Browse Articles

Electric Field Propelled Anion‐Type Solvation Structure Reconstruction With Accelerated Kinetics for Low‐Temperature Zinc Metal Batteries

ABSTRACT Organic‐rich eutectic electrolytes, which have been prevalent to address the electrolyte freezing and Zn dendrite growth challenges for low‐temperature aqueous zinc‐based batteries, suffer from sluggish Zn 2+ desolvation kinetics and mass transport. Here, we introduce aprotic acetone as a cosolvent to improve the performance of aqueous Zn(BF 4 ) 2 ‐based electrolyte under cold environments. Leveraging dynamic keto‐enol tautomerism in the primary solvation sheath of Zn 2+ propelled by the electrical double layer electric field, an anion‐type solvation structure is established, which shortens the Zn 2+ desolvation path with accelerated kinetics and constructs a tough and tight interface with a gradient organic‐inorganic configuration, eventually enabling uniform Zn deposition at low temperatures. As a result, Zn||Zn symmetric cells sustain for 7500 h at 1 mA·cm −2 and over 1200 h with 34.2 % DOD at 10 mA·cm −2 under −40°C. Pouch‐cell properties are demonstrated by matching a PEDOT‐V 2 O 5 cathode, which harvests a high capacity of 150 mAh over 210 cycles under practical conditions (N/P = 4.33 and E/C = 6.0 µL mg −1 ) and holds approaching 100 % capacity retention at −40°C. This work provides an effective strategy toward industrializing practical cold‐resistant zinc‐based batteries via modulating the electrolyte structure.

Alix-mediated selective packaging of β-catenin into extracellular vesicles enhances their proangiogenic function

Real-world use and effectiveness of first-line enfortumab vedotin (EV) with pembrolizumab (P) in patients with advanced urothelial carcinoma (aUC).

692 Background: EV+P significantly improved overall survival (OS) compared with platinum-based chemotherapy in the EV-302 trial and is now established as the new first-line (1L) standard of care for patients (pts) with aUC [PMID: 38446675]. Recent data show that EV+P has become the most commonly used 1L regimen for aUC [PMID: 39174408]. However, there are limited data on the real-world survival outcomes with EV+P. Herein, we sought to assess the use and effectiveness of 1L EV+P in a large real-world dataset. Methods: This study used the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility: diagnosis of aUC between 4/1/2014 and 6/23/2025 and receipt of 1L treatment with EV+P. Pts on clinical trials were excluded. The data cut-off date was 6/30/2025. Uptake of EV+P by year of 1L initiation was summarized using frequency and percentages. Median time to next therapy (TTNT) was defined as time from 1L initiation to 2L initiation or death and censored at the lost to follow-up. Median OS was defined as time from the 1L initiation to death and censored at the lost to follow-up. The Kaplan-Meier method was used to estimate median TTNT and OS, and their 95% confidence intervals (CIs). Results: Of 15,236 pts with aUC in the dataset, 10,960 had 1L treatment information available, of whom 745 received 1L EV+P and included in the analysis. The start date for 1L EV+P was between 2/28/2020 and 6/24/2025. Median age was 74 years (IQR 67 – 80), 74% were male, and 66% were non-Hispanic White. Uptake of EV+P increased over time, comprising 62% of 1L regimens started in 2025. Uptake of EV+P by year of 1L initiation is shown in Table. With a median follow-up time of 10.3 months, median TTNT was 11 months (95% CI 9.5 – 12), with 328 events (44%), and median OS was 17 months (95% CI 15 – 21), with 254 pts (34%) having an event. Conclusions: This is the largest analysis to date evaluating real-world uptake and survival outcomes with 1L EV+P in the US. EV+P demonstrates significant real-world uptake. However, real-world survival outcomes do not match those seen in the EV-302 trial, which suggests a difference in the patient characteristics in real-world than those enrolled in the EV-302 trial. These data may assist with patient counseling and prognostication. Limitations include the retrospective design, missingness, and real-world dataset. Uptake of EV+P by year of 1L initiation in pts with aUC. Year N 1L EV+P n (%) 2020 1006 2 (0.2) 2021 930 3 (0.3) 2022 965 4 (0.4) 2023 919 142 (15) 2024 821 420 (51) 2025 302 186 (62)

Establishment and characterization of a panel of prostate adenocarcinoma XPDX models representing naïve, chemotherapy- and radiotherapy-resistant patient populations.

251 Background: Preclinical models of prostate adenocarcinoma (PRAD) are challenging to establish and maintain. We previously reported (AACR2025) the successful establishment and characterization of ten parental and three conditioned prostate adenocarcinoma models in immunodeficient mice. Using this experience, we have expanded our platform with eight additional PRAD models from patients naïve to or progressing on chemo- and radiotherapies. These models were characterized for receptor expression, genomic alterations, and in vivo drug sensitivity to relevant therapies. Methods: XPDX models representing prostate cancer were established from primary (ST6347, ST7756, ST7888) or metastatic (STM637B, STM655, STM784, STM784B, STM784C) samples implanted into intact immunodeficient male mice. Resulting models were passaged serially and further developed in both intact and castrated mice until growth stabilization. Resulting models were characterized using genomic analysis, including WES and RNA seq , receptor expression, and in vivo drug sensitivity studies. For in vivo studies, docetaxel, abiraterone, and enzalutamide were evaluated at standard treatment regimens. Study endpoints included tumor volume and time from treatment initiation with %T/C values and tumor regression reported at study completion; a %T/C of ≤ 20% versus control was considered sensitive. Tumor regression (%T/C < 0%) versus Day 0 tumor volume was also reported. Results: Differential staining for AR, PSMA, and AR-V7 was reported with these models, consistent with patient pretreatment status. ST7756 and ST7888 were established from naïve patients and ST6347 from a patient treated with docetaxel. Genomic characterization of STM637B, a model from a patient post-targeted and lutetium (177Lu) vipivotide tetraxetan (LVT) treatments, identified TMPRSS2-ERG fusion and PTEN loss. FGFR3 and NF1 aberrations were present in STM655, a model derived from a patient following chemo and LVT therapies. Three models developed from longitudinal sampling designated STM784, STM784B, and STM784C, were established from the same patient following progression on various targeted therapies and LVT, with STM784C collected after additional treatment with a PSMA-targeting Actinium-225 radiotherapy. Differential sensitivity to abiraterone, enzalutamide, and docetaxel was found in evaluated models that aligned with patient pretreatment history. Conclusions: We have established and characterized an expanded panel of PRAD XPDX models including several representing patient post chemo- and radiotherapies. These models can be utilized as a valuable tool in better understanding prostate cancer and in developing novel therapies for drug and radio-resistant patients.

Bladder cancer (BC) screening in un-affected Caucasian ancestry family members of patients who tested positive for germline homologous recombination repair (gHRR) and mismatch repair (gMMR) variants.

TPS879 Background: According to GLOBOCAN, in 2020 there were 573 000 new BC cases and predictions show a significant increase in BC cases from 2020 to 2040 especially in developing countries. This epidemiological trend combined with the highest lifetime costs of any other cancer, requires urgent actions and investment in early detection and screening of individuals at higher risk. The International Agency for Research on Cancer (IARC) reports cigarette smoking as the leading cause of BC and occupational and environmental exposure to carcinogens as the second greatest risk factor behind smoking. However, up to 4.3% of BC patients have a first-degree relative with BC, and up to 50% of urothelial cancer patients have a family history of cancer. BC is rarely attributed to hereditary causes, but recent studies suggest inherited factors may play a larger role respect to the past. Swedish Family-Cancer Database identified a likely genetic predisposition to urinary BC in 7% of cases and an Italian prospective case-control study, found about 30% BC patients harbouring germline at least pathogenic (PV), likely pathogenic (LPV), or variants of unknown significance (VUS). The knowledge of such data prompted us to test the feasibility and performance of a dedicated screening in un-affected Caucasian ancestry family members of BC patients tested positive for gHRR and/or gMMR. Methods: This is an observational, single centre, prospective cohort study of un-affected Caucasian ancestry relatives older than 35 yrs of BC patients tested positive for gHRR and/or gMMR. The study was founded by AIRC - Fondazione AIRC per la Ricerca sul Cancro; registered and emended with the number ID-IG-25027-V1.3. First degree consanguineous (brother-sistes-son-doughter-1stG nephew) relatives of patients with BC positive for gHRR and gMMR, who underwent radical cystectomy, and consanguineous relatives of patients with known BRCA1/2+ cancer or heredo-family cancers are defined as probands. Probands will be offered a genetic counselling and testing for the variants they are likely to have. We will offer a screening program to positive for germline variants un-affected population, consisting of annual urine cytology, urine molecular test, abdominal ultrasounds assessment and cystoscopy when indicated. Positive or suspected cases will undergo trans urethral resection (TUR) for pathological sampling. The main objectives of this exploratory study will be: to report the rate of un-affected subjects who accepted counseling and testing; to identify the frequency of gHRR and gMMT, to describe the genes tested and the distribution of PV, PL and VUS, reporting the cases of BC occurred in screened population. Considering about 80 RC Hospital/year and a yield of 30% of gDRS variants with 2.5 un-affected family members, we foresee to enroll about 50 subject/year. Clinical trial information: r ID-IG-25027-V1.3.

Redefining multimodal treatment in high-volume metastatic hormone-sensitive prostate cancer: Prospective evidence for robot-assisted cytoreductive prostatectomy following triplet systemic therapy.

193 Background: For newly diagnosed high-volume metastatic hormone-sensitive prostate cancer (mHSPC), front-line therapy typically involves androgen-deprivation therapy (ADT) combined with either docetaxel or novel androgen-receptor inhibitors. The role of local treatment (such as cytoreductive prostatectomy or radiation therapy) in men with a high-volume of metastases is not well established. We investigated a strategy of intensive systemic triplet therapy (ADT and darolutamide and docetaxel) followed by robot‐assisted cytoreductive prostatectomy. Methods: In this prospective, single-center study, 30 patients with high-volume mHSPC received six months of intensive therapy (NCT06350825). All patients underwent preoperative evaluation after systemic therapy, during which they achieved ≥90% reduction in PSA (PSA90) and showed no radiographic progression on PSMA PET/CT before proceeding to robot-assisted cytoreductive prostatectomy. The aim was to assess the impact of this multimodal therapy on PSA response, pathological outcomes, and the feasibility of combining systemic therapy with surgery. After surgery, patients continued systemic therapy to evaluate long-term outcomes. Results: With a median follow-up of 20.5 months, survival data remained immature. All patients achieved PSA90, and 73.3% had PSA levels ≤0.2 ng/mL following the intensive systemic therapy. Postoperative pathological analysis showed significant tumor regression: 73.3% of patients were pathologically downstaged. Notably, 7 of 30 patients (23.3%) had either pathologic complete response or minimal residual disease. The triplet regimen was well tolerated, with no grade III or higher adverse events. Only 5 patients (16.7%) experienced grade I–II adverse events, including 2 cases of anastomotic leak, 1 case of pneumonia, and 2 cases of urinary tract infection. These adverse events were all resolved with standard care. At 12 months post‐surgery, 93% of patients reported mild urinary incontinence, as expected following cytoreductive prostatectomy, with no life-threatening surgical complications. Conclusions: This is the first prospective study to explore a darolutamide-based triplet induction regimen followed by cytoreductive prostatectomy in high-volume mHSPC. The results demonstrate that this multimodal approach is both feasible and safe, leading to deep PSA remissions and significant pathological tumor regression. These findings suggest that aggressive induction therapy, followed by prostatectomy, can yield significant clinical responses. However, further randomized trials with longer follow-up are needed to fully assess its impact on long-term survival. Clinical trial information: NCT06350825 .

Eco‐Friendly Centroidal Voronoi‐Tessellated Nanowire Networks for Efficient Ingress Protection and Broadband Acoustic Transparency

ABSTRACT Environmental water and dust ingress pose serious threats to human‐machine interaction (HMI) electronics, necessitating reliable protection from fibrous acoustic vents. However, most existing membranes in acoustic vents face inevitable trade‐offs between waterproofness and acoustic transmittance, while relying heavily on toxic solvents and fluoropolymers. Here, inspired by centroidal Voronoi tessellation (CVT), we use a unique green electro‐nanopatterning technique to develop eco‐friendly CVT nanowire network (EcoCVT‐net) acoustic membranes. Manipulation of a green ternary metastable solution system, and the rapid phase separation induced by non‐solvent seeds in the sprayed droplets of the Taylor cone, enable the assembly of 2D CVT‐nanostructured networks with deep‐subwavelength nanowires (diameter of 15 nm). Such membranes generate a nanoscale pore size of ∼190 nm, superhydrophobicity, and a low airflow resistivity of 7.6 × 10 6  Pa s m −2 , exhibiting both efficient water resistance (110 kPa) and broadband acoustic transparency with negligible sound transmission loss (<0.35 dB) across 63–20 000 Hz. Demonstrated in voice‐based artificial intelligence electronics, our acoustic vents deliver high‐fidelity voice transmission and long‐term IP68‐level protection for over 1000 h. This work provides a sustainable design pathway for fibrous acoustic metamaterials and should prove instrumental for the development of voice‐based HMI technologies.

Acidic Hydrogel Enables Full‐Period Mn ²⁺ /MnO ₂ Conversion in High‐Energy Quasi‐Solid‐State Zn‐MnO ₂ Batteries

ABSTRACT Flexible aqueous Zn‐MnO 2 batteries are regarded as promising power sources for next‐generation portable and wearable electronics owing to their intrinsic safety and cost‐effectiveness. However, their practical applications are hindered by limited energy density, primarily due to the low utilization of MnO 2 cathodes (i.e., the single‐electron redox reaction of MnO 2 ). To overcome this problem, we designed a new acidic hydrogel electrolyte composed of poly(2‐acrylamido‐2‐methylpropanesulfonic acid) and polyacrylamide (PAMPS/PAM) as a proton reservoir to maintain a stable acidic environment and facilitate fast cation transport through abundant sulfonic groups. In addition, hydrogen evolution of the Zn anode in acidic PAMPS/PAM was suppressed using a polymer‐coated Zn anode (P‐Zn). Benefiting from these design choices, the P‐Zn||MnO 2 battery with the acidic PAMPS/PAM and P‐Zn exhibited Mn 2+ /MnO 2 two‐electron conversion during the complete operation cycle. This battery design delivered a high discharge voltage of 1.9 V, a capacity of 592.9 mAh g −1 at 10 A g −1 , and an energy density of 762.6 Wh kg −1 at a power density of 13821.8 W kg −1 while maintaining exceptional durability over 1000 cycles. An as‐fabricated fiber‐shaped Zn||MnO 2 battery further demonstrated the feasibility of this strategy in constructing high energy‐density flexible energy storage devices for wearable electronics.

CLDN5 as a novel modulator of podocyte adhesion to extracellular matrix via β1-integrin binding

Real-world outcomes of radium-223 in the FRONTIER study: Impact of prior up-front therapy in mCRPC.

63 Background: The role of Radium-223 (Ra-223) after up-front therapies for metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Given their widespread adoption, assessing the impact on Ra-223 outcomes is clinically important. Methods: We retrospectively analyzed the FRONTIER database of mCRPC patients treated with Ra-223 at 84 Japanese institutions (2020–2023). Of 844 cases, 591 met eligibility criteria. Patients were grouped as: up-front therapy with docetaxel and/or ARSI (n=189) or ADT monotherapy (n=402). After multiple imputation and 1:1 propensity score matching, 377 patients were analyzed (189 vs. 188). Primary endpoints were OS and CSS; secondary endpoints included time to progression, treatment completion, radiologic response, pain non-deterioration, and skeletal events. Results: After matching, baseline features were well balanced. Six-cycle completion rates were similar (73.0% up-front vs. 68.1% ADT). Median time to progression was 5 months in both groups (p=0.9), with comparable radiologic response and pain outcomes. Disease progression was detected more frequently in the up-front group (86.8% vs. 77.1%, p=0.01). Among patients completing six cycles, median OS did not significantly differ (67 vs. 70 months, HR=0.97, p=0.87). CSS was also similar. Absence of bone-modifying agents was associated with a tripled SSE risk in the up-front group. Conclusions: Ra-223 demonstrated comparable efficacy and safety regardless of prior up-front therapy. Survival was not compromised, supporting its use after treatment intensification and underscoring the need for bone-modifying agents to prevent SSE. Treatment response and progression outcomes after radium-223. Variable Up front therapy(n=189) Vintage hormone therapy(n=188) p-value Radiographic treatment response to Ra-223  Complete response 7/159 (4.4%) 3/147 (2.0%)  Partial Response 23/159 (14.5%) 13/147 (8.8%)  Stable Disease 58/159 (36.5%) 74/147 (50.3%)  Progressive Disease 71/159 (44.7%) 57/147 (38.8%)  Not evaluable/Unknown 30 41  Overall distribution across CR/PR/SD/PD χ² p=0.06  Objective response rate (CR+PR) 30/159 (18.9%) 16/147 (10.9%) 0.07 Progression status at data cut-off  Progressed 164/189 (86.8%) 145/188 (77.1%) χ² p=0.01  Not progressed (censored at cut-off) 25/189 (15.7%) 43/188 (22.9%) Progression-free survival from Ra-223 initiation (months) 5 ( 4-8 ) 5 ( 4-8 ) 0.9 Values are n (%) or median (IQR). Radiographic responses (CR/PR/SD/PD) are among evaluable patients; χ² for distribution; ORR=CR+PR (2×2; Fisher if needed). Progression status is descriptive; PFS by KM/log-rank and Cox. Reasons for PD: n/N (%) among progressed (164/145), multiple responses; 2×2 χ² except Other (Fisher); no multiplicity adjustment.

A liquid biopsy targeted proteomic assay to predict outcomes in castration resistant prostate cancer patients treated with 177Lu-PSMA-617.

250 Background: Plasma-based targeted proteomics is an emerging area with great potential to aid in cancer diagnostics via rapid, repeated, and quantifiable measurements of key biomarkers. We developed a liquid biopsy-based proteomic assay to quantify druggable protein targets in plasma that may predict response to 177 Lu-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC) patients. Methods: Blood was serially collected from 37 mCRPC patients (84 samples in total) as part of a prospective clinical trial. Circulating tumor cells (CTC) were isolated from 27 samples, while plasma was obtained from 84 samples, 10 of which overlapped with the CTC samples. Samples were processed using Astrin Bioscience’s AI-empowered label-free holographic imaging and in-flow protein marker expression to enrich CTCs. CTCs and plasma samples were processed to generate peptides for analysis on a FAIMS equipped Stellar instrument. Heavy labeled peptide standards were used for internal normalization. Each protein evaluated provided single digit attomole limit of detection (LOD). Log-rank tests were performed to assess for overall survival (OS). Results: CTCs were successfully isolated from 27 samples, with a mean CTC count of 3.2 cells/mL and a median of 1.7 CTCs/mL. 28 proteins were selected for targeted proteomic analysis, and we assessed 10 key proteins in our preliminary study. When comparing the CTC proteome vs plasma proteome, we found that only 10% of proteins were unique to CTCs, while 76% were distinct to plasma or shared between CTCs and plasma, supporting the shift to plasma for future analyses. Serum PSA levels correlated with PSA protein expression measured by our assay (r=0.7, p = 0.0005). Serum alkaline phosphatase levels correlated with Trop-2, PSA, AR, DLL3, and PD-L1 protein levels (all p<0.05). PET scan-derived molecular tumor burden correlated with PD-L1 expression (r=0.36 p=0.04) but inversely correlated with CHGA levels (r= -0.41, p=0.01). Higher levels of DLL3 [HR=7.62, (CI 2.85 - 20.37) p=0.01], Trop-2 [HR=2.37, (CI 0.90-6.21) p=0.06] and PD-L1 [HR=3.53, (CI:1.40-8.92) p=0.005] were associated with worse OS. Serial (baseline and on-treatment) sampling of a subset of these patients revealed dynamic changes in proteomic markers including PSMA, PD-L1, and Trop-2 that may predict response to 177 Lu-PSMA-617. Conclusions: We have developed a quantitative proteomic assay capable of detecting attomole concentrations of key druggable proteins in mCRPC patients. The assay’s ability to detect and quantify key therapeutic targets in both CTCs and plasma makes it broadly applicable. This first-of-its-kind proteomic assay can guide precision oncology approaches by profiling and quantifying multiple druggable proteins from individual patients, ultimately minimizing harm and improving targeted therapy selection.

Clinical outcomes of retroperitoneal lymph node dissection in patients with cT _3–4 N _x M ₀ non–clear cell renal cell carcinoma.

472 Background: Non–clear cell renal cell carcinoma (nccRCC) comprises 20–25% of renal cancers and exhibits distinct biological behavior and poorer outcomes compared to clear cell RCC. The clinical value of retroperitoneal lymph node dissection (RPLND) in locally advanced nccRCC remains uncertain. This study aimed to evaluate the oncologic outcomes and prognostic factors associated with RPLND in patients with cT3–4 Nx M0 nccRCC. Methods: We retrospectively reviewed 64 patients with cT3–4 Nx M0 nccRCC who underwent radical nephrectomy and RPLND between 2004 and 2025. Clinicopathologic features, recurrence patterns, and survival outcomes were analyzed. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan–Meier analysis and compared by log-rank test. Prognostic factors were identified using univariate and multivariate Cox regression. Results: The cohort included 39 females (60.9%) and 25 males (39.1%) with a mean age of 46.8 years. Pathologic nodal involvement was present in 34 patients (53.1%). The median follow-up was 48 months; median DFS and OS were 14.6 and 56.2 months, respectively. The 1-, 3-, and 5-year DFS rates were 48.7%, 27.6%, and 23.1%, with OS rates of 93.5%, 68.2%, and 51.4%. On multivariate analysis, pathological nodal positivity (DFS: HR 4.00, 95% CI 1.86–8.54, p < 0.001; OS: HR 7.15, 95% CI 1.55–33.06, p = 0.012) and sarcomatoid differentiation (DFS: HR 3.76, 95% CI 1.52–9.29, p = 0.004; OS: HR 3.40, 95% CI 1.13–10.21, p = 0.029) were independent adverse prognostic factors. Recurrence occurred in 32.8% of patients, predominantly in lymph nodes (28.1%). Distant metastases most frequently involved lymph nodes (28.1%), lungs (21.9%), liver (15.6%), and bone (14.1%). DFS and OS varied significantly by histologic subtype (DFS: p = 0.0041; OS: p = 0.047), with collecting duct and unclassified RCC associated with the poorest outcomes. Conclusions: RPLND is feasible in patients with cT3–4 Nx M0 nccRCC and yields critical prognostic information. Pathologic nodal status and sarcomatoid differentiation are strong predictors of recurrence and survival. Marked heterogeneity across histologic subtypes underscores the need for subtype-specific risk stratification and tailored postoperative management.

A phase 1b/2 study to evaluate the safety and efficacy of igermetostat (XNW5004) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer.

169 Background: Overexpression of EZH2 is associated with poor prognosis in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Inhibition of EZH2 has been reported to overcome enzalutamide (E) resistance in CRPC. Igermetostat is a highly selective, small molecule EZH2 inhibitor. Here, we report the safety and efficacy of igermetostat in combination with E in mCRPC pts from a phase 1b/2 study (NCT06702995). Methods: mCRPC pts who had received one novel hormone therapy (NHT) except E and whose disease had progressed on the received NHT per PCWG3 criteria were eligible for this multicenter, phase 1b/2 study in China. In phase1b, 3+3 design was used for dose escalation in 3 dose levels of igermetostat (800, 1200, 1600mg, p.o, BID) + E (160 mg QD) and 2 of them were selected to confirm RP2D. In phase 2, igermetostat 1200mg BID + E were selected for dose expansion. The primary endpoint was RP2D, safety, and radiographic progression-free survival (rPFS). Best overall response (BOR), ≥50% PSA decline from baseline (PSA 50 ), and pharmacokinetics (PK) were also assessed. Results: As of Sep 05, 2025, 84 mCRPC pts were treated with igermetostat at dose levels of 800mg BID (n=3), 1200mg BID (n=65), or 1600mg BID (n=16) in combination with E. Median age was 69 years. The median lines of prior systemic therapy were 2. 83.3% of the pts received abiraterone previously. 15.5 % of the pts had visceral metastasis. 10.7% of the pts had received prior taxane therapy. The most common treatment emergent AEs (TEAEs) in ≥30% pts included diarrhea (65.5%), anemia (58.3%), nausea (48.8%), vomiting (40.5%), asthenia (36.9%) and decreased appetite (34.5%), with majority of them being grade 1-2. Grade≥3 TEAEs were reported in 25% of the pts (17.9% treatment related). Serious AEs occurred in 13.1% of the pts (4.8% treatment related). No DLT was observed. 53 pts with prior abiraterone treatment were included in the efficacy analysis. Median follow-up was 13.2 months (mo). Median rPFS (mrPFS) was not reached (10.97, NC). The 12-month rPFS rate was 59.8%. Median overall survival (mOS) was not reached. In the 15 pts with baseline measurable disease, BOR rate was 26.7%, including 4 partial responses. PSA 50 occurred in 11 (31.4%) of the 35 PSA-evaluable pts. At 1200 mg BID dose group, median follow-up was 11.9 mo. mrPFS was not reached (11.01, NC). 12-month rPFS rate was 70.8%. mOS was not reached. Igermetostat exposure exhibited dose-dependent increase from 800 to 1600mg in combination with enzalutamide after multiple dose administrations at steady-state. High-fat meal had no clinically meaningful effect on igermetostat exposure. Conclusions: Igermetostat in combination with E shows promising efficacy in post-abiraterone pts with mCRPC, and has a manageable AE profile. The RP2D for igermetostat is 1200 mg BID. Clinical trial information: NCT06702995 .

Scalable Surface Alloying–Dealloying Manufactures Nanoporous Electrodes From Bulk Metals for Ampere‐Level Alkaline Water Electrolysis

ABSTRACT Commercial deployment of alkaline water electrolysis requires electrodes that can sustain ampere‐level current densities while remaining manufacturable at scale; however, most advanced electrocatalysts demonstrated in laboratories lack mechanical robustness and are incompatible with industrial production. Here we report a vapor‐phase surface alloying–dealloying (VPA‐CD) strategy that converts commodity metal sheets directly into bulk‐supported nanoporous electrodes via in situ formation of catalyst layers metallurgically bonded to dense substrates. Applied to Ni‐Mo and Ni‐Fe alloys, this approach yields Mo single‐atom‐doped nanoporous Ni with high hydrogen evolution activity and nanoporous Ni(Fe)/Ni 3 Fe heterostructures with excellent oxygen evolution activity, enabling ampere‐level alkaline electrolysis at low cell voltages. Beyond planar substrates, the method scales to large‐area and patterned architectures that directly integrate flow fields and catalyst layers; the resulting integrated electrolyzer achieves 1.0 A cm −2 at only 1.84 V and remains stable for over 185 h, outperforming commercial benchmarks. These findings establish VPA‐CD as a robust and manufacturable route for engineering nanoporous electrodes, bridging the gap between catalyst discovery and device‐level hydrogen production.

Ultralow‐Frequency Epsilon‐Near‐Zero States in 3D‐Printed High‐Entropy Alloy Metacomposites for Ultra‐Thin Perfect RF Absorption

ABSTRACT Epsilon‐near‐zero (ENZ) materials with radio‐frequency perfect absorption are pivotal for next‐generation electromagnetic stealth, 5G (fifth‐generation mobile networks) signal integrity, and IoT (internet of things) security. Here, 3D‐printed metacomposites achieving low‐frequency ultra‐thin ENZ absorption (>90%, 55–110 MHz, d/△λ<1/2455) are realized by confining high‐entropy alloy (HEA) nanoparticles within hierarchically ordered porous carbon (HOPC). This hierarchical design leverages HEA's flattened band structures to maximize electron effective mass, while interfacial electron redistribution at HEA‐carbon boundaries delocalizes charges and reduces carrier concentration. These dual effects synergistically suppress plasma frequency to 72.4 MHz, converting strong negative permittivity into near‐zero states. A cocktail effect is discovered for reducing the plasma frequency with increasing the entropy. Concurrently, resonant enhancement from three complementary mechanisms—surface plasmons at HEA@graphitic core‐shell interfaces, interfacial polarization in PU/HOPC heterojunctions, and hierarchical pore‐cavity modes—boosts positive permittivity. Engineered cancellation of weakened negative permittivity and reinforced positive permittivity enables an ultra‐broadband |ε'|<1 response spanning 55–110 MHz. The ENZ‐mode perfect absorption of ultra‐thin thickness, ultralow frequency, angle robustness, and broad band is achieved eventually. This work establishes a new paradigm for breaking the Rozanov limit via material‐genesis ENZ engineering, bypassing artificial metamaterial arrays.

Bisphenol-A impairs hippocampal neurogenesis by disrupting Kinesin-1-dependent mitochondrial trafficking

Impact of neoadjuvant chemotherapy on perioperative outcomes following nephroureterectomy.

697 Background: Upper tract urothelial carcinoma (UTUC) is a urologic malignancy for which nephroureterectomy (NU) remains a cornerstone treatment. For high-grade disease, neoadjuvant chemotherapy (NAC) is recommended and has shown survival benefit. However, NAC has been linked to increased frailty and perioperative complications in other malignancies. Limited data exist regarding its impact on perioperative outcomes in patients undergoing NU. We evaluated perioperative outcomes in patients receiving NAC versus NU alone using a large, multi-institutional database. Methods: We analyzed patients undergoing NU for UTUC from 2019–2023, identified through the ACS-NSQIP database using relevant CPT codes. Patients were stratified by NAC receipt prior to NU. Baseline demographics, comorbidities, and 30-day perioperative outcomes were compared using chi-square, Fisher’s exact, and Welch’s t-test. Primary outcomes included 30-day major/minor complications, length of stay (LOS), readmission, reoperation, and mortality. Results: Of 2,872 patients, 300 (10%) received NAC and 2,572 (90%) underwent NU alone. Groups were similar in comorbidities with minor differences in age, race, and BMI. Complication rates were comparable: minor (21% vs 24%, p=0.36) and major (11% vs 12%, p=0.76). The NAC group had longer operative time (256 ± 91 vs 228 ± 89 min, p<0.001) and higher lymphocele rates (4% vs 2%, p=0.003) but were more likely to undergo lymph node dissection (68% vs 43%). No significant differences were seen in LOS (3.5 vs 3.6 days, p=0.63), readmission (9% vs 8%, p=0.62), reoperation (3% vs 3%, p=0.66), or mortality (0% vs 1%, p=0.39). Patients receiving NAC had higher pathologic complete response rates (pT0: 8% vs 4%, p=0.02). Conclusions: In this multi-institutional analysis—representing the largest to date—patients receiving NAC had comparable perioperative outcomes to those undergoing NU alone. NAC was also associated with higher pT0 rates on final pathology. These findings suggest NAC does not worsen perioperative outcomes or significantly contribute to preoperative frailty, while providing benefit in disease downstaging. This analysis supports NAC’s safety for use in appropriately selected patients with high-grade UTUC undergoing NU. 30-day patient outcomes. NU AloneN = 2572 NU with NACN = 300 p-value Minor Complications 550 (21.38%) 71 (23.67%) 0.3635 Bleeding Requiring Transfusion 165 (6.42%) 25 (8.33%) 0.2059 Lymphocele 46 (1.79%) 13 (4.33%) 0.0033* Urinary Leak 37 (1.44%) 1 (0.33%) 0.1129 Major Complications 285 (11.08%) 35 (11.67%) 0.7602 Return to operating room 66 (2.57%) 9 (3%) 0.6556 Readmission 210 (8.16%) 27 (9%) 0.6188 Death 15 (0.58%) 0 (0%) 0.3914 Length of Total Hospital Stay (days) 3.63 ± 3.45 3.47 ± 5.75 0.6259 *Statistically significant.

Beyond <i>BRCA</i> : Real-world outcomes with poly(ADP-ribose) polymerase inhibitors among patients with metastatic castration-resistant prostate cancer and homologous recombination repair mutations.

89 Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) are established therapies for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair mutations(m) (HRRm), with the greatest benefit in pts with BRCA mutation ( BRCA m). However, the real-world (rw) distribution of HRRm and outcomes following PARPi therapy, especially among those with non- BRCA HRRm, are not well defined. Methods: This retrospective cohort study selected from the US-based, EHR-derived deidentified Flatiron Health Research Database containing data from 373,536 pts with prostate cancer. Pts diagnosed with mCRPC between May 1, 2020 and June 30, 2025 and with evidence of an HRRm at any time were included. The PARPi treated subgroup included pts who received a PARPi-containing regimen on or after their mCRPC diagnosis and had an HRRm confirmed before or within the 30 days after PARPi initiation. rw overall survival (rwOS) and rw time to next treatment (rwTTNT) were measured from the start of the earliest PARPi line of therapy in the mCRPC setting using Kaplan-Meier curves and Cox proportional-hazards models adjusted for age, race, ethnicity, and the line (1L-3L+) of the PARPi therapy. Results: Of 27,771 pts diagnosed with mCRPC, 51% (n=14,046) were HRR tested, and 28% (n=3919) of those tested had HRRm. Of pts with HRRm, 34% had BRCA m and 66% had non- BRCA HRRm. ATM (32%), CHEK2 (20%), CDK12 (14%) were the most prevalent non- BRCA HRRm. Among pts with HRRm, PARPi receipt was higher in those with BRCA m 48% (n=636/1330) vs 29% in non- BRCA HRRm (n=739/2589). Of the PARPi treated subgroup (n=1343), 47% had a BRCA m and 53% were non- BRCA HRRm. Overall, PARPi was initiated 39% in 1L, 34% 2L and 27% 3L+; distributions were similar by BRCA status. Most pts in both groups received PARPi monotherapy. Baseline characteristics were similar across BRCA m/non- BRCA HRRm subgroups. Overall, median rwOS (months, 95% CI) was 15.19 (13.12-16.34) in pts with BRCA m vs 12.26 (11.01-13.87) in those with non- BRCA HRRm. Overall, rwTTNT (months, 95% CI) was longer in pts with BRCA m: 7.30 (6.61-7.92) vs 5.69 (5.33-6.25). In the adjusted Cox models, BRCA m was associated with lower hazard of death (0.83; 95% CI 0.71-0.96; p=0.013) and longer rwTTNT (0.78; 95% CI 0.69-0.89; p&lt;0.001). Conclusions: In this large rw-mCRPC cohort, non- BRCA HRRm were more common than BRCA m; yet pts with non- BRCA HRRm were less likely to receive PARPi and experienced shorter survival and treatment duration. Variability in outcomes across HRR subgroups highlights biological and clinical heterogeneity among pts with mCRPC and HRRm and the need for better access to PARPi.

Association of radiomic skeletal muscle features on prostate T1-weighted MRI with major adverse cardiac events in prostate cancer patients.

34 Background: Prostate cancer (PCa) is the most common malignancy among men, yet cardiovascular disease (CVD) remains a leading cause of morbidity and mortality. Recent studies show that baseline skeletal-muscle strength predicts major adverse cardiac events (MACE). As prostate MRI (pMRI) is routine in PCa care, we evaluated whether radiomic features (RFs) of pelvic skeletal muscle predict MACE. Methods: We retrospectively analyzed 225 men with PCa (2010–2025). Baseline 3 T T1-weighted pMRI scans were used to segment the obturator internus, externus, and pectineus muscles. Thirty scans were manually annotated to train an nnUNetv2 model; remaining scans were auto-segmented and verified under radiologist supervision. Haralick/GLCM, gradient-derived, and CoLlAGe (co-occurrence of local anisotropic gradient orientations) features were extracted per IBSI standards. Correlated RFs were removed, significance tested (Wilcoxon p &lt; 0.05), and top five selected by mRMR; univariate Cox models identified RFs with highest concordance index. Results: Of 225 patients, 52 (23.1 %) developed MACE during a median follow-up of 1,641 days. After FDR correction, CoLlAGe Entropy [Gradient Orientations (ColEGO) S4N3; q = 0.012] and ColEGO (S3N3; q = 0.028) remained significant. Five-fold cross-validation AUC = 0.64 ± 0.11 (L1-logistic) and 0.61 ± 0.03 (XGBoost). Conclusions: Pelvic skeletal-muscle RFs from routine pMRI associate with MACE in PCa. These RFs may enable noninvasive cardio-oncology risk stratification, supporting evidence that muscle strength predicts cardiac events. Prospective validation is warranted. RF (IBSI-style descriptive name) Context Test / HR (95 % CI) p/q value Direction Clinical Interpretation ColEGO S4 N3 Binary U = 3179, AUC = 0.65 p = 0.001, q = 0.01 Decreased in MACE Lower entropy means more homogeneous fiber pattern and healthier architecture. ColEGO S3 N3 Binary U = 3373, AUC = 0.63 p = 0.006, q = 0.03 Decreased in MACE Lower entropy reflects preserved muscle integrity and lower CVD risk. GLCM Correlation [Haralick (GLCMH) 3 S7 N3] Binary U = 5431, AUC = 0.60 p = 0.024 Increased in MACE Higher correlation suggests fibrotic/lipid texture linked to adverse remodeling. Gradient Magnitude Variance (GMV) S4 N3 Binary U = 3568, AUC = 0.6 p = 0.024 Decreased in MACE Lower variance suggests smoother edges and uniform density in healthy muscle. GLCMH 3 S8 N4 Binary + Survival U = 3605, AUC = 0.6 / HR = 0.68 (0.50–0.93) p = 0.030 / 0.016 Decreased in MACE (lower hazard) Greater uniformity implies preserved myofiber structure and reduced event risk. GLCMH 3 S8 N3 Survival HR = 0.47 (0.22–0.99) p = 0.046 Decreased in MACE (lower hazard) Predictable texture patterns associate with lower cardiovascular risk. GMV S12 N3 Survival HR = 1.12 (1.01–1.25) p = 0.039 Increased in MACE (higher hazard) Larger-scale variance indicates heterogeneous architecture consistent with fibrosis.

RC48G001: A phase 2 study of disitamab vedotin in HER2-expressing previously treated advanced UC.

LBA631 Background: An estimated 60%-80% of patients (pts) with UC have HER2-expressing tumors. DV is an ADC comprising a novel anti-HER2 antibody, disitamab, and an MMAE payload. DV demonstrated promising antitumor activity and a manageable safety profile as monotherapy in Chinese pts with HER2-expressing (IHC 1+ or greater) la/mUC refractory to prior therapies. We report the primary analysis from Cohorts A and B of the global RC48G001 study assessing DV monotherapy in pts with HER2-expressing la/mUC (HER2-positive: IHC 3+, or IHC 2+/ISH-positive [Cohort A]; HER2-low: IHC 2+/ISH-negative, or IHC 1+ [Cohort B]) who progressed following systemic therapy. Methods: RC48G001 (or C5731002) is a global, multicohort, single-arm, open-label, phase 2 study that enrolled pts with la/mUC who received 1-2 prior systemic therapies (incl. a platinum-containing regimen). HER2 expression was determined by central laboratory using the VENTANA HER2 IHC and HER2 Dual ISH DNA Probe Cocktail assays. Pts received 1.5 mg/kg DV monotherapy IV once per 2-week cycle. The primary endpoint (EP) was cORR per RECIST 1.1 by BICR. Secondary EPs included DOR, DCR, PFS (all per RECIST 1.1 by BICR), OS, and safety. A genAI tool (09/05/25; Pfizer; GPT-4o) assisted with the 1st draft; authors assume content responsibility. Results: At data cutoff (Sep 12, 2025), 73 pts were enrolled in Cohort A and 78 pts in Cohort B. 54.8% and 39.7% of pts had ECOG PS 0, and 68.5% and 82.1% had visceral disease in each cohort, respectively. Cohort A included 69.9% pts with IHC 3+ and 30.1% pts with IHC 2+/ISH-positive la/mUC. Cohort B included 28.2% pts with IHC 1+ and 69.2% pts with IHC 2+/ISH-negative la/mUC. Median follow-up was 11.3 months for Cohort A and 17.1 months for Cohort B. Pts received a median of 9 DV cycles in both cohorts. cORR per BICR was 54.9%, with a CR rate of 16.9%, in Cohort A, and 52.6%, with a CR rate of 18.4%, in Cohort B (Table). mPFS by BICR was 5.7 months in both cohorts. mOS was 20.0 months and 17.0 months in Cohort A and B, respectively. Grade ≥3 TRAEs occurred in 62 (41.1%) pts, with fatigue (13.9%) being the most common. 16.6% of pts discontinued treatment (tx) due to AEs, most commonly peripheral sensory neuropathy (6.0%). Conclusions: This is the first presentation of DV monotherapy outcomes in a global population with HER2-expressing la/mUC. DV demonstrated promising antitumor activity and a manageable safety profile, consistent with results from China, supporting further evaluation. Clinical trial information: NCT04879329 . Cohort A Cohort B n=71 n=76 cORR, a n % (95% CI) - CR - PR 39 (54.9)(42.7, 66.8)12 (16.9) 27 (38.0) 40 (52.6) (40.8, 64.2) 14 (18.4) 26 (34.2) mDOR, a mo (95% CI) 5.8 (4.6, 9.4) 6.9 (4.7, 9.4) DCR, a,b n % (95% CI) 62 (87.3) (77.3, 94.0) 64 (84.2) (74.0, 91.6) n=73 n=78 mPFS, a mo (95% CI) 5.7 (4.1, 7.1) 5.7 (4.6, 6.9) mOS, mo (95% CI) 20.0 (12.8, NE) 17.0 (9.6, 23.9) a By BICR. b Defined as the proportion of pts with confirmed CR/PR, or who met SD criteria at least once after tx initiation at an interval of ≥5 wk.