Guoxiang Fu

The online version contains supplementary material available at 10.1038/s41598-026-49584-y.

Background: Intestinal γδ T‐cell immune characteristics and their relationship with disease activity in Crohn's disease (CD) and ulcerative colitis (UC) remain to be fully clarified. Methods: Biopsies from 21 CD, 21 UC and 21 healthy controls were analyzed by flow cytometry for γδ T‐cell frequency, cytotoxicity (perforin, granzyme‐B), activation (HLA‐DR) and exhaustion (PD‐1). ROC curves were used to evaluate the diagnostic performance of these indices. Vγ subsets were profiled using published scRNA‐seq data. Results: As disease activity increased, intestinal γδ T cells in CD and UC patients decreased and could not activate. The differences were that the cytotoxicity of intestinal γδ T cells in CD patients was always normal as disease activity increased. In contrast, the cytotoxicity of intestinal γδ T cells in UC patients was suppressed. Different Vγ subsets in CD or UC patients showed different immune characteristics, which might lead to different immune characteristics of γδT cells in CD or UC patients at different disease active stages. Furthermore, γδ T cell and HLA‐DR+ γδ T cell ratio were good indicators in diagnosing CD. The ratios of γδ T cell, HLA‐DR+ γδ T cell, PD‐1+ γδ T cell, and Perforin+ γδ T cell exhibited values for diagnosing UC. PD‐1+ γδ T cell ratio was a valuable indicator to help distinguish CD from UC. Conclusion: Intestinal γδ T cells exhibit both shared and divergent features in CD and UC that closely parallel disease activity, supporting their potential as immune biomarkers for diagnosis and discrimination between the two diseases.

Objective: The research was designed to explore the causal relationship between the changing landscape of 63 mitochondrial proteins and inflammatory bowel disease (IBD) by Mendelian randomization.Methods: Use SNPs significantly associated with IBD and their subtypes as instrumental variables. Various methods were utilized to assess the causal relation between mitochondrial function and the onset of IBD and their subtypes.Results: The results after FDR on p values indicated that Peptide chain release factor 1‐like was a causative factor for IBD. NADH dehydrogenase [ubiquinone] flavoprotein 2, hydroxymethylglutaryl‐CoA synthase 9, pyruvate carboxylase, apoptosis‐inducing factor 1, and transmembrane protein 70 with inflammatory bowel disease were identified as protective factors. Peptide chain release factor 1‐like and NADH dehydrogenase [ubiquinone] flavoprotein 2 were identified as causal and protective factors for IBD, respectively. In addition, GrpE protein homolog 1, 39S ribosomal protein L33, and tRNA pseudouridine synthase A are pathogenic in Crohn's disease, and Hydroxymethylglutaryl‐CoA synthase and Pyruvate carboxylase are protective factors. The MR‐presso method rejected outlier SNPs. The relative stability of the outcome data was assessed and validated at multiple levels by various statistical tests including pleiotropy test, heterogeneity test, and Steiger test.Conclusion: This study established a causal relationship between mitochondrial biological function and IBD, including its subtypes.

Background: Elongation Factor Tu GTP Binding Domain Containing 2 (EFTUD2), a conserved spliceosomal GTPase, is involved in craniofacial development and various cancers, but its role in lung adenocarcinoma (LUAD) remains unclear.Methods: EFTUD2 expression in LUAD tissues was analyzed using data from TCGA and GEO, and validated by immunohistochemistry, RT-qPCR, and Western blotting. The relationship between EFTUD2 expression and clinical features was examined using Fisher’s exact test. Diagnostic and prognostic analyses were performed in R. Hub genes related to EFTUD2 were identified through topological algorithms, and immune infiltration was assessed using CIBERSORT. The cGAS-STING pathway and m6A modification were also analyzed in the TCGA LUAD cohort. Functional assays were conducted to assess EFTUD2’s impact on LUAD cell proliferation, cell cycle, invasion, and metastasis, while glycolytic enzyme levels were measured by Western blotting.Results: EFTUD2 was upregulated in LUAD tissues and cells, correlating with N classification, visceral pleural invasion, intravascular tumor embolism, and cytokeratin-19 fragment antigen 21-1. Sixteen EFTUD2-related hub genes were identified. Higher EFTUD2 expression was linked to altered immune cell infiltration, with increased TumorPurity scores and decreased StromalScore, ImmuneScore, and ESTIMATEScore values. Gene enrichment analyses highlighted EFTUD2’s involvement in cell adhesion, immune response. EFTUD2 was strongly associated with the cGAS-STING pathway and m6A modification. EFTUD2 knockdown inhibited LUAD cell proliferation, migration, and tumorigenicity, causing G0/G1 phase cell cycle arrest, and altered glycolytic enzyme expression. These findings may suggest that EFTUD2 positively regulates the progression of LUAD and modulates the glycolytic activity of tumor cells, making it valuable for LUAD treatment and prognosis.Conclusions: EFTUD2 is a potential diagnostic and prognostic marker for LUAD, associated with immune infiltration, the tumor microenvironment, the cGAS-STING pathway, m6A modification, and glycolysis.

Background: Colorectal adenocarcinoma (COAD) is a malignant tumor with high mortality and low 5-year survival rate. Voltage-dependent anion channel 3 (VDAC3) is the least understood isoform of voltage-dependent anion-selective channels in the mitochondrial outer membrane. In this thesis, we aimed to investigate the prognostic value of VDAC3 and provide new insights into colon adenocarcinoma. Methods: We utilized The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, Human Protein Atlas online database, and the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) database to analyze VDAC3 expression in COAD and assess patient survival rates. Univariate and multivariate Cox regression analyses were employed to evaluate VDAC3’s prognostic significance for COAD. Gene set variation analysis (GSVA) was utilized to explore COAD-related signaling pathways associated with VDAC3. Additionally, we predicted the relationship between VDAC3 expression and anticancer drug sensitivity using the CellMiner database. Results: In the TCGA database, VDAC3 demonstrated elevated expression levels in COAD, which was further validated by findings from the GEO database. Survival analysis conducted using Kaplan-Meier (K-M) curves highlighted that the patients with decreased VDAC3 expression exhibited significantly shorter overall survival durations. VDAC3 expression demonstrated correlation with COAD pathological stage. VDAC3 gene mutation was linked to COAD outcomes. Cox regression analysis showed that VDAC3 was an independent predictor. In addition, GSVA analysis showed that VDAC3 was closely related to mitochondria-related biological processes and involved in the occurrence and development of mitochondria-related diseases. Finally, analysis of the CellMiner database predicted that VDAC3 expression was positively correlated with chelerythrine and cladribine, but negatively correlated with Ergenyl. Conclusions: Our study suggests that VDAC3 may be a potential biomarker for early diagnosis, prognosis, and treatment of COAD.

Background: In China, rapid intraoperative diagnosis of frozen sections of thyroid nodules is used to guide surgery. However, the lack of subspecialty pathologists and delayed diagnoses are challenges in clinical treatment. This study aimed to develop novel diagnostic approaches to increase diagnostic effectiveness.Methods: Artificial intelligence and machine learning techniques were used to automatically diagnose histopathological slides. AI‐based models were trained with annotations and selected as efficientnetV2‐b0 from multi‐set experiments.Results: On 191 test slides, the proposed method predicted benign and malignant categories with a sensitivity of 72.65%, specificity of 100.0%, and AUC of 86.32%. For the subtype diagnosis, the best AUC was 99.46% for medullary thyroid cancer with an average of 237.6 s per slide.Conclusions: Within our testing dataset, the proposed method accurately diagnosed the thyroid nodules during surgery.

Frequent RNF43 mutation contributes to moderate