Yu Zeng

Abdominal aortic aneurysm (AAA) is a fatal inflammatory vascular disease without effective clinical treatments. Dietary patterns regulate aortic inflammation, and Mediterranean diet‐derived omega‐3 polyunsaturated fatty acids (ω‐3 PUFA) exert anti‐inflammatory effects, yet their cellular targets in AAA remain unclear. We integrated three single‐cell RNA‐seq cohorts (12 AAA, 3 controls) and constructed a human aortic cell atlas with 64,258 cells. Pseudo‐bulk analysis and CoVarNet multicellular network analysis revealed a core remodeling axis: protective FOLR2 ⁺ resident macrophages were depleted, while a unique AAA‐enriched NLRP3 ⁺ inflammatory macrophage population (M08_Mph_NLRP3) formed the hub of pathological inflammatory networks. Three bulk transcriptomic cohorts and five complementary enrichment approaches verified this signature. An LPS/OX‐LDL/IL‐1β‐stimulated THP‐1 model recapitulated AAA macrophage pathological changes including NLRP3 inflammasome overactivation, enhanced proliferation and migration. Further functional tests demonstrated ω‐3 PUFA markedly blocked inflammasome cascade, reduced IL‐1β/IL‐18 release and reversed all macrophage pathological phenotypes. This study identifies M08_Mph_NLRP3 as the important inflammatory mediator of AAA and provides single‐cell and in vitro functional evidence supporting ω‐3 PUFA as a candidate nutritional agent targeting NLRP3‐driven vascular inflammation.

Neuroblastoma is a pediatric malignancy characterized by significant clinical heterogeneity. Although MYCN amplification is a well‐established marker of high‐risk disease, its interplay with the tumor immune microenvironment—particularly tumor‐associated macrophages (TAMs)—remains poorly understood. In this study, we developed an integrated gene signature incorporating genes associated with both MYCN amplification status and TAM infiltration, leading to the identification of 16 differentially expressed genes implicated in both biological processes. Six of these genes (CMBL, LY6E, KLRB1, CTSH, CD3D, and PTGDS) were utilized to construct a risk‐scoring model that effectively stratified neuroblastoma patients into high‐ and low‐risk groups with significantly distinct clinical outcomes ( p < 0.001). Notably, LY6E emerged as the most prognostically significant gene within the signature. More importantly, we revealed that LY6E modulates M2‐type macrophage polarization in neuroblastoma for the first time, suggesting a novel mechanism through which it may contribute to shaping an immunosuppressive tumor microenvironment.

Papillary thyroid cancer (PTC) is one of the most common malignant tumors in female, and estrogen can affect its progression. However, the targets and mechanisms of estrogen action in PTC remain unclear. Therefore, this study focuses on the relationship between estrogen-related genes (ERGs) expression and prognosis in PTC, particularly neuropeptide U (NMU), and its important role in the development of PTC. We first downloaded expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases for PTC and normal tissue and identified differentially expressed genes (DEGs), which were predominantly enriched for ERGs. Then, we identified ERGs that contributed most to PTC prognosis based on univariate Cox regression and Lasso Cox analysis. We filtered out Transducer of ERBB2 1 (TOB1), trefoil factor 1 (TFF1), phospholipase A and acyltransferase 3 (PLAAT3), NMU, kinesin family member 20A (KIF20A), DNA topoisomerase II alpha (TOP2A), tetraspanin 13 (TSPAN13), and carboxypeptidase E (CPE). In addition, we explored the effect of NMU on the proliferation of PTC cells by in vitro experiments, confirmed high NMU expression in PTC and showed that the proliferative capacity of PTC cells was significantly reduced with NMU knockdown. Moreover, the phosphorylation levels of the Kirsten rat sarcoma virus (KRAS) signaling pathway were significantly lower with NMU knockdown. These results suggest that ERGs, especially NMU, may be novel prognostic indicators in PTC.

Luteolin is a natural flavonoid that has a variety of pharmacological activities, such as anti-inflammatory, anti-allergic, anti-bacterial, anti-viral, apoptosis inhibition, cell autophagy regulation, and anti-tumor activity. It is one of the main ingredients of an expert-recommended herbal formula for the prevention and treatment of coronavirus disease 2019 (COVID-19). This suggests that luteolin has strong pharmacological effects on the prevention and treatment of COVID-19. The aims of this study were to identify the molecular targets of luteolin and to infer the possible mechanisms by which it exerts its pharmacological effects. The GSE159787 data set was obtained from the Gene Expression Omnibus online database, and differentially expressed genes were analyzed. There were 22 upregulated differentially expressed genes enriched in the COVID-19 signaling pathway, suggesting that the upregulation of these genes may be closely related to the occurrence of COVID-19. Molecular docking results showed that luteolin had strong binding efficiency to 20 of these 22 key genes. Six of these genes (CFB, EIF2AK2, OAS1, MAPK11, OAS3, and STAT1) showed strong binding activity. Luteolin can regulate the COVID-19 signaling pathway by combining with these targets, which may have a therapeutic effect on COVID-19.