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Chemotherapy is commonly used for the treatment of cancer but resistance often occurs. Here, the authors identify mitochondrial DLAT as driver of chemotherapy resistance via interaction with (MTHFD2) and develop a decoy peptide which blocks this interaction, restoring sensitivity to chemotherapy.

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.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

Septins are the key component of the cytoskeleton. Here, the authors show that Septin5 is assembled in microtubule-plasma membrane contact sites and mediates insulin secretion in pancreatic islet β-cells through cortical microtubule remodeling.

Human diseases may evolve by migration or spread, but understanding these complex processes is challenging. Here, the authors leverage graph homomorphisms to reconstruct trees describing histories of metastatic migrations and viral host-to-host transmissions.

BPAN is a rare neurodegenerative disease caused by WDR45 mutations. Here, the authors discover that WDR45 can competitively displace G3BP1 from Caprin-1 to promote stress granule disassembly, a function that is disrupted by BPAN-associated WDR45 mutations.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Membrane proteins have been implicated in cancers, but studying the downstream effects of their perturbation remains challenging. Here, the authors map the membrane protein-regulated network of 15 cancers, a resource for prognostic biomarker development and druggable target identification.

Magnetization reversal in magnetic topological insulators drives quantum phase transitions between quantum anomalous Hall, axion insulator, and normal insulator states. Using novel analysis protocol, the authors investigate critical behaviours of these transitions and establish their electronic origin.

Inspired by mechanoreceptors on flying insects, a flapping-wing drone that makes use of strain sensors on the wings and reinforcement-learning-based flight control has been developed. The drone can fly in various unsteady environments, including in windy conditions.

People can easily extract task-relevant gist features from visual scenes and hold those features in working memory. Here, the authors show that this gist information is gradually abstracted from posterior to anterior regions of the brain and stably represented at the anterior region.

Optimizing study design is critical for increasing standardized effect sizes and replicability, and the features that increase replicability in cross-sectional and longitudinal brain-wide association studies are explored.

Accurate prediction of surgical outcomes is essential for selecting treatment plans and ensuring patient satisfaction in corrective jaw surgery (orthognathic surgery). Here, the authors present and validate GPOSC-Net, a generative model for orthognathic surgery planning, to predict surgical movement and synthesize post-operative cephalograms from pre-operative data using a diffusion model.

The authors study the formation and characteristics of a Majorana metallic quantum spin liquid state in Kitaev’s honeycomb model under a moderate external magnetic field. This state represents a novel class of gapless quantum spin liquids stabilized by magnetic field.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Colour code on a superconducting qubit quantum processor is demonstrated, reporting above-breakeven performance and logical error scaling with increased code size by a factor of 1.56 moving from distance-3 to distance-5 code.

Lipid membranes are hard to visualise in tissues with nanoscale precision. The authors report ultrastructural membrane expansion microscopy (umExM), a tool that enables dense membrane labelling for nanoscale imaging of cellular membranes using a standard confocal microscope.

In quantum anomalous Hall (QAH) materials, the mesoscopic scattering length (L_s) plays an instrumental role in determining transport properties. Here, the authors examine L_s in three regimes (QAH, quantum critical, and insulating) with distinct transport behaviours, and find a universal L_s across all regimes.

B cell activation and differentiation entails metabolic remodelling, involving differential utilisation of monocarboxylates such as L-lactate and pyruvate. Here authors show by B-cell-specific genomic deletion of monocarboxylate transporter 1 (MCT1) that the consequential scarcity of pyruvate results in decreased acetylation of Histone H3 at K27, leading to decreased AID transcription and deficient class switching to IgG.

FICTURE is a segmentation-free approach for identifying tissue architecture in spatial transcriptomics data. FICTURE is compatible with both imaging-based and sequencing-based methods and is uniquely suited for handling the largest available datasets.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Diverse plant species synthesize salicylic acid from phenylalanine through a pathway that includes a conserved triple-enzyme module that converts benzoyl-CoA to salicylic acid.

Scaling effects on ferroelectric domains could impact applications for next-generation miniaturized devices. Here brownmillerite oxides are shown to demonstrate ferroelectric domains with widths down to the sub-unit-cell level.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

The molecular mechanisms that achieve ER morphology in neurites are not well understood. This study uses a forward genetic approach to demonstrate that atln-1 is required for neuronal ER morphology and that C. elegans atln-1 mutants exhibit defects in mitochondria fission at dendritic branch points and abnormalities in protein homeostasis.

Electrocatalytic CO₂ reduction has largely been limited to C₁ and C₂ products, especially at high current densities. Here, a Faradaic efficiency of 67% is reported for C₃₊ products from CO₂ at 1.1 A cm⁻² via a formaldehyde condensation mechanism on a phosphorus-rich copper catalyst.

Lithium-rich layered oxides, promising high-energy-density cathode materials, face electrochemical degradation due to structural disordering. Here, the authors report that slab gliding is a key trigger of this disordering and a pivotal unexplored avenue for a reversible anionic redox reaction.

There is no universal model for large earthquake recurrence, and an ensemble forecasting approach is desirable when dealing with paleoseismic records with few data points and large measurement errors.

Different types of cells exhibit a universal power-law rheological behavior which to this date has not been captured by a single theoretical model. Here, the authors propose a self-similar hierarchical cellular model that can naturally reproduce the universal power-law characteristics of cell rheology.

Visium spatial transcriptomics, single-nucleus RNA sequencing and co-detection by indexing are used to identify distinct spatial microregions in tumours and their microenvironment across six diverse solid cancer types.

Cortical microtubules of Toxoplasma gondii are exceptionally stable, but it isn’t known how they are anchored along membranes. Here, Harding et al. show that GAPM proteins localize to the inner membrane complex and are essential for maintaining the structural stability of parasites.

Entanglement entropy exhibits rich phenomenology connected to different kinds of phases in condensed matter. Here, the authors confirm some of these predictions by experimentally probing nonlocal correlations in 1D and 2D phononic crystal based on interconnected resonating acoustic cavities.

The spin-orbit torque (SOT) induced magnetic switching makes metal/magnetic insulators bilayers preferred in the energy efficient spintronic applications. Here the authors show SOT switching in W/TmIG bilayers and reveal the dimension crossover of SOT as a function of TmIG thickness.

The adaptor protein zyxin is known for its mechanosensing function in the maintenance of actin network. Here the authors show that zyxin is key to blood homeostasis and thrombosis by controlling the endothelial release of von Willebrand factor and the formation of actin scaffolds on exocytic granules.

The structure of the mitochondrial inner membrane, or cristae, is important for functional oxidative phosphorylation and energy production. Here, the authors show that loss of myosin 19 impairs cristae structure as well as energy production, connecting motor activity to membrane potential.

PRS-CSx is a polygenic risk score construction method that improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations.

Zhao et al. identify an unexpected role of the nuclear export factor Nxf2 as a partner of Panoramix in mediating piRNA-guided silencing. Nxf2 counteracts Nxf1-centred nuclear RNA transport to prevent the export of transposon transcripts.

A hybrid analogue–digital quantum simulator is used to demonstrate beyond-classical performance in benchmarking experiments and to study thermalization phenomena in an XY quantum magnet, including the breakdown of Kibble–Zurek scaling predictions and signatures of the Kosterlitz–Thouless phase transition.

Mapping the nature of multiprotein nanostructures in cellular contexts remains challenging. Here, Kang and Schroeder et al. report multiplexed expansion revealing, a technique which expands proteins away from each other, for nanoscale localisation and antibody visualisation of >20 proteins in the same specimen.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

Wu et al. report that IFNγ induces the phase separation of KAT8 and IRF1 into condensates that promote PD-L1 upregulation. They further identify a peptide that blocks KAT8–IRF1 condensates, reducing PD-L1 levels and increasing antitumor immunity.