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High‐Throughput Chirality Identification of Chiral Fermion Enantiomers by Ultrafast Terahertz Emission Spectroscopy

ABSTRACT Topological chiral semimetals possess nondegenerate chiral fermions dominated by large Chern numbers, making them an ideal material platform for quantum control of chirality degree of freedom. However, high‐throughput chirality identification of a chiral enantiomer, which is the first and foremost basic characterization, is still lacking. In this work, we demonstrate that terahertz (THz) emission from ultrafast excited circular photogalvanic effects can be used to effectively identify the chirality of topological chiral semimetal. As demonstrated for the topological chiral semimetal RhSn, the emitted THz electric fields excited by certain circularly polarized ultrafast light pulses are reversed for the opposite enantiomer. By comparing the single‐crystal X‐ray diffraction results, we show that THz emission serves as a high‐throughput, contactless, and nondestructive method for identifying the chirality of topological chiral semimetals. Our findings will facilitate and thus promote the study of topological chiral semimetals and further advance the quantum manipulation of the chirality degree of freedom in topological materials.

Archeo‐Inspiration from the Cultural History of Glass: Historic Accounts, Anecdotes and Hard Facts as Challenges to Modern Material Science

Abstract Since its earliest developments, glass has held a unique place in cultural history. Remarkably, many surviving glass artefacts from premodern times still surpass some of today's standard processing techniques, with effects and qualities that feel strikingly contemporary. Valued for its optical purity, chemical and thermal resistance, hardness, and fragile beauty, glass has long captivated both artists and craftsmen. This paper proposes examining glasses within their cultural contexts as a source of inspiration for modern materials science. Throughout history, glass has held societal and symbolic significance, with diverse cultural accounts detailing its properties and uses. While not all historical records describe glass with scientific accuracy, many offer imaginative perspectives that can inform new developments. Just as fields like bionics and biomimetics look to nature for innovation, a culturally reflective scientific approach is suggested to glass material science, a concept “Archeo‐Inspiration” is termed. This concept draws from the material knowledge and creative uses of past societies to inspire future advancements in glass technology and material systems. The aim is to move beyond purely technical evaluation by reconnecting with the rich heritage of glassmaking within its cultural and historical framework. In doing so, the hope is to offer both a retrospective appreciation and a forward‐looking vision for material systems in the 21st century, grounded in the enduring legacy of one of humanity's most versatile and symbolically charged materials.

Fixed low-dose nab-paclitaxel with tislelizumab in non-metastatic bladder cancer: A post-hoc analysis of dose expose in TRUCE-01 and TRUCE-02 trials.

768 Background: Although PD-1 immune checkpoint inhibitors (PD-1 ICIs) show efficacy in bladder cancer, exploring effective immunomodulatory strategies remains necessary. Nab-paclitaxel has demonstrated immunomodulatory properties that may enhance the effectiveness of PD-1 ICIs. Herein, we conducted a post-hoc analysis of two phase II trials conducted in our centre to evaluate whether body surface area (BSA)–adjusted exposure to fixed low-dose nab-paclitaxel affects efficacy or safety when combined with tislelizumab, a type of PD-1 ICIs. Methods: Patients (pts) with non-metastatic muscle-invasive bladder cancer (MIBC) or very high-risk non-muscle-invasive bladder cancer (NMIBC) from the TRUCE-01 (NCT04730219) and TRUCE-02 (NCT04730232) trials were included. All pts received ≥3 cycles of tislelizumab (200 mg iv Q3W) plus fixed-dose nab-paclitaxel (200 mg iv Q3W). The nab-paclitaxel dose per m² (NP-DPM) was calculated as 200 mg divided by BSA (Mosteller formula). Pts were grouped by NP-DPM tertiles: low ( < 102 mg/m²), medium (102–117 mg/m²), and high ( > 117 mg/m²). The primary endpoint was complete response (CR, defined as no residual tumor on pathology). Secondary endpoints included overall survival (OS), metastasis-free survival (MFS), cancer-specific survival (CSS) and nab-paclitaxel–related adverse events (NPRAEs). Results: Of 106 evaluable patients we finally included, the median NP-DPM was 106 mg/m² (IQR 102–117). The CR rates were 63.0%, 56.6%, and 57.7% in the low-, medium-, and high-dose groups, respectively (p = 0.902), with no significant differences within MIBC or NMIBC subgroups. At a median follow-up of 34.4 months, no significant differences were observed in OS (p = 0.051), MFS (p = 0.216), or CSS (p = 0.112) among different NP-DPM groups. Peripheral sensory neuropathy was the only NPRAEs that significantly increased with NP-DPM (0% vs 3.8% vs 19.2%, p = 0.009). Other NPRAEs (alopecia, fatigue, cytopenias) did not differ between groups. Conclusions: Fixed low-dose nab-paclitaxel combined with tislelizumab achieved robust and consistent responses across BSA-based exposure groups, with a favourable safety profile. These results support further evaluation of this chemotherapy–immunotherapy combination as a potential treatment strategy for non-metastatic bladder cancer.

A prospective, multi-center, phase Ib/II trial of first-line cadonilimab plus axitinib in advanced non-clear cell renal cell carcinoma.

506 Background: Non-clear cell renal cell carcinoma (nccRCC) is a rare and heterogeneous disease with limited treatment evidence. Patients with nccRCC generally respond less favorably to systemic immunotherapy than those with clear cell RCC. However, current evidence for the treatment of nccRCC remains limited, underscoring the need for new strategies. Cadonilimab, a bispecific PD-1/CTLA-4 antibody, has shown antitumor activity in various solid tumors, but its efficacy in RCC remains unknown. Here, we report initial results from a phase Ib/II trial of cadonilimab plus axitinib in advanced nccRCC. Methods: This open-label, multi-center, single-arm, phase Ib/II trial included patients with metastatic or unresectable treatment-naive nccRCC, regardless of PD-L1 status, to receive cadonilimab plus axitinib 5 mg b.i.d. In phase I, a 3+3 dose-escalation design was adopted, starting at 10 mg/kg Q3W of cadonilimab with axitinib to evaluate safety. In phase II, an additional 31 patients were enrolled at the recommended phase II dose (RP2D). The primary endpoints were safety assessment in phase Ib and objective response rate (ORR) by RECIST v1.1 in phase II. Results: As of October 1, 2025, A total of 37 patients was enrolled (Phase Ib: n=6; Phase II: n=31), with a median follow-up duration of 14.4 months. In phase Ib, No DLTs were observed. AEs were reported in 100.0% (6/6) of cases. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 66.7% (4/6) of cases, including proteinuria, hypertriglyceridemia, myasthenia gravis, diarrhea and alanine aminotransferase increased. The RP2D for cadolinimab was 10 mg/kg. For secondary endpoints, ORR was 50% (2/4) and DCR was 100% (6/6). In phase II, the ORR was 51.6% (16/31). DCR was 96.8% (30/31). AEs were reported in 100.0% of cases. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 58.1% (18/31) of cases. All AEs were expected and manageable. The median PFS was 16.7 (95%CI, 11.8-NR). The median OS was NR at the data cutoff. For the total cohort, the median PFS was 17.3 (95%CI, 12.1-NR). The median OS was NR at the data cutoff. Conclusions: Cadonilimab combined with axitinib demonstrated encouraging efficacy and tolerability as first-line therapy in advanced nccRCC across subtypes in this multi-center phase Ib/II study. Clinical trial information: NCT05808608 . Summary of efficacy analysis and tumor response review per RECIST v1.1. Phase Ib Phase II Total cohort Objective response rate, n(%) 2 (50) 16 (51.6) 18 (51.4%) Disease control rate, n(%) 6 (100) 30 (96.8) 36 (97.2%) mPFS (95%CI) months NR (17.3, NR) 16.7 (11.8-NR) 17.3 (12.1-NR) mOS (95%CI), months NR (NR, NR) NR (NR, NR) NR (NR, NR)

Long-term efficacy and patient experience with neoadjuvant cabozantinib for locally advanced renal cell carcinoma.

511 Background: Our phase 2 trial (NCT04022343) established that neoadjuvant cabozantinib provided clinical benefit in high-risk clear cell renal cell carcinoma (ccRCC) without complicating subsequent nephrectomy and was associated with increased intratumoral CD8+ T-cell infiltration. Here, we report updated long-term survival and analyze its impact on sarcopenia, frailty, and quality of life (QoL). Methods: Seventeen patients with clinical stage ≥T3 ccRCC received cabozantinib (60 mg daily) for 12 weeks, after which they underwent nephrectomy. Overall (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Skeletal muscle index (SMI) was calculated from segmented muscle area at the L3 vertebra level on MRI scans using Slice-O-Matic software. Frailty was scored as a sum of 5 metrics (shrinking, weakness, exhaustion, low activity, slow walking speed). QoL was assessed with the FKSI-19. Changes from baseline were analyzed using the Friedman and Wilcoxon signed-rank tests. Results: At a median follow-up of 57.7 months, the 5-year OS rate was 81.4% and the 5-year DFS rate was 65.7%. There was no significant change in SMI, indicating no treatment-induced muscle loss. While underpowered, sarcopenic patients had a trend toward less favorable tumor response (22% partial response vs 43% in non-sarcopenic; p=0.63). Frailty scores remained low, indicating a non-frail status, with no clinically significant change during treatment (mean 1.18 to 2.06 on a 25-point scale). Mean QoL scores declined from baseline to week 6 (60.0 vs 48.7; p=0.0004), consistent with the therapy's early side-effect profile, but did not decline at week 12. This decline was not associated with survival outcomes. Conclusions: Long-term follow-up demonstrates encouraging survival for high-risk ccRCC patients received neoadjuvant cabozantinib. The regimen is well-tolerated; patients proceeded to surgery without developing frailty or losing vital muscle mass. QoL stabilized after an initial decrease, suggesting patient adaptation to side effects rather than cumulative toxicity, which supports further investigation of this strategy. Clinical trial information: NCT04022343 . Mean FKSI-19 QoL scores (0=worst, 76=best). Timepoint Mean (±SD) Baseline 60.0 (±10.5) Week 6 48.7 (±10.6) Post- Cabozantinib 48.5 (±9.9)

Interim safety analysis of a randomized phase II trial comparing pembrolizumab with radiation versus pembrolizumab, olaparib, and radiation in localized high risk prostate cancer.

362 Background: Preclinical data suggest synergy between immune checkpoint blockade, PARP inhibition, and radiation. This randomized trial evaluates the safety of pembrolizumab (pembro) with standard-of-care (SOC) radiation and androgen deprivation therapy (ADT), with or without olaparib, in high-risk localized prostate cancer. Methods: Patients with NCCN-defined high- or very high-risk localized prostate cancer were randomized to Arm 1 (1 yr pembro + olaparib 200 mg BID + SOC RT/ADT) or Arm 2 (1 yr pembro + SOC RT/ADT). SOC included ADT (18–24 mo) and IMRT to 70 Gy/28 fractions to prostate/seminal vesicles and 47.6 Gy/28 fractions to pelvic nodes. Safety was assessed per CTCAE v5.0. The primary endpoint is PSA nadir ≤0.06 ng/mL within six months after RT; planned sample size is 64. Results: Eighteen patients were enrolled; one withdrew before treatment, leaving 17 who received ≥1 cycle of pembro. Median age was 68 (range, 53–84) and PSA 9.0 ng/mL (range, 1.5–118). Twelve (67%) had Gleason 4–5, 13 (72%) had PSMA PET–positive nodes, and 15 (83%) met very high-risk criteria. Median pembro exposure was 11 cycles (range, 2–17). Fatigue and GI upset occurred in all patients. Renal/urinary AEs were slightly more common in Arm 1 (86% vs 60%), nearly all grade 1–2. Grade ≥3 events were more frequent in Arm 1, mainly labs (71%), cardiac (29%), infections (29%), and respiratory (29%) while labs (60%), and vascular disorders (50%) in Arm 2. Immune-related AEs included rash, fatigue, nausea, anorexia, musculoskeletal pain, and dry mouth; serious events were myositis (G2), colitis (G3), optic neuropathy (G4), and pneumonitis (G5). Two withdrew and two deaths occurred (immune pneumonitis, unrelated sepsis/MI). Steroids were required in 24%, with 12% also needing additional immunosuppression. Conclusions: Pembro with RT/ADT was feasible and generally tolerable. Adding olaparib did not increase high-grade toxicity, though low-grade urinary AEs were more frequent. All serious immune-mediated AEs, including one treatment-related death, were linked to pembro. Due to slow accrual, the trial was amended to a single-arm study of pembro + olaparib + RT (NCT05568550). Clinical trial information: NCT05568550 .

Engineering Asymmetric and Highly Exposed Fe Single‐Atom Nanozymes for siMMP13 Delivery and Ferroptosis Inhibition in Osteoarthritis Therapy

ABSTRACT Ferroptosis, driven by redox imbalance, plays a critical role in osteoarthritis (OA) progression. Although antioxidant nanozymes hold therapeutic potential, designing highly efficient and targeted systems to inhibit ferroptosis remains challenging. Here, we developed a 2D nitrogen‐doped graphene‐like nanomesh (NGM) loaded with asymmetric and highly exposed Fe single atoms, carried with the cartilage‐targeting WYRGRL peptide and siRNA (siMMP13) to form Fe SAzymes (si‐FeSA/NGM‐W) as ferroptosis inhibitors to alleviate OA. By mixed molten salt and Zn removal, exfoliating Zn‐ZIF into an ultrathin 2D hierarchical porous NGM with topological defects and hierarchical structure, we created a scaffold for anchoring asymmetric and highly exposed Fe single atoms. The abundant Fe‐N 4 ‐Cl coordination active sites then introduce strain and defects, which facilitate electron transfer, enhance radical adsorption, and lower reaction barriers, thereby augmenting multi‐enzyme (SOD/CAT/GPx) activities. This enables the functionalized si‐FeSA/NGM‐W to target cartilage, where it inhibits ferroptosis by downregulating MMP13, upregulating GPX4, restoring mitochondrial function, and modulating inflammation, ultimately achieving targeted OA therapy. Mechanistically, this process involves suppression of the IL‐17 pathway and enhancement of glutathione metabolism. This work presents a targeted nanozyme platform for precise OA therapy via ferroptosis inhibition.

Early prediction of PSA nadir in metastatic castration-sensitive prostate cancer with machine learning approaches.

222 Background: Early achievement of PSA nadir is a well-established prognostic marker in mHSPC. Understanding PSA kinetics is crucial for optimizing treatment and disease management. This study aimed to develop and externally validate a machine learning model predicting the probability of achieving a PSA nadir ≤0.2 ng/mL at sixth month, based on baseline and 3th-month PSA measurements. Methods: This retrospective study included 211 patients with mHSPC (Training set:168 [80%], Test set:43 [20%]).The primary endpoint was achieving a PSA nadir ≤0.2 ng/mL at 6.-month after treatment initiation. Clinical and laboratory variables—including treatment type, Gleason score, metastatic volume and pattern, comorbidity status, age, baseline and 3.-month PSA, ALP, LDH, and hemoglobin—were used as predictors. Data preprocessing involved iterative imputation for missing values, variance thresholding, and feature scaling. Two predictive models, logistic regression and gradient boosting (GB), were developed using a nested cross-validation framework to prevent data leakage and overfitting. Hyperparameters were optimized via grid search, and model performance was assessed on an independent test set (n=43).Calibration, Brier score, bootstrap and decision curve analyses were conducted to evaluate clinical applicability. Model interpretability was examined through SHAP analysis, and external validation was performed on two independent cohorts. Results: In nested cross-validation, the GB model outperformed logistic regression in all metrics except recall and was selected as the final model. In the test set (n = 43), the GB model achieved an accuracy of 86.1%, ROC-AUC of 0.88, sensitivity of 82.6%, and specificity of 90.0%. SHAP analysis revealed that 3.-month PSA, ALP, LDH, and hemoglobin were the most influential features. The model demonstrated good calibration (Brier score = 0.12) and provided positive net clinical benefit between 20% and 78% risk thresholds. In the two center external validation cohort (n = 66), the model maintained strong predictive performance (ROC-AUC = 0.85, accuracy = 86.4%, sensitivity=75.0%, specificity=94.7%). Conclusions: Our GB based model accurately predicted 6.-month PSA nadir achievement in mHSPC and demonstrated robust generalizability. This model may assist clinicians in early identification of patients unlikely to achieve a PSA nadir, supporting timely treatment intensification and personalized disease management.

Investigation of the natural killer (NK) cell axis in decoy-resistant IL18 treatment in bladder cancer (BCa).

790 Background: Bladder cancer (BCa) is the most common malignancy of the urinary tract and the sixth most prevalent cancer in the United States. Despite advances in immunotherapy, many patients experience limited responses. The recent approval of the IL-15 superagonist, N-803, has renewed interest in cytokine-based immunotherapy. Among innate cytokines, IL-18—a member of the IL-1 family—plays a critical role in activating NK cells. However, clinical translation of IL-18 has been limited by high circulating levels of IL-18 binding protein, a soluble decoy receptor that neutralizes its activity in the tumor microenvironment. To overcome this barrier, we investigated a rationally engineered, decoy-resistant IL-18 variant (DR-18) designed to restore cytokine signaling and enhance anti-tumor immunity in BCa. Methods: We assessed DR-18 efficacy using a combination of in vitro and in vivo models of BCa . In vitro assays included BCa cell lines and primary patient-derived tumor and immune cells to evaluate direct and immune-mediated effects. In vivo studies utilized syngeneic, orthotopic murine models, as well as a humanized BCa model. Immune responses were characterized by multiparametric flow cytometry, NK cell functional assays and single-cell RNA sequencing, with emphasis on NK cell activation, phenotype, and effector function. Results: In vitro, DR-18 consistently enhanced NK cell proliferation and activation, as evidenced by increased expression of activation receptors, inflammatory cytokines, and cytotoxic mediators. In vivo, DR-18 treatment led to a marked reduction in tumor burden across non–muscle-invasive, muscle-invasive, and recurrence models of BCa. The loss of efficacy upon NK or T cell depletion indicated an NK cell–dependent priming of T cell responses. Multi-omic immune profiling, integrating transcriptomic and flow cytometric analyses, revealed upregulation of genes and surface markers associated with cell recruitment, inflammation, and stemness. These findings underscore DR-18’s ability to reprogram NK cells toward an adaptive, memory-like state with enhanced effector persistence, contributing to durable antitumor immunity and improved therapeutic outcomes in BCa. With the human DR-18 molecule currently in clinical trials for solid tumors, we also investigated human DR-18 in collaboration with Simcha Therapeutics and found it to be effective both in vitro and in vivo in humanized BCa models, further supporting its translational potential. Conclusions: DR-18 elicits potent NK cell–dependent antitumor activity in BCa, bridging innate and adaptive immunity. These findings, together with the ongoing clinical evaluation of DR-18 in solid tumors, underscore its potential for rapid clinical translation and support investigation of DR-18, alone or in combination with immune checkpoint inhibitors and antibody–drug conjugates, to improve patient outcomes in BCa.

A multicenter phase II study of first-line modified FOLFIRINOX in patients with advanced urachal cancer (ULTIMA; KCSG GU20-03).

758 Background: There is no established standard treatment for recurrent or metastatic urachal cancer (UrC). Combination regimens containing 5-fluorouracil (5-FU), oxaliplatin, and irinotecan have demonstrated promising efficacy and manageable toxicity in various gastrointestinal malignancies and may also be effective in UrC. We conducted a multicenter phase II study to evaluate the efficacy and safety of modified FOLFIRINOX in patients with advanced UrC. Methods: Patients with recurrent or metastatic UrC and measurable disease received modified FOLFIRINOX (oxaliplatin 85 mg/m² over 2 hours, irinotecan 150 mg/m² over 1.5 hours, leucovorin 400 mg/m² over 2 hours, and 5-FU 2400 mg/m² over 46 hours) together with prophylactic pegteograstim 6 mg subcutaneously on day 3 of each 2-week cycle, up to 12 cycles (or until disease progression or unacceptable toxicity). Tumor response was assessed every 6 weeks. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and incidence of febrile neutropenia. Simon’s minimax two-stage design was used to test the null hypothesis of P₀ = 17% versus the alternative P₁ = 36%, with α = 0.05 and β = 0.20. Results: Between April 2021 and April 2025, 35 patients with advanced UrC were enrolled across six centers. The median age was 51 years (range, 28–68), and 24 patients (68.6%) were male. The most common metastatic sites were lung (48.6%), peritoneum (37.1%), and lymph nodes (31.4%). As of October 2025, 33 patients had discontinued treatment; 27 completed all 12 planned cycles. A total of 464 cycles were administered, with a median of 12 (range, 6–43) cycles per patient. The ORR was 57.1% (2 complete and 18 partial responses), and the disease control rate was 100%. After a median follow-up of 26.4 months, the median PFS was 9.5 months (95% CI, 8.7–10.2), and the estimated median OS was 25.5 months (95% CI, 16.5–34.6). Treatment was well tolerated with no unexpected toxicities. The most common any-grade adverse events (AEs) were peripheral neuropathy (74.3%), nausea (65.7%), thrombocytopenia (37.1%), fatigue (28.6%), anorexia (20.0%), and mucositis (20.0%). Grade 3 AEs included thrombocytopenia (8.6%), neutropenia (5.7%), anemia (5.7%), nausea (2.9%), and diarrhea (2.9%). No febrile neutropenia or grade 4 AEs were observed. Conclusions: The ULTIMA trial is the first prospective phase II study in advanced urachal cancer and met its primary endpoint, demonstrating encouraging ORR and PFS. Modified FOLFIRINOX was well tolerated, with no febrile neutropenia under prophylactic pegteograstim support. This regimen may be considered a potential standard treatment option for patients with advanced urachal cancer. Clinical trial information: NCT04611724 .

Predictive value of microsatellite instability/mismatch repair deficiency phenotype in upper tract urothelial carcinoma: A systematic review and meta-analysis.

701 Background: Lynch syndrome (LS) has been established as a significant risk factor for developing upper tract urothelial carcinoma (UTUC); however, clinicopathological characteristics and survival outcomes in this population remain contentious. This meta-analysis was designed to systematically evaluate clinicopathological features and survival outcomes in UTUC patients with microsatellite instability (MSI) or mismatch repair deficiency (dMMR), phenotypes associated with LS. Methods: A systematic literature search was conducted in PubMed, Web of Science, Embase, and Cochrane databases from January 2002 to April 2025. Clinicopathological endpoints included family history of malignancy, personal history of prior malignancies, tumor stage, tumor grade, and lymph node metastasis (LNM). The primary survival outcome was overall survival (OS). The protocol has been registered with PROSPERO (Registration ID: CRD42024558925). Results: 27 studies, encompassing 3,545 cases, were ultimately included. Meta-analysis revealed that LS-UTUC was significantly associated with: a) a history of prior malignancies (OR 6.05, 95% CI 2.93; 12.48), b) lower tumor stage (OR 0.59, 95% CI 0.44; 0.79), c) predominance of G2 (G1 vs G2: OR 0.31, 95% CI 0.13; 0.72; G2 vs G3: OR 1.68, 95% CI 1.06; 2.67), and d) reduced incidence of LNM (OR 0.33, 95% CI 0.14; 0.78). Furthermore, LS-UTUC patients demonstrated notably improved OS (HR 0.63, 95% CI 0.43; 0.91). However, significant heterogeneity persists in both LS detection methodologies and diagnostic thresholds, and the limited number of included studies precluded assessment of associations with other survival outcomes. Conclusions: The unique profile of LS-UTUC—encompassing high prior cancer risk, early-stage/G2-predominant pathology, and favorable survival—calls for integrated LS screening in UTUC management. These findings advocate for the integration of universal LS screening into UTUC management to enable risk-adapted strategies. Prospective studies are warranted to standardize diagnostics and evaluate the efficacy of targeted therapies, such as immune checkpoint inhibitors, in this unique population.

Achieving a Record Fill Factor of Approaching 84% and 21% Efficiency in Binary Organic Solar Cells via Solid Additive Engineering

ABSTRACT Solid additives, as an efficient approach of morphology control in organic solar cells (OSCs), remain not fully understand in terms of the influence of their intermolecular interactions with photoactive molecules on morphological evolution and ultimate device performance. Herein, the intermolecular interactions between solid additives and photoactive molecules were precisely tuned through molecular isomerization engineering. Three isomers of iodine‐substituted 1,2,4‐trichlorobenzene were adopted as the solid additives. The four strongly electronegative halogen atoms readily produce intense interactions with the photoactive materials, thereby enhancing their J ‐type stacking and broadening the absorption spectrum. Crucially, the iodine substituent position on the solid additives was altered, which improved their miscibility and intermolecular interactions with photoactive materials, forming a bicontinuous interpenetrating network. Consequently, the binary OSCs achieved an impressive fill factor of approximately 84% with an efficiency of nearly 21% (certified as 20.42%), ranking among the top OSC performances to date. Furthermore, the device demonstrated excellent storage stability, with an extrapolated T 80 (maintaining 80% of its initial efficiency) exceeding 10 000 h.

Histone fold domain positioning dictates cotranslational heterodimeric assembly of paralogous TAF12/TAF12L in Candida albicans

Real-world analysis of renal cell carcinoma with sarcomatoid differentiation treated with first-line immunotherapy combinations: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

448 Background: Sarcomatoid renal cell carcinoma (sRCC) is aggressive with poor outcomes. Dual checkpoint blockade (nivolumab–ipilimumab; NIVO-IPI) and immune–VEGF combinations (IO-VEGF) are standard therapies, but real-world data are limited. Methods: We retrospectively analyzed IMDC sRCC treated first-line with NIVO-IPI or IO-VEGF between 2000–2025. Favorable-risk patients were excluded to focus on a clinically homogeneous intermediate/poor-risk cohort. Objective response rate (ORR; proportion achieving complete or partial response) was assessed per investigator evaluation. Additional outcomes included treatment duration (time from therapy start to discontinuation for any reason including toxicity or response), time to next treatment (TTNT), and overall survival (OS). Kaplan–Meier estimates and log-rank tests compared survival distributions, while multivariable Cox regression adjusted for key prognostic variables and metastatic sites. Results: A total of 337 intermediate/poor-risk patients were included, of whom 87 received IO-VEGF and 250 received NIVO-IPI. Baseline characteristics (Table 1) showed no significant between-group differences. The ORR was nearly identical between regimens at 49.3% with IO-VEGF and 49.1% with NIVO-IPI (p = 0.95). Among evaluable patients (IO-VEGF n=73; NIVO-IPI n=226), complete response rate was 5.5% vs 11.5% (p=0.136) and primary progressive disease rate was 26.0% vs 25.7% (p=0.951) for IO-VEGF and NIVO-IPI respectively. Median treatment duration was longer with IO-VEGF (12.6 vs 5.0 months; log-rank p = 0.026). Median time to next treatment (TTNT) was 32.2 months for IO-VEGF and 27.6 months for NIVO-IPI (unadjusted log-rank p = 0.28; adjusted HR 1.24, 95% CI 0.81–1.96, p = 0.35). Bone metastases independently predicted shorter TTNT (HR 2.05, p < 0.001). Median overall survival (OS) was 24.0 months with IO-VEGF and 30.2 months with NIVO-IPI (unadjusted log-rank p = 0.65; adjusted HR 0.85, 95% CI 0.58–1.25, p = 0.40). Worse OS was associated with Karnofsky Performance Status < 80% (HR 1.70, p = 0.02) and the presence of bone metastases (HR 2.03, p < 0.001). Conclusions: In IMDC intermediate/poor-risk sRCC, NIVO-IPI and IO-VEGF regimens did not demonstrate statistically significant differences in ORR, TTNT, or OS. Bone metastases and reduced performance status consistently predicted poorer outcomes, highlighting the importance of accounting for disease burden and functional status when selecting first-line therapy and designing future studies. Baseline characteristics. Characteristic IO-VEGFN = 87 NIVO-IPIN = 250 p-value Intermediate risk, N (%) 55 (63.2%) 142 (56.8%) 0.36 Poor risk, N (%) 32 (36.8%) 108 (43.2%) Median Age 62.5 62.1 0.82 Bone Metastases, N (%) 28 (32.6%) 81 (32.5%) 0.99

Genomic heterogeneity in urothelial carcinoma with trophoblastic differentiation: Real world data.

858 Background: Urothelial carcinoma with trophoblastic differentiation (TUC) represents a rare and aggressive variant that has been previously reported in both the upper and lower urinary tract. Although isolated cases have described its distinct histopathological and immunohistochemical (IHC) features, comprehensive characterization of this variant remains limited. Genomic data on TUC is exceedingly scarce, making its clinical behavior difficult to characterize. In this study, our objective is to define the genomic features of this uncommon histologic variant by evaluating results from clinical next-generation sequencing. Methods: From our institution-based data set, we retrospectively reviewed patients diagnosed with TUC on surgical pathology report between 2020 to 2025. Patients were included if they had undergone standard-of-care comprehensive whole exome genomic profiling (Altera, Caris, Foundation One, or other). Patient, clinical, and pathological findings were collected. Tumor mutational burden (TMB) was retrieved from assay reports and categorized as low (≤5 mut/Mb), intermediate (6–19 mut/Mb), or high (≥20 mut/Mb). Data was extracted from PDF reports and converted to CSV format manually or with PythonV3.13.5 and subsequently analyzed. Median time to follow up, overall and recurrence free survival analysis were performed. Results: Eighteen patients were diagnosed with confirmed TUC; five had available genomic data. The median age was 74 years, and all patients were non-Hispanic White. Smoking history included two active and three former users. Three tumors originated in the bladder and two in the ureter, with pathological stages pT1 (n = 2), pT2 (n = 2), and pT3 (n = 1). At last follow-up, three patients were alive with disease, and two had no evidence of disease. Genomic profiling revealed low-to-intermediate TMB. Pathogenic and recurrent alterations most frequently involved TERT (~80%), FGFR3 (~40%), ERCC2 (~40%), KMT2D (~40%), and TP53 (~40%). Interestingly, one patient harbored coexisting KRAS and BRAF mutations—a rare finding in UC—suggesting potential clonal divergence in this variant. Median overall survival and recurrence-free survival were not reached and median time to follow up was 18.5 months. Conclusions: This study represents one of the first reports of real-world genomic profiling in the TUC variant. We highlight the notable inter-patient heterogeneity and genomic diversity of this variant with an interesting take on TERT mutation coappearing with KRAS and BRAF mutations. These findings emphasize the need for further comprehensive genomic investigation to improve the interpretation of its biological behavior and to guide the development of targeted therapeutic strategies.

Promoter methylation of aquaporin 1 as a prognostic biomarker in clear cell renal cell carcinoma.

518 Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, yet reliable biomarkers for early detection and prognosis remain limited. We initially conducted a comprehensive screening of membrane proteins and selected Aquaporin 1 (AQP1) for further investigation based on its significantly altered expression patterns. Aberrant AQP1 expression has been implicated in ccRCC, and recent evidence suggests that its regulation via promoter DNA methylation may contribute to gene expression changes during tumor progression. Methods: We first analyzed data from The Cancer Genome Atlas (TCGA) ccRCC cohort to assess the correlation between AQP1 promoter methylation and mRNA expression levels. We then performed high-resolution bisulfite amplicon sequencing (BSAS) on approximately 53 paired ccRCC tumor and adjacent non-tumor tissue samples to map detailed methylation patterns. Methylation diversity was quantified using Shannon and Simpson indices, and clustering analysis was applied to define distinct methylation profiles. Statistical associations were evaluated between methylation states, recurrence risk (including hazard ratios), and clinicopathological parameters. Results: TCGA data revealed a significant inverse correlation between AQP1 promoter methylation and mRNA expression. In our BSAS analysis, complete promoter methylation was significantly less frequent in tumor tissues compared to non-tumor tissues. Clustering analysis demonstrated marked differences in methylation pattern composition between tumor and adjacent normal tissues. In tumor samples, high methylation levels were associated with a poor prognosis, whereas in non-tumor tissues, pronounced demethylation correlated with increased recurrence risk. Furthermore, elevated methylation entropy in both tissue types was linked to higher recurrence rates, suggesting that epigenetic heterogeneity may reflect tumor microenvironmental stress. Conclusions: AQP1 promoter methylation offers a promising prognostic ccRCC biomarker. Methylation dynamics in non-tumorous tissue could be used to develop non-invasive methods to monitor ccRCC recurrence risk. Comprehensive screening analysis of membrane proteins. Gene W W_p Variance 95% CI Lower 95% CI Upper AQP1 0.968 0.011 211.469 164.175 282.725 AQP4 0.923 <0.001 6.084 4.724 8.135 Choline_T 0.753 <0.001 253.825 197.059 339.353 ECAD 0.893 <0.001 62.859 48.801 84.04 GLUT1 0.817 <0.001 0.003 0.002 0.004 GLUT3 0.65 <0.001 20.236 15.71 27.055 LAT1 0.171 <0.001 145.687 107.536 208.577 MDR1 0.462 <0.001 11.942 9.272 15.967 MGMT 0.812 <0.001 0.027 0.021 0.036 RAD51 0.542 <0.001 0.005 0.003 0.006 RARb 0.599 <0.001 1.362 1.057 1.821 TMEFF2 0.555 <0.001 24.24 18.819 32.407

Immune senescence and antigen presentation defects in BCG-unresponsive bladder cancer.

823 Background: Intravesical Bacillus Calmette-Guérin (BCG) remains the cornerstone therapy for high-risk non–muscle invasive bladder cancer (NMIBC). However, up to 40% of patients experience recurrence or progression following adequate BCG therapy. Identifying molecular determinants of BCG unresponsiveness is crucial for patient stratification and development of alternative intravesical immunotherapies. We aimed to define tumor immune microenvironmental features of BCG unresponsiveness using single-cell and bulk transcriptomic approaches and to validate these findings in independent multi-institutional datasets. Methods: Pre-treatment tumors from 10 high-risk NMIBC patients (5 BCG-responsive, 5 BCG-unresponsive) underwent single-cell RNA sequencing (scRNA-seq). Unsupervised clustering and cell type annotation were performed to identify distinct tumor microenvironmental populations. Differential pathway and gene set enrichment analyses were used to explore key functional differences between groups. Transcriptomic modules derived from scRNA-seq were validated using our institutional microarray cohort (YUHS, n = 54) and multiple external cohorts (CBNUH, LEED, UROMOL, BRS; total > 350 patients) through gene set enrichment, deconvolution, and survival analyses. Results: Thirteen major cell populations were identified. BCG-unresponsive tumors exhibited an increased proportion of GZMK ⁺ CD8⁺ T cells characterized by senescence-like features (elevated GZMK , CXCR4 , reduced GZMB , CXCL13 ) and decreased proliferative activity. Plasmacytoid dendritic cells were markedly depleted, with concomitant suppression of interferon signaling and epithelial antigen presentation pathways. The interferon and antigen presentation modules derived from scRNA-seq were consistently reproduced in both our YUHS microarray data and the external validation cohorts, where high module activity significantly stratified recurrence-free survival (HR = 0.45, p < 0.01). Conclusions: BCG-unresponsive NMIBC exhibits an “immune senescence” tumor microenvironment, defined by dysfunctional GZMK ⁺ CD8⁺ T cells, dendritic cell depletion, and defective epithelial antigen presentation. The reproducibility of these features across multi-cohort transcriptomic datasets underscores their translational value as potential biomarkers for predicting BCG response and guiding development of novel intravesical immunotherapy strategies.

Space‐Time Wavefront Synchronized Terahertz Metasurface

ABSTRACT Wireless communications demand high data rates, low latency, and ultra‐reliable performance for future applications. This necessitates the development of high‐speed, and programmable arrays across the spatial, temporal, and wave domains to compensate for path loss, extend spectral links, and expand spatial coverage. The current works face several challenges, including slow switch speed, narrow bandwidth, and constrained dual‐space coverage in unconnected transmission–reflection integrated links. Here, we demonstrate two types of terahertz metasurfaces from the angle of energy‐time and frequency‐time functions, respectively, both have the ps‐scale modulation speed under pulsed light excitations, and the space‐time synchronized transmission and reflection links. In these devices, the terahertz wavefront can be modulated for energy covering 81.4% bandwidth using pump light with fluence of 100 µJ/cm 2 , exhibiting dual‐space synchronization with up to 92.2% similarity in holographic experiments. Our space‐time ultrafast modulations enable dynamic beam steering, achieving over 88.6% modulation depth with a 4 × 42° field‐of‐view. Further, ultrafast beam steering with 21.8° dynamic range is experimentally characterized for the first time within a single pump pulse duration, approximately 250 ps. This novel scheme holds promise for the active manipulation of terahertz signals, which is crucial for photonics‐terahertz systems in next‐generation communications by smart structure materials.

Cu ₂ FeS ₂ : Discovery of an Exceptional Thermoplasmonic Semiconductor via Arrested Cation Exchange

ABSTRACT In this work, we report the discovery and cation exchange‐mediated synthesis of Cu 2 FeS 2 , a compound predicted computationally but never observed in nature or realized in the laboratory. Our findings reveal that it possesses an anomalous electronic structure among analogous Cu‐Fe‐S semiconductors due to the unique valence configuration. More strikingly, this unprecedented material displays ultrahigh molar extinction coefficients (ε > 10 7 M −1 cm −1 ) throughout the visible to near infrared (NIR) spectrum arising from remarkable localized surface plasmon resonances (LSPRs), coupled with intense electron‐phonon interactions that enable ultrafast lattice heating on the 100 fs timescale. Such intrinsic attributes unequivocally designate Cu 2 FeS 2 as an ideal thermoplasmonic material. It demonstrates superior photothermal conversion efficiencies (PCE) spanning both visible and NIR wavelengths, outperforming assorted well‐established photothermal materials including Au nanoparticles and MXene nanosheets. As a demonstration, we leverage its prominent thermoplasmonic functionality to drive efficient photothermal dry reforming of methane under low light intensities. Beyond the results presented here, Cu 2 FeS 2 is expected to provide a fertile ground for transformative investigations in many diverse fields of science.

Modulating Ultraviolet‐Visible‐Near Infrared Emission in Hybrid Metal Halides via ns ² Ion Doping

Abstract Tunable broad‐spectrum luminescent materials covering the ultraviolet (UV), visible, and near infrared (NIR) regions are essential for next‐generation optoelectronic technologies. However, conventional systems are often limited by inefficient UV emission and the inability to integrate multiple spectral components within a single material. Here, a design strategy that combines ns 2 ‐ion with controlled lattice distortion is introduced to overcome these challenges. Using 4,4‐difluoropiperidine (DFPD) as the organic cation, a family of hybrid metal halide phosphors, [(DFPD) 2 MCl 4 ·H 2 O, M = Cd/Zn] doped with different ns 2 ion (Sn 2+ , Pb 2+ , Sb 3+ , Bi 3+ , and Te 4+ ) is synthesized. It is revealed that reduced lattice distortion correlates with enhanced photoluminescence quantum yield (PLQY), enabling broadband self‐trapped exciton emission spanning the UV–vis–NIR range within a single host matrix. Leveraging the highly efficient UV emission of 2% Pb‐doped (DFPD) 2 CdCl 4 ·H 2 O (PLQY: 93%), a high‐performance white light emitter with a color rendering index of 92.9 and a correlated color temperature of 6087 K is demonstrated. The materials further exhibit promising functionality in NIR imaging and multi‐level anti‐counterfeiting. This work elucidates the interplay between lattice distortion and exciton dynamics in Cd/Zn‐based hybrid metal halides, providing fundamental insights into their photophysics and establishing a versatile strategy for designing next‐generation broadband multifunctional optoelectronic materials.