Browse Articles

Bioinspired conductive and antibacterial hydrogel bionanocomposite based on tragacanth gum, polyaniline and osteoconductive SiO2 nanoparticles as a scaffold for bone tissue engineering application

Enoxaparin induces apoptosis and autophagy, modulates inflammatory signaling, and reduces oxidative DNA damage in breast and liver cancer cells

Temperature-dependent distribution and life history traits of the pestiferous slug Deroceras laeve in the Sikkim-Darjeeling Himalayas

Phenotypic and genetic factors that affect the likelihood of Standardbred foals achieving a race start

Propensity Score–Matched External Controls in Rare Disease Trials: A Promising Tool Requiring Rigorous Validation

Vertical stratification of soil stoichiometric drivers across urban forest parks in Shenzhen, China

Integrative Molecular Analysis Reveals Determinants of Clinical Outcomes in <i>TP53</i> -Mutated Diffuse Large B-Cell Lymphoma

PURPOSE Mutations in TP53 , detected in over 20% of diffuse large B-cell lymphomas (DLBCLs), are associated with poor prognosis. However, clinical outcomes among patients with TP53 -mutant disease vary, with some patients showing treatment responses similar to those with wild-type TP53 . This study aims to understand the clinical and molecular determinants underlying poor outcomes in TP53 -mutant DLBCL. METHODS Clinical and molecular data for 3,091 patients were derived from 10 cohorts of patients with newly diagnosed DLBCL treated with frontline rituximab-based immunochemotherapy regimens. Targeted or whole-exome/whole-genome sequencing was available for all patients. Bulk RNA-seq was analyzed for 591 patient samples. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). RESULTS TP53- mutant DLBCL differed from wild-type disease in pattern and number of genetic lesions, malignant B-cell expression states, and tumor microenvironment composition. TP53 mutations were 6-fold more prevalent than MYC/BCL2/BCL6 double-/triple-hit status, but conferred similar adverse prognostic risk. Among patients with TP53 -mutant disease, variant allele frequency (VAF) further stratified risk, with patients featuring VAF ≥ 75% (indicative of loss of heterozygosity) experiencing significantly inferior PFS/OS. Downregulation of interferon signaling and lower macrophage content were identified in TP53 -mutant samples derived from patients with poor outcomes or VAF ≥ 75%. TP53 mutations were adversely prognostic among patients with DLBCL assigned to specific LymphGen subtypes (EZB, MCD), malignant B-cell states (S1), and ecotypes (LE4, LE7, LE8), whereas outcomes were similar to wild-type disease within other molecular subtypes. In re-examination of the Phoenix trial data, addition of ibrutinib to R-CHOP improved PFS in patients with TP53 -mutant DLBCL and abrogated the deleterious impact of high VAF, irrespective of patients' age. CONCLUSION The poor prognosis of TP53 -mutant DLBCL is dependent on intrinsic features, such as VAF, and modulated by co-occurring genomic lesions or lymphoma cell-intrinsic or microenvironmental expression patterns.

Debris variability and velocity estimation using Electrical Resistivity Tomography and DInSAR techniques of Durung Drung glacier, northwestern Himalaya

Neoadjuvant Sacituzumab Govitecan in Patients With Muscle-Invasive Bladder Cancer: Primary Results of the SURE-01 Trial

PURPOSE To evaluate neoadjuvant sacituzumab govitecan (SG), followed by radical cystectomy (RC), in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for/refuse neoadjuvant chemotherapy (NAC). We report the results of the primary analysis and biomarker analyses of the phase II SURE-01 trial (ClinicalTrials.gov identifier: NCT05226117 ). PATIENTS AND METHODS Patients were age 18 years and older, had Eastern Cooperative Oncology Group performance status 0-1, had histologically confirmed cT2-T4aN0M0 MIBC, were ineligible/refusing NAC, and were scheduled for RC received four cycles of SG 10 mg/kg on day 1 and day 8, once every 3 weeks, followed by RC. The primary outcome measure was the pathologic complete response (pT0N0) rate. Transcriptome-wide analyses and comprehensive genomic profiling assays were performed on baseline tumor samples. RESULTS From March 2022 to July 2025, 44 patients were treated and efficacy evaluable. After the initial eight patients enrolled, the protocol was amended with a SG dose of 7.5 mg/kg, with primary prophylaxis for neutropenia, due to the occurrence of two deaths (one treatment-related). Subsequent grade 3-4 treatment-related adverse-events occurred in 5 patients (13.9%). Twenty-six patients (59.1%) had a cT3-4 stage and 20 (45.5%) had a variant histology. Fourteen patients (31.8%) refused to undergo RC, accounting for 12 repeating a transurethral resection of the bladder tumor and two undergoing active surveillance. The median follow-up was 22 months (IQR, 15-26). In the intention-to-treat population, although the protocol-defined ypT0N0 rate was 9.1% (95% CI, 2.5 to 21.7), the overall ypT0N0-x rate was 29.5% (95% CI, 16.7 to 45.2), with an enrichment of ypT0 responses in nonluminal subtypes (46% v 14% of luminal). The 24-month event-free survival (EFS) rate was 71.4% (95% CI, 58 to 87.8), with longer EFS for participants with lower TOP1-expressing tumors. CONCLUSION Neoadjuvant SG, at the reduced dose of 7.5 mg/kg, was active with a manageable safety profile, corroborating TROP2 as a suitable target for MIBC.

Unhealthy lifestyle and cardiovascular disease risk in older adults aged 75+ without prior cardiovascular events: a nationwide cohort study

In DeFi-ance of “More Is Better”: Questioning Long-Term Nirogacestat Use in Desmoid Tumors

A non-invasive targeting approach using RK-50 for stereotactic-guided focused ultrasound blood brain barrier opening in mice

Abstract Focused ultrasound (FUS) combined with micro/nanobubbles enables transient, localized blood brain barrier opening (BBBO) for targeted drug delivery to the brain. Although imaging-guided FUS methods provide accurate targeting, they require specialized infrastructure that increases cost and workflow complexity. Commercial stereotactic FUS platforms such as the RK-50 offer an accessible alternative, but standard procedures rely on a scalp incision to identify bregma for atlas registration, introducing tissue injury and potential confounds for repeat-BBBO studies. Here, we describe and validate a fully non-invasive targeting approach for FUS BBBO in mice using the RK-50 platform. Our novel targeting method achieved accurate, reproducible targeting without surgical exposure. Evans blue extravasation and atlas co-registration demonstrated sub-millimeter targeting accuracy at bregma and confirmed reliable BBBO in the cortex, hippocampus, and cerebellum. Across these anatomically distinct targets, passive cavitation detection showed broadly comparable acoustic emissions profiles. We further compared this non-invasive workflow with the standard incisional approach in a repeat-BBBO paradigm and observed similar acoustic emissions and comparable delivery of both small molecule and large molecule (antibody) reporters. Together, these findings establish a high-fidelity, incision-free targeting strategy that preserves the accessibility of stereotactic FUS while reducing procedural burden and improving suitability for longitudinal preclinical BBBO studies.

Umbilical Cord Blood and Nonengrafting Allogeneic Cell Therapies

Outside Back Cover: Piezoelectric Nanozymes With Acoustically Rejuvenated Catalytic Activities Rewire Lipid Metabolism for Two‐Pronged Ferroptotic Therapy (Angew. Chem. Int. Ed. 30/2026)

Dynamic Anion Space Gradient Distribution Drives Wide‐Temperature‐Range All‐Solid‐State Lithium‐Ion Batteries

ABSTRACT To address the critical challenges of poor ionic conductivity, insufficient interfacial stability, and narrow operating temperature range in all‐solid‐state lithium batteries (ASSLBs), this work develops a dynamic anion functionalization strategy to design and synthesize a new class of yttrium‐based rare‐earth halide solid‐state electrolytes (SSEs). It is found that the dynamic anions can not only statically modify the lattice but also undergo reversible dynamic migration during cycling, thereby transforming the traditional single‐cation conductor into a cation‐anion synergistic conductor, which significantly enhances the overall ionic conductivity. Furthermore, the dynamic anions facilitate a gradient LiF protection layer on the cathode side to improve high‐voltage compatibility and form a dense Li 3 N–LiF–LiI composite adaptive interphase on the anode side, effectively suppressing dendrites and stabilizing the interface. The assembled ASSLBs based on the dynamic anion strategy demonstrate stable operation across a wide temperature range from extreme cold (−30°C) to high temperatures (140°C), while delivering high specific capacity, long cycle life, and outstanding safety characteristics. Our findings establish a new paradigm for developing next‐generation ASSLBs capable of reliable operation under extreme conditions.

Effect of optimal control on SI epidemic model

Reply to: In DeFi-ance of “More Is Better”: Questioning Long-Term Nirogacestat Use in Desmoid Tumors

Design and implementation of a high-sensitivity receiver channel for the BeiDou RDSS

Development and External Validation of a Transcriptome-Based Multivariable Prediction Model for Treatment-Free Remission in Chronic Myeloid Leukemia

PURPOSE Treatment-free remission (TFR) is a major therapeutic objective in chronic myeloid leukemia (CML). However, nearly 50% of patients relapse after tyrosine kinase inhibitor (TKI) discontinuation, and no robust predictive biomarker is currently available. METHODS We profiled peripheral blood cell transcriptomes at imatinib (IMA) discontinuation in patients from the multicenter STIM2 trial (n = 96) to develop a transcriptome-based model predicting TFR by 2 years. A DESEQ2-based machine learning approach was compared with classical machine learning algorithms. The signature was then externally validated in an independent real-world cohort of patients attempting IMA or nilotinib cessation (n = 70). The biologic processes associated with the signature were further explored. RESULTS We identified a 50-gene signature discriminating patients with sustained 2-year TFR from those experiencing molecular relapse (area under the receiver operating characteristic curve [AUROC], 0.83 [95% CI, 0.73 to 0.93] and 0.75 [95% CI, 0.55 to 1.00] in the training and internal validation cohorts, respectively). The discriminative performance was confirmed in the external test cohort, both as a binary predictor of 2-year TFR (AUROC, 0.71 [95% CI, 0.58 to 0.83] overall; 0.77 [95% CI, 0.61 to 0.92] in IMA-treated patients) and as a time-to-event predictor (log-rank P = .0042). The high TFR-signature group showed a higher proportion of myeloid immune cells and natural killer T cells, with an enrichment in Hedgehog signaling, whereas the low TFR-signature group demonstrated a higher proportion of lymphoid cells with an enrichment in mTOR signaling and a trend for oxidative phosphorylation activation. T-cell receptor and immunoglobulin heavy-chain repertoire analyses showed significantly greater polyclonality in the high TFR-signature group. CONCLUSION These findings demonstrate that transcriptomic profiling at TKI discontinuation can predict TFR outcomes in patients with CML and provide biologic insights into the mechanisms underlying sustained TFR.

CO ₂ ‐Derived Graphite: A Critical Material for Terrestrial and Martian Sustainability

ABSTRACT CO 2 , one of the major contributors to global climate change, is a promising carbon feedstock for graphite synthesis. Graphite is the only carbon‐based critical material recognized by numerous countries and international organizations, with various applications including energy storage on Earth and Mars. Herein, this study realizes the mild, efficient in situ synthesis of graphite from CO 2 , H 2 O, and borate, which are abundant on both planets. At 220°C and 5.0 MPa with NaBH 4 , graphite is obtained with 79.2% selectivity and 93.1 wt.% purity, and byproduct NaBO 2 can be electrochemically recycled for sustainable material utilization. Mechanistic investigations reveal that CO 2 reacts with NaBH 4 to form methane, ethylene, and propadiene. Methane and ethylene generate aromatics, while propadiene promotes polymerization into graphite. As a Zn‐based battery anode, the graphite retains 90.9% capacity after 2500 cycles at 1.0 A·g −1 for Zn‐CO 2 ||MnO 2 , confirming excellent energy storage performance. This work not only provides a novel, sustainable strategy for CO 2 utilization and storage but also aims to bridge terrestrial environmental crisis mitigation and extraterrestrial in‐situ resource utilization, laying a foundational basis for material, environmental, and energy sustainability on Earth and Mars.