Browse Articles

Acquisition of Philadelphia chromosome at relapse in a case of Ph-like B-ALL

A novel triple-knockout allogeneic BCMA CAR T cell therapy (CT0590) in multiple myeloma: preclinical and phase I study

Host-versus-graft reaction (HvGR) is a major challenge in allogeneic chimeric antigen receptor (CAR) T cell therapy. To counter host natural killer (NK) cell attacks, we armored allogeneic, human leukocyte antigen (HLA)-I deficient, B-cell maturation antigen (BCMA)-targeting CAR T cells with an NKG2A CAR. In vitro and animal studies demonstrated that allogeneic CAR-NKG2A T cells effectively resisted host NK cell-mediated killing. BCMA and NKG2A dual-targeting allogeneic CAR T cells (CT0590) resisted killing by NK cells and showed robust antitumor activity in preclinical in vivo models. On the basis of these data, a first-in-human study (NCT05066022) enrolled five patients (four with relapsed and refractory multiple myeloma [RRMM] and one with primary plasma cell leukemia [pPCL]). CT0590 was well-tolerated and caused no dose-limiting toxicities, treatment-related death, or graft-versus-host disease. Three patients achieved confirmed responses, including two with stringent complete response (sCR). Notably, sCR in the patient with RRMM was still ongoing (duration of response > 23 months) at the time of data cutoff, and sCR in the patient with pPCL lasted for 20 months. Both patients showed robust expansion of universal CAR (uCAR) T cells (Cmax > 280,000 copies/µg gDNA) and higher baseline NKG2A expression on NK cells than nonresponders. These results suggest that CAR-NKG2A technology may overcome HvGR, especially in patients with elevated NKG2A expression on NK cells. Further studies of CT0590 in RRMM and pPCL are warranted.

How does NSD2 fuel multiple myeloma?

Anti-CD7 fratricide-resistant chimeric antigen receptor T cells for relapsed/refractory acute myeloid leukemia

Abstract Autologous second-generation CD7-directed chimeric antigen receptor T cells, expressing an anti-CD7 protein expression blocker to prevent self-killing fratricide, were infused in 3 pediatric/young adult patients with relapsed/refractory CD7+ acute myeloid leukemia, resulting in measurable residual disease negativity. The safety profile was favorable.

Programmable Optical Megapixel Nano‐Kirigami Matrix

ABSTRACT Pixel‐programmable miniaturized optical arrays with large pixel count are essential for cutting‐edge fields such as micro‐displays, photonic chips, and light detection modules. In recent advances, a universal strategy with ultrahigh pixel count and highly flexible programmability remains lacking. Here we report a programmable optical nano‐kirigami matrix with pixelated electromechanical reconfigurations. Deformable pixel arrays with high duty cycle and optical contrast are conceptually designed and experimentally realized based on a suspended turn‐shaped nano‐kirigami configuration. By employing the central plate to induce electrostatic force and the deformed arms to scatter incident light, switchable optical encryption and reconfigurable information display are demonstrated by programing the nano‐kirigami matrices with a pitch size of only a few micrometers. Furthermore, line‐level modulation based programmable information transmission and light projection are achieved by using a stripe‐shaped addressable nano‐kirigami matrix with 3.87 megapixels, showcasing an optical micro‐array with large pixel count and flexible programmability. Our work enables the high visibility and precise addressability of freely controllable electromechanical arrays with massive pixels, which could greatly improve the practical applicability for miniaturized optical arrays and brings potential applications in micro‐displays, photoelectronic chips, intelligent machine visions, hyperspectral image sensors, etc.

Bioinspired (Glyco)Polypeptides for Ice‐Control and Cell Cryopreservation

ABSTRACT Cryopreservation is a powerful technology providing fundamental support for basic biomedical research and clinical translation. Currently, cryoprotectants are commonly incorporated during the cryopreservation of cells to preserve their phenotypes and post‐thaw functionality. However, existing cryoprotective strategies still face crucial challenges in developing highly efficient and biocompatible approaches for storing various types of cells. Inspired by antifreeze (glycol)proteins, which are endogenous in antifreeze or freeze‐tolerant organisms for survival under subzero conditions, (glyco)polypeptides and analogues are developed with ice‐controlling properties and cryoprotective effects to maintain cellular viability and function after cryopreservation. The protein‐mimetic structures endow (glyco)polypeptides with advantages of biocompatibility, chemical structural diversity, multiscale tunability, and potential for economically large‐scale preparation. This review summarizes the synthesis, secondary structures, and self‐assembly behaviors of these (glyco)polypeptides, serving as a valuable bridge connecting polymer architectures to their applications as macromolecular cryoprotectants. The roles of (glyco)polypeptides are emphasized, including their activities and underlying protective mechanisms in ice nucleation, ice shaping, and ice recrystallization inhibition, as well as their cryopreservation performance for cells. Finally, in view of the requirement for a precise understanding of structure–property relationships, the prospects of multifunctional (glyco)polypeptides are discussed, with an outlook on the integration of machine learning.

Autonomous pathfinding for underactuated AUVs using FDHNN

Microsoft upgrades controversial quantum chip — researchers are still sceptical

Assessing the usefulness of digital contact tracing using real-world contact data

Theoretical and experimental investigation of NiFe2O4 and CaMnO3 nanoparticles to study their structural, magnetic, and polarization properties for energy-related applications

Sustainable removal of Acid Black 172 from wastewater using Lantana camara derived biochar insights from adsorption and statistical physics modeling

Swin-DRNet: A robust transformer framework for diabetic retinopathy screening under heterogeneous imaging conditions

Sustainable ionic liquid-assisted cloud point extraction for enrichment of trace copper(II) in water and food samples prior to spectrophotometric determination

Abstract This work introduces a novel, cost-effective, and sustainable ionic liquid–assisted cloud point extraction (IL-CPE) technique for the enrichment and spectrophotometric quantification of trace copper(II) at 436 nm. The method employs the complexation of Cu(II) with (Z)-4-bromo-2-(((2-hydroxyphenyl)imino)methyl)phenol at pH 6.5, succeeded by extraction with 1-butyl-3-methylimidazolium hexafluorophosphate and Triton X-114. Under optimal circumstances, the approach exhibited remarkable linearity (2.0–300 µg L⁻¹, R 2  = 0.9997), substantial sensitivity with a preconcentration and enrichment factors 100 and 12.5, respectively, and a minimal detection limit of 0.6 µg L⁻¹. Precision and reliability of the novel IL-CPE method was validated by low relative standard deviation for 100 and 200 µg L⁻¹ ( n  = 10) was 1.6% and 2.0%, respectively, and accuracy was substantiated by the use of certified reference materials and actual environmental samples, encompassing water and food matrices. Moreover, the method’s environmental effect was meticulously assessed utilizing several Green Analytical Chemistry metrics (AGREE, AGREEprep, ComplexMoGAPI, AGSA) and practical indices (BAGI, CACI). The evaluation via the RGB algorithm and Carbon Footprint Reduction Index (CaFRI) verifies that this method is a sustainable, eco-friendly, and very dependable option for regular trace metal detection.

Phase 3 clinical trial of the combination of erlotinib plus ramucirumab compared with osimertinib in untreated advanced or recurrent non-small cell lung cancer with EGFR L858R mutation: The REVOL858R trial (WJOG14420L).

LBA8518 Background: Among common EGFR-mutant NSCLC, L858R mutation is suggested to be less sensitive to EGFR-TKIs and associated with poorer prognosis than ex 19 del. REVOL858R is the first randomized phase III trial conducted exclusively in patients with advanced/recurrent EGFR L858R–mutant NSCLC, comparing a treatment strategy of erlotinib plus ramucirumab (E+RAM) followed by osimertinib (OSI) upon detection of acquired T790M with first-line OSI monotherapy. Methods: Eligible patients were treatment-naive adults (≥20 years) with advanced/recurrent EGFR L858R–positive NSCLC and ECOG PS 0–1. Patients were randomized 1:1, stratified by clinical stage (IIIB/IIIC/IV vs postoperative recurrence), sex, and baseline brain metastasis (BM). Patients received OSI 80 mg once daily (Arm A) or E+RAM (E 150 mg once daily plus RAM 10 mg/kg every 2 weeks; Arm B). In Arm B, tumor rebiopsy or liquid biopsy at termination of E+RAM was mandated; patients with detected T790M subsequently received OSI, whereas those without T790M discontinued protocol treatment. The primary endpoint, time to failure of strategy (TFS), was defined as time from randomization to disease progression or death during OSI, or during the primary treatment when OSI was not administered (in Arm B). Results: Overall, 232 patients were randomized (Arm A n=116; Arm B n=116). Baseline characteristics were generally well balanced between the two arms. In the full analysis set, median TFS was 14.8 months in Arm A and 16.6 months in Arm B (HR 1.03; 95% CI 0.78–1.38; log-rank p=0.49). Key secondary endpoints and selected prespecified subgroup analyses of TFS are summarized in Table. The most common AEs (any grade) were diarrhea (41% vs 54%) and acneiform rash (30% vs 71%) in Arm A vs Arm B. Hypertension and proteinuria were observed in 39% and 18% of patients in Arm B, respectively. Interstitial lung disease occurred in 12 patients (10%) in Arm A, and 2 patients (2%) in Arm B. AEs leading to discontinuation of protocol treatment occurred in 21% vs 36% of patients (Arm A vs Arm B). Conclusions: A planned E+RAM-to-OSI strategy did not improve TFS compared with upfront OSI in EGFR L858R–mutated NSCLC. Safety findings were consistent with known profiles, with higher discontinuation for tolerability in the strategy arm. Trial information: jRCTs051200142. Clinical trial information: 051200142. Key secondary endpoints. Key secondary endpoint, median (months) Arm A (OSI) Arm B (E+RAM) HR (95% CI) OS 44.0 (31.1-NR) 38.4 (33.3-NR) 0.98 (0.66-1.45) 3-y OS (%) 56.1% 57.2% – ORR (%) 73.2% 66.3% – PFS1 14.8 14.9 1.08 (0.81-1.44) PFS2 23.8 25.1 0.96 (0.70-1.33) Time to treatment failure 12.6 11.2 1.34 (1.02-1.77) Key prespecified TFS subgroups <65 years / ≥65 years 18.4 / 14.8 21.2 / 16.0 0.90 (0.40-1.99) / 1.06 (0.78-1.45) With / Without baseline BM 11.8 / 19.2 14.7 / 17.8 0.81 (0.49-1.34) / 1.11 (0.79-1.57)

Electron ptychography reveals correlated lattice vibrations at atomic resolution

Abstract Electron Ptychography is a computational imaging technique capable of performing phase retrieval at atomic resolution. Here we introduce the CAVIAR framework (Correlated Atomic Vibration Imaging with sub-Angstrom Resolution) that reveals spatial correlations in atomic displacements at the atomic scale. Using realistically simulated data for a symmetric Σ 9 grain boundary in silicon and experimental data of a hexagonal boron nitride bicrystal, we observe correlations between atomic movements in the range of 10-20 pm at room temperature in agreement with our expectation. From only the atomic masses and temperature as input, we obtain frequencies of the longitudinal and transverse acoustic and optic phonons from just a few nm 3 volume, in agreement with inelastic neutron scattering. This ability to spatially resolve correlated atomic motion distinguishes CAVIAR and positions it as a complementary tool to vibrational electron energy loss spectroscopy for exploring atom dynamics at the finest scale.

Antioxidant, antimicrobial, and AMPA receptor modulatory activities of selected medicinal plant extracts reveal multitarget pharmacological potential

From Molecular Complexity to Personalized Care in Chronic Myelomonocytic Leukemia

PIP2 activation of the cardiac IKs potassium channel

Hybrid and advanced convolution techniques for highly accurate, reliable and automated ECG classification

Abstract Cardiac arrhythmias are a leading cause of cardiovascular mortality worldwide, and auto- mated analysis of electrocardiogram (ECG) recordings is an unmet clinical need. This paper introduces a hybrid 1D Convolutional Neural Network (CNN) architecture for automated ECG heartbeat classification that captures both multi-scale morphological and long-range temporal dependencies. The architecture combines Dynamic Kernel Switching (DKS) with adaptive gating over kernel sizes {3 , 5 , 7}, a Self-Attention module, and Dilated Convolutions at dilation rates 2 and 4. For low-power edge deployment on Neural Processing Units (NPUs) and FPGA/ASIC platforms, three quantization paths are evaluated: (1) Dynamic Post-Training Quantization (PTQ) with INT8 weights and FP32 I/O, (2) Full-Integer PTQ with INT8 weights and activations, and (3) Quantization-Aware Training (QAT). With a corrected stratified 72/8/20 train/validation/test protocol, focal loss ( γ  = 2 . 0), AdamW optimization and cosine learning rate decay, the proposed model achieves 98.99% test accuracy and a macro F1-score of 0.9484 on the MIT-BIH Arrhythmia Database (16,219 held-out test beats, five AAMI classes). Five-fold stratified cross-validation confirms statistical robustness: 98 . 93% ± 0 . 10% accuracy with 95% confidence interval [98.84%, 99.02%]. A comprehensive seven-variant ablation study covering Self-Attention, CBAM, CSA, and SimSA demonstrates that the proposed DKS + Self-Attention combination outperforms all alternatives. Generalization is further validated on five independently withheld MIT-BIH patient recordings (10,444 beats), achieving 92.86% accuracy and macro F1 of 0.8219. The model comprises only 331,733 parameters and reduces to ≈0 . 32 MB under Dynamic PTQ, enabling direct TFLite/INT8 conversion for RTL-level FPGA deployment.

Node-sparing modified short-course radiotherapy combined with CAPOX and tislelizumab versus conventional short-course preoperative chemoradiotherapy for proficient mismatch repair or microsatellite stable locally advanced rectal cancer (mRCAT-III): A multicenter, randomized, open-label, phase 3 trial.

LBA3515 Background: Total neoadjuvant chemoradiotherapy is the standard of care for locally advanced rectal cancer (LARC) to control local recurrence and achieve organ preservation. However, for proficient mismatch repair (pMMR) or microsatellite stable (MSS) LARC, which accounts for nearly 90% of rectal cancers, conventional chemoradiotherapy has limited efficacy and is associated with significant side effects. Recent studies have shown that combining radiotherapy with immunochemotherapy can improve pathological complete response (pCR) rates, but the inclusion of tumor-draining lymph nodes (TDLNs) in the conventional irradiation field may impair T-cell immunity and reduce response to immunotherapy. Our previous single-arm phase II trial demonstrated that node-sparing modified short-course radiotherapy combined with chemotherapy and PD-1 blockade could achieve a high pCR rate of 78.8% in pMMR LARC. 1 Building on these findings, we initiated this phase III trial to compare this new treatment regime with conventional short-course chemoradiotherapy in improving pCR rates. 2 Methods: This is a phase III, open-label, multicenter, randomized trial conducted across 17 hospitals in China. A total of 154 eligible MSS/pMMR middle or low rectal cancer patients (cT3-4N0/+M0) will be recruited and randomly assigned (1:1) to two groups: control group (conventional short-course chemoradiotherapy), experimental group (node-sparing modified short-course chemoradiotherapy plus PD-1 blockade). The innovative node-sparing modified short-course radiotherapy targets only the primary tumor bed, excluding TDLNs. Following randomization, patients will receive short-course radiotherapy (conventional or node-sparing) followed by four cycles of CAPOX ± tislelizumab: tislelizumab 200 mg IV on day 1, oxaliplatin 130 mg/m² IV on day 1, and capecitabine 1000 mg/m² orally on days 1-14, and Total mesorectal excision (TME) will be performed at weeks 14-15. The primary endpoint is pCR rate, while secondary endpoints include organ preservation rate, disease-free survival, overall survival, adverse effects, and quality of life. The primary and secondary endpoints will be analyzed in the intent-to-treat (ITT) population. Safety analyses will be performed in the safety population, defined as patients who received at least one dose of study treatment. Results: 247 patients were assessed for eligibility, a total of 154 patients were enrolled in the ITT population (77 per group). Baseline characteristics were well balanced between the two groups. In the ITT population, the experimental group demonstrated a significantly superior pCR rate compared to the Control group: 61.4% (47/77) vs 28.6% (22/77) (P < 0.001). The MPR rate was also significantly higher in the experimental group (80.5% vs 50.6%). All patients in both groups received sphincter-sparing surgery. Regarding safety, the incidence of grade 3-4 treatment-related adverse events (TRAEs) was comparable between the experimental and control groups (23.4% vs 22.1%). Immune-related adverse events (irAEs) occurred in 7.8% (6/77) of patients in the experimental group, primarily grade 1-2. Conclusions: Compared with conventional short-course preoperative chemoradiotherapy, node-sparing modified radiotherapy combined with CAPOX and PD-1 blockade significantly improved pCR rates in patients with pMMR/MSS LARC, with a manageable safety profile. This regimen represents a promising and highly effective neoadjuvant strategy for MSS rectal cancer. Clinical trial information: NCT06507371. Reference：1. Annals of Oncology (2024) 24 (suppl_1): 1-20. 10.1016/iotech/iotech100744; 2. 2025;43 16_suppl. https://doi.org/10.1200/jco.2025.43.16_suppl.tps3641. Clinical trial information: NCT06507371 .