Biological significance of METTL5 in atherosclerosis: comprehensive analysis of single-cell and bulk RNA sequencing data.

BACKGROUND: N6-methyladenosine (m6A) methylation is involved in the pathogenesis of atherosclerosis (AS). Limited studies have examined the role of the m6A methyltransferase METTL5 in AS pathogenesis. METHODS: This study subjected the AS dataset to differential analysis and weighted gene co-expression network analysis to identify m6A methylation-associated differentially expressed genes (DEGs). Next, the m6A methylation-related DEGs were subjected to consensus clustering to categorize AS samples into distinct m6A subtypes. Single-cell RNA sequencing (scRNA-seq) analysis was performed to investigate the proportions of each cell type in AS and adjacent healthy tissues and the expression levels of key m6A regulators. The mRNA expression levels of METTL5 in AS and healthy tissues were determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: AS samples were classified into two subtypes based on a five-m6A regulator-based model. scRNA-seq analysis revealed that the proportions of T cells, monocytes, and macrophages in AS tissues were significantly higher than those in healthy tissues. Additionally, the levels of m6A methylation were significantly different between AS and healthy tissues. METTL5 expression was upregulated in macrophages, smooth muscle cells (SMCs), and endothelial cells (ECs). qRT-PCR analysis demonstrated that the METTL5 mRNA level in AS tissues was downregulated when compared with that in healthy tissues. CONCLUSIONS: METTL5 is a potential diagnostic marker for AS subtypes. Macrophages, SMCs, and ECs, which exhibit METTL5 upregulation, may modulate AS progression by regulating m6A methylation levels.

Coupling the effects of extreme temperature and air pollution on non-accidental mortality in Rencheng, China.

Background: Extreme temperatures and air pollution have raised widespread concerns about their impact on population health. Aim: To explore the quantitative exposure risks of high/low temperatures and types of air pollutants on the health of various populations in urban areas in China, this study assessed the effects of temperature and air pollutants on daily non-accidental deaths in Rencheng District, Jining City, China from 2019 to 2021. Methods: A combination of Poisson regression models and distributed lag non-linear models was used to examine the relationships between temperature, air pollutants, and daily non-accidental deaths. We found that temperature and air pollutants had a significant non-linear effect on non-accidental mortality. Both high and low temperatures had a noticeable impact on non-accidental deaths, with heat effects occurring immediately and lasting 2-3 days, while cold effects lasted for 6-12 days. The relative risks of non-accidental deaths from PM2.5, NO2, and SO2 were highest in winter and lowest in autumn. The relative risk of non-accidental deaths from O3 was highest in spring, with no significant variations in other seasons. Older adults (≥75) and outdoor workers were at the greatest risk from temperature and air pollutant exposure. Conclusions/interpretation: Exposure to extreme temperatures and air pollutants in the Rencheng District was associated with an increased mortality rate. Under the influence of climate change, it is necessary for policymakers to take measures to reduce the risk of non-accidental deaths among residents.

Identifying the oncogenic roles of FAP in human cancers based on systematic analysis.

BACKGROUND: Fibroblast activation protein-α (FAP) is a specific marker of cancer-associated fibroblasts (CAFs) and plays a crucial role in tumor development. However, the biological processes underlying FAP expression in tumor progression and tumor immunity have not been fully elucidated. METHODS: We utilized RNA-seq data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to perform differential analysis of FAP expression in tumor tissues and matched-normal tissues. The relationship between FAP expression and clinical prognosis, DNA methylation, and tumor-infiltrating immune cells in pan-cancer was assessed using R Studio (version 4.2.1). Additionally, we employed gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) to investigate the biological functions and pathways associated with FAP expression. RESULTS: FAP exhibits high expression in most malignancies, albeit to a lesser extent in CESC, KICH, UCEC, SKCM, THCA, and UCS. Furthermore, FAP is either positively or negatively associated with the prognosis of several malignancies. In seven types of cancer, FAP expression is positively correlated with DNA methylation. CIBERSORT analysis revealed an inverse correlation between FAP expression and T cells, B cells, monocytes, and NK cells, while it exhibited a positive correlation with M0, M1, and M2 macrophages. Enrichment analysis further demonstrated that FAP modulates the cell cycle, epithelial-mesenchymal transition (EMT) process, angiogenesis, and immune-related functions and pathways. CONCLUSION: Our findings indicate a close relationship between FAP expression and tumorigenesis as well as tumor immunity. FAP has the potential to serve as a diagnostic, prognostic, and immunotherapy marker.