Background: Memory B cells and microRNAs (miRNAs) play important roles in the progression of gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD). However, few studies have investigated the use of memory B-cell-associated miRNAs in predicting the prognosis of STAD. Methods: We identified the marker genes of memory B cells by single-cell RNA sequencing (scRNA-seq) and identified the miRNAs associated with memory B cells by constructing an mRNA‒miRNA coexpression network. Then, univariate Cox, random survival forest (RSF), and stepwise multiple Cox regression (StepCox) algorithms were used to identify memory B-cell-associated miRNAs that were significantly related to overall survival (OS). A prognostic risk model was constructed and validated using these miRNAs, and patients were divided into a low-risk group and a high-risk group. In addition, the differences in clinicopathological features, tumour microenvironment, immune blocking therapy, and sensitivity to anticancer drugs in the two groups were analysed. Results: Four memory B-cell-associated miRNAs (hsa-mir-145, hsa-mir-125b-2, hsa-mir-100, hsa-mir-221) with significant correlations to OS were identified and used to construct a prognostic model. Time-dependent receiver operating characteristic (ROC) curve analysis confirmed the feasibility of the model. Kaplan‒Meier (K‒M) survival curve analysis showed that the prognosis was poor in the high-risk group. Comprehensive analysis showed that patients in the high-risk group had higher immune scores, matrix scores, and immune cell infiltration and a poor immune response. In terms of drug screening, we predicted eight drugs with higher sensitivity in the high-risk group, of which CGP-60474 was associated with the greatest sensitivity. Conclusions: In summary, we identified memory B-cell-associated miRNA prognostic features and constructed a novel risk model for STAD based on scRNA-seq data and bulk RNA-seq data. Among patients in the high-risk group, STAD showed the highest sensitivity to CGP-60474. This study provides prognostic insights into individualized and precise treatment for STAD patients.

The oyster Crassostrea hongkongensis is eaten raw and whole, so the endogenous peptides carried by its tissue reach the intestinal lumen unprocessed; functional work on food-derived peptides has concentrated on cationic sequences. This study asked whether the endogenous peptide population of this species is anionically skewed and whether a preparation of that population alters the cytoskeletal gene programme of human intestinal epithelial cells. The published plasma peptidome of this species (PXD025247) was re-analysed, an endogenous peptide fraction below 10 kDa was prepared from oyster soft tissues without adding any protease, and the preparation was applied to differentiated Caco-2 monolayers at 0.1–2.0 mg/mL for 6–24 h; nine transcripts were measured by quantitative PCR against vehicle, protease-digested and digestion-only controls. Of 333 peptides, 157 (47.1%) carried a net charge of −1 or lower at pH 7, 148 (44.4%) were near-neutral and 28 (8.4%) carried +2 or above, and anionic peptides outnumbered cationic peptides in all four detection strata (36.4–58.3% against 4.8–9.1%). Actin-family proteins were the largest precursor source (186 peptides, 55.9%; 68.3% coverage of actin). The preparation was recovered at 2.41 ± 0.23 mg/g of wet tissues and, at 2.0 mg/mL, increased transcription of the SRF targets CCN1 (2.91-fold), VIL1 (2.29-fold), MYH9 (2.17-fold) and ACTN1 (1.83-fold) (p < 0.01 for each) and of TMSB4X, CFL1 and PFN1 (1.90-, 1.75- and 1.55-fold; q < 0.05), whereas SRF and MRTFA transcripts were unchanged; proteinase K digestion abolished the response. An endogenous peptide preparation from oyster soft tissues therefore acts on the cytoskeletal gene programme of human intestinal epithelial cells, and the anionically skewed majority of this peptidome is the fraction that warrants direct functional characterisation.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate below 10%. Cancer-associated fibroblasts (CAFs) promote epithelial–mesenchymal transition (EMT) and metastasis, yet the specific CAF subtypes and molecular axes driving PDAC progression remain incompletely understood. Here, using multi-omics data from PDAC samples, we identified a malignant ductal subpopulation, termed Ductal-T0, characterized by the highest EMT activity and prominent acquisition of myofibroblastic CAF (myCAF)-like transcriptional programs. Computationally, we predicted that myCAF-secreted THBS2 and FN1 engage the ITGA3/ITGB1/SDC1/SDC4 receptor axes in Ductal-T0 cells, which could activate TNF, NF-κB, TGF-β, and PI3K-AKT-signaling pathways to promote EMT. Pseudotime trajectory and velocity analyses suggested that Ductal-T0 cells exhibited the highest propensity to acquire myCAF-like features among all ductal subpopulations. Survival analysis revealed that an increased proportion of Ductal-T0 cells and elevated abundance of THBS2-ITGA3/ITGB1 and THBS2-SDC1 ligand–receptor pairs were significantly associated with poor prognosis. Spatial transcriptomics further revealed that myCAFs and Ductal-T0 cells co-localized at the tumor margin, which may contribute to reduced immune cell presence via dense extracellular matrix (ECM) barrier formation—a computationally inferred model of EMT-associated immune exclusion and metastatic progression—and identify THBS2 as a promising candidate for future therapeutic investigation to disrupt CAF–tumor crosstalk in PDAC.