Tumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC). We conducted analyses using LC-MS/MS on clinical prostate cancer tissue before and after hormone therapy. We established tumor xenograft mouse models, primary tumor cells, and human-derived organoids to detect the novel mechanism of NED and to identify potential therapies. The hormone therapy-induced upregulation of acetate metabolism was mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2), which increased c-MYC expression for NED induction. Notably, combined treatment with an ACSS2 inhibitor and enzalutamide significantly reduced the xenograft tumor volume. Our findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC.

Metabolic rewiring is a starter for lineage plasticity, which is an important driver of prostate development, tumorigenesis and treatment resistance. Androgen-targeted therapies are central to prostate cancer (PCa) management, yet the mechanisms leading prostate development-particularly the metabolic signaling within basal cells during treatment-remain poorly understood. To fulfill this gap, we used multiple models to reveal the metabolic alterations in prostate basal cells. Our study reveals the role of the RBP4-STRA6 axis in modulating retinol metabolism and transporting retinol from adipocyte into prostate cells, contributing to prostate development and basal cell differentiation during androgen deprivation. Through multi-omics analyses, we demonstrate that RBP4-STRA6 axis dependent retinol metabolism is increased with androgen deprivation. Retinol metabolism rewiring is modulated by the androgen receptor (AR) and can regulate basal cell plasticity under androgen deprivation therapy (ADT). Retinol metabolism maintains prostate basal cell lineage plasticity during hormone therapy through the PPARγ signaling pathway, compensating for the AR signaling pathway inhibition by sustaining energy homeostasis and promoting basal cell differentiation. Notably, we identified a basal cell cluster (BC5) characterized by high Retinol metabolism and activated PPARγ signaling pathway, which plays a crucial role in basal-luminal differentiation and prostate growth. This study underscores the importance of RBP4-STRA6 dependent Retinol metabolism, mediating the crosstalk between adipocytes and prostate basal cells, in maintaining prostate development during hormone therapy and provides a foundation for future clinical interventions and diet strategies aimed at enhancing the sensitivity of androgen deprivation in prostate diseases.

Objectives: To address SPECT’s radioactivity, complexity, and costliness in measuring renal function, this study employs artificial intelligence (AI) with non-contrast CT to estimate single-kidney glomerular filtration rate (GFR) and split renal function (SRF). Methods: 245 patients with atrophic kidney or hydronephrosis were included from two centers (Training set: 128 patients from Center I; Test set: 117 patients from Center II). The renal parenchyma and hydronephrosis regions in non-contrast CT were automatically segmented by deep learning. Radiomic features were extracted and combined with clinical characteristics using multivariable linear regression (MLR) to obtain a radiomics-clinical-estimated GFR (rcGFR). The relative contribution of single-kidney rcGFR to overall rcGFR, the percent renal parenchymal volume, and the percent renal hydronephrosis volume were combined by MLR to generate the estimation of SRF (rcphSRF). The Pearson correlation coefficient (r), mean absolute error (MAE), and Lin’s concordance coefficient (CCC) were calculated to evaluate the correlations, differences, and agreements between estimations and SPECT-based measurements, respectively. Results: Compared to manual segmentation, deep learning-based automatic segmentation could reduce the average segmentation time by 434.6 times to 3.4 s. Compared to single-kidney GFR measured by SPECT, the rcGFR had a significant correlation of r = 0.75 (p < 0.001), MAE of 10.66 mL/min/1.73 m², and CCC of 0.70. Compared to SRF measured by SPECT, the rcphSRF had a significant correlation of r = 0.92 (p < 0.001), MAE of 7.87%, and CCC of 0.88. Conclusions: The non-contrast CT and AI methods are feasible to estimate single-kidney GFR and SRF in patients with atrophic kidney or hydronephrosis. Critical relevance statement: For patients with an atrophic kidney or hydronephrosis, non-contrast CT and artificial intelligence methods can be used to estimate single-kidney glomerular filtration rate and split renal function, which may minimize the radiation risk, enhance diagnostic efficiency, and reduce costs. Key Points: Renal function can be assessed using non-contrast CT and AI. Estimated renal function significantly correlated with the SPECT-based measurements. The efficiency of renal function estimation can be refined by the proposed method. Graphical

Renal fibrosis, a progressive pathological feature of chronic kidney disease (CKD), is driven by impaired autophagic processes and persistent immune activa

Background and objectives: Vesicovaginal fistula (VVF) is a devastating condition for female patients. We aimed to summarize our experience in the management of VVF and the surgical outcomes at our center and propose an algorithm for clinical practice. Materials and methods: We conducted a retrospective study of patients with VVF who underwent surgical treatment at our center between January 2013 and December 2024. All patients were classified into non-irradiated and irradiated groups. Medical data were analyzed, including patient demographics, fistula characteristics, vaginal width, surgical procedures, surgical outcomes, and perioperative complications. Results: We included 64 patients with VVF (20 non-irradiated and 44 irradiated). The fistula size in the irradiated group was mostly > 1.5 cm, whereas the size was 3 cm in the fistula repair group, whereas it was < 3 cm in the urinary diversion group. For the non-irradiated group, we all performed fistula repair surgery, while only 47.7% in the irradiated group, where the remaining underwent urinary diversion (29.5%) or fistula repair + urinary diversion (22.7%). The irradiated group had a higher fistula recurrence rate than the non-irradiated group in both transvaginal (18.5% vs. 6.25%) and transabdominal (50% vs. 0%) approaches. Conclusion: We proposed an algorithm for the surgical management of VVFs based on radiation history, fistula size (>3 cm), and vaginal width (<3 cm). We suggest that transvaginal approach is the first option for fistula repair. For irradiated VVFs, transvaginal fistula repair with tissue interposition combined with permanent cystostomy demonstrated high success in our series, which is a valuable method.