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RNF90 promotes hepatic steatosis by degrading CPT1α to suppress fatty acid oxidation

Adjuvant vs switch-maintenance checkpoint inhibition in urothelial carcinoma: A systematic review and meta-analysis of randomized trials through July 2025.

732 Background: Immune checkpoint inhibitors (ICIs) are used in urothelial carcinoma (UC) as adjuvant therapy after radical cystectomy or nephroureterectomy and as switch-maintenance after response or stable disease to platinum chemotherapy. Randomized controlled trials (RCTs) show setting-specific benefits, but pooled evidence is limited. Methods: Following PRISMA guidelines, PubMed, Embase, Cochrane CENTRAL, and ASCO/ESMO/ASCO Genitourinary (GU) proceedings were searched through July 31, 2025. Eligible studies were phase II/III RCTs of programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors in adjuvant or switch-maintenance UC with placebo, observation, or best supportive care (BSC) controls. Outcomes were disease-free survival (DFS; adjuvant) and overall survival (OS; both). Grade ≥3 adverse events (AEs) were summarized. Random-effects meta-analyses were performed. Results: Five RCTs (N=3,028) were included: adjuvant nivolumab (CheckMate 274), pembrolizumab (AMBASSADOR), atezolizumab (IMvigor010), and switch-maintenance avelumab (JAVELIN Bladder 100) and pembrolizumab (HCRN GU14-182). Adjuvant pooled DFS favored ICIs (HR 0.77, 95% CI 0.67–0.90). Pooled OS was not significant (HR 0.87, 95% CI 0.75–1.01): CheckMate 274 trended positive; AMBASSADOR and IMvigor010 were neutral. In maintenance, pooled OS favored ICIs (HR 0.71, 95% CI 0.59–0.87), driven by JAVELIN. Biomarkers showed PD-L1 enrichment in CheckMate 274 (DFS HR 0.52) and JAVELIN (OS HR 0.56), DFS benefit regardless of PD-L1 in AMBASSADOR, and circulating tumor DNA (ctDNA) stratification in IMvigor010 (ctDNA-positive OS HR 0.59). Grade ≥3 AEs were more common with ICIs. Conclusions: Adjuvant ICIs reduce recurrence but OS benefit remains inconsistent, likely due to design, cross-over, and later ICI use. Switch-maintenance provides a consistent OS advantage and is standard of care. PD-L1 and ctDNA may refine selection. These findings highlight differing maturity of evidence between perioperative strategies and guide sequencing in UC. RCTs of adjuvant and switch-maintenance ICI in UC. Trial Setting N Intervention Comparator Primary Endpoint(s) Key Outcomes CheckMate 274 Adjuvant 709 Nivolumab Placebo Disease-free survival (DFS; ITT and PD-L1 ≥1%) DFS HR 0.70; interim overall survival (OS) HR 0.76 AMBASSADOR / A031501 Adjuvant 702 Pembrolizumab Observation Co-primary: DFS and OS DFS HR 0.73; interim OS HR 0.98 IMvigor010 Adjuvant 809 Atezolizumab Observation DFS DFS HR 0.89; OS HR 0.91 (ITT); circulating tumor DNA (ctDNA)-positive OS HR 0.59 JAVELIN Bladder 100 Switch-maintenance 700 Avelumab Best supportive care (BSC) OS (overall and PD-L1+) OS HR 0.69; PD-L1+ OS HR 0.56 HCRN GU14-182 (phase II) Switch-maintenance 108 Pembrolizumab Placebo Progression-free survival (PFS) PFS HR 0.65; median OS 22.0 vs 18.7 mo

Single-cell transcriptomic investigation of the cell-of-origin and oncogenic pathways across variant histologies of renal cell carcinoma.

552 Background: RCC has multiple distinct molecular and histological subtypes. Prior studies suggest that clear cell RCC (ccRCC) and papillary RCC (pRCC) originate from the proximal tubule (PT), while chromophobe RCC (chRCC) arises from the distal tubule/collecting duct. Cell-of-origin (COI) analysis provides insight into lineage-specific dependencies and signaling pathways, which can uncover novel therapeutic targets. Using a single-cell RNA sequencing (scRNA-seq) dataset, we conducted COI, differential gene expression and signaling pathway analysis in multiple RCC subtypes. Methods: ccRCC, pRCC, chRCC and unclassified RCC (uRCC) samples were analyzed via scRNA-seq. A normal kidney scRNA-seq reference was used from the KPMP (V1.5). A logistic regression model was trained using KPMP epithelial clusters with a previously described gene set (Labaki, et.al. JCO, 2025). This model was applied to tumor clusters to quantify the probability of similarity to normal epithelial clusters. Differential gene and pathway enrichment analysis was conducted on tumor clusters and the most similar epithelial cluster. Results: 84,362 tumor cells from 28 RCC tumors were identified (chRCC = 5 patients, 35,897 cells; pRCC = 3, 929; ccRCC = 14, 18,418; uRCC = 4, 29,119). The reference dataset included 171,390 normal epithelial cells annotated into major nephron cell types. Applying the COI model, ccRCC and pRCC tumor clusters demonstrated the greatest similarity to PT cells (probability (prob)-0.63 and 0.83, respectively). In contrast, chRCC most resembled α-intercalated cells (ICA) (prob-0.88). uRCC tumors had interpatient heterogeneity, with one patient (uRCC-1) resembling ICA (prob-0.75) and three patients (uRCC-2) resembling PT (prob-0.58). Comparing tumor cell clusters with their COI revealed that chRCC and uRCC-1 shared several upregulated oncogenic pathways (mTOR and MAPK), and 305 upregulated genes, including NUPR1, KLK1/4, IGF1, and IRS2 . pRCC demonstrated enrichment of IL-15 signaling and antigen processing/presentation pathways, with upregulation of HLA-A, -B, -C, -E, and -F . ccRCC and uRCC-2 exhibited high transcriptional similarity, with 812 shared differentially expressed genes. Both subtypes showed upregulation of glycolytic programs and glycolytic genes ( SLC2A1 and HK1) , accompanied by downregulation of fatty acid metabolism. Conclusions: COI analysis in our pan-RCC scRNA-seq dataset confirmed distinct COIs for RCC subtypes and aided in classifying uRCC relative to other histologies. Subtype-specific pathway upregulation included mTOR signaling in chRCC/uRCC-1 and antigen-presentation in pRCC, supporting the potential for mTOR-targeted and immunotherapy approaches in these subtypes. These findings underscore the utility of COI-based approaches for refining RCC classification and uncovering therapeutic vulnerabilities.

Effect of maximal transurethral resection before neoadjuvant chemotherapy on pathological response and survival in patients undergoing radical cystectomy for muscle-invasive bladder cancer: A multicenter retrospective study.

777 Background: Bladder-preserving trimodal therapy, which combines maximal transurethral resection (TUR) and concurrent chemoradiation, is recognized as a promising alternative for treating muscle-invasive bladder cancer (MIBC). However, the impact of maximal TUR—defined as visually complete tumor resection—performed prior to neoadjuvant chemotherapy (NAC) on oncological outcomes in patients undergoing radical cystectomy (RC) remains unclear. Methods: This multicenter retrospective study included 550 patients with MIBC who received 2–4 cycles of NAC followed by RC. Patients were divided into two groups: those who underwent maximal TUR prior to NAC (maximal TUR group) and those who did not (control group). Rates of pathological downstaging, <ypT2, and ypT0 were compared between the two groups. Multivariable Cox proportional hazards regression analysis was used to evaluate the effect of maximal TUR on recurrence-free survival (RFS). Results: The median age and follow-up duration were 69 years and 54 months, respectively. The maximal TUR group showed significantly higher rates of downstaging (76% vs. 61%, P < 0.001), <ypT2 (73% vs. 39%, P < 0.001), and ypT0 (46% vs. 15%, P < 0.001) compared to the control group. RFS was significantly longer in the maximal TUR group ( P < 0.001). After adjusting for confounding variables, maximal TUR remained significantly associated with improved RFS ( P = 0.032; hazard ratio: 0.616; 95% confidence interval: 0.396–0.958). Subgroup analyses demonstrated that the survival benefit of maximal TUR was consistent across both <cT3 and cN0 ( P = 0.001) and ≥cT3 and/or ≥cN1 ( P = 0.014) subgroups. Cancer-specific survival and overall survival were also significantly longer in the maximal TUR group ( P < 0.001 and P = 0.004, respectively). Conclusions: Maximal TUR prior to NAC may contribute to improved oncological outcomes in patients undergoing RC for MIBC. Multivariable analysis for RFS. Factor P value HR 95% CI Performance status Continuous 0.064 1.482 0.977–2.250 Histological type Pure UC 0.828 1.048 0.684–1.606 Tumor grade Grade 3 0.346 0.802 0.507–1.268 Pathological T stage ≥ pT3 0.013 1.723 1.121–2.649 LVI Positive <0.001 2.945 1.875–4.625 Pathological N stage ≥ pN1 0.009 1.760 1.154–2.684 Surgical margin Positive 0.380 1.334 0.701–2.538 Urinary diversion Neobladder 0.006 0.615 0.434–0.871 Maximal TUR Performed 0.032 0.616 0.396–0.958

Predictive role of peripheral blood erythroblasts for treatment intensification in metastatic hormone-sensitive prostate cancer.

65 Background: Androgen deprivation therapy (ADT) combined with an androgen receptor pathway inhibitor (ARPI) represents the standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). However, no consensus exists regarding which patients benefit from treatment intensification with docetaxel (triplet therapy). Circulating erythroblasts, a marker of bone marrow infiltration, represent a widely available yet unvalidated biomarker for treatment guidance. We investigated the predictive value of baseline erythroblasts in selecting mHSPC patients for triplet therapy. Methods: This multicenter retrospective study included patients treated between 2022 and 2024 for high-volume mHSPC according to CHAARTED criteria who received either doublet (ADT+ARPI) or triplet (docetaxel+ADT+ARPI) therapy. The primary endpoint was 2-year progression-free survival (PFS), defined as time from treatment initiation to clinical or radiological progression, initiation of new systemic therapy, or death from any cause. Cardinality matching at a 2:1 ratio was performed to balance potential confounding variables. Results: A total of 234 patients were included (141 triplet, 93 doublet). After matching, 122 patients remained in the triplet group and 61 in the doublet group. With median follow-up of 23.5 months for the triplet group and 33.9 months for the doublet group, 2-year PFS rates were 71.9% and 57.8%, respectively (HR 0.62, 95% CI 0.40-0.95, p=0.027). Subgroup analysis demonstrated significantly greater survival benefit from triplet therapy in patients with detectable baseline erythroblasts (PFS: HR 0.29, 95% CI 0.11-0.76; OS: HR 0.24, 95% CI 0.07-0.77) compared to those without erythroblasts (PFS: HR 0.66, 95% CI 0.37-1.19; OS: HR 0.52, 95% CI 0.26-1.06). Conclusions: The baseline presence of circulating erythroblasts serves as a strong predictive marker for benefit from docetaxel intensification in patients with high-volume mHSPC. This readily available biomarker may guide patient selection for triplet therapy, pending prospective validation.

Chemomechanical Origin of Morphological Disparity in Lithium Metal Electrodeposition

ABSTRACT The morphology of electrochemically deposited lithium (Li) critically governs the cycling stability and safety of Li metal batteries, yet the underlying controlling factors remain poorly understood. Even within the same coin cell, Li deposits can exhibit strikingly different morphologies, for example, sparse whiskers coexisting with particle‐like deposits, indicting strong local variations in growth conditions. By combining cryogenic transmission electron microscopy with phase‐field modeling, here we identify the root cause of this disparity. We reveal that the morphological divergence originates from the variations in structure and chemical composition of the initial SEI layer formed on the copper (Cu) substrate. Solvent‐derived organic SEI favors whisker growth, whereas salt‐derived SEI promotes particle formation. This study establishes a direct mechanistic link between SEI chemomechanical properties and Li morphology, providing design principles for tailoring SEI layers to control Li deposition.

In Situ Synchrotron Radiation and Neutron Diffraction Reveal A‐Site Substitution Pathways and Structural Reconstruction in Mo ₂ Ga ₂ C MAX‐Like Phase

ABSTRACT Layered MAX‐like carbides, which integrate metallic and ceramic characteristics, hold great promise for applications in harsh environments, yet the atomic‐scale mechanisms of A‐site substitution remain insufficiently understood. Here, we synthesize a heterostructured MAX phase through Lewis molten‐salt treatment of Mo 2 Ga 2 C, a 221‐type layered precursor. Rietveld refinements of X‐ray diffraction (XRD) and neutron diffraction data, along with high‐resolution scanning transmission electron microscopy and energy‐dispersive X‐ray mapping, reveal that the hetero‐MAX phase consists of Mo 2 SnC and Mo 2 Ga 0.5 Sn 0.5 C (molar ratio 1:2.72). In situ synchrotron radiation XRD uncovers a multi‐step A‐site substitution pathway involving intermediate Mo 2 (Ga x Sn 1−x ) 2 C phases and a transformation from double to single A‐layers. Density functional theory calculations confirm the thermodynamic stability and formation mechanism of the final structure. The Ga‐to‐Sn substitution drives A‐site reconstruction and local chemical optimization, resulting in significantly improved corrosion resistance in acidic, alkaline, and saline solutions. This work reveals previously unrecognized A‐site dynamics and offers a viable design strategy for chemically robust MAX phases under harsh conditions.

Gangliosides in molecular interactions and cell regulation

Demographic predictors of primary retroperitoneal lymph node dissection (P-RPLND) vs. primary chemotherapy (P-Ch) in the treatment of clinical stage IIA/B (CSIIA/B) non-seminomatous testicular germ cell tumors (NSGCTs).

594 Background: Traditional treatment for CSIIA/B NSGCTs has been primary cisplatin-based chemotherapy (P-Ch) or primary RPLND (P-RPLND). However, P-Ch may have long term sequela including ototoxicity, peripheral neuropathy, pulmonary fibrosis, decreased fertility, and secondary malignancies. Recent studies have reintroduced P-RPLND as an alternative to P-Ch to minimize long-term toxicity without negatively impacting oncologic outcomes. This study aims to characterize non-clinical factors influencing the decision between P-Ch and P-RPLND for patients with CSIIA/B NSGCT and the overall survival (OS) associated with these modalities. Methods: The National Cancer Database (NCDB) was queried to identify patients with CSIIA/B NSGCT diagnosed 2004-2021. Patients were classified as having received P-Ch or P-RPLND based on date fields. Demographic differences were determined using chi-squared analysis. Odds ratios were calculated using multivariate binomial logistic regression, and OS was assessed using multivariate Cox regression while controlling for age, clinical stage, comorbidities, income, and housing status. Results: 5,514 patients (mean age 30.3 years, 81.6% white, 73.5% privately insured) were included. A total of 4,017 (74.2%) patients received P-Ch while 1,163 (25.8%) underwent P-RPLND. Patients insured with Medicaid and those in the lowest education quartile were significantly less likely to undergo P-RPLND (OR: 0.76, 95% CI: 0.70-0.83, p = 0.007; OR: 0.77, 95% CI: 0.63-0.95, p = 0.02). Patients with higher disease stage (CSIIB vs. CSIIA) and LVI+ at orchiectomy were less likely to undergo P-RPLND (OR: 0.59, 95% CI: 0.52-0.67, p < 0.001; OR: 0.79 95% CI: 0.69-0.91, p = 0.002). Of the entire cohort, the P-Ch group had 235 deaths (5.9%) while 1,397 underwent P-RPLND with 57 deaths (4.0%). Conclusions: Patients with lower socioeconomic status (SES) such as Medicaid insurance and those with lower levels of education are significantly less likely to undergo P-RPLND for CSIIA/B NSGCTs. While P-RPLND remains an extremely effective treatment modality in select patients, those with lower SES disproportionately receive chemotherapy as initial treatment.

miR-371a-3p as a potential biomarker for monitoring disease activity and therapeutic response in metastatic seminoma and non-seminomatous germ cell tumor patients treated with BEP chemotherapy.

616 Background: MicroRNA 371 (miR-371a-3p) is a promising biomarker for germ cell tumors. Its expression in blood may provide a non-invasive method for monitoring disease activity and treatment response. The aim of this study was to analyze miRNA-371 levels before and after BEP-chemotherapy (bleomycin, etoposide, cisplatin) in patients with metastatic seminoma and non-seminomatous germ cell tumor (NSGCT). Methods: A retrospective analysis of miR-371a-3p expression was performed in patients who received systemic BEP chemotherapy between 2022 and 2025. miRNA expression levels were quantified from serum samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Crossing point (Cp) values were determined for each sample and converted into relative quantification (RQ) values using the ΔΔCp method. The dynamics of miRNA levels and their correlation with clinical response were evaluated. RQ levels <5 were considered negative, and >10 were considered positive. Results: MiRNA-371 levels were significantly higher before chemotherapy than after treatment (median 138.6 vs 4.19; p=0.0010) in patients with seminoma. In 7 of 11 patients, the levels dropped to undetectable, and in two patients to the indeterminate range. Two patients showed persistently positive miRNA-371 levels after chemotherapy despite radiological regression; they developed early relapse. In patients with intermediate measurements during chemotherapy (e.g. after 2 of the 3 cycles), a statistical significant (p=0.0078) decrease was also observed, although most values remained positive (median 445.5 vs 11.71). In the NSGCT cohort, data were available from before treatment and the admission day of the third treatment cycle. miR-371a-3p levels declined significantly (p = 0.0156) after two cycles of BEP. However, most patients remained positive. Pre-chemotherapy miRNA-371 levels correlated significantly with initial tumor size (Spearman r = 0,8239, p = 0.0001), while post-chemotherapy levels showed no correlation with residual tumor size (Spearman r = -0.01425, p = 0.9645). Conclusions: MiRNA-371 levels decrease significantly after PEB chemotherapy in patients with seminoma and non-seminomatous germ cell tumor. Our findings support the role of miRNA-371 as a potential biomarker for monitoring disease activity and treatment response in germ cell tumors.

RNA based liquid biopsy testing of urine to predict pathological complete response to radiomolecular instillation NAC therapy before surgery: The Bladder BRIDGister experience.

643 Background: Patients with MIBC achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NACT) have improved prognosis. While gene expression profiles from tumor tissues are predictive of response, so far no expression profiling of tumor cells in urine is established to detect tumor cells or monitor response towards ongoing treatment. However, tumor specific gene expression in urine samples may enable non-invasive testing and may distinguish responding from non-responding tumors for early treatment adoption / intensification at each neaoadjuvant treatment cycle. Methods: Tumor cells were isolated from 10 ml urine collected before TUR biopsy and before each cycle of treatment as well as before deep TURB or cystectomy. Similiarly whole urine was drawn before and at each cycle. FFPE tissues as well as matched urine samples from 12 patients receiving systemic chemotherapy +/- intravesical Radioligandtherapy were prospectively collected, RNA extracted, and relative gene expression subtyping markers and targets were analysed by RT-qPCR.Dynamics of urine expression profiles were compared to treatment time point and pathological outcome. Results: RNA expression profiling of matched TUR biopsy tissue and by filtering tumor cells from urine samples allowed robust detection of molecular marker profiles identical to matched tissue profiles. The high dynamic range of KRT5 and KRT20 mRNA allowed detection of 100 tumor cells per 10 ml urine and enabled molecular subtyping into luminal and non luminal subtypes. Interestingly, while non luminal tumors with high KRT5 mRNA expression predicted to not respond to chemotherapy exhibited no KRT5 mRNA decline at sequential time points before each neoadjuvant chemotherapy, the addition of Lu 177 based radioligand therapy broke chemotherapy resistance and resulted in stepwise drop of KRT5 mRNA at each therapy cycle. Fast decline of KRT mRNA expression indicated complete response towards combination therapy already within the first 6 weeks. Conclusions: The results contribute to our findings of treatment efficacy of radioligand instillation therapies in otherwise chemotherapy resistant tumors. Moreover, by comparing gene expression profiles from urine samples before and before each cycle of therapy the response could be recapitulated and detected already after one week of monotherapy radioligand treatment. This suggests that expression profiling from urine samples is feasible andallows non invasive prediction of treatment outcome, which will be further analyzed in upcoming phase I/II intravesical radioligand therapy trials of the Bladder BRIDGister clinical trial group.

Real-world comparative effectiveness of novel doublet therapies for metastatic hormone-sensitive prostate cancer.

70 Background: Metastatic hormone-sensitive prostate cancer (mHSPC) is an advanced form of prostate cancer with a 5-year survival below 40%. Treatment guidelines recommend androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPIs), docetaxel, or both. However, no head-to-head randomized trials have compared available doublet therapies, and real-world evidence remains limited. This study evaluated the real-world comparative effectiveness of ADT-based doublet regimens. Methods: Using the Komodo Health Claims Database, we identified US men aged ≥18 years with mHSPC who initiated ADT within 4 months of diagnosis. Eligible patients received index treatment with abiraterone, apalutamide, enzalutamide, or docetaxel within 4 months of ADT initiation between January 2019 and December 2023, with follow-up through June 6, 2025. Patients receiving triplet therapy, multiple index treatments, or with other cancer types were excluded. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Progression was defined as time from index treatment date to metastatic castration-resistant prostate cancer (mCRPC), based on treatment initiation and hormone-resistance diagnosis code. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals using overlapping propensity score weights generated from machine learning-based generalized boosted models for confounding adjustment. Results: This study included 9,141 US men with mHSPC (abiraterone + ADT = 3,968; apalutamide + ADT = 1,096; enzalutamide + ADT = 1,902; docetaxel + ADT = 2,175). Each ADT-based ARPI doublet (abiraterone, apalutamide, and enzalutamide) demonstrated superior PFS compared to docetaxel + ADT, primarily due to prolonged time to mCRPC progression. However, no significant differences in PFS were detected among the three ARPI regimens. For OS, no significant differences were observed between any ARPI doublet and docetaxel + ADT, nor within the ARPI regimens. Full survival results are shown in Table 1. Conclusions: Real-world evidence shows superior PFS with each ARPI + ADT regime versus docetaxel + ADT for mHSPC, with comparable OS. Given similar survival outcomes among ARPI doublets, treatment selection may be guided by cost, toxicity profiles, and patient-specific factors. PFS and OS adjusted hazard ratios (aHR). Treatment Comparator PFS: aHR (95% CI) OS: aHR (95% CI) ABI + ADT DOC + ADT 0.55 (0.49 – 0.62) * 0.99 (0.86 – 1.14) APA + ADT DOC + ADT 0.59 (0.54 – 0.65) * 0.91 (0.75 – 1.11) ENZ + ADT DOC + ADT 0.59 (0.51 – 0.67) * 0.88 (0.75 – 1.04) APA + ADT ABI + ADT 0.99 (0.88 – 1.12) 0.92 (0.77 – 1.10) ENZ + ADT ABI + ADT 0.93 (0.84 – 1.03) 0.89 (0.78 – 1.03) APA + ADT ENZ + ADT 1.07 (0.93 – 1.22) 1.03 (0.85 – 1.25) ABI: abiraterone, ADT: androgen deprivation therapy, APA: apalutamide, DOC: docetaxel, ENZ: enzalutamide. *Significant findings.

100‐Fold Scaling‐Up, Gram‐Level and Direct Ambient Synthesis of Perovskite Quantum Dots with High Batch Consistency

ABSTRACT Perovskite quantum dots (PQDs) show promising potential in the optoelectronic field, but their commercial application is limited by the scalability in laboratory scale and complicated synthesis in an inert atmosphere, especially in I‐based red‐emission PQDs. The PQDs are disturbed by the performance decrease in the scalable synthesis caused by the trap states from weakly‐bonded ligand loss and uneven nucleation/growth from the complicated injection process. Here, a 100‐fold scalable (800 mL) and gram‐level (2.19 g) synthesis of CsPbI 3 pure‐red PQDs is achieved in ambient air. This is realized by a strongly‐coordinated dual‐ligand strategy with phosphorus‐oxygen groups to interact strongly with Pb 2+ and protect PQDs from moisture/oxygen, ensuring the ambient air scalable synthesis. The 100‐fold scaled‐up PQDs show no significant emission shift or broadening (ΔPL = 0.7 nm, ΔFWHM = 0.8 nm) and remain over 80% PLQY. Also, pure‐red light‐emitting diode (LED) based on the scalable PQDs reserves 86.3% EQE of LEDs based on small‐scale PQDs, showing the excellent batch consistency and commercial potential of PQDs.

Robust Sustainable Biomass Fluorescent Wood for Heavy Metal Removal and Solar Water Purification

ABSTRACT Heavy metal contamination in aquatic environments represents a severe threat to global ecological security. While conventional method such as fluorescent probes, have been investigated for detection purposes, their real‐world deployment remains hampered by inherent drawbacks such as limited sensitivity and poor reusability. Herein, we introduce a “living” composite material, fabricated by incorporating ratiometric fluorescent metal–organic frameworks (MOFs) into the natural microchannels of wood, setting a new benchmark for environmental remediation. Specifically, ZIF‐8‐hybridized fluorescent carbon dots (DRZ‐CDs) were firmly immobilized onto a delignified wood (DW) matrix through electrostatic interactions and chelation, resulting in a bifunctional material (DRZ‐CDs‐DW). The composite exhibits good performance, with an exceptional Cu 2+ adsorption capacity of 298.72 mg/g and a low detection limit of 2.3 nM. Going beyond high removal efficiency, we further demonstrate a transformative “waste‐to‐resource” strategy, in which the exhausted adsorbent (DRZ‐CDs‐DW+Cu 2+ ) is transformed via in situ sulfidation into a photothermal evaporator (DRZ‐CDs‐DW‐CuS). The resulting system achieves an evaporation rate of 3.54 kg·m −2 ·h −1 , generating purified water, and is suitable for practical uses such as plant irrigation. In summary, by effectively merging fluorescent carbon dot (CDs) functionalization, wood structural engineering, and solar‐driven interfacial evaporation, this work realizes a synergistic combination of environmental cleanup and resource upcycling.

Signal peptide peptidase– and SPP-like 3–dependent shedding of α1,6-fucosyltransferase differentially affects core fucosylation

Fruquintinib combined with everolimus in Chinese patients with advanced/metastatic clear cell renal cell carcinoma (ccRCC) after progression on immune checkpoint inhibitors (ICIs): Results from a phase II single arm clinical trial.

497 Background: Patients with clear cell renal cell carcinoma (ccRCC) progressing after immune checkpoint inhibitors (ICIs) therapy have limited therapeutic options. The combination of everolimus with VEGFR-TKIs has been recognized as a promising second-line therapeutic strategy. Fruquintinib (Fru, a selective VEGFR inhibitor) has demonstrated promising antitumor activity in patients with treated ccRCC. We conducted a phase II study (NCT06317298) aimed to evaluate the combination of fruquintinib and everolimus (Eve) in ccRCC patients who experienced disease progression following prior ICI-containing therapy. Methods: Pts with histologically confirmed ccRCC who had disease progression after combination therapy with an ICI plus a TKI were eligible. In the dose-establishing phase, based on a standard 3+3 design, pts were treated with Fru (3 mg, 4 mg, 5 mg; starting from 4 mg) once daily (QD) on d1-21 plus Eve 5 mg QD, at 4-week cycles, until intolerable toxicity, disease progression, or patient withdrawal. This analysis was designed to conduct before dose-expansion phase, on which pts would receive the combination of Fru+Eve at the dose regimen established during the dose-establishing phase. The primary endpoints were determination of the MTD and objective response rate (ORR) as assessed by RECIST 1.1 criteria. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), and safety. Results: Nine pts were enrolled in the dose-establishing phase. Median age was 54 (41-71) years and all pts were male and all received at least one line of TKIs and ICI. Seven pts were classified as having intermediate/high-risk disease according to the IMDC criteria. At the data cut-off date (September 30th, 2025), 4 pts remained on study treatment. No DLTs were observed during the evaluation period. All pts experienced at least one treatment-related adverse event (TRAE) of any grade, with hypertension (9/9, 100%), mucositis (4/9, 44.4%) and fatigue (3/9, 33.3%) being the most frequently observed. All TRAEs were grade 1~2 except 1 patient with grade 3 diarrhea. 2 patients temporarily interrupted for reversible grade 2 interstitial lung disease due to Eve. No serious adverse events, TRAEs leading to permanent drug discontinuation, or death were reported. Of all 9 pts, the confirmed ORR was 66.7% (95% CI: 29.9-92.5) and the confirmed DCR was 77.8% (95%CI: 40.0-97.2). At a median follow-up of 12.0 (95% CI: 5.0-not estimable) months, the median PFS was 10.0 (95% CI: 2.0-13.0) months. Conclusions: Preliminary data showed promising antitumor activity of Fru at 5mg QD 3 weeks-on/1 week-off plus Eve 5mgQD in patients with ICI-pretreated ccRCC. The safety profile of fruquintinib combined with everolimus were tolerable and manageable. Clinical trial information: NCT06317298 .

Integrative genomic landscape of germline exome alterations in renal cell carcinoma, unclassified with medullary phenotype.

524 Background: SMARCB1-deficient Renal Medullary Carcinoma (RMC) is a rare non-clear cell renal cell carcinoma predominantly affecting children and young adults of African descent with sickle hemoglobinopathies, most commonly sickle cell trait due to germline mutations in the HBB gene. SMARCB1-deficient renal cell carcinoma, unclassified with medullary phenotype (RCCU-MP) is a rare RMC subtype not associated with sickle hemoglobinopathies. Aside from confirming sickle hemoglobinopathies, germline testing is not established for RMC or RCCU-MP, and RCCU-MP germline risk factors are unknown. We herein report the largest assembled series of RMC and RCCU-MP germline profiles reported to date. Methods: We retrospectively analyzed germline whole-exome sequencing (WES) from patients with RCCU-MP (n = 11), RMC (n = 23), clear-cell RCC (ccRCC; n = 12), and chromophobe RCC (chRCC; n = 11). HBB sickle hemoglobinopathy gene mutations served as internal controls for RMC. To mitigate ancestry confounding, we compared findings with independent cohorts of African American patients with RCC (n = 11), prostate (n = 7), and urothelial carcinomas(n = 5). Clinical and demographic variables were abstracted from the electronic medical record. Associations between genomic features and clinicodemographic variables were evaluated. Survival analyses were performed using Kaplan-Meier methodology and Cox proportional hazards models. Results: Patients with both RCCU-MP and RMC were young (median age 35 and 28 years, respectively) and enriched for advanced stage at testing. Median overall survival (OS) was shortest for RMC (1.7 years), followed by RCCU-MP (1.8), chRCC (2.9), and ccRCC (4.7). Global germline mutational burden showed no tumor-type–specific enrichment. However, RCCU-MP demonstrated a distinct excess of homologous recombination repair (HRR) pathway protein truncating variants (PTVs), most notably in ATM and RAD50, versus RMC, ccRCC, and chRCC. In contrast, RMC showed the expected enrichment of HBB. No additional hemoglobinopathy-related germline variants beyond HBB were identified in any group. Conclusions: Germline HRR-pathway disruption is enriched in SMARCB1-deficient RCCU-MP lacking sickle hemoglobinopathies, whereas canonical RMC remains defined by HBB variants without broader hemoglobinopathy signals. These data support targeted referral to genetics and incorporation of HRR testing in RCCU-MP work-ups, and motivate mechanistic and therapeutic studies of DNA-damage response biology in this medullary phenotype.

The GAIN trial: Gemcitabine alternating with intravesical BCG randomized against BCG alone for patients with recurrent “BCG-exposed” high-grade non-muscle invasive bladder cancer (NMIBC) (ALLIANCE A032303).

TPS909 Background: BCG-Exposed NMIBC (a high grade recurrence within 24 months of prior BCG, but not meeting “unresponsive” criteria) is a large patient population with a critical need for more effective treatment strategies that prevent the development of BCG unresponsive disease/progression. The current standard of care is re-treatment with BCG alone, but only ~50% of patients derive clinical benefit. While intravesical gemcitabine (with or without docetaxel) is sometimes used, multiple retrospective studies have found that GemDoce is no better than re-treatment with BCG alone for patients with BCG-exposed NMIBC. A chemoimmunotherapy strategy of intravesical Gemcitabine with BCG (GemBCG) combines the two most effective, inexpensive, and commonly used treatments for NMIBC. Based on compelling biologic rationale and preclinical data, a phase I/II (n=52) trial was initiated of GemBCG in BCG-exposed NMIBC (NCT04179162). GemBCG has minimal side effects (3.8% [2/52] with Grade 3 TRAEs (no grade 4/5 seen) with similar side effects and tolerability to BCG alone. GemBCG has a outstanding early efficacy signal (6-month complete response of 97% [28/29] in patients with CIS, compared to ~50% 6-month complete response w/ BCG alone for BCG exposed CIS). GemBCG has promising preliminary longer term efficacy (18-month HG-RFS of 76% compared to ~45-55% reported with BCG alone, GemDoce, and recombinant BCG in BCG exposed NMIBC). Correlative studies support the hypothesis that the addition of gemcitabine to BCG can favorably modulate the tumor immune microenvironment. Methods: Based on the above rationale, we initiated the “GAIN” trial (A032303/ NCT07000084), a prospective, multicenter, open-label phase III study for patients with BCG-exposed NMIBC randomized to either: re-treatment with BCG only (Arm A, SOC) or Gemcitabine + BCG (GemBCG, Arm B). BCG-exposed NMIBC is defined as a high grade NMIBC (Ta, T1, Tis/CIS) that has recurred within 24 months of prior BCG, but NOT otherwise currently meeting BCG unresponsive NMIBC. The primary objective is to compare high grade recurrence-free survival (HG-RFS) between the two treatment arms. Notable aspects of the trial include: (1) the reduced burden on investigators and research teams due to the NCI’s new streamlined data initiative, (2) liberal inclusion/exclusion criteria and pragmatic design to improve generalizability of results, and (3) Cystoscopic biopsies/TURBT at week 13/month 3 for all participants (both CIS and “papillary only”) for multiple reasons including to allow for earlier detection of BCG unresponsive disease for patient safety, increased rigor of the trial, and objectively evaluate urinary biomarkers/urinary tumor DNA. Clinical trial information: NCT04179162 .

Phase 2 expansion study of ²¹² Pb-ADVC001 in metastatic prostate cancer: The TheraPb trial.

TPS280 Background: 212 Pb-ADVC001 (ADVC001) is an alpha-emitting PSMA-targeting radioligand therapy (RLT) designed to deliver radiation at a cellular level. ADVC001 demonstrated favorable safety and promising anti-tumor activity in participants with PSMA-avid metastatic castration-resistant prostate cancer (mCRPC) enrolled in the TheraPb Phase 1b dose escalation (NCT05720130). There were no dose-limiting toxicities in Phase 1b, the maximum tolerated dose was not reached and dosimetry and pharmacokinetic (PK) studies supported proceeding to Phase 2 expansion to further evaluate the therapeutic efficacy and safety of 2 recommended dose levels of ADVC001. Methods: TheraPb Phase 2 evaluates ADVC001 using a randomized multi-dose-response design and adaptive dosing strategies to optimize clinical outcomes in three distinct indications in metastatic prostate cancer: Group 1: metastatic hormone-sensitive prostate cancer (mHSPC) with a sub-optimal PSA response defined as PSA ≥ 0.2 ng/mL despite receiving androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPi) without evidence of disease progression. Group 2: progressive mCRPC post ≥ 1 ARPi; 177 Lutetium ( 177 Lu)-PSMA-naïve and not previously treated with chemotherapy for CRPC. Group 3: progressive mCRPC with prior exposure to 177 Lu-PSMA. All participants are randomized 1:1 to receive either 160 or 200 MBq of ADVC001. Each participant receives up to 4 doses of ADVC001 as induction therapy. Additional doses may be administered as maintenance therapy for a total of up to 12 doses. ADVC001 is administered according to an adaptive dosing schedule and rules allowing for a treatment pause (‘treatment holiday’) based on response with the possibility of subsequent therapy restarts. All participants continue ADT throughout the study. Group 1 participants receive ongoing ARPi as per standard of care, and Group 2 participants also are randomized to receive ADVC001 ± concomitant ARPi. The primary objective is to determine the efficacy of ADVC001 utilizing PSA, conventional imaging and PSMA PET/CT. Assessment of tumor response is undertaken by a blinded independent central review in accordance with the Response Evaluation Criteria in Solid Tumours (RECIST v1.1) and the Prostate Cancer Clinical Trials Working Group. Secondary objectives are to assess safety including late radiation adverse events of special interest, tolerability, dosimetry and PK. Exploratory objectives are to evaluate quality of life, biomarkers and predictors for response and toxicity, and exploratory imaging. Participants are followed for up to 5 years. The TheraPb study is active at 3 clinical sites and will enroll up to 100 participants. Clinical trial information: NCT05720130 .

Strain‐Induced Detectivity Enhancement in Intrinsically Stretchable Organic Photodetectors

ABSTRACT Intrinsically stretchable organic photodetectors (IS‐OPDs) are essential for next‐generation wearable electronics requiring both mechanical durability and reliable optical sensing. However, current performance of IS‐OPDs degrades under tensile strain due to inherent trade‐offs between mechanical and optoelectronic properties in photoactive layers. Here, we report the development of the IS‐OPD that exhibits strain‐induced detectivity ( D ) enhancement, enabled by designing mechanically robust and efficient bilayer‐type photoactive architecture (EBL‐D). Specifically, we incorporate percolated polymer donor ( P D ):elastomer networks at the bottom layer, which simultaneously offer excellent stretchability and efficient charge transport. Subsequently, we deposit a small‐molecule acceptor layer atop the P D :elastomer layer, expanding the optical absorption range into the near‐infrared region while minimizing undesirable charge recombination. The resulting IS‐OPD based on the EBL‐D architecture maintains high responsivity and effectively suppresses dark current under strain. Consequently, the device exhibits 1.5‐fold improvement in specific detectivity from 1.9 × 10 13 to 2.8 × 10 13 Jones at λ = 860 nm under 75% strain, corresponding to a 1.3‐fold increase in D after accounting for the enlarged photoactive area. To the best of our knowledge, this work is the first to experimentally demonstrate strain‐induced D enhancement in stretchable OPDs.