Denglong Wu

Spermatogonial stem cells (SSCs) sustain lifelong sperm production, yet the mechanisms that protect their genomes remain incompletely understood. Inte- grated human testicular transcriptomic and proteomic analyses identify REV7, encoded by MAD2L2, as a testis-enriched DNA damage response factor. REV7 expression is reduced in residual SSCs from men with non-obstructive azoosper- mia. Germline-specific Rev7 deletion in mice depletes the SSC pool, disrupts sper- matogenesis, and causes infertility. Following DNA double-strand break induction, REV7 rapidly accumulates at damage sites. REV7 deficiency impairs SSC prolifer- ation and stemness, delays DDR signal resolution, increases DNA damage, disrupts cell-cycle progression, and promotes apoptosis. Mechanistically, REV7 supports SHLD2 of Shieldin recruitment and favors non-homologous end joining over ho- mologous recombination. Drug induced Rev7 deletion in adult SSCs suppresses spermatogenesis-related transcriptional programs before overt stem-cell loss. These findings establish REV7 as a genome-protective factor that links DNA double-strand break repair to SSC homeostasis, spermatogenic capacity, and male fertility.

Androgens and the androgen receptor ( AR ) play a central role in the development and progression of prostate cancer. While biochanin A (BCA) has been reported to suppress androgen synthesis and overcome resistance to abiraterone and enzalutamide, its direct effects on AR , particularly mutant AR , remain unclear. In this study, we systematically investigated the binding affinity and functional impact of BCA on a panel of clinically relevant AR mutations to identify patient subgroups that may benefit from BCA treatment. Our results demonstrated that BCA exhibits high-binding affinity toward the ART877A and ARW741C mutants. Our findings reveal a previously unrecognized mechanism by which BCA directly targets specific AR mutants, in addition to inhibiting androgen biosynthesis. This study provides mechanistic insights into the mutation-selective activity of BCA and supports its potential clinical application in molecularly stratified prostate cancer.

The mechanisms underlying lung metastases in bladder cancer (BLCA) remain poorly understood. Cancer-associated fibroblasts (CAFs) are key modulators of the metastatic microenvironment, but how they are activated and contribute to BLCA lung metastases remains unclear. Single-nucleus RNA sequencing was conducted on metastatic lung lesions from patients with BLCA to characterize the tumor microenvironment. Functional and molecular biology experiments, including co-culture assays, luciferase reporter assays, chromatin immunoprecipitation and in vivo lung metastasis models, were performed to explore the mechanisms by which tumor-derived factors and CAFs-secreted exosomes contribute to metastasis. The results revealed that CAFs were enriched in metastatic lung lesions and activated by tumor-derived WNT7A via the Wnt/β-catenin pathway. These activated CAFs promoted BLCA cell proliferation, stemness and migration through the exosomal delivery of miR-1910-5p, which directly suppressed CTDNEP1 expression and activated MYC signaling. Mechanistically, RBMX was identified as a regulator of miR-1910-5p packaging into CAFs-derived exosomes. In vivo, inhibition of CAFs-derived exosomes secretion reduced lung metastasis, highlighting their critical role in metastasis formation. In conclusion, this study uncovers a novel reciprocal activation loop between tumor cells and CAFs in BLCA lung metastases, where tumor-secreted WNT7A activates resident pulmonary CAFs, which in turn enhance tumor malignancy through exosomal delivery of miR-1910-5p. This exosome-mediated crosstalk promotes metastatic progression via the CTDNEP1/MYC signaling pathway. These findings provide potential therapeutic targets for mitigating metastatic progression in BLCA.

Copper is one of the heavy metals that people are frequently exposed to in their daily lives and has been reported to be associated with a variety of diseases. However, the association between serum copper and the risk of overactive bladder (OAB) is currently unknown. The purpose of this study was to assess the potential risky association between serum copper and OAB in adults. A cross-sectional study involving 4600 adult participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2016 was performed. OAB was assessed by the Overactive Bladder Symptom Score (OABSS). The association between serum copper and OAB was evaluated using univariate and multivariate weighted logistic regression models and subgroup analyses. Ultimately, 962 OAB participants and 3638 non-OAB participants were included. Serum copper concentrations were significantly higher in the OAB group compared to the non-OAB group (127.50 vs. 117.86). Univariate weighted logistic regression demonstrated that the highest tertile of serum copper was positively associated with the risk of OAB compared to the lowest tertile (OR = 2.761, 95% CI: 2.139–3.565, p < 0.001). Serum copper was still positively correlated with OAB after adjusting for all covariates (OR = 1.551, 95% CI: 1.140–2.109, p = 0.005). And the trend test was also statistically significant (p for trend = 0.004). Subgroup analyses indicated that the association between serum copper and OAB was significant in females (OR = 1.630, 95% CI: 1.064–2.497, p = 0.025). Excess serum copper is positively correlated with OAB risk, especially in females. The toxic effects of copper must be viewed with caution, and prospective cohort and mechanistic investigations are needed to validate the causal effects of copper on OAB.

Purpose Diagnostics for urothelial carcinoma have low sensitivity, thereby negatively impacting diagnostic outcomes. Herein, we present Biovue^Uro, a machine learning-based urine DNA biomarker tool for urothelial carcinoma detection. We developed Biovue^Uro to monitor DNA mutation and methylation in urine samples. Methods The study involved 63 patients with malignant urothelial carcinoma, 13 patients with benign lesions, 115 patients with urinary symptoms, and 106 healthy participants undergoing physical check-ups. Detection was performed using real-time fluorescence quantitative polymerase chain reaction. Biovue^Uro can detect six single nucleotide polymorphism sites in FGFR3, PIK3CA, and TERT, and aberrant methylation in HIST1H4F, NRN1, and POU4F2. Ten machine-learning algorithms were employed to train the data and classify patients and healthy controls. Results The optional model demonstrated high diagnostic efficacy in distinguishing patients with high-grade urothelial carcinoma from non-patients. In the validation set, the receiver operating characteristic curve, sensitivity, specificity, accuracy, and positive and negative predictive values were 96.1% (95% CI 89.3–100), 94.7%, 99.1%, 98.5%, 94.7%, and 99.1%, respectively. For distinguishing patients with early-stage urothelial carcinoma from non-patients, the values in the training set were 91.7% (95% CI 84.2–99.1), 80%, 98.3%, 95.1%, 90.9%, and 95.8%, and those in the validation set were 92.5% (95% CI 86.6–98.4%), 80%, 95.7%, 93%, 80%, and 95.7%, respectively. The study’s limitations include a relatively small cohort size, restricted regional diversity and a lack of long-term follow-up data to assess disease progression and treatment outcomes. Conclusions In summary, Biovue^Uro, a machine learning-enhanced multi-analyte liquid biopsy integrating mutation polymorphisms and methylation profiling, demonstrates superior diagnostic accuracy for urothelial carcinoma compared to conventional urinary tests and methylation-based assays. Its robust sensitivity for early-stage tumors, high specificity for high-grade lesions, and non-invasive nature underscore its potential as a clinically actionable tool for urothelial carcinoma detection. Longer-term outcomes and regional diversity should be evaluated.

Purpose of Review This review explores the clinical applications of PSMA-PET/CT in patients with intermediate to high-risk prostate cancer, focusing on its role in diagnostic reassessment, therapeutic redirection, and potential survival benefits. By evaluating its translational pathway, we aim to provide a structured analysis of its impact on patient management and treatment outcomes. Recent Findings Prostate cancer remains a significant health challenge, and advancements in imaging techniques such as PSMA-PET/CT have shown promise in improving diagnostic accuracy and guiding treatment decisions. Emerging evidence highlights its superior sensitivity and specificity compared to conventional imaging, facilitating better staging, detection of metastases, and therapy selection. However, challenges persist in standardizing clinical applications, integrating findings into treatment guidelines, and addressing economic considerations. Summary This review synthesizes the latest research findings and cost-effectiveness analyses to establish a comprehensive translational framework for PSMA-PET/CT in prostate cancer management. By consolidating diverse evidence, we aim to provide the medical community with clearer insights into its clinical utility, address ongoing controversies, and propose strategies to minimize treatment risks. The conclusions drawn from this study aspire to refine treatment protocols and enhance clinical outcomes for patients with this prevalent malignancy.

Purpose: This study aimed to report a newly developed, high‐fidelity synthetic simulator to simulate excision and primary anastomotic (EPA) bulbar urethroplasty and its clinical use for new practitioners in shortening the learning curve.Material and Methods: The bulbar urethral anastomosis simulator consists of several standardized components created according to the actual size of the male patient. Interns, novice residents, and fellows inexperienced with urethral reconstruction (n = 10, 5, 5) from different medical centres were invited to participate in the training programme. Two reconstructive urology experts monitored each practice. Following the training, three kinds of validity testing were used to assess the simulator: face, content, and construct. In the intern group, the task performance in the first five training sessions and the last five training ones were compared using a self‐control approach. In the resident and fellow group, the real surgical data, including estimated blood loss, operative duration, and 6‐month post‐operative success rate of trainees after training, are plotted, which are compared with that of reconstructive urology experts (n = 5) included retrospectively to study the effectiveness of the simulator in shortening the learning curve.Results: The overall mean satisfaction rate for the simulators was inspiring and evaluated by experts. In the intern group, significant improvement can be achieved through 10 training sessions (p < 0.05). In clinical practice, the intraoperative indicators and surgical success rate of both the training groups showed the tendency to close or even better than those in the expert group. In terms of the learning curve, training groups performed better compared with experts in the early stages of their careers.Conclusions: In conclusion, this synthetic training simulator for bulbar urethral anastomosis is novel, effective, and convenient for beginners of different groups. The training course can bridge the gap between preclinical use and actual surgery via this simulator.