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Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

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.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Efficient voltage-controlled regulation of water and ion transport was achieved in stable Zr₄-Ti₃C₂T_x membranes. Under negative voltage, water diffusion was enhanced while ion transport was suppressed. This provides a promising strategy to overcome the intrinsic permeability– selectivity trade-off.

Resolution of G4s has been suggested to be required for efficient DNA replication. Here, the authors show that the nuclease DNA2 and the DNA repair complex MutSα (MSH2-MSH6) are required to remove G4 stabilized by environmental compounds to allow efficient telomere replication.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

The authors developed a screen to find compounds that modulate intracellular Staphylococcus aureus metabolism and discovered KL1, which sensitizes persisters to antibiotics by reversing host-induced tolerance.

Here the authors present a method to transform polygenic scores into disorder probabilities using only GWAS summary statistics, genotype data and a prior - no tuning sample is needed. The method enables individualized, well-calibrated predictions.

In this study, the authors combine interpolation techniques and deep learning methods, introducing Interpolating Neural Networks (INNs) to model complex systems with high accuracy and low computational cost.

Membrane budding plays pivotal roles in cellular processes, but a fully artificial system mimicking natural budding processes remains elusive. Here, the authors report a DNA origami-based membrane budding system that recapitulates key aspects of clathrin-mediated endocytosis without relying on components of cellular budding machineries.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

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.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

An outstanding question about the iron-based superconductors has been whether or not their magnetic characteristics are dominated by itinerant or localized magnetic moments. Absolute measurements and calculations of the magnetic response of undoped and Ni-doped BaFe₂As₂ indicate the latter.

Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.

Khetarpal et al. show that the metabolic regulator PGC-1α is essential in heart muscle cells for exercise-driven cardiac growth, and that suppression of the stress-induced myokine GDF15 is required to enable cardiomyocyte adaptations to training.

Interactions between qubits and defect-related two-level systems in superconducting qubit devices are a major source of noise fluctuations that hinder error-mitigation performance. Here, the authors experimentally show that modulating this interaction can reduce noise fluctuation and improve error mitigation performance.

NV center-based quantum sensors integrated into diamond anvil cells have enabled magnetic imaging under high pressure but are less suited for studying magnetic van der Waals materials. Here, the authors demonstrate magnetic imaging of micrometer-sized flakes of 1T-CrTe2 under high pressure using spin-centers in a thin hBN layer.

The sub-arc mantle has remained persistently oxidized since ~0.8 billion years ago, unaffected by increasing atmospheric and oceanic oxygen, according to machine learning techniques that classified arc basalts and revealed stable V/Sc.

The functional organization of the posterior parietal cortex (PPC) for guiding eye movements has remained unknown. Here, the authors use functional ultrasound neuroimaging to reveal small, tuned clusters in PPC that reliably encode where we look over months to years.

Here the authors use a range of approaches to examine the interplay between genetic variants linked to risk for polygenic skin diseases and transcription factors (TFs) important for skin homeostasis. The findings implicate dysregulated binding of specific TF families in risk for diverse skin diseases.

People living in rural areas of the United States have poorer outcomes from acute COVID-19. Here, the authors show that higher mortality rates among rural dwellers persist for up to two years after the initial infection, even after accounting for baseline risk factors.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

In this study, authors use molecular dynamics simulations to explore why Tantalum (Ta) and Zirconium (Zr) have different glass-forming abilities. It is shown that Ta’s lower critical cooling rate is due to stronger competing ordering effects and local icosahedral structures, which influence crystallisation pathways.

Lipid nanoparticles (LNPs) are a versatile class of clinically approved drug delivery vehicles, particularly for nucleic acid cargoes, but they often suffer from instability issues. Here, the authors report that the room temperature stability of small interfering RNA LNPs formulated with unsaturated ionizable lipids can be improved by inclusion of mildly acidic, antioxidant-containing buffers.

Spatial transcriptomic studies and lineage tracing reveal that, after brain injury, transient profibrotic fibroblasts develop from existing brain fibroblasts, infiltrate lesions, regulate the local immune response and lead to beneficial scar tissue formation.

While the connectivity of VTA dopamine neurons is well studied, less is known about the connectivity of VTA glutamate and GABA neurons. Here, authors show that these neurons form local circuits to modulate reward, aversion, feeding and locomotion.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Multiancestry fine-mapping of brain protein quantitative trait loci coupled with Mendelian randomization analyses identifies protein–trait pairs consistent with causal effects across neurological and psychiatric conditions.

A terahertz field exceeding 1 V nm⁻¹ induced a structural phase transition in the top atomic layer of a bulk WTe₂ crystal. Differential imaging revealed a surface shift of 7 ± 3 pm and an electronic signature consistent with a topological phase transition.

Aerosol deposition onto the surface of the ocean has been underestimated, suggesting that aerosol lifetimes over the ocean are longer than previously appreciated, according to a global compilation of cosmogenic beryllium isotope data.

The role of the tumour microenvironment in the response to immune checkpoint inhibitors in metastatic melanoma remains poorly understood. Here, single cell profiling of metastatic melanoma samples identifies associations of the mature dendritic enriched in immunoregulatory molecules subtype with immunotherapy response.

Dextran sulfate sodium is a colitis inducer that stimulates a ROS–Src–IP6K2 signaling axis to generate 5-IP₇, which sterically inhibits PI(4,5)P₂ phosphatases to promote PI(4,5)P₂-mediated E-cadherin endocytosis and epithelial junction breakdown.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

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.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

Antibody–bottlebrush conjugates expand the options for drug cargos compared to antibody–drug conjugates.

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.

Analysis of samples from the asteroid Ryugu provide evidence of late fluid flow in a carbonaceous asteroid, indicating that such bodies may have retained two to three times more water than previously thought.

Al-Hilal, Chrysovergi et al. identify a role for durotaxis in lung fibrosis and metastatic pancreatic cancer, mediated by the FAK–paxillin mechanosensor complex, and demonstrate therapeutic targeting of this pathway using the small molecule JP-153.

The Einstein Probe has discovered a fast X-ray transient, EP240414a, associated with a broad-lined type Ic supernova. Its unusually soft spectrum and weak jet add to the diversity of stellar deaths and suggest a previously unknown Wolf–Rayet star explosion mechanism.

The diversity of ponerine ants varies widely across the globe. This study finds that the origin and early colonization in Gondwana’s tropical regions mainly shaped this distribution, while differences in diversification and dispersal have balanced regional diversity over time.

A geological, petrographic and geochemical survey of distinctive mudstone and conglomerate outcrops of the Bright Angel formation on Mars reveals textures, chemical and mineral characteristics, and organic signatures that warrant consideration as potential biosignatures.

A modelling study based on satellite observations, machine learning and a chemical transport model quantifies the global and regional exposure to particulate-matter pollution and the human health impacts related to the 2023 Canadian wildfires.

The role of autoantibodies in bullous pemphigoid (BP) and their impact on keratinocytes and the response to BP pathology remains underexplored. By leveraging transcriptomics analysis and large-scale protein assays, here the authors identify keratinocyte MyD88 as a regulator of the pro-inflammatory response in BP, uncovering the role of keratinocytes in this disease pathology.

A pore-modulated pyrolysis reactor that enables catalyst-free and energy-efficient upcycling of plastic waste is demonstrated. The graded-pore structure imposes molecular-weight-dependent transport barriers, establishing a gating effect that enhances product selectivity and yields aviation fuel precursor (C₈–C₁₈) with high efficiency.