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Tan and colleagues present “cycling molecular assemblies” that borrow cellular lipidation machinery to build nanostructures inside the Golgi apparatus. These tools enable rapid organelle imaging and selective destruction of cancer cells.

The existence of a long-lived, prethermal regime in many-body systems with tunable heating rates, driven by structured random protocols, is observed using a 78-qubit superconducting quantum processor.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Phosphorylation-dephosphorylation and ubiquitination tune TCR signaling to avoid self-reactivity. Kim and colleagues show that acetylation also modulates TCR signaling.

How site-specific tumor microenvironment (TME) drives the metastasis of high-grade serous ovarian cancer (HGSOC) remains unclear. Here, the authors employ an integrated single cell multi-omics approach to map the spatiotemporal heterogeneity of HGSOC metastasis TME and identify an interaction network within the TME driven by SELENOP⁺ macrophages and pre-exhausted CD8⁺ T cells.

The authors leverage experimental and phylogenetic data to propose that anammox bacteria during the Archaean period could have harvested photoholes from cyanobacterial mats for use as an electron acceptor prior to the availability of nitrite.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

X-ray study of compressed water shows that superionic ice adopts mixed close-packed structures rather than a single phase - a far more complex behaviour than expected, mirroring solid ice’s rich phases and informing planetary interior models.

Scanning nitrogen-vacancy microscopy unveils super-moiré spin textures emerging in twisted double-bilayer CrI₃ and provides real-space evidence of antiferromagnetic Néel-type skyrmions spanning multiple moiré cells.

SleepGPT is a time-frequency foundation model for sleep decoding, built on a generative pretrained transformer, achieving superior performance in various downstream tasks across datasets.

Dyskalemia is a dangerous potassium imbalance requiring rapid treatment. Here, the authors show, in a randomized trial of 14,989 patients, that real-time AI-ECG alerts increased hyperkalemia (69.1% vs. 41.6%, HR 2.23, 95% CI 1.44–3.46) but not hypokalemia treatment (HR 1.14, 95% CI 0.74–1.77).

Shang, Zhao, Ying and colleagues report that the mechanosensor PIEZO1 senses blood shear stress in hematopoietic stem cells, driving proliferation and myeloid bias. This axis links mechanical force to inflammation-induced aging, and PIEZO1 emerges as a potential therapeutic target.

Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing profiling of human retinal samples from diverse ancestries create an epitranscriptomic atlas characterizing over 130 cell types. Integration with genome-wide association study and expression quantitative trait loci data provides further insights into gene regulation and disease etiology.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

BioPathNet predicts drug–disease indications, synthetic lethality and lncRNA–mRNA interactions using a deep learning framework.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Without key cell cycle control genes, SAR11 cells experience aneuploidy and growth inhibition when exposed to changes in nutrients, carbon sources or temperature stress, a vulnerability that may represent an evolutionary trade-off for adaptation to oligotrophic environments.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

A study examines the effects of mutations that occur naturally in T cell cancers, reporting that such mutations can potentially be exploited to increase the potency of T cell therapies.

Highly ionically conductive and flexible solid-state composite battery electrolytes are engineered by alternately stacking inorganic Li_xM_yPS₃ (M = Cd or Mn) nanosheets with lithium-containing organic polymers in a perpendicular orientation to the surface of the electrodes.

Native crystallographic defects are often introduced during synthesis of battery materials, but has been overlooked. Here, using in situ synchrotron X-ray probes and electron microscopy, the authors have revealed their adverse effect during battery operation.

Plasmacytoid dendritic cells produce type I interferons in response to viral sensing. Here the authors show that amines inhibit these plasmacytoid dendritic cell responses through CXCR4 engagement.

Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.

Metabolite signatures were identified for subtypes of dietary carbohydrate, including added sugar, whole grain and refined grain, and showed different associations with type 2 diabetes, providing an objective measure of dietary risk.

Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.

A combination of scanning probe microscopy and quantum sensing is used to investigate changes in water structure under confinement. A liquid–solid phase transition is observed in thin films of water below a confinement size of 2 nm at ambient temperature.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

A van der Waals heterostructure made from atomic layers of ferroelectric CuCrP₂S₆ and ferromagnetic Fe₃GeTe₂ can offer reversible, non-volatile ferroelectric control of two-dimensional magnetism.

Here, with multi-omics analyses of human cohorts and murine models, the authors identify Odoribacter splanchnicus depletion to impair intestinal P-glycoprotein function via loss of microbial, GDP-L-fucose, which in turn promotes eIF4E phosphorylation and c-Jun–driven ABCB1 expression, maintaining xenobiotic efflux.

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.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

An annotation-free vision–language model based on contrastive learning performs pathology localization and clinical diagnosis on a wide variety of medical image datasets.

He et al. present a parameter-efficient fine-tuning method for single-cell language models that improves performance on unseen diseases, treatments and cell types.

Previous studies have implicated interleukin-24 (IL-24) in neutrophilic asthma. Here the authors show the function of IL-24 release from eosinophils in eosinophilic asthma in mouse models of asthma and that IL-24 promotes eosinophil recruitment to the lungs and is involved in disruption of epithelial barrier integrity.

Interwoven magnetic and non-magnetic layers in TbTi₃Bi₄ overcome kagome frustration, producing coupled elliptical-spiral magnetic and spin-density-wave orders and a very large anomalous Hall effect driven by strong electron–magnetic field interactions.

This study evaluates the potential of wetland conservation and restoration to improve water quality and highlights the important role of wetlands in nitrogen removal across European river basins.

Li and colleagues describe a monocyte-specific transcriptional state along with a persistent elevation of inflammatory markers specifically found in individuals with long COVID who had mild-to-moderate disease during acute SARS-CoV-2 infection.

Cosgun et al. show that, in B cell leukemia, β-catenin expression is maintained at low levels through glycogen synthase kinase 3B (GSK3β)-mediated phosphorylation. Inhibition of GSK3β results in β-catenin–Ikaros–NuRD complex formation, leading to B-ALL cell death through MYC repression.

Dendrobium is a genus of mostly epiphytic and lithophytic orchids. Here, the authors conduct comparative genome analysis for 24 chromosome-level genome assemblies and genome skimming sequencing data for 204 species in this genus, and reveal genomic variation, biosynthesis and evolutionary adaptation in Dendrobium orchids.

A nerve cuff composed of bioresorbable and ultrasound-activated triboelectric polymers is used to block pain in rats and pigs.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Cheng et al., use non-infectious stable viral replicon cell lines in genome-wide CRISPR KO screens across diverse viral pathogens to identify host factors specifically involved in the intracellular stages of viral replication.

A biohybrid chiral hydrogel combining cell-membrane-coated nanoparticles with a D-chiral matrix reduces tumour stemness via biochemical and biophysical regulation, boosting radioimmunotherapy and preventing postoperative glioblastoma recurrence.

Heterologous production of natural products in non-native bacteria can be used to increase yields of certain bioactive compounds; however, producing small molecules inside bacteria has numerous limitations. Two reports of the in vitro reconstruction of entire biosynthetic pathways highlight the advantages and challenges of this approach for pathway engineering.

Morehead et al. introduce the benchmark PoseBench and evaluate the strengths and limitations of current AI-based protein–ligand docking and structure prediction methods.