Maternal high-fat diet can affect intrauterine fetal development by regulating body metabolism. Meanwhile, differentially expressed circRNAs in the placenta during a high-fat diet regulate placental nutrient transport and fetal development in multiple ways.

Current technologies that are used for genome-wide microRNA (miRNA) prediction are mainly based on BLAST tool. They often produce a large number of false positives. Here, we describe an effective approach for identifying orthologous pre-miRNAs in several primates based on syntenic information. Some of them have been validated by small RNA high throughput sequencing data. This approach uses the synteny information and experimentally validated miRNAs of human, and incorporates currently available algorithms and tools to identify the pre-miRNAs in five other primates. First, we identified 929 potential pre-miRNAs in the marmoset in which miRNAs have not yet been reported. Then, we predicted the miRNAs in other primates, and we successfully re-identified most of the published miRNAs and found 721, 979, 650 and 639 new potential pre-miRNAs in chimpanzee, gorilla, orangutan and rhesus macaque, respectively. Furthermore, the miRNA transcriptome in the four primates have been re-analyzed and some novel predicted miRNAs have been supported by the small RNA sequencing data. Finally, we analyzed the potential functions of those validated miRNAs and explored the regulatory elements and transcription factors of some validated miRNA genes of interest. The results show that our approach can effectively identify novel miRNAs and some miRNAs that supported by small RNA sequencing data maybe play roles in the nervous system.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a life-threatening condition with >80% mortality upon rupture and no effective pharmacotherapy available. Despite epidemiological evidence linking metformin use to reduced AAA progression, its mechanism remains elusive. Notably, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, encoded by Ppargc1a ) is downregulated in human AAA, yet its functional role in metformin’s protection is unknown. METHODS: We employed porcine pancreatic elastase (PPE)-induced murine AAA, VSMC-specific Ppargc1a knockout ( Ppargc1a ^VSMC-KO ), primary VSMC senescence models, and pharmacological inhibition (Compound C for AMPK; Ex-527 for SIRT1) to define the AMPK–SIRT1–PGC-1α axis. RESULTS: Metformin significantly inhibited AAA expansion, suppressed VSMC senescence (p53/p21↓, SA-β-gal↓), and preserved contractile phenotype (SMTN↑, IL-6/TNF-α↓). Crucially, all benefits were abrogated in Ppargc1a ^VSMC-KO mice, which exhibited accelerated aneurysm growth, mitochondrial fragmentation, ATP depletion, and ROS accumulation. Mechanistically, metformin activated AMPK/SIRT1 to upregulate PGC-1α; AMPK or SIRT1 inhibition blocked this cascade and reversed protection. CONCLUSION: Metformin restrains AAA by restoring VSMC mitochondrial homeostasis via the AMPK/SIRT1→PGC-1α axis, positioning PGC-1α as a non-redundant, cell-autonomous guardian against vascular degeneration. These findings provide a mechanistic foundation for repurposing metformin and developing PGC-1α-targeted therapies in AAA.