An angiogenesis-associated gene-based signature predicting prognosis and immunotherapy efficacy of head and neck squamous cell carcinoma patients.

OBJECTIVES: To develop a model that can assist in the diagnosis and prediction of prognosis for head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Data from TCGA and GEO databases were used to generate normalized gene expression data. Consensus Cluster Plus was used for cluster analysis and the relationship between angiogenesis-associated gene (AAG) expression patterns, clinical characteristics and survival was examined. Support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) analyzes and multiple logistic regression analyzes were performed to determine the diagnostic model, and a prognostic nomogram was constructed using univariate and multivariate Cox regression analyses. ESTIMATE, XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, CIBERSORT algorithms were used to assess the immune microenvironment of HNSCC patients. In addition, gene set enrichment analysis, treatment sensitivity analysis, and AAGs mutation studies were performed. Finally, we also performed immunohistochemistry (IHC) staining in the tissue samples. RESULTS: We classified HNSCC patients into subtypes based on differences in AAG expression from TCGA and GEO databases. There are differences in clinical features, TME, and immune-related gene expression between two subgroups. We constructed a HNSCC diagnostic model based on nine AAGs, which has good sensitivity and specificity. After further screening, we constructed a prognostic risk signature for HNSCC based on six AAGs. The constructed risk score had a good independent prognostic significance, and it was further constructed into a prognostic nomogram together with age and stage. Different prognostic risk groups have differences in immune microenvironment, drug sensitivity, gene enrichment and gene mutation. CONCLUSION: We have constructed a diagnostic and prognostic model for HNSCC based on AAG, which has good performance. The constructed prognostic risk score is closely related to tumor immune microenvironment and immunotherapy response.

Causal Effects of Gut Microbiota on Age-Related Macular Degeneration: A Mendelian Randomization Study.

Purpose: Recently, the association between gut microbiota and age-related macular degeneration (AMD) through the gut-retina axis has attracted great interest. However, the causal relationship between them has not been elucidated. Using publicly available genome-wide association study summary statistics, we conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiota and the occurrence of AMD. Methods: The study used a variety of quality control techniques to select instrumental single nucleotide polymorphisms (SNPs) with strong exposure associations. We used a set of SNPs as instrumental variable that were below the genome-wide statistical significance threshold (5 × 10-8). Additionally, a separate group of SNPs below the locus-wide significance level (1 × 10-5) were selected as instrumental variables to ensure a comprehensive conclusion. Inverse variance-weighted (IVW) analysis was the primary technique we used to examine causality in order to confirm the validity of our findings. The MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis were used to evaluate the horizontal pleiotropy, heterogeneities, and stability of the genetic variants. Results: IVW results showed that genus Anaerotruncus (P = 5.00 × 10-3), genus Candidatus Soleaferrea (P = 1.83 × 10-2), and genus unknown id.2071 (P = 3.12 × 10-2) were protective factors for AMD. The Eubacterium oxidoreducens group (P = 3.17 × 10-2), genus Faecalibacterium (P = 2.67 × 10-2), and genus Ruminococcaceae UCG-011 (P = 4.04 × 10-2) were risk factors of AMD. No gut microbiota (GM) taxa were found to be causally related to AMD at the phylum, class, order, and family levels (P > 0.05). The robustness of MR results were confirmed by heterogeneity and pleiotropy analysis. (P > 0.05). We also performed a bidirectional analysis, which showed that genus Anaerotruncus, genus Candidatus Soleaferrea, genus unknown id.2071 and the Eubacterium oxidoreducens group had an interaction with AMD, whereas genus Faecalibacterium showed only a unilateral unfavorable effect on AMD. Conclusions: We confirmed a causal relationship between AMD and GM taxa, including the Eubacterium oxidoreducens group, Faecalibacterium, Ruminococcaceae UCG-011, Anaerotruncus, and Candidatus Soleaferrea. These strains have the potential to serve as new biomarkers, offering valuable insights into the treatment and prevention of AMD.

Sterility of Aedes albopictus by X-ray Irradiation as an Alternative to γ-ray Irradiation for the Sterile Insect Technique.

The mosquito Aedes albopictus can transmit various arboviral diseases, posing a severe threat to human health. As an environmentally friendly method, sterile insect technology (SIT) is considered an alternative to traditional methods such as chemical pesticides to control Ae. albopictus. In SIT, the sterility of male mosquitoes can be achieved by γ-ray or X-ray radiation. Compared with γ-rays, X-rays are easier to obtain, cheaper, and less harmful. However, there is a lack of comparative assessment of these two types of radiation for SIT under the same controlled conditions. Here, we compared the effects of X-ray and γ-ray radiation on the sterility of Ae. albopictus males under laboratory-controlled conditions. Neither type of radiation affected the number of eggs but significantly reduced the survival time and hatch rate. The same dose of γ-rays caused a higher sterility effect on males than X-rays but had a more significant impact on survival. However, X-rays could achieve the same sterility effect as γ-rays by increasing the radiation dose. For example, X-rays of 60 Gy induced 99% sterility, similar to γ-rays of 40 Gy. In the test of male mating competitiveness, the induced sterility and the male mating competitiveness index were also identical at the same release ratio (sterile males/fertile males). At a release ratio of 7:1, nearly 80% of eggs failed to hatch. Sterile males produced by X-ray and γ-ray radiation had similar male competitiveness in competition with field males. In conclusion, a higher dose of X-rays is required to achieve the same sterility effect, compared to γ-rays. When γ-rays are not readily available, high-dose X-rays can be used instead. This study provides data supporting the selection of more suitable radiation for the field release of sterile male mosquitoes.

A Signature Based on Costimulatory Molecules for the Assessment of Prognosis and Immune Characteristics in Patients With Stomach Adenocarcinoma.

Although costimulatory molecules have been shown to boost antitumor immune responses, their significance in stomach adenocarcinoma (STAD) remains unknown. The purpose of this study was to examine the gene expression patterns of costimulatory molecule genes in patients with STAD and develop a predictive signature to aid in therapy selection and outcome prediction. We used 60 costimulatory family genes from prior research to conduct the first complete costimulatory molecular analysis in patients with STAD. In the two study groups, consensus clustering analysis based on these 60 genes indicated unique distribution patterns and prognostic differences. Using the least absolute shrinkage and selection operator and Cox regression analysis, we identified nine costimulatory molecular gene pairs (CMGPs) with prognostic value. With these nine CMGPs, we were able to develop a costimulatory molecule-related prognostic signature that performed well in an external dataset. For the patients with STAD, the signature was proven to be a risk factor independent of the clinical characteristics, indicating that this signature may be employed in conjunction with clinical considerations. A further connection between the signature and immunotherapy response was discovered. The patients with high mutation rates, an abundance of infiltrating immune cells, and an immunosuppressive milieu were classified as high-risk patients. It is possible that these high-risk patients have a better prognosis for immunotherapy since they have higher cytolytic activity scores and immunophenoscores of CTLA4 and PD-L1/PD-L2 blockers. Therefore, our signature may help clinicians in assessing patient prognosis and developing treatment plans.

Association of KCNQ1rs2237892C⟶T Gene with Type 2 Diabetes Mellitus: A Meta-Analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM. OBJECTIVE: To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility. METHODS: A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger's test were used to evaluate the publication bias of the selected included literature. RESULTS: Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P < 0.00001), recessive (OR: 0.73; 95% CI: 0.45,1.18; P < 0.00001) genetic model under the full population was observed between KCNQ1rs2237892C⟶T gene polymorphism and T2DM without a significant relationship. In a stratified analysis by race, a meaningful association was found in non-Asian populations under the allelic genetic model, but no association was found in Asian populations. CONCLUSION: This meta-analysis showed no significant association between the rs2237892 polymorphism of the KCNQ1 gene and the risk of T2DM.