Extracellular vesicles (EVs) are nanoscale particles with a lipid bilayer membrane structure secreted by various cell types. Nearly all human cells secrete EVs, primarily mediating intercellular communication. In recent years, scientists have discovered that EVs can carry multiple biological cargos, such as DNA, non-coding RNAs (ncRNAs), proteins, cytokines, and lipids, and mediate intercellular signal transduction. Bone is a connective tissue with a nerve supply and high vascularization. The repair process after injury is highly complex, involving interactions among multiple cell types and biological signaling pathways. Bone regeneration consists of a series of coordinated osteoconductive and osteoinductive biological processes. As mediators of intercellular communication, EVs can promote bone regeneration by regulating osteoblast-mediated bone formation, osteoclast-mediated bone resorption, and other pathways. This review summarizes the biogenesis of EVs and the mechanisms by which EV-mediated intercellular communication promotes bone regeneration. Additionally, we focus on the research progress of EVs in various diseases related to bone regeneration. Finally, based on the above research, we explore the clinical applications of engineered EVs in the diagnosis and treatment of bone regeneration-related diseases.

Tumor drug resistance exhibits substantial heterogeneity across cancer types, reflecting distinct molecular mechanisms in each malignancy. To characterize this complexity, we developed a pan-cancer transfer learning framework that integrates bulk RNA-seq data with a residual variational autoencoder (Res VAE) backbone. Five models were trained on the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, which includes drug response profiles for 72 chemotherapeutic agents. Among them, three models are specially designed by incorporating variational autoencoders and large pretrained models (LLMs): the LLM large VAE (VAE_LL), the LLM small VAE (VAE_LS), and the LLM distillation VAE (VAE_LD). Random Forest (RF) and eXtreme Gradient Boosting (XGB) were included as ensemble learning baselines. After internal cross-validation, the top four models (VAE_LL, VAE_LD, XGB, and RF) were applied to five representative TCGA cohorts comprising 1,836 patients. For each cancer type, resistance to nine clinically relevant first-line drugs was modeled, resulting in 180 drug–cancer prediction tasks. Among all models, VAE_LD achieved the best overall performance, with a mean AUC of 0.81 and an F1 score of 0.92 on the GDSC benchmark, and maintained strong predictive power in the clinical validation phase. Interpretation analyses identified tumor-specific resistance biomarkers with clinical significance. In lung adenocarcinoma, elevated expression of TFF1 was repeatedly associated with resistance to Gefitinib and correlated with poor patient prognosis, indicating its potential as a therapeutic target. In glioblastoma, OPALIN, LTF, IL2RA, and SLC17A7 were implicated in Temozolomide resistance through pathways related to epithelial differentiation and angiogenesis. In conclusion, the VAE_LD model offers a high-performing and interpretable approach for predicting drug resistance across multiple tumor types. It supports the identification of clinically actionable biomarkers and provides a robust framework for precision oncology applications.