Prostate cancer (PCa) is the most common malignant tumor with a high global incidence in males. The mechanism underlying PCa progression is still not clear. This study observed that NRP1 was highly expressed in PCa and associated with poor prognosis in PCa patients. Functionally, NRP1 depletion attenuated the proliferation and migration ability of PCa cells in vitro and in vivo, while NRP1 overexpression promoted PCa cell proliferation and migration. Moreover, it was observed that NRP1 depletion induced G1 phase arrest in PCa cells. Mechanistically, HIF1α is bound to the specific promoter region of NRP1, thereby regulating its transcriptional activation. Subsequently, NRP1 interacted with EGFR, leading to EGFR phosphorylation. This study also provided evidence that the b1/b2 domain of NRP1 was responsible for the interaction with the extracellular domain of EGFR. Moreover, EGFR mediated NRP1-induced activation of the AKT signaling pathway, which promoted the malignant progression of PCa. In addition, the administration of NRP1 inhibitor EG01377 significantly inactivated the EGFR/AKT signaling axis, thereby suppressing PCa progression. In conclusion, the findings from this study highlighted the molecular mechanism underlying NRP1 expression in PCa and provide a potential predictor and therapeutic target for clinical prognosis and treatment of PCa.

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.