parental mental illness),school(relationship with teachers,relationship with classmates,school-bullying victimisation and perpetration)and social(social support,satisfaction with society).Results In total,37.9%,19.0%and 5.5%of the students reported suicidal ideation,plans and attempts in the past 6 months,respectively.The estimated network revealed that suicidal ideation,plans and attempts were collectively associated with a history of self-harm,sleep problems,childhood abuse,school bullying and victimisation.Centrality analysis indicated that the most influential nodes in the network were history of self-harm and childhood abuse.Notably,the network also showed unique correlates of suicidal ideation(sex,weight=0.60;impulsivity,weight=0.24;family violence,weight=0.17;relationship with teachers,weight=-0.03;school-bullying perpetration,weight=0.22),suicidal plans(social support,weight=-0.15)and suicidal attempts(relationship with mother,weight=-0.10;parental mental llness,weight=0.61).Conclusions This study identified the correlates of suicidal ideation,plans and attempts,and provided practical implications for suicide prevention for young adolescents in China.Firstly,this study highlighted the importance of joint interventions across multiple departments.Secondly,the common risk factors of suicidal ideation,plans and attempts were elucidated.Thirdly,this study proposed target interventions to address the unique influencing factors of suicidal ideation,plans and attempts.

Advances in microfluidic-based DNA methylation analysis

DNA methylation has been extensively investigated in recent years,not least because of its known relationship with various diseases.Progress in analytical methods can greatly increase the relevance of DNA methylation studies to both clinical medicine and scientific research.Microflu-idic chips are excellent carriers for molecular analysis,and their use can provide improvements from multiple aspects.On-chip molecular analysis has received extensive attention owing to its advantages of portability,high throughput,low cost,and high efficiency.In recent years,the use of novel microfluidic chips for DNA methylation analysis has been widely reported and has shown obvious superiority to conventional methods.In this review,wefirst focus on DNA methylation and its applications.Then,we discuss advanced microfluidic-based methods for DNA methylation analysis and describe the great progress that has been made in recent years.Finally,we summarize the advantages that microfluidic technology brings to DNA methylation analysis and describe several challenges and perspectives for on-chip DNA methylation analysis.This review should help researchers improve their understanding and make progress in developing microfluidic-based methods for DNA methylation analysis.

A Review on Sources,Extractions and Analysis Methods of a Sustainable Biomaterial:Tannins

Condensed and hydrolysable tannins are non-toxic natural polyphenols that are a commercial commodity industrialized for tanning hides to obtain leather and for a growing number of other industrial applications mainly to substitute petroleum-based products.They are a definite class of sustainable materials of the forestry industry.They have been in operation for hundreds of years to manufacture leather and now for a growing number of applications in a variety of other industries,such as wood adhesives,metal coating,pharmaceutical/medical applications and several others.This review presents the main sources,either already or potentially commercial of this forestry by-materials,their industrial and laboratory extraction systems,their systems of analysis with their advantages and drawbacks,be these methods so simple to even appear primitive but nonetheless of proven effectiveness,or very modern and instrumental.It constitutes a basic but essential summary of what is necessary to know of these sustainable materials.In doing so,the review highlights some of the main challenges that remain to be addressed to deliver the quality and economics of tannin supply necessary to fulfill the industrial production requirements for some materials-based uses.

Telomerase-related advances in hepatocellular carcinoma:A bibliometric and visual analysis

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,and overall publication count,while Zucman-Rossi J ranked first in citation count.The five most popular journals were the World Journal of Gastroenterology,Hepatology,Journal of Hepatology,Oncotarget,and Oncogene,while Nature Genetics,Hepatology,and Nature Reviews Disease Primers had the most citations.We extracted 2293 keywords from the publications,120 of which appeared more than ten times.The most frequent were HCC,telomerase and human telomerase reverse transcriptase(hTERT).Keywords such as mutational landscape,TERT promoter mutations,landscape,risk,and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years.CONCLUSION Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.