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Fungal diseases threaten crops worldwide. By resolving the cryo-EM structure of fungal succinate dehydrogenase, researchers designed an inhibitor with broad antifungal activity, strong field performance, and reduced environmental toxicity.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

Zhang et al. show that the activation of RIPK1 is suppressed by acetylhypusination in a spermidine-dependent manner. Disruption of this axis contributes to RIPK1-mediated vascular pathology to promote insulin resistance and diabetic kidney pathology.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

Under low-protein conditions, decrease of protein NUFIP1 is found to impair DNA damage response and induce necroptosis in the intestine, thereby contributing to intestinal inflammation in male mice with inflammatory bowel disease.

Stress urinary incontinence (SUI) is a significant clinical challenge where less invasive treatment strategies that also address the pathophysiology of SUI are desirable. Here, Fang et al. engineer an injectable, thermo-responsive composite hydrogel incorporated with programmed stem cells that provides structural support to the atrophic urethral sphincter and promotes urethral sphincter regeneration, angiogenesis, and neurogenesis as a treatment strategy for SUI.

Two deep-learning frameworks — GHIST and iSCALE — turn routine histology images into a rich molecular resource, and predict spatial gene expression at single-cell resolution (GHIST) and at super-resolution across large tissue sections (iSCALE), for scalable, data-driven tissue biology.

A combination of adenovirus-vectored and subunit protein intranasal vaccine enhances immune response against SARS-CoV-2 variants in animal models and humans.

Sequencing the genome and microbiome of about 1,500 tick samples from regions across China revealed host–microbe associations in ticks that could have implications for controlling ticks and tick-borne diseases.

PLD4 loss-of-function mutations in patients with systemic lupus erythematosus leads to excessive activation of TLR7 and TLR9.

The Wnt signalling pathway is essential for development and the maintenance of stem cells. Here, the authors reveal how LGR4 and RSPO2 modulate ZNRF3 conformations and assembly heterogeneity, stabilising ZNRF3 in its inactive state to enhance Wnt signalling. These findings offer insights for the development of targeted therapies for Wnt-driven cancers.

Alternative expression analysis by sequencing (ALEXA-seq) aligns RNA-seq reads from different cell types to a database of alternative expression sequence features and quantifies isoforms that are differentially expressed between samples.

The ability to pursue a stronger recall response on secondary antigen encounter is a hallmark for T cell immunity. Here the authors show that the histone component, H2A.Z, may contribute to CD8 T cell recall readiness by depositing to specific locations and introducing a specific epigenetic landscape in CD8 memory T cells to facilitate more prompted activation of related genes.

Comprehensive molecular characterisations could shed light on the high heterogeneity and poor prognosis of gliomas. Here, the authors perform proteomic profiling of 188 glioma patients, revealing immune and metabolic neuron-related subgroups as well as metabolic biomarkers linked to prognosis.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

The role of the tumor microenvironment in immunotherapy response in intrahepatic cholangiocarcinoma remains unclear. Here, single cell RNA and TCR sequencing of samples before and after immunotherapy highlights the role of CD8 T-cell status conversion and exhaustion induced by Macro CD5L+ in treatment response.

Freestanding membranes of hafnium zirconium oxide can be created using pulsed laser deposition method and used as the top-gate dielectric in molybdenum disulfide transistors.

Maintaining proper reactive oxygen species (ROS) balance is critical for cellular and individual health, yet its dynamic nature encumbers monitoring and assessment. Here the authors propose a platform using mass cytometry-based detection, termed SN-ROP, to identify distinct ROS profiles associated with specific immune cell functions and disease states.

In urethral damage, exogenous implants designed for urethral repair are hindered by the open and harsh urethral microenvironments and the isotropic compression and swelling properties of the material. Here, Yang et al. develop a tri-layer hydrogel with anti-fouling and low-swelling properties for scarless urethral repair.

Chronic visceral pain is frequently accompanied by changes in food preference and the underlying neural circuitry mechanisms remain unclear. Here, the authors elucidate a circuit from cholecystokinin neurons in the paraventricular hypothalamus (PVH^CCK) projecting to glutamatergic neurons in the anterior cingulate cortex (ACC^Glu) to regulate food preference accompany with chronic visceral pain.

The combination of anti-PD-1 treatment with cisplatin and 5-fluorouracil in patients with previously untreated, PD-L1-positive esophageal squamous cell carcinoma improved progression-free survival and overall survival.

Sirtuin 5 (SIRT5) has been associated to colorectal cancer and metabolic regulation. Here, the authors show that SIRT5 silencing reduces nucleotide availability leading to DNA damage and tumor suppression in colorectal cancer models.

The knowledge of how electrons behave under magnetic field provides inherent information for exotic quantum states. Here, Fu et al. find different g-factors of topological surface states in Bi₂Se₃ and Sb₂Te₂Se, which suggests possible control of such states in spin-related applications.

The mechanisms linking neuropsychiatric and metabolic disorders remain unclear. The authors show a pancreas–hippocampus feedback loop whereby metabolic and circadian factors drive behavioral fluctuations, with potential relevance for bipolar disorder.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

In a prespecified interim analysis of the randomized, double-blind phase 3 COMPASSION-15 trial, patients with advanced HER2-negative gastric/GEJ cancer treated with the anti-PD-L1/CTLA-4 bispecific Ab cadonilimab plus chemotherapy showed significantly improved overall survival compared with patients treated with placebo plus chemotherapy as first-line treatment.

Multipolarons provide a potential platform for manipulating electrons. Here, the authors demonstrate the creation and manipulation of multipolarons in CrBr₃ via the tip of a scanning tunneling microscope.

Worldwide, the number of only-child families is increasing. This research examines how growing up without siblings affects adult brain structure, function and connectivity, cognition, personality and mental health.

Obesity can affect bone marrow cell differentiation and the generation of myeloid and lymphoid cells. Here, the authors show that diet and obesity, as well as low-dose lipopolysaccharide, can alter Toll-like receptor 4 signaling bone marrow cells to skew the myeloid-lymphoid homeostasis in mice.