Browse Articles

Harnessing the Magic Methyl Effect: Manipulating Photoluminescence and Photochromism of Salicylaldehyde Benzoylhydrazones in the Solid State

Abstract Photoluminescence and photochromism are pivotal in developing solid‐state photoresponsive materials, yet achieving precise tuning through subtle molecular structure modifications remains challenging. Herein, we demonstrate a universal “magic methyl” strategy to effectively manipulate the photoluminescence and photochromism of salicylaldehyde benzoylhydrazones in the solid state. Interestingly, the In (n = 1–4) series exhibits weak photochromism but excitation‐dependent (Ex‐De) emission with green fluorescence ( cis ‐keto) and cyan fluorescence (excimer), an exceptional phenomenon to Kasha's rule. More importantly, by replacing the hydrogen atom in the ─NHCO─ group with a methyl group, the obtained IIn (n = 1–4) series displays quenched fluorescence but pronounced photochromism. This subtle structural modification allows IIn series to reversibly switch the powder colors between white and orange under 365 and 520 nm light irradiation within seconds. The photochromic behavior persists from ambient temperature to ‐193 °C across different substituents. Notably, compound II3 , featuring a fluorine substituent, exhibits an exceptionally long half‐life of ∼240 min for its out‐of‐equilibrium trans ‐keto tautomer, attributed to intramolecular hydrogen bonding from ─F···HN─ within this form. These exceptional photophysical properties suggest promising applications in anti‐counterfeiting, smart coatings, and encrypted information storage, providing insightful strategies for developing organic small molecule based solid‐state photoresponsive materials.

Inside Front Cover: Circularly Polarized Organic Long‐Persistent Luminescence from Polymer Films Doped with Chiral Cu(I) Complexes (Angew. Chem. Int. Ed. 10/2026)

Inside Back Cover: Multidirectional Charge Separation in Self‐Assembled Aggregates of Perylenebisimide‐Porphyrin Bola‐Supra‐Amphiphiles (Angew. Chem. Int. Ed. 10/2026)

Sn‐Triggered Bridging‐Oxygen of lr─O─Ru Deprotonation Enhances Acidic Oxygen Evolution Reaction

ABSTRACT The development of efficient and stable electrocatalysts for the oxygen evolution reaction (OER) is crucial for advancing the commercialization of proton exchange membrane water electrolyzers (PEMWEs). Here, we report a ternary oxide catalyst, Ir‐RuSnO x , in which atomically dispersed Ir substitutes surface Ru sites to construct an Ir─O─Ru atomic interface. The catalyst requires an overpotential of only 165 mV to deliver 10 mA cm − 2 and maintains stable operation for over 350 h at 100 mA cm − 2 . When integrated into a PEMWE, Ir‐RuSnO x sustains continuous operation at 1 A cm − 2 for 800 h without observable degradation. Combined electrochemical and theoretical studies reveal that Sn acting as a strong electron donor, enhances electron localization at the bridging oxygen (O bri ) within the Ir─O─Ru motif. This enables O bri as a proton acceptor, facilitating deprotonation of O─H and OO─H species at Ru sites, thereby forming O bri ─H intermediates, lowering the energy barrier of the rate‐determining step (RDS), and accelerating OER kinetics. Simultaneously, Sn incorporation increases the electron density of the Ir─O─Ru structure, strengthening its resistance against oxidative degradation. These findings offer a path to achieving both high activity and long‐term durability in acidic OER electrocatalysts.

Residual Strain Evolution in Perovskite Solar Cells throughout Fabrication to Operation: Mechanisms, Characterization, and Regulation

ABSTRACT Perovskite solar cells (PSCs) have achieved a power conversion efficiency (PCE) of over 27%, but further improvements of both PCEs and stability are needed for commercialization. One of the key factors hindering their development is the unpredictable residual strain in perovskites. The unstable octahedral structure of the perovskite cage leads to easy changes in bond lengths, bond angles, and crystal structure. It in turn generates, accumulates, and causes the non‐uniform distribution of residual strain, ultimately affecting device performance. Therefore, given the versatility and precise tunability, residual strain engineering provides an effective pathway to optimize the performance of PSCs. This review summarizes the causes of residual strain during device fabrication and operation, qualitative/quantitative/auxiliary characterization methods, and various effective strain regulation methods in the past two years. Finally, unresolved scientific issues and future research directions in strain engineering are discussed. This comprehensive review aims to provide researchers with the latest advances in strain engineering, deepen fundamental understanding of strain effects, and eventually help enhance the performance of PSCs.

Associations of DNA damage repair (DDR) pathway class and allelic configuration with survival in metastatic renal cell carcinoma.

455 Background: Alterations in DNA damage repair (DDR) pathways occur in a subset of metastatic renal cell carcinoma (mRCC) and may influence therapeutic response and outcomes. While DDR mutations are increasingly detected on tumor genomic profiling, the combined effect of DDR pathway class and allelic configuration on survival in mRCC remains poorly characterized. Methods: We retrospectively identified 17 patients with pathogenic DDR mutations treated for mRCC between 2016–2025 at a comprehensive cancer center. DDR genes were categorized by pathway: homologous recombination repair (HRR: BRCA2, FANCA, RAD51C ), mismatch repair (MMR: MLH1, MSH6 ), base excision repair (BER: MUTYH ), and non-homologous end joining (NHEJ: ATM, RAD50 ). Allelic configuration (mono- vs. biallelic) was determined from review of aggregate genomic data. Overall survival (OS) was measured from first systemic therapy to death or last follow-up. Kaplan–Meier estimates and log-rank tests compared OS across DDR classes and allelic groups. Results: Median age was 70 years (IQR 63–78); 88% male. Histology included clear cell (76%) with sarcomatoid features present in 18% of these, and non-clear cell (24%). By IMDC criteria, 35% were poor-risk and 65% intermediate-risk. Common DDR alteration were BRCA2 (18%), ATM (12%), RAD50 (12%), and MUTYH (12%); 29% had biallelic loss. Median OS for the cohort was 19.1 months (range 4.7–74.9). Patients with HRR alterations (n = 4) had significantly longer OS than those with non-HRR DDR mutations (n = 13) (χ²(1) = 6.86, p = 0.0088). OS differed across pathway classes (χ²(3) = 8.30, p = 0.04). Monoallelic cases trended toward longer OS (31.7 vs. 11.9 months; p = 0.13). HRR-mutated tumors had only one observed death versus nine in non-HRR, indicating a favorable prognosis. Conclusions: In this single-institution cohort, DDR pathway class and allelic configuration were associated with survival in mRCC. HRR mutations conferred markedly improved OS, whereas biallelic DDR loss was linked to poorer outcomes. These findings highlight the potential prognostic and therapeutic relevance of DDR biology in mRCC and support integration of DDR pathway and allelic status into biomarker-driven trial design.

Outcomes of delayed cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma treated with immune checkpoint inhibitor therapy.

462 Background: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has evolved in the immune checkpoint inhibitor (ICI) era. We evaluated outcomes of patients with clear cell mRCC treated with first-line ICI therapy who subsequently underwent delayed CN. Methods: Using the Canadian Kidney Cancer information system (CKCis), a multi-institutional database, we retrospectively identified patients with clear cell mRCC treated with first-line ICI-based therapy who subsequently underwent CN. Clinical characteristics, treatment details, use of metastasis-directed therapy, and survival outcomes were collected. Descriptive statistics were applied and Kaplan–Meier methods were used to estimate progression-free survival (PFS) and overall survival (OS). Results: A total of 61 patients underwent delayed CN from January 2017 to June 2024 from a cohort of 1560 patients. Median age at CN was 64 years; 84% were male. All patients had intermediate (47%) or poor-risk (53%) by IMDC criteria. Sarcomatoid features were present in 22%. Lung (77%), lymph node (48%), and bone (18%) were the most common metastatic sites. Most patients had less than 3 sites of disease (65.6%). The most common ICI regime was ipilimumab + nivolumab (85%). Median time from ICI therapy initiation to CN was 11.5 months. A total of 38 patients (62%) who received first-line ICI therapy have discontinued treatment and remain alive, with only 20% (N = 12) requiring second-line therapy. With a median follow-up of 44 months, median OS was not reached; 2- and 5-year OS rates were 88% and 74%, respectively. Median PFS was 35 months, with 2- and 3-year PFS of 61% and 50%. Conclusions: In this retrospective series, delayed CN following ICI therapy in carefully selected patients was associated with durable disease control and encouraging long-term survival. Future analyses will explore pathologic response. These results highlight the need for randomized trials of deferred CN in the ICI era. Characteristic (N=61) Value Ipilimumab + Nivolumab 52 (85%) Pembrolizumab + Axitinib 9 (15%) Metastasis Directed Therapy  Radiation therapy 18 (30%)  Metastasectomy 12 (20%) Complete Response pre-CN 8 (13%) Discontinuation of systemic therapy 38 (62%) 5-year OS 74% 5-year PFS 50%

Does time to recurrence after radical cystectomy for bladder cancer impact subsequent survival?

874 Background: It has been long theorized that patients with earlier recurrence after radical cystectomy (RC) for bladder cancer have worse subsequent survival. However, it remains unclear whether time to recurrence is an independent predictor of survival or merely a surrogate for underlying factors such as adverse pathology. In this study, we assessed the impact of time to recurrence on the subsequent survival following RC for bladder cancer. Methods: We reviewed our IRB-approved RC database for patients who experienced recurrence following RC for bladder cancer between 1983 and 2024. Time to recurrence was categorized into four quartiles. Cox regression analyses were used to assess predictors of subsequent survival post-recurrence. Results: 935 patients who experienced recurrence post-cystectomy were included in the analysis. Time to recurrence was categorized into four quartiles: ≤ 4 months (Q1), 4-9 months (Q2), 9-20 months (Q3), and > 20 months (Q4). Patients who recurred later were more likely to be younger, male, and present with organ confined disease. Adverse pathological features, including variant histology and lymphovascular invasion, were less commonly observed among those with later recurrence. Univariate cox regression showed that recurrence between 9-20 months or later than 20 months was associated with better survival compared to recurrence within the first 4 months (HR: 0.77 and HR: 0.67, respectively.) Multivariate analysis demonstrated that, after adjusting for confounders including age at recurrence, pathological staging, and lymphovascular invasion, patients with recurrence after 20 months had a 19% decreased risk of death following recurrence (HR: 0.81, 95% CI: 0.66 – 0.99, p = 0.049). Conclusions: Recurrence after 20 months following RC is independently associated with superior survival, even after adjusting for major confounding factors. This may suggest that late recurrences possess distinct biological characteristics that influence their behavior. Demographics and perioperative characteristics stratified by time to recurrence quartiles. Patient characteristics Q1 (N=234) Q2 (N=243) Q3 (N=231) Q4 (N=175) P value Age at Recurrence (yrs.) 70.0 ± 10.1 68.1 ± 11.3 69.2 ± 10.8 69.9 ± 10.0 0.203 Sex (Male) 164 (70.1%) 176 (72.4%) 186 (80.5%) 175 (77.1%) 0.043 Neoadjuvant chemotherapy 65 (27.8%) 83 (34.2%) 45 (19.5%) 33 (14.5%) <0.001 Pathological Staging Organ-confined (≤ (y)pT2N0) 22 (9.4%) 54 (22.2%) 66 (28.6%) 104 (45.8%) <0.001 Extravesical (> (y)pT2N0) 66 (28.2%) 73 (30.0%) 43 (18.6%) 41 (18.1%) Lymph-node positive (pN+) 146 (62.4%) 116 (47.7%) 122 (52.8%) 82 (36.1%) Total Positive Lymph Nodes, median (IQR) 2.0 (0.0, 9.0) 0.0 (0.0, 3.0) 1.0 (0.0, 5.0) 0.0 (0.0, 1.0) <0.001 Histologic subtype (Variant histology) 82 (35.0%) 79 (32.5%) 57 (24.7%) 47 (20.7%) 0.002 Presence of lymphovascular invasion 155 (66.2%) 118 (48.6%) 123 (53.3%) 99 (43.6%) <0.001

Contemporary analysis of the prognostic significance of intraductal carcinoma of the prostate (IDC-P).

126 Background: IDC-P has become increasingly recognized for its poor prognosis among histologic subtypes. While prior studies have linked IDC-P with higher grade and advanced stage, population-level data remain limited. We utilized the National Cancer Database (NCDB) to identify national treatment patterns and evaluate the overall survival (OS) of IDC-P compared with acinar adenocarcinoma. Methods: The NCDB was queried from 2004 to 2021 for PCa patients with adenocarcinoma or IDC-P. Patient and tumor characteristics and treatment utilization were compared. Temporal trends in IDC-P were analyzed. OS was compared with Kaplan-Meier (KM) method, log-rank, and Cox Proportional Hazards model, adjusting for demographics, stage, comorbidities, Gleason Group, and treatment. Results: Of 2,107,942 PCa patients, 4,242 (0.2%) had IDC-P histology. IDC-P diagnoses increased over time (OR 1.06 per year, p<0.001), particularly after WHO recognition in 2016 (47.9% vs 36.8%, p<0.001). IDC-P patients had higher utilization of radical prostatectomy (RP) (69.5% vs 47.2%), pelvic lymph node dissection (50.2% vs 30.7%), androgen deprivation therapy (ADT) (35.7% vs 25.0%), and chemotherapy (3.4% vs 1.2%) (all p<0.001). Adjuvant (5.9% vs 3.0%) and salvage radiotherapy (3.3% vs 1.6%), serving as surrogate markers of biochemical recurrence, were also more common (p<0.001) as defined by < and ≥6 months post-RP, respectively. IDC-P patients had worse OS overall (14.1 vs 16.5 years, p<0.001), though the difference was attenuated in localized disease (cT1–4N0M0; 16.3 vs 16.7 years, p<0.001). After adjustment for comorbidities, stage, grade, and treatment, IDC-P was not independently associated with higher mortality. Conclusions: Our population-level analysis confirmed that IDC-P is associated with a more aggressive clinical phenotype. Despite this, we found that oncologic outcomes did not differ once disease severity and treatment were accounted for. Guideline-concordant management remains appropriate, though the rising detection of IDC-P and its biologic underpinnings merit ongoing investigation. Multivariable Cox proportional hazards model. Variable (Reference) aHR (95%CI) p-value Age (cont.) 1.048 (1.042-1.053) <0.001 Histo (Ref = Adenocarcinoma) Intraductal Carcinoma 1.138 (0.638-1.967) 0.644 Gleason Group (Ref = 1) 2 3 4 5 1.088 (0.883-1.341)1.290 (1.045-1.594)1.533 (1.239-1.897)2.081 (1.690-2.563) 0.4300.018<0.001<0.001 cT (Ref = 0-1) 2+ 1.458 (1.332-1.596) <0.001 cN (Ref = 0) 1+ 1.272 (1.149-1.408) <0.001 cM (Ref = 0) 1 2.969 (2.692-3.276) <0.001 Definitive Tx (Ref = No Surgery) Surgery Alone Surgery, XRT within 6 months Surgery, XRT after ≥6 months 0.474 (0.412-0.546)0.310 (0.199-0.482)0.360 (0.223-0.582) <0.001<0.001<0.001 Hormone Therapy (Ref = No) Yes 0.901 (0.799-1.016) 0.088 Chemotherapy (Ref = No) Yes 1.198 (1.044-1.376) <0.001

Photovoltage‐Driven Two‐Transistor–One‐Diode Perovskite Pixels for In‐Cell Optical Sensing Displays

ABSTRACT In‐cell optical sensing displays are essential for next‐generation interactive electronics, yet conventional architectures rely on separate light‐emitting diodes (LEDs) and photodetectors (PDs), limiting pixel density and efficiency. Achieving both functions within a single diode is intrinsically difficult because electroluminescence requires strong excitonic recombination, whereas photodetection benefits from efficient carrier separation. Here, we realize stable dual‐mode operation by stabilizing intermediate‐n quasi‐2D phases and suppressing non‐radiative losses with a fluorinated acid passivator, and by engineering high‐mobility transport layers with a dissociative (type‐II) perovskite/electron transport layer heterojunction to assist exciton dissociation under photovoltaic operation. The resulting bifunctional diode enables an opto‐dynamic random‐access memory (opto‐DRAM) pixel, a two‐transistor–one‐diode (2T1D) architecture conceptually analogous to a two‐transistor–one‐capacitor (2T1C) DRAM gain‐cell, where photovoltage‐driven rather than photocurrent‐driven detection enables self‐amplified sensing when coupled to thin‐film transistors. The sky‐blue PeLED achieves an external quantum efficiency of 20.4% at 100 cd m −2 and a record power efficiency of 41.8 lm W −1 , while as the coupled sensing pixel it exhibits a maximum responsivity of 4.17 × 10 4 A W −1 and a specific detectivity of 6.46 × 10 13 Jones. Monolithic integration yields an active‐matrix display capable of switchable emission and imaging functions offering a scalable platform for compact, energy‐efficient, and multifunctional optoelectronics.

Broadband Circularly Polarized Light Detection via Spin‐Selective Charge Transport in Quantum Dot Photodiodes

ABSTRACT Circularly polarized light (CPL) detection provides polarization‐resolved information, enabling advanced applications in quantum technologies, bioimaging, secure communications, and multi‐level optical data processing. However, conventional CPL photodetectors typically rely on intrinsically chiral absorbers, restricting operation to the UV–vis range and hindering extension into the near‐infrared (NIR) and shortwave infrared (SWIR), which are critical for deep tissue imaging and low‐visibility sensing. Here, we demonstrate broadband CPL detection with quantum dot (QD) photodiodes that exploit the chiral‐induced spin selectivity effect in chiral‐ZnO charge transport layers. Chiral ligand‐functionalized ZnO electron transport layers selectively transmit spin‐polarized charge carriers from QDs, enabling CPL‐specific photocurrent generation even in spectral regions without intrinsic chiral absorption. Heavy‐metal‐free Cu–In–Se QD‐photodiodes exhibit outstanding specific detectivity ( D * ) of 1.28 × 10 12 Jones without external bias and broadband CPL detection ( g Iph : ∼0.17 at 260 nm and ∼0.13 at 780 nm), while PbS QD‐devices extend CPL detection across 250–1700 nm (UV–Vis–NIR–SWIR) with superior performance ( D * : 1.45 × 10 12 Jones). The chiral‐transport‐driven strategy offers fundamental insights into CPL photodetection and establishes a scalable and optically passive platform for broadband polarization‐resolved optoelectronics.

Trends in high grade prostate cancer at diagnosis in the United States from 2004-2022.

341 Background: Prostate cancer represents a heterogeneous disease with varying clinical significance, from indolent cases requiring minimal intervention to aggressive malignancies with high mortality. High-grade prostate cancer, defined as Gleason score ≥8 (Grade Group ≥4), is associated with increased metastatic potential and reduced cancer-specific survival. This study evaluated changes in prostate cancer grade over time in the USA. Methods: Using the most recent National Cancer Data Base from 2025, we identified all men diagnosed with prostate cancer from 2004 to 2022. High grade disease was defined as biopsy Gleason Score ≥ 8 (Grade Group ≥4). Results: A total of 2,259,526 men diagnosed with prostate cancer were identified, of whom 423,953 (18.8%) had high-grade disease. The proportion of newly diagnosed high-grade cases rose from 12,297 (11.9%) in 2004 to 35,193 (24.9%) in 2022. Univariate logistic regression showed increasing age, Black identifying (vs. White), and diagnosis at non-academic centers (vs. academic) as associated with higher odds of high-grade disease. In multivariate analysis, increasing age (OR 1.058 per year [95% CI 1.058–1.059, p<0.001]), academic center (vs. non-academic) (OR 1.038 [95% CI 1.03–1.05, p<0.001]), and racial identity (Black vs. White OR 1.25 [95% CI 1.24–1.27, p<0.001]; American Indian/Alaskan Native vs. White OR 1.27 [95% CI 1.19–1.36, p<0.001]) were associated with higher likelihood of high-grade disease. Conclusions: We observed a continuous rise in high-grade prostate cancer incidence suggesting an identified cause. While the unadjusted proportion of high-grade diagnoses was lower at academic centers, after adjusting for age, the odds were actually higher at academic centers compared to non-academic. The increasing incidence of high-grade disease may reflect improved diagnostics (e.g., MRI-targeted biopsy), but the steady rise—alongside more metastatic disease—may signal a concerning shift in the underlying biology of prostate cancer that warrants further study. Acknowledgements: The National Cancer Database (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC’s NCDB and participating hospitals are the source of the de-identified data used herein; they have not verified and are not responsible for the statistical validity or the conclusions drawn by the authors. Proportion of high-grade disease by era and treatment center. Era Percent of men with high grade disease at diagnosis overall Percent of men with high grade disease, diagnosed at academic center (Unadjusted)* Percent of men with high grade disease, NOT diagnosed at academic center (Unadjusted) 2004-2007 12.2% 11.76% 12.42% 2008-2011 13.4% 12.59% 13.87% 2012-2017 21.0% 20.27% 21.53% 2018-2022 24.7% 24.18% 25.02% *After adjusting for age, the odds of high-grade diagnosis were higher at academic centers than non-academic.

Clinical efficacy of belzutifan in pre-treated renal cell carcinoma: A real world retrospective cohort benchmarked to LITESPARK-005.

464 Background: Based on LITESPARK-005 trail, Belzutifan was FDA-approved to treat advanced RCC following ICI and a VEGF-TKI. We conducted a retrospective cohort study to report the real-world outcomes of Belzutifan in pre-treated RCC patients. Methods: A retrospective chart review of all patients who received Belzutifan at the Mayo Clinic Comprehensive Cancer Center between Dec 2023 and Sep 2025 was conducted. Patients treated for sporadic RCC were eligible; those with von Hippel–Lindau disease, non-RCC pathologies (e.g., Pheochromocytoma, ovarian cancer) were excluded. Radiologic response was assessed by trained curators using RECIST-defined criteria, approximated through systematic review of radiology reports with clinician adjudication when needed. Progression-free survival (PFS), defined as the time from treatment initiation to radiographic progression or death, was estimated using the Kaplan–Meier method. Non-progressors were censored at the last radiology assessment. Patients who discontinued therapy for non-progression reasons were censored at the last radiology assessment prior to discontinuation. Any-cause hypoxia and anemia were reported using CTCAEv5 definitions. Results: A total of 158 patients were identified; 83 (52.5%) who received Belzutifan for sporadic RCC were included. The remaining were excluded for VHL disease (68, 43%) or other pathologies (7, 4.4%). Median follow up was 12 months, 67% were male, median age was 70 (range 39, 94) with 57 patients (69%) were ≥ 65. 28 patients (34%) had a poor IMDC score at baseline. The cohort received a median of 3 previous lines of therapy (range 1,8). Median treatment duration was 3 months (IQR: 1-9.5). Median PFS was 5.7 months (95% CI, 3.8–8.7). At 12 and 18 months, 23.1% and 13.9% of patients, respectively, remained alive and progression-free. Corresponding OS rates at these time points were 60.2% and 51.5%. A confirmed ORR occurred in 12 patients (14.4%). Hypoxia occurred in 44 (53%) patients, median onset 31 days (range 1–270) and 29 (34.9%) required hospitalizations. Median hemoglobin (Hb) levels at baseline were 12.65 g/dl (range, 7.2-15.5), and 68 (82%) patients developed Hb decline on Belzutifan, 27 (32.5%) required transfusions. Conclusions: In an older, high-risk cohort with higher number of prior lines of therapy, Belzutifan yielded PFS/OS and ORR landmarks comparable to the trial supporting its effectiveness in the real world. Outcomes compared with LITESPARK-005 trial. Variable Real world cohort (Mayo Clinic) LITESPARK-005, Belzutifan arm Median PFS (months, 95% CI) 5.7 (3.8-8.7) 5.6 (3.9-7) 12-month PFS rate (%, 95% CI) 23.1% (14.4-33.4) 33.4% (28.4-33.5) 18-month PFS rate (%, 95% CI) 13.9% (7.7-23.9) 24% (19-29.4) 12-month OS rate (%, 95% CI) 60.2% (48.9-70.8) 67.9% (62.9-72.4) 18-month OS rate (%, 95% CI) 51.5% (40.6-62.9) 55.2% (50-60.1) ORR (%, 95% CI) 14.4% (7.7-23.9) 21.9% (17.8-26.5)

Effect of epidural analgesia vs. combined intravenous patient-controlled analgesia and transversus abdominis plane block on postoperative outcomes after radical cystectomy.

875 Background: Intravenous patient-controlled analgesia (IV-PCA) and epidural analgesia are commonly used methods for postoperative pain management following major surgery. Although previous systematic reviews have suggested that epidural analgesia may provide superior pain control compared to IV-PCA, it is also associated with potential complications such as hematoma, abscess formation, and catheter migration. Ultrasound-guided transversus abdominis plane (TAP) block is a simple, safe, and minimally invasive regional anesthesia technique. However, the combined effect of IV-PCA and TAP block on postoperative outcomes remains unclear. Methods: This multicenter retrospective study included 473 patients who underwent radical cystectomy (RC) under general anesthesia. Patients were divided into two groups: those who received epidural analgesia (epidural group) and those who received IV-PCA combined with TAP block (study group). The primary endpoint was the rate of perioperative complications of grade ≥3. Secondary endpoints included length of hospital stay after RC, time to initiation of oral feeding, and 90-day readmission rate. Multivariable analysis was performed to identify risk factors associated with grade ≥3 complications. Results: The median age was 69 years. Of the 473 patients, 355 (75%) received epidural analgesia and 118 (25%) received IV-PCA plus TAP block. No TAP block-related complications were observed. The rates of any-grade and grade ≥3 perioperative complications did not differ significantly between the epidural and study groups (64% vs. 68%, P = 0.469; 23% vs. 19%, P = 0.334, respectively). In univariable analyses, age and type of urinary diversion were significantly associated with grade ≥3 complications, whereas sex, performance status, body mass index, American Society of Anesthesiologists physical status, and robot-assisted radical cystectomy were not. After adjusting for these confounding variables, IV-PCA combined with TAP block was not significantly associated with an increased risk of grade ≥3 complications. The study group had significantly shorter hospital stays and earlier initiation of oral feeding compared to the epidural group ( P = 0.007 and P < 0.001, respectively). The 90-day readmission rates were comparable between the epidural and study groups (29% vs. 25%, P = 0.435). Conclusions: Although IV-PCA combined with TAP block did not reduce the rate of perioperative complications, it was associated with shorter hospital stays and earlier initiation of oral intake following RC. Multivariable analysis for grade ≥3 complications. Multivariable Factor P value Odds ratio 95% CI Age Continuous 0.044 1.029 1.001–1.059 Urinary diversion Neobladder <0.001 0.420 0.262–0.674 IV-PVC plus TAP Performed 0.137 0.664 0.387–1.140

Severe acute kidney injury after abiraterone vs enzalutamide in advanced prostate cancer: A SEER–Medicare study.

120 Background: Acute kidney injury (AKI) is a frequent complication among older adults with cancer, linked to short-term mortality, prolonged hospitalization, and progression to chronic kidney disease (CKD). Traditional androgen deprivation therapy has been associated with AKI, but contemporary evidence for androgen receptor pathway inhibitors (ARPIs) is limited. Abiraterone acetate with prednisone (AAP) may increase renal vulnerability via mineralocorticoid excess and steroid effects, whereas enzalutamide (ENZA) has other mechanisms. We quantified the risk of AKI-related hospitalization following ARPI initiation and, comparing AAP with ENZA overall and within key clinical subgroups. Methods: Using SEER–Medicare data, we identified men with advanced prostate cancer (PCa), with no prior AKI, who initiated AAP (2013–2018) or ENZA (2013–2019). AKI hospitalizations were identified using inpatient ICD-9/10 codes. Follow-up ran from ARPI start to first AKI hospitalization, death, loss of Medicare coverage, or December 31, 2020. Fine–Gray sub-distribution hazard models were used to estimate adjusted hazard ratios (HRs). Results: We included 5,574 patients with PCa (2,948 AAP; 2,626 ENZA); 78% were ≥75 years. The 12-month cumulative incidence of AKI hospitalization was higher with AAP vs ENZA (17.9% vs 13.6%). At 12-months post treatment initiation, cumulative risk of AKI was substantially higher in patients with pre-existing CKD vs without CKD (27.2% vs 9.2%; p<0.05) and with congestive heart failure (CHF) vs without CHF (23.9% vs 11.7%; p<0.05). Risk factors associated with increased hospitalization with AKI included older age, higher CCI, pre-existing CKD and CHF (Table 1). Conclusions: AAP was associated with a higher adjusted hazard of AKI hospitalization than ENZA. Clinically, these data support (i) preferring ENZA over AAP when oncologically acceptable in patients at elevated renal risk (CKD, CHF, high comorbidity, older age, Black race), and (ii) structured renal monitoring after ARPI initiation, with tighter surveillance for AAP users and those with CKD/CHF. Key predictors of AKI hospitalization after ARPI initiation (adjusted) with selected baseline differences. Risk factor Comparison Adjusted HR 95% CI (lower) 95% CI (upper) Age group ≥75 vs 65–74 1.24 1.09 1.42 Race Black vs White 1.30 1.05 1.62 Marital status Unmarried vs Married 1.33 1.09 1.63 Charlson comorbidity index 1 vs 0 1.23 1.06 1.42 ≥2 vs 0 1.61 1.27 2.04 ARPI agent AAP vs ENZA 1.25 1.10 1.41 Treatment year 2013–2016 vs 2017–2019 1.56 1.37 1.79 Pre-existing CKD Yes vs No 2.54 2.20 2.94 Pre-existing CHF Yes vs No 1.53 1.25 1.88 Charlson Comorbidity Index did not include AMI, CHF and DM in its calculation. Model was adjusted for age group, race, marital status, education, income, SEER region, state buy-in, dual eligibility, CCI, ARPI agent, treatment year, pre-existing CKD, DM, CHF and AMI.

Receptor‐Mimetic Stereo Olfaction for Simultaneous Odor Recognition and Spatial Localization

ABSTRACT Odor plumes are chemophysical fields where molecular identity is coupled to transport phenomena including diffusion and turbulence. In animals, decoding this joint information underlies navigation and social behavior. However, artificial systems treat identity and location as independent problems, solved by distinct modalities. Here we present AROMA (Artificial Receptor‐Olfaction Mimetic Array), a stereo olfaction strategy in which receptor‐mimetic sensors capture plume dynamics, enabling concurrent decoding of mixture composition and 3D source location from analyte‐dependent kinetic patterns. AROMA is built on mixed‐ligand gold nanoparticles whose phase‐separated monolayers and non‐additive interfacial energetics emulate the promiscuous selectivity of olfactory GPCRs. Deployed in an antenna‐like, spatially separated configuration, these sensors convert evolving concentration fields into disparities in onset, rise, and amplitude that encode geometric information. Trained on 50 plume trials of six‐odorant mixtures sampled by a 30‐channel array in an 18 cm cubic chamber, a multi‐task Transformer achieves 86.7% mixture identification accuracy and a 3D localization error of 2.84 ± 0.87 cm. We demonstrate room‐scale source tracking with a mobile robot indoors under natural airflow. By translating plume dynamics into a unified latent representation, AROMA advances artificial olfaction from static molecular discrimination toward spatial intelligence, offering a general framework for environmental monitoring and autonomous navigation.

Constructing Ion Bridges With Competitive Coordination Effects to Promote Li ⁺ Conduction in Solid‐State Electrolytes for High‐Performance Lithium Metal Batteries

ABSTRACT Composite solid electrolytes (CSEs) based on poly(vinylidene fluoride)‐co‐hexafluoropropylene (PVDF‐HFP) and Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 (LLZTO) are considered among the most promising SEs for achieving high‐energy‐density solid‐state batteries. However, low ionic conductivity and poor interfacial compatibility pose significant challenges for their practical applications. Herein, a strategy involving the construction of Li x TaO x F 5‐ x (LTOF) ion bridges with competitive coordination effects on the LLZTO surface is proposed. This approach alleviates restrictions on Li + transport and enhances Li + transport kinetics. The introduction of LTOF weakens Li + coordination strength, suppresses electron localization at the LLZTO/PVDF‐HFP interface, and simultaneously reduces PVDF‐HFP crystallinity. This creates multiple efficient Li + transport pathways and an interphase with excellent compatibility. Consequently, the prepared electrolyte exhibits a high ionic conductivity of 1.21 mS cm − 1 . Attributing to easier lithium salt dissociation, the solid electrolyte interface enriched with inorganic components, e.g. LiF/Li 3 N/Li 2 S, enables the Li|CSE‐9TF|Li cell to maintain stable plating/stripping for over 1100 h at a current density of 0.8 mA cm − 2 . The assembled LiFePO 4 ||Li cells deliver high capacity retention (93.4%) and approaching 100% coulombic efficiency after 1000 cycles at 1C. This work proposes a strategy for regulating the coordination environment and improving interfacial compatibility through surface oxyhalide layers, facilitating new progress in the practical application of CSEs.

Salvage radiotherapy after radical prostatectomy in a Japanese cohort: Analysis from the MICAN study.

342 Background: The clinical benefit of salvage radiotherapy (SRT) for biochemical recurrence (BCR) after radical prostatectomy (RP) remains controversial, particularly regarding patient selection. We evaluated the impact of SRT on oncologic outcomes in a large Japanese cohort using the MICAN registry. Methods: The MICAN study is a multicenter retrospective registry of patients who underwent RP between 2010 and 2020 in Japan. Among 3,463 cases, we identified 610 patients who experienced postoperative PSA recurrence, had no prior neoadjuvant therapy, and were pN0 or pNx. These were divided into those who received SRT (Group A, n=308) and those who did not (Group B, n=302). SRT was delivered to the prostate bed at 60–72 Gy. Primary endpoints were overall survival (OS) and androgen deprivation therapy-free survival (ADT-FS). Multivariate analysis was conducted using Cox proportional hazards models. Results: Median PSA recurrence-free survival was comparable (19.3 vs 19.1 months; P=0.132). Group A was significantly younger (67 vs 70 years; P<0.001) and had a higher rate of positive surgical margins (51.8% vs 44.1%; P=0.036). Ten-year OS was not significantly different overall (93.6% vs 89.9%; P=0.285), but SRT significantly improved OS in patients with positive margins (97.3% vs 84.0%; P=0.007). No OS benefit was observed among patients with negative margins. pGG was the only independent predictor of OS in multivariate analysis. However, SRT significantly prolonged ADT-FS (10-year: 55.3% vs 37.1%; P<0.001), and both pGG and SRT remained significant in multivariate analysis. Conclusions: In this Japanese multi-institutional cohort, SRT significantly improved ADT-free survival after PSA recurrence, with a survival benefit observed specifically in patients with both positive surgical margins and high-grade disease (pGG 4–5).

TANKeR-70: TGF-β-receptor type 2 knockout allogeneic NK cells for renal cell carcinoma expressing CD70.

TPS571 Background: Clear cell renal cell carcinoma (ccRCC) frequently expresses CD70. Chimeric antigen receptor (CAR) natural killer (NK) cells may have a more favorable toxicity profile than CAR T cells and warrant further exploration as a novel cancer treatment. Transforming growth factor beta receptor 2 (TGFβR2) is expressed on immune effector cells and its ligand, transforming growth factor-beta (TGFβ) has been associated with suppression of antitumor immune cell activity in longitudinal biopsies of patients with ccRCC treated with triple immunotherapy using nivolumab + ipilimumab + anti-VEGF TKI (Nat Commun. 2025; PMID: 39794332). The MD Anderson Institute for Cell Therapy Discovery and Innovation developed TGFBR2 KO CAR.70/IL-15 NK cells, an off-the-shelf umbilical cord-derived IL-15-transduced CAR NK cell product targeting CD70 with knockout of TGFβR2 to decrease the immunosuppressive effects of TGFβ in the tumor microenvironment. We hypothesize that TGFBR2 KO CAR.70/IL-15 NK cells will be a safe, tolerable, and feasible treatment for patients with treatment refractory ccRCC. Methods: This is a Phase I study testing the safety and efficacy of TGFBR2 KO CAR.70/IL-15 NK cells in metastatic ccRCC refractory to immune checkpoint and tyrosine kinase inhibitors. Expression of CD70 ≥10% by immunohistochemistry is required for enrollment. The primary objective is to determine the safety, tolerability, maximum tolerated dose and optimal cell dose. Secondary endpoints are objective response rate per RECIST v1.1, progression-free survival, and overall survival. Exploratory endpoints include CAR NK cell persistence; longitudinal changes in serum IL6, IFNγ, and TNFα; and changes in tumor tissue molecular features pre- and post-treatment. Patients will receive lymphodepleting chemotherapy with dexamethasone (to facilitate engraftment) followed by fludarabine 30 mg/m 2 /day and cyclophosphamide 500 mg/m 2 /day (days -5 to -3), with a single CAR NK infusion given on day 0. The dose-escalation phase will use the Bayesian optimal interval (BOIN) design assess up to 4 dose levels (ranging from 1.3 x 10^7 up to 4.0 x 10^8 cells) with N = 18 maximum total patients. Toxicity, efficacy, and NK cell engraftment kinetics will be used to determine the optimal cell dose which will subsequently be tested in up to 12 additional patients in the dose-expansion phase to further collect toxicity and preliminary efficacy data. Accrual to this study at MD Anderson opened in October 2025. Clinical trial information: NCT07072234 .

Patient-derived primary prostate cancer epithelial cultures for studying prostate cancer cell evolution under hypoxia.

397 Background: Genetic instability is a hallmark of cancer and a driving force of tumourigenesis. An emerging concept is that hypoxia can potentiate genetic instability and tumour evolution leading to a poor clinical prognosis in localised prostate cancer. Mechanistic studies that explicitly test the ability for hypoxia to drive an increased DNA mutation burden and subsequent chromosomal instability(CIN) are lacking in sporadic and hereditary prostate cancer. We hypothesised that constant hypoxia selection pressure would increase clonal and sub-clonal selection for mutator phenotypes and CIN, beyond that achieved by aberrant cancer driver gene expression alone. Methods: We created isogenic single-hit and multi-hit prostate cell models for TP53, ATM, BRCA2 and RB loss and/or c-MYC overexpression using human telomerase ( hTERT )-immortalized prostate epithelial cell (PrEC) cultures. PrEC cultures were derived from morphologically-normal areas of radical prostatectectomy specimens. Isogenic cells were grown ex vivo under oxia (21% O 2 ), acute on chronic hypoxia (72h x 1% O 2 ) or constant long term, hypoxia exposure (20 generations x constant 1% O 2 ). Resulting DNA mutation burden and chromosomal instability were assayed using a combination of whole genome sequencing, RNAseq and immunofluorescent assessment of mitotic aberrations (antibodies against centrin-1, H3 phospho-serine10 and DAPI-DNA counterstain). Results: Under oxia, de novo percent genome alteration and micronuclei frequency was highest in the combined c-MYC/TP53 -/- clones compared to single gene c-MYC, BRCA2 -/- , ATM -/- or TP53 -/- clones. When growing the cells under acute on chronic hypoxic conditions (72 h, 1% O 2 ), there was an increase in micronuclei and centrosome aberrations across all genetic clone sub-types, with the highest incidence in c-MYC/TP53 -/- clones. Continued passaging of these cells led to increasing aneuploidy over time. Our CIN results were even more striking when using the PrEC cells with inactivated TP53 and RB (due to SV40 large T antigen transduction) following 20 generations of constant hypoxia. The observed increased percent genome alteration (45% increasing to 84%) was associated with increased micronuclei, PGCCs, erroneous anaphases and whole-genome duplication. In situ validation of these in vitro mechanistic studies is underway using spatial transcriptomic and whole genome profiling of 30 primary high-risk sporadic and hereditary prostatectomy specimens stained for hypoxic biomarkers (HYPROGEN trial: NCT05702619). Conclusions: Our results suggest that hypoxia augments genetic instability and CIN in cells secondary to cancer driver gene aberrations giving rise to clonal populations with selective advantage. These findings support the testing of therapeutic strategies that address both hypoxia and cancer driver mutations as a means to improve outcomes.