Apalutamide, a novel endocrine therapy agent, has been shown to significantly improve the prognosis of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, resistance to apalutamide has also been reported, and the underlying mechanism for this response has yet to be clearly elucidated. First, this study established apalutamide-resistant prostate cancer (PCa) cells, and confirmed that apalutamide activated the release of calcium ions (Ca²⁺) and endoplasmic reticulum stress (ERS) to enhance autophagy. Second, RNA sequencing, western blotting, and immunohistochemistry revealed significantly decreased Calpain 2 (CAPN2) expression in the apalutamide-resistant PCa cells and tissues. Furthermore, immunofluorescence and transmission electron microscopy (TEM) showed that CAPN2 promoted apalutamide resistance by activating protective autophagy. CAPN2 promoted autophagy by reducing Forkhead Box O1 (FOXO1) degradation while increasing nuclear translocation via nucleoplasmic protein isolation and immunofluorescence. In addition, FOXO1 promoted protective autophagy through the transcriptional regulation of autophagy-related gene 5 (ATG5). Furthermore, a dual-fluorescence assay confirmed that transcription factor 3 (ATF3) stimulation promoted CAPN2-mediated autophagy activation via transcriptional regulation. In summary, CAPN2 activated protective autophagy by inhibiting FOXO1 degradation and promoting its nuclear translocation via transcriptional ATG5 regulation. ATF3 activation and transcriptional CAPN2 regulation jointly promoted this bioeffect. Thus, our findings have not only revealed the mechanism underlying apalutamide resistance, but also provided a promising new target for the treatment of metastatic PCa.

Objectives: To describe urology rotation exit-assessment outcomes and explore variation across resident subgroups. Methods: This retrospective single-center study included all 130 eligible residents who completed a urology rotation and exit assessment between May 2024 and April 2025. Pass rates were analyzed using exact tests, while theoretical and comprehensive rotation assessment scores were analyzed using non-parametric tests with Holm adjustment. National examination outcomes were summarized descriptively. Results: Overall, 124 residents passed the rotation exit assessment (95.38%). No statistically significant subgroup differences were detected in pass rates or locally scaled theoretical examination scores; however, the two examination formats were not formally equated. Comprehensive rotation assessment scores were higher among residents from the urology training base than among those from other training bases (median, 89.00 vs. 82.75; adjusted p < 0.001) and among postgraduate than undergraduate residency trainees (86.00 vs. 80.00; adjusted p < 0.001), and differed across trainee categories (adjusted p = 0.003). Licensing-examination pass rates were 100%, 100%, and 89.58% in the eligible 2021–2023 cohorts; completion-examination pass rates were 85.71% and 98.25% in the eligible 2021–2022 cohorts. Conclusions: Most residents met the local rotation exit-assessment standard. The subgroup differences were exploratory and should not be interpreted as evidence of causal effects or training-program effectiveness. These findings provide a descriptive baseline for local quality review and future prospective research.

Background: Metastasis is the leading cause of mortality in prostate cancer (PCa), with bone being the most common site of dissemination. The survival of tumor cells in the circulation following detachment from the extracellular matrix (ECM) is an essential prerequisite for cancer metastasis, yet the underlying mechanisms remain incompletely understood. Methods: To investigate the cellular adaptations that support survival under ECM-detached conditions, we established detachment-resistant (DR) models using PC-3 and LNCaP cells. COMP expression was examined in PCa clinical tissues and DR cells. Functional and mechanistic studies were then performed both in vitro and in vivo. Results: COMP was highly expressed in PCa tissues and DR PCa cells. COMP upregulation promoted ferroptosis resistance by reducing intracellular Fe²⁺ accumulation and lipid peroxidation, thereby facilitating PCa progression and metastasis. Mechanistically, COMP directly bound to mucin 1 (MUC1) via a high-affinity Arg628-Asp543 salt bridge, which promoted MUC1 phosphorylation and enhanced its signaling activity. p-MUC1 subsequently inhibited the Hippo signaling pathway, promoting nuclear translocation of Yes-associated protein 1 (YAP1). YAP1 cooperated with TEAD transcription factors to drive transcription of nuclear protein 1 (NUPR1), which activated lipocalin-2 (LCN2), an iron-transporting protein that critically regulates intracellular iron homeostasis and redox balance, thereby conferring ferroptosis resistance. Importantly, suppressing COMP significantly inhibited PCa bone and lung metastasis in vivo. Conclusion: This study reveals that COMP facilitates PCa bone metastasis by enhancing ferroptosis resistance through the MUC1/YAP1/NUPR1/LCN2 axis, suggesting that inhibition of COMP combined with ferroptosis activators may represent a promising therapeutic strategy to suppress PCa bone metastasis.