Specific Genes Research Articles

Deciphering the cellular and molecular landscapes of Wnt/β-catenin signaling in mouse embryonic kidney development

BackgroundThe Wnt/β-catenin signaling pathway is critical in kidney development, yet its specific effects on gene expression in different embryonic kidney cell types are not fully understood. MethodsWnt/β-catenin signaling was activated in mouse E12.5 kidneys in vitro using CHIR99021, with RNA sequencing performed afterward, and the results were compared to DMSO controls (dataset GSE131240). Differential gene expression in ureteric buds and cap mesenchyme following pathway activation (datasets GSE20325 and GSE39583) was analyzed. Single-cell RNA-seq data from the Mouse Cell Atlas was used to link differentially expressed genes (DEGs) with kidney cell types. β-catenin ChIP-seq data (GSE39837) identified direct transcriptional targets. ResultsActivation of Wnt/β-catenin signaling led to 917 significant DEGs, including the upregulation of Notum and Apcdd1 and the downregulation of Crym and Six2. These DEGs were involved in kidney development and immune response. Single-cell analysis identified 787 DEGs across nineteen cell subtypes, with Macrophage_Apoe high cells showing the most pronounced enrichment of Wnt/β-catenin-activated genes. Gene expression profiles in ureteric buds and cap mesenchyme differed significantly upon β-catenin manipulation, with cap mesenchyme showing a unique set of DEGs. Analysis of β-catenin ChIP-seq data revealed 221 potential direct targets, including Dpp6 and Fgf12. ConclusionThis study maps the complex gene expression driven by Wnt/β-catenin signaling in embryonic kidney cell types. The identified DEGs and β-catenin targets elucidate the molecular details of kidney development and the pathway's role in immune processes, providing a foundation for further research into Wnt/β-catenin signaling in kidney development and disease.

Selection of Reference Genes in Siraitia siamensis and Expression Patterns of Genes Involved in Mogrosides Biosynthesis.

Siraitia siamensis is a traditional Chinese medicinal herb. In this study, using S. siamensis cultivated in vitro, twelve candidate reference genes under various treatments were analyzed for their expression stability by using algorithms such as GeNorm, NormFinder, BestKeeper, Delta CT, and RefFinder. The selected reference genes were then used to characterize the gene expression of cucurbitadienol synthase, which is a rate-limiting enzyme for mogroside biosynthesis. The results showed that CDC6 and NCBP2 expression was the most stable across all treatments and are the best reference genes under the tested conditions. Utilizing the validated reference genes, we analyzed the expression profiles of genes related to the synthesis pathway of mogroside in S. siamensis in response to a range of abiotic stresses. The findings of this study provide clear standards for gene expression normalization in Siraitia plants and exploring the rationale behind differential gene expression related to mogroside synthesis pathways.

RAB13 regulates macrophage polarization in sepsis

To select the core target (RAB13) in sepsis patients’ peripheral blood and investigate its molecular functions and possible mechanisms. The peripheral blood of sepsis patients (n = 21) and healthy individuals (n = 9) within 24 h after admission were collected for RNA-seq, and differential gene screening was performed by iDEP online analysis software (P < 0.01; log2FC ≥ 2) and enrichment analysis, the potential core target RAB13 was screened out. The association between RAB13 expression and sepsis severity was explored using multiple datasets in the GEO database, and survival analysis was conducted. Subsequently, peripheral blood mononuclear cells (PBMCs) from sepsis and control groups were isolated, and 10 × single-cell sequencing was used to identify the main RAB13-expressing cell types. Finally, LPS was used to stimulate THP1 cells to construct a sepsis model to explore the function and possible mechanism of RAB13. We found that RAB13 was a potential core target, and RAB13 expression level was positively associated with sepsis severity and negatively correlated with survival based on multiple public datasets. A single-cell sequencing indicated that RAB13 is predominantly localized in monocytes. Cell experiments validated that RAB13 is highly expressed in sepsis, and the knockdown of RAB13 promotes the polarization of macrophages towards the M2 phenotype. This mechanism may be associated with the ECM-receptor interaction signaling pathway. The upregulation of RAB13 in sepsis patients promotes the polarization of M2-like macrophages and correlates positively with the severity of sepsis.

Effects of simulated space conditions on CD4+ T cells: a multi modal analysis.

The immune system is an intricate network of cellular components that safeguards against pathogens and aberrant cells, with CD4+ T cells playing a central role in this process. Human space travel presents unique health challenges, such as heavy ion ionizing radiation, microgravity, and psychological stress, which can collectively impede immune function. The aim of this research was to examine the consequences of simulated space stressors on CD4+ T cell activation, cytokine production, and gene expression. CD4+ T cells were obtained from healthy individuals and subjected to Fe ion particle radiation, Photon irradiation, simulated microgravity, and hydrocortisone, either individually or in different combinations. Cytokine levels for Th1 and Th2 cells were determined using multiplex Luminex assays, and RNA sequencing was used to investigate gene expression patterns and identify essential genes and pathways impacted by these stressors. Simulated microgravity exposure resulted in an apparent Th1 to Th2 shift, evidenced on the level of cytokine secretion as well as altered gene expression. RNA sequencing analysis showed that several gene pathways were altered, particularly in response to Fe ions irradiation and simulated microgravity exposures. Individually, each space stressor caused differential gene expression, while the combination of stressors revealed complex interactions. The research findings underscore the substantial influence of the space exposome on immune function, particularly in the regulation of T cell responses. Future work should focus expanding the limited knowledge in this field. Comprehending these modifications will be essential for devising effective strategies to safeguard the health of astronauts during extended space missions. The effects of simulated space stressors on CD4+ T cell function are substantial, implying that space travel poses a potential threat to immune health. Additional research is necessary to investigate the intricate relationship between space stressors and to develop effective countermeasures to mitigate these consequences.

Multi-Omics Analysis Reveals the Molecular Mechanisms of the Glycolysis and TCA Cycle Pathways in Rhododendron chrysanthum Pall. under UV-B Stress

UV-B radiation is becoming a bigger threat to plants as a result of the ozone layer’s depletion. As an alpine plant, Rhododendron chrysanthum Pall. (R. chrysanthum) may grow regularly under UV-B radiation throughout its lengthy acclimatization period, although the mechanism of acclimatization is still poorly understood. The current investigation uncovered a number of adaptation strategies that R. chrysanthum has developed in reaction to UV-B rays. UV-B radiation impeded photosynthesis and damaged the photosystem, according to OJIP testing. Through transcriptomics and proteomics analyses, this study found that the differential proteins and differential genes of R. chrysanthum were significantly enriched in glycolysis and tricarboxylic acid (TCA) cycle pathways after UV-B treatment. The metabolomics results showed that a total of eight differential metabolites were detected in the glycolytic and TCA cycle pathways, and the changes in the expression of these metabolites reflected the final outcome of gene regulation in the glycolytic and TCA cycle pathways. The combined experimental results demonstrated that R. chrysanthum’s photosynthetic system was impacted by UV-B stress and, concurrently, the plant activated an adaptation mechanism in response to the stress. To maintain its energy supply for growth, R. chrysanthum adapts to UV-B stress by adjusting the expression of the relevant proteins, genes, and metabolites in the glycolytic and TCA cycling pathways. This study provides a new perspective for understanding the changes in the carbon metabolism of R. chrysanthum under UV-B stress and its mechanisms for UV-B resistance, and provides an important theoretical basis for the study of enhancing plant resistance to stress.

582. LOW EXPRESSION OF FRG1 PROMOTES MIGRATION AND INVASION IN ESOPHAGEAL CANCER

Abstract Purpose Distant metastasis is the primary cause of mortality among patients with esophageal cancer. Although FRG1 is known to play a role in the metastasis of various cancers, its specific function in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. In this study, we aimed to explore the role and potential molecular mechanism of FRG1 in the metastasis of ESCC. Methods Whole-exome sequencing was performed in ESCC patients who experienced distant metastasis (DM group) and those without metastasis within two years (non-DM group). Bioinformatics analysis and Immunohistochemistry (IHC) validation were conducted. In vitro, FRG1-overexpressed ESCC cell lines were established with lentivirus and validated by western blots. The wound-healing assay, transwell migration and invasion assay were performed in esophageal cancer cell lines. Additionally, RNA sequencing was conducted in ESCC cells to identify potential pathways involved. Results Mutations in FRG1 were more frequently observed in DM group compared to those in non-DM group. IHC revealed that the expression of FRG1 in DM group was significantly lower than non-DM group. In vitro, our results showed that ESCC cells with low FRG1 expression exhibited enhanced migration and invasion capabilities. Conversely, overexpression of FRG1 inhibited migration and invasion in ESCC cells. Mechanistically, RNA sequencing analysis showed a total of 93 differential expression genes between FRG1-overexpressed cells and the negative control. Notably, most differential genes were mainly enriched in the PPAR pathway and tyrosine metabolism pathway. Conclusion Our findings suggest that low FRG1 expression in patients may be indicative of rapid distant metastasis. The significant impact of FRG1's abnormal expression on the migration and invasion of ESCC cells highlights its potential as a therapeutic target for treating esophageal squamous cell carcinoma.

Predicting biomarkers in laryngeal squamous cell carcinoma based on the cytokine-cytokine receptor interaction pathway

ObjectiveTo analyze and validate differential genes in the cytokine-cytokine receptor interaction CCRI pathway in laryngeal squamous cell carcinoma (LSCC) using bioinformatics and Mendelian randomization (MR) to find potential biomarkers for LSCC. MethodsFive sets of LSCC-related gene chips were downloaded from the GEO database, and four sets of combined datasets were randomly selected as the test set and one set as the validation set to screen for differential genes in the CCRI pathway; two-way Mendelian randomization was performed to analyze the causal relationship between cytokine receptor as the exposure factor and LSCC as the outcome variable; and the causal relationship was analyzed by DGIdb, Miranda, miRDB, miRWalk, TargetScan, spongeScan, and TISIDB databases to analyze the relationship between differential genes and drugs, immune cell infiltration, and mRNA-miNA-lncRNA interactions. ResultsA total of 7 differentially expressed genes CD27, CXCL2, CXCL9, INHBA, IL6, CXCL11, and TNFRSF17 were screened for enrichment in the CCRI signaling pathway; MR analysis showed that the CCRI receptor was a risk factor for LSCC (IVW: OR = 1.629, 95 % CI:1.060–2.504, P = 0.026); Seven differential genes were correlated with drugs, immune cells and mRNA-miNA-lncRNA, respectively; the CCRI differential gene expression analysis in the validation set was consistent with the test set results. ConclusionThis study provided CCRI differential gene expression by bioinformatics, and MR analysis demonstrated that cytokine receptors are risk factors for LSCC, providing new ideas for the pathogenesis and therapeutic targets of LSCC.

Bioinformatics screening and verification of ischemic stroke-related key genes and drug prediction.

Stroke is one of the major causes of disability and death worldwide. The lack of effective medical treatment for stroke heightens the need for new therapeutic targets. In this study, we obtained two microarray data sets from the Gene Expression Omnibus (GEO) database and identified differential genes (DEGs) between MCAO and control groups. Then, enrichment analysis of the DEGs was performed using DAVID and Metascape. The results show 27 DEGs shared between the two datasets. The functional enrichment analysis showed that these genes are mainly enriched in immune response, complement and coagulation cascades, apoptotic processes. The four hub genes (C1qc, Fcgr2b, C1qb, and Cd14) were screened out using the Cytoscape. Next, real-time PCR and Western blot analysis showed that expression of C1q and CD14 increased at 14 days after tMCAO. Furthermore, we took eight small molecule compounds with the lowest score using Cmap and studied their background characteristics. These results are built on a meta-analysis of data, which are generally accessible from the online space. Finally, we evaluated the protective effect of the rolipram through behavior tests after tMCAO, and results showed that the rolipram significantly attenuated neurobehavioral dysfunction at 14 days after brain ischemia. The present results provide novel insights into the biological process and potential therapeutic drugs involved in stroke.

Single-Cell Sequencing Analysis and Bulk-Seq Identify IGFBP6 and TNFAIP6 as Novel Differential Diagnosis Markers for Postburn Pathological Scarring

BackgroundIf not accurately differentiated and treated, postburn pathological scars, such as keloids and hypertrophic scars, can lead to diverse clinical outcomes. However, differential diagnosis at the molecular level for postburn pathological scars remains limited. Using single-cell sequencing analysis, we investigated the genetic nuances of pathological scars at the cellular level. This study aimed to identify molecular diagnostic biomarkers to distinguish between postburn keloids and hypertrophic scars. MethodsSingle-cell sequencing, differential expression, and weighted co-expression network analyses were performed to identify potential key genes for discriminating between keloids and hypertrophic scars. Postburn clinical samples were collected from our centre to validate the expression levels of the identified key genes. ResultsSingle-cell sequencing analysis unveiled 29 and 30 cell clusters in keloids and hypertrophic scars, respectively, predominantly composed of fibroblasts. Bulk differential gene analysis showed 96 highly expressed genes and 69 lowly expressed genes in keloids compared to hypertrophic scars. By incorporating previous research, Gene Set Enrichment Analysis was conducted to select fibroblasts as the focus of research. According to the single-cell data, 301 genes were stably expressed in fibroblasts from both types of pathological scars. Consistently, Weighted Gene Co-expression Network Analysis revealed that the blue module genes were mostly hub genes associated with fibroblasts. After intersecting fibroblast-related genes in single-cell data, Weighted Gene Co-expression Network Analysis-hub module genes, and bulk differential expression genes, Insulin-Like Growth Factor Binding Protein 6 and Tumour Necrosis Factor Alpha Induced Protein 6 were identified as key genes to distinguish keloids from hypertrophic scars, resulting in diagnostic accuracies of 1.0 and 0.75, respectively. Immunohistochemical Staining and Quantitative Reverse Transcription PCR revealed that the expression levels of Tumour Necrosis Factor Alpha Induced Protein 6 and Insulin-Like Growth Factor Binding Protein 6 were significantly lower in postburn keloids than in hypertrophic scars. ConclusionsTumour Necrosis Factor Alpha Induced Protein 6 and Insulin-Like Growth Factor Binding Protein 6, exhibiting high diagnostic accuracy, provide valuable guidance for the differential diagnosis and treatment of postburn pathological scars.

Relaxin-2 promotes osteoblastic differentiation mediated by epidermal growth factor and epidermal growth factor receptor signaling.

Loss of osteogenic differentiation potential of osteoblasts has been associated with the pathogenesis of osteoporosis. Thus, stimulation of osteoblastic differentiation is a therapeutic strategy for osteoporosis. Relaxin-2 is a peptide hormone with potent biological functions. However, the effects of Relaxin-2 in osteoblastic differentiation and osteoporosis have not been reported before. Here, we report a novel physiological role of Relaxin-2 in promoting osteoblastic differentiation and mineralization of MC3T3-E1 cells. Our results indicate that exposure to Relaxin-2 upregulated the expression, and elevated the activity of alkaline phosphatase (ALP) when MC3T3-E1 cells were cultured in osteogenic differentiation medium (OM). Additionally, Relaxin-2 upregulated the mRNA levels of osteocalcin (ocn), osteopontin (opn), and collagen type I alpha 1 (Col1a1). The alizarin red S staining assay revealed that Relaxin-2 promoted the mineralization of MC3T3-E1 cells. We also found that Relaxin-2 increased the expression of Runx-2 as well as the epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). Importantly, silencing of EGF abolished the effects of Relaxin-2 in osteoblastic differentiation and related gene expression. These findings suggest that Relaxin-2 stimulates osteogenic differentiation through activating EGF/EGFR signaling.

OVOL2 regulates the expression of trophoblast differentiation and epithelial identity-associated genes in the mouse placenta

OVOL2 regulates the expression of trophoblast differentiation and epithelial identity-associated genes in the mouse placenta

S. cerevisiae ERG5DeltaNTH1DeltaAMS1Delta Construction Enhancing Stress Tolerance for Ethanol Production Increase in the Presence of Inhibitors and Mechanism Analysis based on the Comparative Transcriptomics

Saccharomyces cerevisiae is considered the most promising large-scale production strain with ethanol as the main product. The fermentation of Saccharomyces cerevisiae is generally inhibited under various stress conditions. Various inhibitors in the hydrolysate severely inhibit yeast proliferation and yeast accumulation. In this study, S. cerevisiae ERG5, NTH1, and AMS1 were knocked out to improve the yeast stress tolerance by the Clustered Regularly Interspaced Short Palindromic Repeats Cas9 (CRISPR-Cas9) technology. The result indicated that the stress tolerance of S. cerevisiae ERG5ΔNTH1ΔAMS1Δ mutant (S. cerevisiae SCENA) was remarkably improved compared with the wild-type strain. The contents of fecosterol, trehalose, and mannan in S. cerevisiae SCENA were 1.67, 1.53, and 1.47 folds compared with those in the control. The ethanol concentration in S. cerevisiae SCENA reached 16.5 g/L, which was 1.23 folds compared with the control using rice bran hydrolysate. Further, the transcriptome analysis indicated down-regulated differential expression genes (DEGs) in S. cerevisiae SCENA were mainly from cellular response to glucose, cell periphery, and plasma membrane. Up-regulated DEGs were mainly from spore wall assembly, fungal-type cell wall assembly, and ascospore wall assembly. Thus, S. cerevisiae SCENA could effectively produce ethanol using the fermentation of lignocellulosic hydrolysate in the presence of inhibitors by regulating fecosterol, trehalose, and mannan metabolisms.

Characterization of the Prognosis and Tumor Microenvironment of Cellular Senescence-related Genes through scRNA-seq and Bulk RNA-seq Analysis in GC.

Cellular senescence (CS) is thought to be the primary cause of cancer development and progression. This study aimed to investigate the prognostic role and molecular subtypes of CS-associated genes in gastric cancer (GC). The CellAge database was utilized to acquire CS-related genes. Expression data and clinical information of GC patients were obtained from The Cancer Genome Atlas (TCGA) database. Patients were then grouped into distinct subtypes using the "Consesus- ClusterPlus" R package based on CS-related genes. An in-depth analysis was conducted to assess the gene expression, molecular function, prognosis, gene mutation, immune infiltration, and drug resistance of each subtype. In addition, a CS-associated risk model was developed based on Cox regression analysis. The nomogram, constructed on the basis of the risk score and clinical factors, was formulated to improve the clinical application of GC patients. Finally, several candidate drugs were screened based on the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset. According to the cluster result, patients were categorized into two molecular subtypes (C1 and C2). The two subtypes revealed distinct expression levels, overall survival (OS) and clinical presentations, mutation profiles, tumor microenvironment (TME), and drug resistance. A risk model was developed by selecting eight genes from the differential expression genes (DEGs) between two molecular subtypes. Patients with GC were categorized into two risk groups, with the high-risk group exhibiting a poor prognosis, a higher TME level, and increased expression of immune checkpoints. Function enrichment results suggested that genes were enriched in DNA repaired pathway in the low-risk group. Moreover, the Tumor Immune Dysfunction and Exclusion (TIDE) analysis indicated that immunotherapy is likely to be more beneficial for patients in the low-risk group. Drug analysis results revealed that several drugs, including ML210, ML162, dasatinib, idronoxil, and temsirolimus, may contribute to the treatment of GC patients in the high-risk group. Moreover, the risk model genes presented a distinct expression in single-cell levels in the GSE150290 dataset. The two molecular subtypes, with their own individual OS rate, expression patterns, and immune infiltration, lay the foundation for further exploration into the GC molecular mechanism. The eight gene signatures could effectively predict the GC prognosis and can serve as reliable markers for GC patients.

Deciphering the Anhydrobiosis and Plant Parasitism of Wheat Seed Gall Nematode through Transcriptomic Analysis

The wheat seed gall nematode (Anguina tritici L.) poses a significant threat to wheat and barley production. Central to its survival is the ability to endure desiccation through anhydrobiosis, setting it apart from other nematodes. Unraveling the molecular mechanisms governing anhydrobiosis and plant parasitism in A. tritici is crucial for devising effective management strategies. A comprehensive transcriptomic analysis was conducted to elucidate the genetic pathways involved in these processes. Employing next-generation sequencing technologies, gene expression profiling was performed across three developmental stages, namely anhydrobiotic J2, revived J2 and the adult. Transcriptomic profiling yielded 139,002 transcripts in anhydrobiotic J2s, 156,731 in revived J2s, and 80,282 in adult stages, with a cumulative assembly size of 133.2 Mb. Differential gene expression analysis revealed that 1,223 genes were significantly upregulated whereas 1,934 genes were downregulated in anhydrobiotic J2s in comparison to revived J2s. Comparative transcriptomic analysis across nematode species highlighted conserved and species-specific genes. Functional annotation identified key genes associated with anhydrobiosis, plant parasitism, glycosylation, and longevity mechanisms. Real-time PCR validation corroborated differential expression patterns. The present study provides gene homologs and longevity pathways, which indicate similarity of the mechanism of dauer larva formation and survival strategies to that of Caenorhabditis elegans. Comprehensive understanding of the molecular basis for survival and parasitic strategies of A. tritici, shall provide potential targets for novel control interventions to mitigate nematode’s impact on wheat crops.

540. INFILTRATION OF RESECTED OESOPHAGEAL ADENOCARCINOMA WITH ANTIGEN-EXPERIENCED PD-1 AND CD39 POSITIVE CD8+ TISSUE RESIDENT MEMORY CELLS CORRELATE WITH IMPROVED SURVIVAL

Abstract Background The development of novel treatments for oesophageal adenocarcinoma (OAC) represents an area of significant unmet need. Despite the application of immune checkpoint blockade alongside chemotherapy as standard of care for some patients with metastatic OAC, responses to immunotherapies are modest and 5-year survival is 17%. The reasons for this remains unclear and while tumour infiltration with CD8+ T lymphocytes (TILs) at the time of resection is associated with improved outcomes, this heterogeneous population remains incompletely characterised in OAC. Tissue resident memory cells (TRM) are increasingly understood as key mediators of immunotherapy response but their role in OAC is poorly understood. Methods Tumour samples were accessed by punch biopsy from the central portion of cancers resected from 44 patients undergoing curative surgery for OAC. Samples were assessed by multi-parametric flow cytometry for the presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of antigen-experienced PD-1 and CD39 positive CD8+ OAC TILs were sorted, and bulk RNA sequencing (RNAseq) undertaken using a modified SmartSeq2 protocol allowing differential gene expression analysis and gene set enrichment analysis. Flow cytometric assessment of functionality was completed. Results Resected OAC are often highly infiltrated with antigen experienced CD8+ TILs expressing high levels of PD-1 and CD39 and an abundance of this population correlates with improved survival (%PD-1/CD39+ &amp;gt;Median, OS HR 0.12). RNAseq of sorted TILs identified this PD-1+ and CD39+ lymphocyte population as enriched for precursor exhausted-like CD8+ TRM (NES 2.01 p=0.00). This is correlated by their CD103+ and TIM3- predominance on flow cytometry in keeping with TRMsassociated with immunotherapy response in other cancers. This population demonstrated a maintained proliferative potential, an ability to degranulate and produce the key effector molecules IFN-γ, TNF-α and Granzyme B. Conclusions An abundance of a PD-1 and CD39 positive CD8+ TIL population, consistent with a precursor exhausted-like TRM population with maintained proliferative and functional capacity, is observed to correlate with improved outcomes following curative surgery for OAC. This TRM population is consistent with analogous populations observed to be responsible for immunotherapy response in other cancers and their identification may predict benefit from such approaches in OAC and allow better patient selection for treatment with immune checkpoint inhibitors.

Joint genotype and ancestry analysis identify novel loci associated with atopic dermatitis in African American population

Atopic dermatitis (AD) is a chronic itchy inflammatory disease of the skin. Genetic studies have identified multiple risk factors linked to the disease; however, most of studies have been derived from European and East Asian populations. The admixed genome of African American (AA) may provide an opportunity to discovery ancestry-specific loci involved in AD susceptibility. Herein, we present joint analysis of ancestry and genotype effects followed with validation using differential gene expression analysis on AD using 710 AD cases and 1015 non-AD controls from the AA population, genotyped using MEGA followed by imputation using the CAAPA reference panel. The joint analysis identified two novel AD-susceptibility loci, rs2195989 in gene ANGPT1 (8q23.1) and rs62538818 in the intergenic region LURAP1L—MPDZ (9p23). Admixture mapping (AM) results showed potential genomic inflation, and we implemented genomic control and identified five ancestry-of-origin loci with European ancestry effects. The multi-omics functional prioritization of variants in AM signals prioritized the loci SLAIN2, RNF39, and FOXA2. GWAS identified variants significantly associated with AD in the AA population, including SGK1 (rs113357522, OR = 2.81), EFR3A (rs16904552, OR = 1.725), and MMP14 (rs911912, OR = 1.791). GWAS variants were common in the AA but rare in the European population, which suggests an African ancestry-specific risk of AD. Four genes (ANGPT1, LURAP1L, EFR3A, and SGK1) were further validated using qPCR from AD and healthy skin. This study highlighted the importance of genetic studies on admixed populations, as well as local ancestry and genotype-ancestry joint effects to identify risk loci for AD.

CD8+ T cell associated scoring model helps prognostic diagnosis and immunotherapy selection in patients with colon adenocarcinoma

ObjectiveT cell-mediated immunity plays a crucial role in the immune response against tumors, with CD 8+ T cells playing a leading role in the eradication of cancer cells. Material and methodsA total of 5 datasets were included in this study. Single cell transcriptome data were used to discover CD8+ T cell marker genes, and Bulk transcriptome data from TCGA and GEO were jointly analyzed to screen candidate prognostic genes. lasso regression was performed to construct prognostic models. Immunotherapy cohort (IMvigor 210 and GSE78220) was applied to validate the diagnostic power of markers. ResultSingle-cell transcriptome data identified 65 CD8+ T cell marker genes, highlighting their importance in T cell-mediated immune responses. Among these, 11 genes were identified as CD8+ T-associated differential genes through analysis of bulk data from TCGA and GEO. A prognostic model for 5 genes was identified based on Lasso regression, dividing colon adenocarcinoma (COAD) patients into high- and low-risk groups. This model exhibited higher prognostic accuracy compared to traditional clinicopathological characteristics (age, pathological stage, histological grading). Moreover, the risk score derived from this model successfully differentiated patient responses to immunotherapy, as validated in the IMvigor 210 and GSE78220 cohorts. ConclusionOur research introduces a novel prognostic signature based on CD8+ T cell marker genes, demonstrating significant predictive power for prognosis and immunotherapy response in COAD patients. This model offers a potential tool for improving patient stratification and personalizing treatment strategies.

Comparative Analysis of Gene Expression Profiles in Ovarian Clear Cell Carcinoma and High-Grade Serous Ovarian Cancer.

To evaluate disparities in gene expression profiles between Ovarian Clear Cell Carcinoma (OCCC) and High-Grade Serous Ovarian Carcinoma (HGSOC). A descriptive study. Place and Duration of the Study: The Second People's Hospital of Jingdezhen, Jiangxi, China, between 31st December 2017 and December 2023. Basic and clinical diagnostic information, along with genetic test reports, were compiled from all patients within the included groups. Differential gene expression between the two cohorts was scrutinised to elucidate its clinical significance. Comparative analysis revealed nine differentially expressed genes in OCCC relative to HGSOC, with six exhibiting significant disparities (p <0.05). These genes are implicated in pivotal cellular processes including the cell cycle, apoptosis, DNA damage repair, and the PI3K pathway. Notably, aberrant expression patterns, such as overexpression of MET and downregulation of PTEN and SMARCA4, correlated with adverse prognosis and survival outcomes in selected patients. Distinctive gene expression profiles between OCCC and HGSOC underscore disparate tumorigenic mechanisms, thereby laying a foundation for the tailored therapeutic interventions. Further elucidation of the identified differentially expressed genes is warranted to delineate their role in OCCC pathogenesis and prognostic significance. Ovarian clear cell carcinoma, High-grade serous ovarian cancer, Gene expression profiles, Homologous recombination repair.

CD8+ T cell‑related KCTD5 contributes to malignant progression and unfavorable clinical outcome of patients with triple‑negative breast cancer.

Triple‑negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer that lacks expression of estrogen receptor, progesterone receptor, and HER2, making it more challenging to treat with targeted therapies. The present study aimed to identify CD8+ T cell‑associated genes, which could provide insight into the mechanisms underlying TNBC to facilitate developing novel immunotherapies. TNBC datasets were downloaded from public databases including The Cancer Genome Atlas, Molecular Taxonomy of Breast Cancer International Consortium, and Gene Expression Omnibus. Candidate genes were identified integrating weighted gene co‑expression network analysis (WGCNA), differential gene expression, protein‑protein‑interaction network construction and univariate Cox regression analysis. Kaplan‑Meier survival, multivariate Cox regression and receiver operating characteristic analysis were performed to evaluate the prognostic value of hub genes. Knockdown experiments, alongside wound healing, Cell Counting Kit‑8 and Transwell migration and invasion assays were performed. In total, seven gene modules were associated with CD8+ T cells using WGCNA, among which potassium channel tetramerization domain 5 (KCTD5) was significantly upregulated in TNBC samples and was associated with poor prognosis. KCTD5 expression inversely associated with infiltration ratios of 'Macrophages M1', 'Plasma cells', and 'γδ T cells', but positively with 'activated Mast cells', 'Macrophages M0', and 'Macrophages M2'. As an independent prognostic indicator for TNBC, KCTD5 was also associated with drug sensitivity and the expression of programmed cell death protein 1, Cytotoxic T‑Lymphocyte‑Associated Protein 4 (CTLA4), CD274), Cluster of Differentiation 86 (CD86), Lymphocyte‑Activation Gene 3 (LAG3), T Cell Immunoreceptor with Ig and ITIM Domains (TIGIT). Knockdown of KCTD5 significantly inhibited viability, migration and invasion of TNBC cells in vitro. KCTD5 was suggested to impact the tumor immune microenvironment by influencing the infiltration of immune cells and may serve as a potential therapeutic target for TNBC.

Single-cell RNA sequencing integrated with bulk RNA sequencing analysis reveals the protective effects of lactate-mediated lactylation of microglia-related proteins on spinal cord injury.

Spinal cord injury (SCI) results in significant neurological deficits, and microglia play the critical role in regulating the immune microenvironment and neurological recovery. Protein lactylation has been found to modulate the function of immune cells. Therefore, this study aimed to elucidate the effects of glycolysis-derived lactate on microglial function and its potential neuroprotective mechanisms via lactylation after SCI. Single-cell RNA sequencing (scRNA-seq) data were obtained from figshare to analyze cellular and molecular alterations within the spinal cord post-SCI, further focusing on the expression of microglia-related genes for cell sub-clustering, trajectory analysis, and glycolysis function analysis. We also evaluated the expression of lactylation-related genes in microglia between day 7 after SCI and sham group. Additionally, we established the mice SCI model and performed the bulk RNA sequencing in a time-dependent manner. The expression of glycolysis- and lactylation-related genes was evaluated, as well as the immune infiltration analysis based on the lactylation-related genes. Then, we investigated the bio-effects of lactate on the inflammation and polarization phenotype of microglia. Finally, adult male C57BL/6 mice were subjected to exercise first to increase lactate level, before SCI surgery, aiming to evaluate the protective effects of lactate-mediated lactylation of microglia-related proteins on SCI. scRNA-seq identified a subcluster of microglia, recombinant chemokine C-X3-C-motif receptor 1+ (CX3CR1+) microglia, which is featured by M1-like phenotype and increased after SCI. KEGG analysis revealed the dysfunctional glycolysis in microglia after SCI surgery, and AUCell analysis suggested that the decreased glycolysis an increased oxidative phosphorylation in CX3CR1+ microglia. Differential gene analysis suggested that several lactylation-related genes (Fabp5, Lgals1, Vim, and Nefl) were downregulated in CX3CR1+ microglia at day 7 after SCI, further validated by the results from bulk RNA sequencing. Immunofluorescence staining indicated the expression of lactate dehydrogenase A (LDHA) in CX3CR1+ microglia also decreased at day 7 after SCI. Cellular experiments demonstrated that the administration of lactate could increase the lactylation level and inhibit the pro-inflammatory phenotype in microglia. Functionally, exercise-mediated lactate production resulted in improved locomotor recovery and decreased inflammatory markers in SCI mice compared to SCI alone. In the subacute phase of SCI, metabolic remodeling in microglia may be key therapeutic targets to promote nerve regeneration, and lactate contributed to neuroprotection after SCI by influencing microglial lactylation and inflammatory phenotype, which offered a novel approach for therapeutic intervention.