Acute kidney injury (AKI) is sustained by reciprocal amplification of oxidative stress, innate immune signaling, and maladaptive immune-parenchymal crosstalk. Here, we developed a lipid nanoparticle containing a ceria nanozyme and a STING-targeting CasRx plasmid and functionalized it with D4F, an 18-residue apolipoprotein A-I mimetic peptide composed of D-amino acids. The resulting D4F-CeO2@LNP-CasRx(STING) formulation retained radical-scavenging activity, supported CasRx encapsulation, and showed enhanced cellular and renal delivery. In macrophages, the formulation reduced oxidative stress and total STING abundance together with downstream TBK1 and IRF3 phosphorylation, shifted the CD86/CD206 profile toward a less inflammatory state, and altered the secretome in a manner that protected hypoxia-challenged tubular epithelial cells. In kidney organoids and peripheral-blood-mononuclear-cell-coupled organoid cultures, D4F functionalization improved intratissue accumulation, increased the frequency of CD4+FOXP3+ T cells, and attenuated the hypoxia-associated DNA damage response and tubular injury. In mice with renal ischemia-reperfusion injury, treatment reduced STING signaling in CD11b+ renal macrophages, improved renal function and histology, and lowered whole-kidney inflammatory and injury readouts. Spatial transcriptomic and proteomic analyses were consistent with contraction of inflammatory immune states and restoration of repair-associated programs. These findings support a DNA-delivering nanozyme strategy for renal immune-niche modulation in AKI.

PR domain zinc finger protein 1 (PRDM1) functions as a critical transcriptional repressor. The role of PRDM1 in various tumors is controversial, and its specific mechanism in bladder cancer (BCa) remains unclear. In the present study, we demonstrated that PRDM1 expression is downregulated in both human BCa tissues and BBN-induced mouse models of BCa. Gain- and loss-of-function experiments revealed that PRDM1 delays cell cycle progression, suppresses BCa cell proliferation, and enhances chemosensitivity, whereas PRDM1 knockdown promotes cell proliferation and induces chemoresistance. Ovarian tumor deubiquitinase 6 A (OTUD6A) is a deubiquitinating enzyme that prevents the proteasomal degradation of CDC6. PRDM1 directly binds to the OTUD6A promoter and suppresses its transcription, thereby reducing CDC6 deubiquitination and promoting its degradation. Knockdown of CDC6 or OTUD6A abrogates the protective effects of PRDM1 both in vitro and in vivo. Consistently, PRDM1 expression is negatively correlated with CDC6 and OTUD6A expression in BCa tissues. Collectively, these findings demonstrate that PRDM1 acts as a tumor suppressor in BCa by inhibiting OTUD6A transcription and promoting CDC6 degradation. We propose a PRDM1‒OTUD6A‒CDC6 axis model, providing novel insights into PRDM1 as a potential therapeutic target in BCa.

Objective: Detrusor overactivity (DO) is a severe urological disorder in spinal cord injury (SCI) patients. Conventional pharmacological interventions, such as antimuscarinic agents, show limited therapeutic efficacy and are often associated with adverse effects. Emerging evidence indicates that prostaglandin E2 (PGE2) and its E-prostanoid 3 (EP3) receptor play a pivotal regulatory role in bladder function. This study aimed to investigate whether EP3 receptor antagonism can alleviate DO after SCI. Methods: Bladder PGE2 and cyclooxygenase-2 levels were assessed after SCI. Urodynamic alterations were evaluated by cystometry. The EP3 receptor antagonist L- 826266 (0.1 or 1.0 mg/kg) was intravenously administered to SCI rats. Urodynamic parameters, bladder cyclic adenosine monophosphate levels, histopathological changes, and preliminary systemic safety parameters were further assessed. L-826266 was also tested in PGE2-induced and acetic acid-induced overactive bladder (OAB) models and in healthy rats. Results: SCI increased bladder PGE2 and cyclooxygenase-2 levels and induced nonvoiding contractions (NVCs) during bladder storage phase. Both doses of L-826266 (0.1 and 1.0 mg/kg) increased the intercontraction interval, bladder capacity, and voiding efficiency and reduced NVC frequency in SCI rats. L-826266 also increased bladder cyclic adenosine monophosphate levels without obvious systemic toxicity or histopathological aggravation. In PGE2-induced OAB rats, L-826266 increased bladder capacity and reduced NVC frequency, whereas it had minimal effects on acetic acidinduced OAB. In healthy rats, only 1.0 mg/kg L-826266 prolonged the intercontraction interval and increased bladder capacity. Conclusion: EP3 receptor antagonist significantly reduced DO in SCI rats, which provides novel insights into the therapeutic agents for bladder dysfunction after SCI. Cite this article as: Lv LC, Xu XJ, Guo DY, et al. Therapeutic effects of prostaglandin E2 receptor subtype 3 blockade on spinal cord injury-induced detrusor overactivity. Urol Res Pract. 2026;52, doi:10.5152/tud.2026.26041

BACKGROUND:Magnetic resonance imaging-targeted prostate biopsy relies heavily on costly software-fusion platforms, limiting global accessibility. OBJECTIVE:We aimed to determine whether cognitive fusion (mental registration) is noninferior to software-based fusion targeted biopsy for detecting clinically significant prostate cancer (csPCa). DESIGN, SETTING, AND PARTICIPANTS:This multicenter, randomized, blinded, noninferiority trial enrolled 648 predominantly biopsy-naive men (prostate-specific antigen 4-20 ng/ml; Prostate Imaging Reporting and Data System ≥3) at nine centers in China. INTERVENTION:Participants were randomly assigned 1:1 to cognitive fusion or software-based fusion targeted biopsy, followed by systematic biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary outcome was csPCa (ISUP grade group ≥2) detection on targeted biopsy, evaluated using generalized estimating equations with a prespecified -10 percentage point noninferiority margin. RESULTS AND LIMITATIONS:In the intention-to-treat population (327 cognitive and 321 software), targeted biopsy detected csPCa in 32% and 34% of the patients, respectively. The adjusted risk difference was -1.02 percentage points (90% confidence interval [CI], -5.6 to 3.6), establishing noninferiority. Combined targeted and systematic biopsy detected csPCa in 35-39% of the patients, respectively (difference, -1.50% [90% CI, -6.4 to 3.4]). A significant body mass index (BMI) interaction was observed (p < 0.001): cognitive fusion performed best in men with BMI <24 kg/m2, whereas software-based fusion improved detection in men with BMI ≥24 kg/m2. Adverse event rates were comparable (15% vs 18%). Limitations include conducting the trial predominantly in Asian populations, necessitating cautious geographic extrapolation of specific BMI cutoffs. CONCLUSIONS:Cognitive fusion is diagnostically noninferior to software-based fusion within a prespecified -10% margin overall. However, a significant BMI interaction raises serious concerns regarding the diagnostic feasibility of cognitive fusion in obese populations, where software-based fusion is strictly superior. Future prospective trials in both Asian and Western populations must evaluate the BMI effect as a primary end point. TRIAL REGISTRATION:ClinicalTrials.gov NCT04271527.

4518 Background: Nectin-4 is an adhesion molecule that is highly expressed in variety of solid tumors, especially in urothelial cancer, cervical cancer, esophageal cancer and breast cancer. BFv is a novel site-specific ADC targeting Nectin-4, and Toripalimab is a novel recombinant humanized anti-PD-1 monoclonal antibody. Previous results of BFv and Toripalimab in la/mUC patients have shown promising efficacy and well-tolerable toxicity. Here we report follow-up results of BFv and Toripalimab in la/mUC patients. Methods: This is an open-label, multicenter, phase 1b/2 study to evaluate the safety and efficacy of BFv combined with Toripalimab in la/mUC. Patients received BFv (1.0 or 1.25mg/kg) on D1/D8 and Toripalimab (240mg) on D1, 21 days per cycle. Primary objective was safety, and secondary objectives were efficacy, pharmacokinetics and immunogenicity. Results: As of 1 Dec 2025 (median follow-up time: 16.0 months), 47 assessable patients with la/mUC were enrolled and received the combination therapy of BFv and toripalimab. 7 of them (3 received BFv 1.0mg/kg; 4 received BFv 1.25mg/kg) have been previously treated for la/mUC and other 40 (all received BFv 1.25mg/kg) were treatment-naïve patients. In the overall population, ORR was 83.0% (95%CI 69.2-92.4), CR rate was 12.8%. All CR patients were still on treatment and the longest treatment duration has already exceeded two years. DCR was 89.4% (95%CI 76.9-96.5), median PFS was 12.9 months (95%CI 6.5-NA) and median DOR was not reach. Median OS also was not reach, OS rate at 18 months was 68.1% (95%CI 52.7-79.4). Subgroup analysis showed significant benefits to all patients, which might indicate that compared to traditional chemotherapy, BFv plus toripalimab could bring patients greater benefits and a longer survival time, especially in those elderly and patients with impaired kidney function. Safety profile was consistent with previous results, and there was no other new safety signals of BFv or toripalimab observed in this study. Conclusions: BFv plus toripalimab in patients with la/mUC demonstrated remarkable efficacy and well-tolerated safety profile. A pivotal phase 3 study is ongoing currently. Clinical trial identification: NCT06592326 , NCT06079112 .

Autosomal-dominant polycystic kidney disease (ADPKD) remains refractory to curative therapy partly due to the lack of human models that recapitulate its adult-onset nature, genetic context, and multi-segment origin. Here, we established expandable, multi-lineage adult renal organoids (MAROs) directly from surgical specimens of ADPKD patients and healthy donors, creating a three-dimensional (3D) high-content screening platform. Patient-derived MAROs faithfully reproduced hallmark cystogenic features, including elongated primary cilia, polarity disruption, and elevated Rho GTPase/planar cell polarity (PCP) signaling. Single-cell transcriptomics of PKD1/PKD2-mutant organoids revealed genotype-specific alterations. Genetic ablation of IFT88 disrupted cilia and selectively attenuated Rho/PCP activity in mutant backgrounds, supporting a cilia-dependent cyst-activating (CDCA) mechanism in cystogenesis. Microfluidic perfusion accelerated cyst expansion and amplified Rho/PCP signaling. A high-throughput drug screen identified Rho GTPase inhibitors, including ML141, as effective cyst-reducing agents across genotypes without compromising viability. Our findings establish a patient-derived organoid platform that captures ADPKD pathology and nominates Rho pathway modulation as a therapeutic strategy.

Metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel and androgen receptor signaling inhibitors (ARSIs) has limited treatment options. Although enzalutamide has shown activity after abiraterone and docetaxel, robust evidence from randomized phase III trials is lacking. Deutenzalutamide, a novel derivative with slower metabolism and improved pharmacokinetics, may offer enhanced safety and efficacy. This phase III, double-blind trial conducted at 36 centers in China enrolled patients whose disease progressed on or who were intolerant to abiraterone and docetaxel, or who were ineligible for docetaxel. Patients were randomized (2:1) to receive deutenzalutamide 80 mg once daily or placebo until progression or unacceptable toxicity; the primary endpoint was radiographic progression-free survival (rPFS). Of 417 patients (276 deutenzalutamide; 141 placebo), all had previously received abiraterone, and 68% had also received docetaxel. Deutenzalutamide significantly improved rPFS (HR, 0.58; P = 0.0001), reducing the risk of progression by 42%. Although the initial OS analysis was not significant (HR, 0.95), sensitivity analyses adjusting for subsequent therapies showed significant OS benefits (HR, 0.65-0.73). Treatment-related grade 3 or higher adverse events occurred in 22.3% of patients treated with deutenzalutamide, compared with 15.0% with placebo. The most common treatment-related adverse event was anemia, reported at any grade in 21.2% versus 17.9%, with grade 3/4 anemia in 6.6% versus 2.9%, respectively. Notably, no seizures or falls were reported. In summary, deutenzalutamide significantly prolonged rPFS and, after adjustment, showed a potential OS benefit with a favorable safety profile, supporting its promise as a new treatment option for mCRPC. Clinical trial registration: NCT03851640.

Background:Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that originate from neuroendocrine cells. They are common in the digestive system (such as the stomach, intestines, and pancreas) and the respiratory system, but they are rare in the urinary system, comprising less than 1%-2% of urinary malignancies. These tumors typically lack specific clinical symptoms and are usually diagnosed through postoperative pathological examinations. Due to their rarity, the clinical awareness of NENs remains insufficient in the community. Methods:Clinical data of 10 patients diagnosed with urinary tract neuroendocrine neoplasms (UT-NENs) were retrospectively collected and analyzed. We summarized their clinical characteristics and treatment outcomes, with the aim to improve our understanding of urinary tract NENs and further optimize personalized therapeutic strategies for these rare tumors. Result:In our study, 4 out of 10 patients were admitted for hematuria. Seven out of 10 patients had lesions in the bladder. Five of 6 cases with NEN muscularis propria invasion occurred in the bladder. All 3 deceased patients had bladder NEN. None of them received postoperative radiotherapy and chemotherapy. Five out of 6 surviving patients received postoperative radiotherapy and chemotherapy. Conclusion:Hematuria is the main symptom in UT-NENs. The bladder is the most common location of UT-NENs, while bladder lesions are more likely to present as poorly-differentiated neuroendocrine carcinoma. In the present case series, patients who received postoperative radiotherapy and chemotherapy showed a trend toward better long-term prognosis and survival.

Neurogenic bladder dysfunction impairs bladder sensation and contraction, causing severe renal complications. The bladder's large isotropic expansion hinders the development of implantable bioelectronic devices for monitoring and electrical stimulation. Addressing this, we report an implantable soft bladder-machine interface (BdMI) that integrates seamlessly with the bladder, providing monitoring and electrical stimulation. This BdMI features a conductive thin film capable of keeping functions under isotropic stretch up to 800%, created without the complex pre-stretching of its elastic substrate. We elucidate its stretchability mechanism and validate the BdMI in rat models, which enables simultaneous intravesical pressure detection, detrusor electromyographic monitoring, and electrical stimulation therapy. Implanted for 7 days, the BdMI operates efficiently and markedly reduces involuntary bladder contraction frequency post-stimulation. These findings validate the potential of BdMI in offering real-time, physiological feedback and electrical stimulation-based regulation for neurogenic bladder pathologies, marking a significant advancement in the field.

Neurogenic bladder (NB) secondary to spinal cord injury (SCI) progresses from early-stage bladder inflammation to late-stage fibrosis, ultimately resulting in renal dysfunction. However, effective therapeutic options for NB remain limited, and patients currently rely exclusively on catheterization-based management to prevent upper urinary tract deterioration. Polydopamine nanoparticles (PDA NPs), a mussel-inspired polymer formed through the oxidative self-polymerization of dopamine, exhibits inherent bioadhesive properties and notable anti-inflammatory activity. Herein, we develop an intravesical delivery system (PFD@PDA NPs) composed of polydopamine nanoparticles loaded with pirfenidone (PFD), an FDA-approved drug for idiopathic pulmonary fibrosis (IPF), for the localized management of NB. Following intravesical instillation, PFD@PDA NPs can firmly adhere to the bladder wall, traverse the mucosal barrier, and sustain prolonged retention under urinary flow. Mechanistically, PFD@PDA NPs alleviate inflammation by scavenging reactive oxygen species (ROS), targeting mitochondria to protect mitochondrial function, and suppressing ferroptosis, while concurrently inhibiting fibrosis by downregulating TGF-β signaling to reduce fibroblast activation and extracellular matrix deposition. Besides, this localized delivery approach preserves bladder function, protects the upper urinary tract, and minimizes the hepatotoxicity associated with oral PFD. By enabling stage-specific intervention against early-stage bladder inflammation and late-stage fibrosis, this intravesical delivery system offers a clinically translatable approach for managing SCI-induced NB.

Background: Spinal cord injury-induced neurogenic lower urinary tract dysfunction (SCI-NLUTD) tends to be accompanied by bowel dysfunction, sexual dysfunction, and psychological disorders. To date, a convenient and concise tool for the comprehensive assessment of these symptoms in patients with SCI-NLUTD has been lacking. Objective: This study aimed to design and evaluate a comprehensive patient-reported outcome measuring system for SCI-NLUTD patients to facilitate patient follow-up and treatment. Methods: A draft questionnaire was designed based on a review of the literature and input from patients and experts, and was refined using the Delphi method. The scale was administered to 185 patients with SCI-NLUTD. Reliability was assessed using Cronbach’s alpha and test–retest reliability coefficients, while validity was evaluated through exploratory factor analysis, and in terms of content validity index, content validity ratio, and kappa statistics. Results: The final SCI-NLUTD scale includes 7 domains, 23 items, and 1 item assessing urination pattern. It demonstrated good internal consistency (Cronbach’s alpha = 0.775) and test–retest reliability (0.731–0.998). Validity was confirmed (Kaiser–Meyer–Olkin = 0.784, content validity index ≥0.89, content validity ratio ≥0.78, and kappa statistics ≥0.89). Results were visualized using radar charts to facilitate clearer tracking of symptom profiles. Conclusion: The SCI-NLUTD scale is a reliable, valid, and convenient tool for comprehensive assessment of SCI-NLUTD symptoms, aiding in treatment planning and monitoring patients’ quality of life.