Browse Articles

Metaplasticity‐Enabled Graphene Quantum Dot Devices for Mitigating Catastrophic Forgetting in Artificial Neural Networks (Adv. Mater. 6/2025)

Buried Interface Modulation Using Self‐Assembled Monolayer and Ionic Liquid Hybrids for High‐Performance Perovskite and Perovskite/CuInGaSe ₂ Tandem Photovoltaics

Abstract Effective modifications for the buried interface between self‐assembled monolayers (SAMs) and perovskites are vital for the development of efficient, stable inverted perovskite solar cells (PSCs) and their tandem photovoltaics. Herein, an ionic‐liquid‐SAM hybrid strategy is developed to synergistically optimize the uniformity of SAMs and the crystallization of perovskites above. Specifically, an ionic liquid of 1‐butyl‐3‐methyl‐1H‐imidazol‐3‐iumbis((trifluoromethyl)sulfonyl)amide (BMIMTFSI) is incorporated into the SAM solution, enabling reduced surface roughness, improved wettability, and a more evenly distributed surface potential of the SAM film. Leveraging this optimized substrate, a favorable growth of high‐quality perovskite crystals is achieved. Furthermore, the introduced functional ions readily bond with the perovskites, effectively passivating undesirable cation or halide vacancies of the perovskite near the buried interface. Remarkably, high power conversion efficiencies (PCEs) of 25.68% and 22.53% are obtained for normal‐bandgap (≈1.55 eV) and wide‐bandgap (WBG) (≈1.66 eV) PSCs along with improved operational stability. Additionally, a champion PCE of 19.50% is achieved for semitransparent WBG PSCs, further delivering an impressive PCE of 28.34% for integrated four‐terminal tandem photovoltaics when combined with CuInGaSe 2 solar cells.

First results of nivolumab (NIVO) plus ipilimumab (IPI) vs NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) from CheckMate 8HW.

LBA143 Background: The CheckMate 8HW study met its dual primary endpoint with NIVO + IPI demonstrating superior progression-free survival (PFS) by blinded independent central review (BICR) vs chemotherapy (chemo) in patients (pts) with centrally confirmed MSI-H/dMMR mCRC in the first-line (1L) setting (HR 0.21; 95% CI 0.14–0.32; P < 0.0001). We report first results from the other dual primary endpoint of PFS for NIVO + IPI vs NIVO across all lines of therapy in pts with centrally confirmed MSI-H/dMMR mCRC. Methods: Immunotherapy-naive pts with unresectable or mCRC and MSI-H/dMMR status by local testing who had received 0 or 1 prior line of therapy were randomized 2:2:1 to (i) NIVO (240 mg) Q2W (6 doses, then NIVO 480 mg Q4W), (ii) NIVO (240 mg) + IPI (1 mg/kg) Q3W (4 doses, then NIVO 480 mg Q4W), or (iii) chemo ± targeted therapies. Pts who had received ≥ 2 prior lines of therapy were randomized 1:1 to the NIVO + IPI or NIVO arms. Treatments continued until disease progression or unacceptable toxicity (all arms), or a maximum of 2 years (NIVO ± IPI arms). Results: Across all lines of therapy,707 pts were randomized to NIVO + IPI (n = 354) or NIVO (n = 353); 55% and 52% received study treatment in the 1L setting, respectively. Of all randomized pts, 296 in the NIVO + IPI arm and 286 in the NIVO arm had centrally confirmed MSI-H/dMMR status. With 47.0 months (mo) of median follow-up (range, 16.7–60.5), NIVO + IPI demonstrated clinically meaningful and statistically significant improvement in PFS by BICR vs NIVO (HR 0.62; 95% CI 0.48–0.81; P = 0.0003) and higher 12-, 24-, and 36-mo PFS rates vs NIVO (Table). Objective response rate (ORR) by BICR was significantly higher with NIVO + IPI vs NIVO (71% vs 58%; P = 0.0011; Table); best overall response of progressive disease was reported in 10% and 19% of pts, respectively. No new safety concerns were identified (Table). Conclusions: In the first randomized study to compare dual- vs single-agent immunotherapy in MSI-H/dMMR mCRC, NIVO + IPI demonstrated superior PFS vs NIVO across all lines of therapy, with a manageable safety profile. These results establish NIVO + IPI as the potential new standard-of-care treatment for MSI-H/dMMR mCRC. Clinical trial information: NCT04008030 . Efficacy by BICR (all lines; centrally confirmed MSI-H/dMMR by IHC and/or PCR test) NIVO + IPI(n = 296) NIVO(n = 286) Median PFS (95% CI), mo NR (53.8–NE) 39.3 (22.1–NE) HR (95% CI); P value 0.62 (0.48–0.81); 0.0003 PFS rate (12/24/36-mo), % 76/71/68 63/56/51 ORR, n (%); 95% CI, % 209 (71); 65–76 165 (58); 52–64 P value 0.0011 Safety (all lines; all treated), n (%) NIVO + IPI (n = 352) NIVO (n = 351) Any-grade/grade 3–4 TRAEs 285 (81)/78 (22) 249 (71)/50 (14) Any-grade/grade 3–4 TRAEs leading to discontinuation 48 (14)/33 (9) 21 (6)/14 (4) Treatment-related deaths 2 (< 1) 1 (< 1) IHC, immunohistochemistry; NE, not estimable; NR, not reached; PCR, polymerase chain reaction; TRAE, treatment-related adverse event.

TYRA-430: First reversible FGFR4/3 inhibitor designed to overcome current challenges in FGF19-driven hepatocellular carcinoma treatment.

583 Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy that accounts for approximately 80-90% of all primary liver cancers and is projected to become the third leading cause of cancer-related mortality by 2030. Previous work demonstrated that human Fibroblast Growth Factor 19 (FGF19) was overexpressed in 20-30% of HCC, thereby exerting an oncogenic effect via signaling through its cognate receptors FGFR4, FGFR3, and the co-receptor Klotho b (KLB). Multiple selective covalent FGFR4 inhibitors have been clinically evaluated in FGF19-overexpressing HCC. However, selective inhibition of FGFR4 alone was insufficient and resulted in low response rates and limited duration, likely due to redundant signaling through FGFR3. Here we describe the first report on the preclinical profile of TYRA-430, a first-in-class reversible FGFR4/3 inhibitor. Methods: The preclinical profile of TYRA-430 was assessed in vitro in HCC cellular assays and in vivo in mouse xenograft models. The in vitro potency was assessed by measuring cell viability using Cell Titer-Glo 2.0 Luminescent assay. Percentage of tumor growth inhibition (TGI) was used as a measure to evaluate in vivo efficacy of TYRA-430. Results: TYRA-430 exhibited potency against Ba/F3 cells dependent on wildtype FGFR3 and FGFR4, as well as the known Cys552 and Val550 gatekeeper (GK) resistance mutations in FGFR4. In vitro data showed that TYRA-430 displayed superior potency over the reversible multi-kinase inhibitors sorafenib and lenvatinib, and the covalent FGFR4 inhibitors fisogatinib (BLU-554) and roblitinib (FGF401) in KLB/FGF-19/FGFR3/4 driven models of HCC (Hep3B, HuH-7, and JHH-7 cells). Furthermore, in a human HuH-7 HCC xenograft model in nu/nu mice, TYRA-430 achieved 96% tumor growth inhibition (TGI), compared to 75% TGI for lenvatinib and 86% TGI for FGF401. Additionally, in the GA180 FGF19-driven gastric cancer PDX model, TYRA-430 demonstrated superior efficacy with 93% tumor growth inhibition (TGI), compared to 56% TGI achieved by roblitinib. Conclusions: TYRA-430 was active and potent in multiple KLB/FGF-19/FGFR3/4 models of human hepatocellular carcinoma in vitro and in vivo . Moreover, TYRA-430 displayed potent activity against known FGFR4 resistance mutations compared to covalent FGFR4-specific inhibitors in the clinic. TYRA-430 will be investigated in a Phase 1 clinical trial in hepatocellular carcinoma and other advanced solid tumors.

Chemoradiotherapy (CRT) followed by sequential tislelizumab (TIS) + CAPOX and TIS monotherapy for organ preservation in locally advanced low rectal cancer.

TPS315 Background: CRT followed by total mesorectal excision (TME) is the standard care for patients with locally advanced low rectal cancer (≤ 5cm from the anal margin). However, TME may lead to permanent colostomy and severely impact quality of life. Organ preservation is, therefore, a critical unmet need for these patients. The proportion of patients achieving clinical complete response (cCR) after CRT is relatively low, with the literature reporting around 20%. Total neoadjuvant therapy (TNT) has been investigated to increase cCR rate. Several clinical trials demonstrated that PD-1 inhibitor combined with TNT could result in significate improvement in pathological complete response rate (pCR rate, 39.8% vs 15.3%, p < 0.001 in UNION study) or complete response rate (pCR+cCR rate, 44.8% vs 26.9%, p = 0.031 in a randomized phase 2 study) compared with TNT alone in rectal cancer patients. The RELIEVE-01 study (NCT06390982) was designed to evaluate the efficacy in organ preservation with CRT followed by sequential TIS + CAPOX and TIS monotherapy in patients with low rectal cancer. Methods: This multicenter, single-arm, phase 2 study will enroll 46 pts with histopathologically confirmed rectal adenocarcinoma (≤ 5cm from the anal margin), pMMR/MSI-L/MSS, cT1-3N1M0/T2-3N0M0, and ECOG PS ≤1. Pts will initially receive 6 weeks of CRT (50.4 Gy/28F, capecitabine 825 mg/m 2 , bid, d1-5 each week), followed by 4 cycles of TIS + CAPOX (TIS, 200 mg, IV, d1; capecitabine 1000 mg/m 2 , bid, d1-14; oxaliplatin 130 mg/m 2 , d1) in a 21-day cycle. Then, clinical response will be assessed to determine the subsequent treatment. Patients with cCR will receive TIS + CAPOX (4 cycles) and TIS (up to 9 cycles), and then be managed using the W&W strategy. Patients with non-cCR will undergo TME. Patients with near-cCR will be given local excision, and those achieving pCR will receive the same treatment as cCR patients, and for those with non-pCR after local excision, TME will be performed. The primary endpoint is rate of CR (cCR plus pCR post local resection). Secondary endpoints include organ-preserving rate, event-free survival rate and OS rate at 1, 2 and 3 years, respectively. Recruitment is ongoing. Clinical trial information: NCT06390982 .

Soft‐Actuated Cuff Electrodes with Minimal Contact for Bidirectional Peripheral Interfaces (Adv. Mater. 5/2025)

Digesting danger: A two-decade study exploring the association between food processing and colon cancer.

87 Background: Dietary patterns play a significant role in cancer prevention and progression, yet the specific association of food processing with colon cancer remains largely under-investigated. The NOVA classification system categorizes foods by their level of processing, providing a unique way to examine this relationship. Colon cancer remains a leading global health concern, and emerging evidence points to diet as potential contributors. This study explores associations between NOVA-classified foods and colon cancer, offering new insights into the role of food processing in cancer development. Methods: Survey data from the NHANES database (from 1999 to 2018) was probed for demographic and clinically relevant data, and day one food journals were converted into NOVA classifications. Participants aged 20 and older were included for analysis, including those with and without colon cancer (n=339 and 47615, respectively). Independent two-sample t-tests were conducted to compare the mean proportion of daily energy consumption of various NOVA food categories between the two groups, and a Benjamini-Hochberg correction was applied to adjust for multiple comparisons at p<0.05. Sensitivity analyses were performed using total grams and percent total caloric intake as inputs. Subgroup analyses were conducted via a logistic regression model including BMI, age, ethnicity, gender, education, country of birth, and military service. Results: Individuals with colon cancer had higher intake of ham and salted meats (NOVA 3, adjusted p=0.028) compared to those without cancer. Conversely, individuals without cancer consumed more legumes (NOVA 1, adjusted p=0.028), oils (NOVA 2, adjusted p=0.023), and “other processed foods” that did not fall into a specific processed food category (NOVA 3, adjusted p=0.038). Subgroups analyses revealed a greater association with colon cancer for age greater than 50 and non-hispanic White ethnicity. Conclusions: To our knowledge, this is the only study at this scale that evaluates colon cancer prevalence in the context of dietary behaviors stratified by level of industrial processing. The significant associations between ham and salted meats consumption, age greater than 50, and non-Hispanic White ethnicity with increased cancer prevalence highlight the impact of dietary and demographic patterns on colorectal carcinogenesis. Additional studies are needed to confirm these hypotheses in the prospective setting.

Tislelizumab (TIS) + chemotherapy (chemo) vs placebo (PBO) + chemo as first-line (1L) treatment in gastric/gastroesophageal junction adenocarcinoma (GC/GEJC) patients with/without peritoneal or liver metastases: A post hoc analysis of RATIONALE-305 study.

414 Background: Gastric cancer patients with peritoneal or liver metastases had poor prognosis, and the efficacy of immunotherapy in these patients remains unclear. The global phase 3 RATIONALE-305 study (NCT03777657) demonstrated that tislelizumab combined with chemotherapy could bring survival benefits to 1L treatment of GC/GEJC patients. Here, we assessed the efficacy of TIS + chemo vs PBO + chemo in patients with/without peritoneal or liver metastases in RATIONALE-305. Methods: Patients with systemic treatment-naïve GC/GEJC were randomly assigned (1:1) to receive either TIS + chemo or PBO + chemo. Regression analyses were conducted to explore the associations between peritoneal or liver metastases and OS. Relative treatment effect between tislelizumab and placebo was assessed in each subgroup. The Kaplan-Meier method was used to estimate the median OS, and hazard ratios (HRs) for OS were estimated using Cox proportional hazards models. Results: Among the 997 randomized patients (TIS + chemo, n=501; PBO + chemo, n=496), 434 (43.5%) had peritoneal metastases (220 in TIS arm; 214 in PBO arm) and 378 (37.9%) had liver metastases (190 in TIS arm; 188 in PBO arm) at baseline. Regression analyses showed peritoneal and liver metastases were significantly associated with shorter OS. Baseline characteristics were balanced between TIS and chemo arms within each subgroup, including PD-L1 expression levels. As of data cut-off on Feb 28, 2024, OS was longer in the TIS arm compared with the PBO arm in patients with peritoneal metastases (HR= 0.78, 95% CI 0.64-0.96) or without (HR = 0.79, 95% CI 0.65-0.95). OS improvement was also observed in patients with liver metastases (HR = 0.77, 95% CI 0.62-0.96) or without (HR = 0.80, 95% CI 0.67-0.95). Conclusions: This post hoc analysis demonstrated OS improvement with TIS + chemo vs PBO + chemo in GC/GEJC patients with/without peritoneal or liver metastases. To our knowledge, RATIONALE-305 is the first global pivotal study reporting survival benefits with TIS + chemo as 1L treatment for GC/GEJC, irrespective of peritoneal or liver metastases. Clinical trial information: NCT03777657 . With metastases Without metastases TIS arm PBO arm TIS arm PBO arm Peritoneum n=220 n=214 n=281 n=282 Median OS, mo (95% CI) 12.3 (10.6-14.3) 11.8 (10.6-13.0) 17.3 (15.0-20.3) 14.0 (12.6-16.0) HR (95% CI) 0.78 (0.64-0.96) 0.79 (0.65-0.95) Liver n=190 n=188 n=311 n=308 Median OS, mo (95% CI) 13.9 (11.4-15.6) 12.9 (10.9-14.5) 16.0 (13.6-18.0) 12.9 (11.9-14.4) HR (95% CI) 0.77 (0.62-0.96) 0.80 (0.67-0.95)

The relationship between the tumor microenvironment of hepatocellular carcinoma and apparent diffusion coefficient.

616 Background: The tumor microenvironment is critical for the acquisition of tumor malignancy in various cancer types. The objectives of this study were to investigate whether the levels of cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) reflect the prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy (Hx) and to determine whether the apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) reflects CAF and TAM expression. Methods: The study cohort comprised 109 patients who underwent initial curative resection for HCC. Alpha smooth muscle actin (αSMA) was selected as a CAF marker and CD204 as a TAM marker. Protein expression was immunohistochemically evaluated in the intratumoral regions of resected specimens. Clinicopathological factors, including the long-term prognosis after Hx, were investigated between αSMA-negative and -positive tumors and between CD204-negative and -positive tumors. The correlation between CAF/TAM marker expression and the calculated minimum ADC using DWI was also evaluated. Results: αSMA-positive expression was correlated with tumor number, invasive growth pattern, and advanced stage. CD204-positive expression was correlated with the presence of venous invasion. Both αSMA-positive expression and CD204-positive expression were significant prognostic factors in the univariate analysis of overall survival and disease-free survival. αSMA/CD204 double positivity was associated with an extremely poor prognosis after Hx and was a significant independent prognostic factor for overall survival ( p =0.02, hazard ratio: 3.27). Patients with double positivity also showed a significantly higher ADC low rate (83%). Conclusions: Expression of both CAF and TAM markers reflected a poor prognosis after Hx. Furthermore, the preoperative ADC could be a clinical surrogate marker in the tumor microenvironment in patients with HCC.

Perioperative nivolumab results in favourable long-term outcomes in patients with locally advanced resectable non-small-cell lung cancer

Electrically Generated Exciton Polaritons with Spin On‐Demand (Adv. Mater. 8/2025)

The <i>sp</i> Hybridization of Tin Single Atoms for Dendrite‐Free Sodium Metal Batteries

Abstract Restricting the growth of sodium (Na) dendrites at the atomic level is the premise to enable both the stability and safety of sodium metal batteries (SMBs). Here, the universal synthesis of the fourth main group element (Sn, Ge, Pb) as single metal atoms anchored on graphene (Sn, Ge, Pb SAs/G) with sp hybridization for dendrite‐free sodium metal anode is reported. The in situ real‐time observation of Na growth on Sn SAs/G uncoils a kinetically uniform planar deposition at the atomic level for substantially suppressing the dendrite growth. The symmetrical Sn SAs/G‐Na battery exhibits high Coulombic efficiency of 99.8% for 200 cycles, long‐term cyclability with 600 h at 4 mA cm −2 , and ultralow overpotential of 40 mV at 8 mA cm −2 . Further, the full batteries Na 3 V 2 (PO 4 ) 3 ||Sn SAs/G‐Na show unprecedented rate capability of 67 mAh g −1 at 20 C and a capacity retention as high as 91% after 500 cycles. The theoretical calculations of Na deposition on different M SAs/G (M═Sn, Ni, Zn, Fe, Co) reveal that the 5 s 2 5 p 2 electron configuration of Sn SAs/G realizes the planar deposition mechanism of Na clusters along the graphene plane. Therefore, this work provides an atom‐level accurate miniaturization strategy for constructing dendrite‐free SMBs.

A qualitative study of the home-based time burdens faced by persons affected by GI cancer.

822 Background: As cancer care is increasingly delivered at home, more tasks and responsibilities fall on patients and informal care partners. This is especially relevant for people with GI cancer who often have specific home-based care needs such as feeding, ostomy care, 5-fluorouracil chemotherapy, and complex medication management. Home-based time costs are undercounted in current measures of time toxicity that only include care received in formal healthcare settings. Methods: We conducted semi-structured interviews with patients with GI cancer and their care partners at a single tertiary cancer center in MN, USA from March-Oct 2023. Interviews explored cancer care tasks at home, associated time burdens, and how they compare to in-facility care. We analyzed interview transcripts using a grounded theory approach to identify themes. Results: We included 33 individuals (11 aged &gt;60y, 21 female, 25 white) including 15 patients (8 colorectal cancer, 8 ECOG 0) and 18 care partners (15 lived with the patient, 7 working at least part-time). We identified 5 themes (Table). Conclusions: This foundational work characterizes time burdens of home-based cancer care for persons affected by GI cancer. In addition to providing the first input on incorporating home-based time burdens into objective measures of time toxicity, we highlight the complexity of assessing time burden which is context and role-dependent. Theme Subtheme Quote Unexpected home-based care is time burdensome Challenge with home as a site of healthcare, difficult transition from hospital to home ‘’What they would do at the clinic behind the scenes she was doing on my kitchen table.” (Patient) Other burdens compound time burdens Logistic/administrative, emotional, symptom “The time spent on administrative things and coordinating [...] are more stressful than going to the clinic.” (Patient) Time burdens evolve over the disease course and differentially impact patients and care partners Cancer care constantly changes, discomfort with some tasks at home, less support provided if more competent, home-based care allows for connection “They’re in a season of remission and [...] we want to live as normal a life as we can. And then there are other seasons where it’s the absolute opposite.” (Care partner) Factors influencing the choice of home-based care Need to manage family duties, supportive care partners matter, value connection with nurses, decreased travel “There is a different cost when you start doing things at home, especially when you have small children because if they’re witnessing it, that’s emotional.” (Patient) Home-based care is generally perceived as less time-burdensome than similar cares provided in-facility Different opinions on whether home-based care should be included in time toxicity measure “If you’re just talking about video visits I wouldn't consider that time toxic. But if I’m going [to the clinic], I’ve pretty much lost the whole day.” (Patient)

KIRROS: A phase II trial in progress of first-line atezolizumab (atezo) with or without bevacizumab (bev) in patients with unresectable hepatocellular carcinoma (HCC) and Child-Pugh B (CPB) cirrhosis.

TPS647 Background: HCC treatment is more complex for the sizable proportion of patients with CPB cirrhosis. These patients have poor survival due to both the cancer and underlying liver dysfunction. As such, they are typically excluded from pivotal clinical trials for first-line systemic therapy for unresectable HCC. The IMbrave150 trial established atezo + bev as a global standard of care for unresectable HCC, demonstrating a statistically significant improvement in overall survival (OS), progression-free survival (PFS) and confirmed objective response rate (ORR) of atezo + bev vs sorafenib (Finn N Engl J Med 2020; Cheng J Hepatol 2022). Real-world studies have consistently suggested benefit of atezo + bev in patients with HCC and CPB cirrhosis (e.g., Tanaka Hepatol Res 2022, D’Alessio Hepatol [Baltimore, Md] 2022). However, prospective clinical trial data are needed to comprehensively characterize safety and efficacy in this population. Single-agent immunotherapy is often used in patients with HCC and CPB cirrhosis given potential safety concerns of combination therapy. Safety data from real-world studies are limited by ascertainment and measurement biases. Therefore, a prospective study is warranted to address the unmet need for safety and efficacy data for first-line atezo ± bev in patients with CPB cirrhosis. Methods: KIRROS (NCT06096779) is a prospective, open-label, multicohort, multicenter phase II study in patients aged ≥18 years who have measurable and confirmed unresectable HCC, and CPB-7 or -8 cirrhosis who have not received prior systemic therapy. Eligible patients will be recruited into 2 cohorts for which endpoints will be non-comparatively assessed: Cohort A (n=60) patients will be treated with atezo 1200 mg intravenous (IV) + bev 15 mg/kg every 3 weeks (Q3W), and Cohort B (n=60) patients, those who do not meet Cohort A inclusion criteria (e.g., main portal vein tumor thrombus and proteinuria), will receive atezo 1200 mg IV Q3W only. Patients will receive treatment until unacceptable toxicity or loss of clinical benefit. The primary objective is to evaluate the safety of the treatment regimens as determined by incidence, nature and severity of adverse events and laboratory abnormalities graded per the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Secondary objectives are to estimate efficacy with ORR, duration of response, and PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC modified RECIST, as well as OS. Quality-of-life secondary endpoints include patient-reported tolerability of the treatment regimens assessed by PRO-CTCAE and EORTC IL46, and health-related quality of life per EORTC QLQ-C30 and QLQ-HCC18 scores. As of September 2024, the KIRROS study is recruiting patients at 40 sites in the US and Puerto Rico. Clinical trial information: NCT06096779 .

Association of GPR120 and NGF with perineural invasion in cholangiocarcinoma: Clinical and experimental insights.

622 Background: Cholangiocarcinoma (CCA) is a highly malignant biliary tumor characterized by frequent perineural invasion (PNI), which is associated with a poor prognosis; however, the underlying mechanisms remain unclear. G-protein-coupled receptor 120 (GPR120) has been implicated in the development of various tumors, while nerve growth factor (NGF) has a strong correlation with PNI. This study aims to elucidate the role of GPR120 in the production of NGF and to investigate the mechanisms by which PNI is induced in CCA. Methods: We conducted a retrospective review of medical records for 386 patients with cholangiocarcinoma (CCA), including both extrahepatic (ECC) and intrahepatic (ICC) types, who underwent curative resection at the Department of General Surgery, First Affiliated Hospital of Soochow University, between January 2015 and December 2021. NGF and GPR120 expression were assessed in 60 paraffin-embedded archived CCA tissue samples via immunohistochemical staining (IHC), with an additional 60 normal bile duct samples serving as controls. All tissues were sourced from the aforementioned 386 patients, none of whom received preoperative treatment. Tumors were staged according to AJCC classification. Western blot analysis was employed to evaluate NGF and GPR120 expression in CCA cell lines (QBC 939, RBE, HUCCT-1, and HCCC-9810). To assess the invasion and migration capabilities of CCA cell lines, QBC 939 and HCCC-9810 were treated with TUG-891 (a GPR120 agonist) and AH7614 (a GPR120 inhibitor). Results: Both GPR120 and NGF were found to be upregulated in CCA tissues, correlating with aggressive clinicopathological features. IHC staining revealed cytoplasmic localization of GPR120 and NGF, with significantly higher expression in cancerous tissues compared to adjacent noncancerous samples. Among the 386 patients, PNI was observed in 339 (87.8%). PNI correlated with tumor diameter, CA 19-9 levels, TNM stage, preoperative bilirubin levels, tumor differentiation, and preoperative drainage. Notably, GPR120 expression increased in poorly differentiated tumors and advanced clinical stages, indicating a clinical association with CCA progression. In vitro studies demonstrated that GPR120 promoted invasion and migration in the QBC 939 and HCCC-9810 cell lines. Western blot analysis confirmed elevated GPR120 levels in these lines, which also exhibited higher NGF expression. The GPR120 inhibitor AH7614 significantly reduced invasion in QBC 939 and HCCC-9810 cells, while the GPR120 agonist TUG-891 showed no effect on any of the CCA cell lines tested. Conclusions: GPR120 and NGF are implicated in perineural invasion (PNI) in CCA, with a notable correlation between GPR120 and NGF in the context of PNI occurrence.

Getting the right combination to break the epigenetic code

Soft Sputtering of Large‐Area 2D MoS₂ Layers Using Isolated Plasma Soft Deposition for Humidity Sensors (Adv. Mater. 8/2025)

Recent Advances in Next‐Generation Textiles

Abstract Textiles have played a pivotal role in human development, evolving from basic fibers into sophisticated, multifunctional materials. Advances in material science, nanotechnology, and electronics have propelled next‐generation textiles beyond traditional functionalities, unlocking innovative possibilities for diverse applications. Thermal management textiles incorporate ultralight, ultrathin insulating layers and adaptive cooling technologies, optimizing temperature regulation in dynamic and extreme environments. Moisture management textiles utilize advanced structures for unidirectional transport and breathable membranes, ensuring exceptional comfort in activewear and outdoor gear. Protective textiles exhibit enhanced features, including antimicrobial, antiviral, anti‐toxic gas, heat‐resistant, and radiation‐shielding capabilities, providing high‐performance solutions for healthcare, defense, and hazardous industries. Interactive textiles integrate sensors for monitoring physical, chemical, and electrophysiological parameters, enabling real‐time data collection and responses to various environmental and user‐generated stimuli. Energy textiles leverage triboelectric, piezoelectric, and hygroelectric effects to improve energy harvesting and storage in wearable devices. Luminous display textiles, including electroluminescent and fiber optic systems, enable dynamic visual applications in fashion and communication. These advancements position next‐generation textiles at the forefront of materials science, significantly expanding their potential across a wide range of applications.

Phase Ib study of gevokizumab (GEVO) in combination with standard-of-care (SoC) anticancer therapies in patients (pts) with metastatic colorectal cancer (mCRC), metastatic gastroesophageal cancer (mGEC), and metastatic renal cell cancer (mRCC).

135 Background: GEVO, a humanized monoclonal antibody, binds to interleukin-1β (IL-1β) and inhibits its activity. We report results from a phase Ib study of GEVO + SoC anticancer therapies in pts with mCRC/mGEC/mRCC. Methods: This open-label study enrolled pts aged ≥18 years in cohorts A (first line mCRC, [A]), B (second line [2L] mCRC, [B]), C (2L mGEC, [C]) and D (2L/third line mRCC, [D]). The primary objectives were to determine the pharmacodynamically-active dose (PAD) of GEVO monotherapy in A/B, the safety and tolerability, and the recommended dose for expansion (RDE) of GEVO + SoC in A/B/C/D, and the efficacy of GEVO + SoC at RDE in A/B/C measured by the progression-free survival (PFS) rate. The proof of concept (PoC) criteria for PFS rates were ≥42% at 15 months (m) (lower 80% CI limit ≥29%) in A, ≥48% at ~9 m (lower 80% CI limit ≥37%) in B, ≥51% at 6 m (lower 60% CI limit ≥38%) in C. The relationship between baseline levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and IL-1β, and on-treatment decrease of circulating tumor DNA (ctDNA) levels with clinical response was explored. Results: As of March 1, 2023, 71 (A), 62 (B), 26 (C) and 7 pts (D) were treated. The PAD was established as 120 mg GEVO intravenous (IV) every 4 weeks (Q4W) and the RDE as 120 mg GEVO IV Q4W + SoC. There were 2 dose-limiting toxicities: grade 4 decreased neutrophil count (1 pt in C) and grade 3 hyponatremia (1 pt in D). The most frequent grade ≥3 treatment-related adverse events (≥15% of all pts) were neutropenia (A/B: 21.1%/22.6%), decreased neutrophil count (A/B/C: 18.3%/17.7%/15.4%) and hyponatremia (D: 28.6%). The PFS rates were 29.0% (80% CI: 20.4, 38.2), 39.4% (80% CI: 29.8, 48.9), 20.0% (60% CI: 13.3, 27.6) in A/B/C, respectively. In B, median PFS and overall survival (OS) were significantly longer in pts with baseline hs-CRP &lt;10 mg/L (low [L]) than ≥10 mg/L (high [H]), IL-6 &lt;9.58 pg/mL (L) than ≥9.58 pg/mL (H), and IL-1β &lt;0.12 pg/mL (L) than ≥0.12 pg/mL (H). In A + B, a median on-treatment decrease of ctDNA fraction by &gt;72% (H) was associated with significantly longer OS. Conclusions: The safety and tolerability of GEVO combinations was acceptable. The primary PFS rates did not meet the PoC criteria. Baseline levels of hs-CRP, IL-6 and IL-1β in pts with 2L mCRC, and on-treatment reduction of ctDNA in pts with 1L + 2L mCRC may have prognostic value. Clinical trial information: NCT03798626 . Variables PFS HR (95% CI) p-value OS HR (95% CI) p-value Ahs-CRP L / HIL-6 L / HIL-1β L / H 1.74 (0.81, 3.73)1.38 (0.70, 2.72)1.50 (0.74, 3.01) 0.1550.3520.259 1.99 (0.66, 5.98)1.73 (0.71, 4.20)0.98 (0.38, 2.52) 0.2210.2250.973 Bhs-CRP L / HIL-6 L / HIL-1β L / H 2.56 (1.27, 5.18)2.92 (1.33, 6.40)2.41 (1.13, 5.13) 0.0090.0070.022 3.04 (1.40, 6.60)3.25 (1.43, 7.36)3.60 (1.54, 8.44) 0.0050.0050.003 A + BctDNA decrease L / H 0.65 (0.39, 1.10) 0.108 0.45 (0.24, 0.83) 0.011

Physical activity and sedentary behavior patterns after early-onset colorectal cancer diagnosis.

74 Background: Sedentary lifestyle and physical inactivity are established risk factors for colorectal cancer diagnosed among adults younger than age 50 years (early-onset CRC). However, patterns of physical activity (PA) and sedentary behavior (SB) in patients after an early-onset CRC diagnosis are less understood. Methods: The Reproductive Health After Cancer Diagnosis and Treatment (REACT) Study is a patient-partnered, cross-sectional study in cooperation with 23 community partners and patient advocates that recruited adults with a first primary cancer (diagnosis age: 18-49 years) over an 8-week period (October to December 2021). Patient-reported sociodemographic, cancer and cancer impact, PA and SB questions were prospectively collected via questionnaire. Frequency, duration and intensity of leisure-time, work-related and transportation-related PA were summed as minutes per week (min/wk). Time spent on SB was calculated by hours spent sitting on a typical day. Diagnosis age- and year-adjusted Spearman correlation coefficients were calculated between PA and SB by cancer treatment status. Results: A total of 131 patients were diagnosed with a first primary early-onset CRC between 2016 and 2021 (median [IQR] age, 40.0 [35-45] years; 82.4% female) in REACT. One hundred thirteen patients (86.3%) were concerned about their physical fitness or getting enough exercise after cancer diagnosis—of whom 62.8% (n=71 of 113) were somewhat or very concerned about their physical fitness/exercise. Among 80 patients with early-onset CRC and complete PA/SB data (86.3% female), 28.8% were not adherent to PA guidelines for aerobic activity (≥150 min/wk) and 56.3% reported long sedentary time (&gt;6 hr/day). The proportion of patients across PA/SB groups also statistically significantly differed by treatment status among those diagnosed between 2019 and 2021 (p=0.049), but not between 2016 and 2018 (p=0.25). While PA was not significantly correlated with SB for early-onset CRC patients who were not actively undergoing treatment (r=-0.16, p =0.32), there was a statistically significant moderate inverse correlation between PA with SB among early-onset CRC patients under active cancer treatment (r=-0.58, p =0.004). Conclusions: One in every 2 early-onset CRC patients reported long sedentary time and one in every 4 early-onset CRC patients in this study did not meet the Physical Activity Guidelines for Americans. With over 80% of patients expressing concern about their physical activity and exercise after an early-onset CRC diagnosis, and differences in PA/SB patterns observed by treatment status, these findings warrant prospective, longitudinal studies of objectively-measured PA and SB among young patients in order to support tailored strategies (e.g., exercise prescriptions) that improve patient health and outcomes across the CRC continuum.