Background: Defective efferocytosis in ulcerative colitis (UC) exacerbates inflammation due to impaired clearance of apoptotic cells, yet the molecular mechanisms linking efferocytosis-related genes to therapeutic outcomes remain unclear. This study aims to investigate the role of efferocytosis in UC and the key regulatory mechanism of efferocytosis.Methods: Multi-omics integration of single-cell and bulk transcriptomic data from human UC colonic mucosa identified efferocytosis-active cellular subpopulations. Machine learning algorithms screened hub genes, followed by molecular docking to assess interactions with UST. A mouse colitis model was used to verify the inflammatory damage of UC and the key genes that play the role in efferocytosis.Results: In UC, the “eat me” and “digest me” signaling pathways are predominantly upregulated in myeloid cells, while the “find me” signaling cascade shows marked activation in stromal cells. Macrophages characterized by the M2 polarization demonstrate enhanced phagocytic proficiency and are instrumental in the engulfment and clearance of apoptotic cells, thereby alleviating the inflammatory cascade in UC. Six hub genes (ANXA1, PANX1, ANXA5, CD93, SERPINE1, MFGE8) were associated with UC progression and correlated with clinical response to UST. Molecular docking analysis revealed strong binding affinities between these gene-encoded proteins and UST. Transcriptomic and proteomic analyses confirmed dysregulated expression of these hub genes in the colitis model.Conclusion: This study reveals cellular heterogeneity at different stages of efferocytosis in UC, identifies efferocytosis-related genes as critical regulators of mucosal repair and predictors of UST efficacy. Findings emphasize targeting macrophage-driven efferocytosis to resolve inflammation, offering novel strategies for improving treatment outcomes.

Chronic migraine (CM) is a debilitating neurological disorder, yet the glial-specific mechanisms underlying its pathophysiology in the trigeminal nucleus caudalis (TNC)—a critical hub for craniofacial pain processing—remain poorly understood. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to resolve cell-type-specific transcriptional landscapes in a nitroglycerin (NTG)-induced CM rat model, with a particular focus on microglia and astrocytes. We identified 19 transcriptional clusters representing nine major cell types, among which reactive microglia (NTG-Mic) and astrocytes (NTG-Asts) were markedly expanded. The NTG-Mic displayed a glycolysis-dominant, complement-enriched state, whereas the NTG-Asts exhibited concurrent activation of amino acid transport and cytokine signaling pathways. Pseudotime trajectory analysis revealed bifurcated glial activation paths, with NTG driving both cell types toward terminal reactive states. Intercellular communication inference uncovered suppressed homeostatic interactions (e.g., CSF1-CSF1R) alongside enhanced proinflammatory signaling (e.g., FGF1-FGFR2, PTN-SDC4), particularly affecting neuron–glia and glia–glia crosstalk. Together, these findings define a high-resolution atlas of glial reprogramming in CM, implicating state-specific metabolic–immune transitions and dysregulated glial communication as potential targets for therapeutic intervention.