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ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

By studying fossil corals on Ishigaki Island in Japan, Debaecker et al. find evidence of repeating megathrust earthquakes over the last 5,000 years, revealing long-term earthquake supercycles and highlighting significant future earthquake and tsunami hazards.

Transition metal-catalysed carbene reactions facilitate a number of transformations in organic chemistry. Here the authors report iron-catalysed cascade reactions—involving carbene and carbene radical intermediates—of alkyne-tethered diazo compounds for the construction of carbocyclic molecules.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

A Dirac-vortex topological photonic crystal fiber is experimentally realized with broadband single polarization single-mode properties.

Experiments under upper-tropospheric conditions map the chemical formation of isoprene oxygenated organic molecules (important molecules for new particle formation) and reveal that relative radical ratios control their composition

Nanofibrils constructed from oat protein and carrying iron nanoparticles can increase absorption compared with ferrous sulfate in human studies, offering a promising fortification strategy for treating iron deficiency and improving human nutrition.

Antibody-conjugated Mesenchymal stromal cells (Ac-MSC) carrying internalized therapeutic agents represent a promising therapeutic approach for the treatment of autoimmune disease. Here, an ac-MSC-based drug delivery system, consisting of anti-CD4 antibody-conjugated MSCs loaded with a RORγt inverse agonist, is engineered to achieve selective targeting of pathogenic CD4 T cells and to deliver therapeutic benefits in mouse models of psoriasis and arthritis.

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.

Untargeted metabolomics faces challenges in metabolite origin inference and metabolite annotation. Here, the authors present TidyMass2, a user-friendly computational framework with metabolite origin inference and feature-based functional module analysis to enhance biological interpretation.

Despite advances in enzyme design and engineering, the development of biocatalysts featuring a combination of tailored stereoselectivity with broad substrate scope has been very difficult. Focusing on a new-to-nature reaction, the authors report a mechanism-based, multi-state computational design workflow for the generation of ‘generalist’ cyclopropanases capable of transforming a broad range of substrates with tailored and divergent stereoselectivity.

A large-twist-angle bilayer graphene platform exhibits a quantized ratio of displacement to magnetic field at Landau-level crossings, offering a route to high-resolution cryogenic magnetometry.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Splitting water using sunlight is a promising route to green hydrogen, yet inefficient charge carrier utilization in photocatalysts limits their solar-to-hydrogen efficiency. Here the authors introduce excitonic quantum superlattices to prolong exciton lifetimes and optimize charge steering, achieving a solar-to-hydrogen efficiency of 3% under ambient conditions.

In this phase 2 ZUMA-14 clinical trial, Strati et al. reported the safety and efficacy of axicabtagene ciloleucel plus rituximab in adult participants with chemorefractory large B cell lymphomas and compared the results with previous findings from ZUMA-1 cohort 1.

Two main acceleration mechanisms in the auroral acceleration region are electric potential and Alfvénic acceleration but associated energy dynamics are not completely resolved. Here, the authors show that Alfvén waves power the Earth’s auroral arc through a static potential drop in the auroral acceleration region.

Here, the authors develop AMPLiT a tool for screening antimicrobial peptides in metagenomic datasets, and apply it to human coprolite metagenomes, finding that Segatella copri, an ancient prevalent human gut bacterium declined in modern populations, harbors unexplored antimicrobial reservoir, offering an alternative approach against modern pathogenic infections.

A global synthesis of >600 studies finds that across agro-ecosystems, grasslands and forests in temperate and tropical zones, increasing plant diversity has a consistently positive effect on plant performance and the suppression of antagonists.

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.

This work transforms oxygen from an embrittling contaminant into a key asset in titanium alloys, simultaneously overcoming the strength-ductility trade-off and oxygen embrittlement.

Using ancient DNA, isotopes and proteomics, this work reveals social inequality and mobility in Eastern Zhou China, showing female sacrifices, dietary disparities across classes, kinship networks among elites, and rare evidence of social mobility.

Neuromorphic computing processes data faster and with less energy than electronics. Here, authors demonstrate a reconfigurable photonic reservoir computer that performs multiple machine learning tasks in parallel at ultrafast rates while using extremely low energy per operation.

The cellular makeup of the primate cochlea, crucial for hearing, remains poorly understood. Here, authors show a detailed map of primate cochlear cells, revealing both conserved and species-specific features.

In this work, authors present their goal-directed subgroup identification (GD-SI) framework, reconciling biological heterogeneity with clinical actionability, and offering a scalable infrastructure for precision trial design and personalized sepsis management.

The mechanisms underlying oligodendrocyte precursor cells (OPCs) and neuron interactions remain unclear. Here, the authors show that chromatin remodeler BAF155 regulates OPC differentiation and myelination by coordinating synaptic genes for OPC neuron communication, contributing to autism-like behavioral deficits in mice

Major depressive disorder has been linked to peripheral immune dysfunction. Here, the authors identify elevated stem cell-like memory CD8⁺ T cells in patients and in a murine stress model show migration to the intestine via PPBP-CXCR2 and suggest gut CD8 cells modulate tyrosine metabolizing bacteria and homovanillic acid potentiating neuroinflammation and depressive phenotype.

Natural disasters induce power outages with unequal impacts on poverty and non-poverty counties in China. Climate change will further exacerbate this disparity.

A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

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.

Bronchiectasis and asthma can co-exist in the same patient, and the characteristics may be different from bronchiectasis alone. Here the authors characterise the function of ILC3 cells and how IL-17C potentiates IL-17A expression promoting a neutrophil dominated asthma endotype in mouse bronchiectasis-asthma models.

The study presents a generative spike-based framework to re-establish functional connectivity across pathway-damaged brain regions, enabling biomimetic neural prostheses and closed-loop brain stimulation.

Aircraft measurements over the Amazon show that new particle formation in the upper troposphere emerges when isoprene, emitted by forests, undergoes oxidation in the presence of nitrogen oxides produced by lightning.

Here the authors report an analysis of two large nationwide cohort studies, the UK biobank and NHANES, suggesting that accelerated biological aging mediate a proportion of the association between social determinants of health and all-cause and cause-specific mortality.

Gas evolution severely limits the performance of LiFe_xMn_1−xPO₄ batteries, yet its mechanisms remain unclear. Now it has been shown that CO₂ originates mainly from the cathode and H₂ from Mn/Fe-catalysed reactions at the anode, while a uniform carbon coating effectively suppresses metal dissolution and stabilizes cycling.

The authors show that α-synuclein is an amphiphile for condensates and localizes to the condensate surface by reversible adsorption into multiple, heterogeneous layers, driven by surface charge. The adsorption can be modulated by biomolecules, including RNA, proteins and lipids, which slows down α-synuclein aggregation.

Intracellular redox state orchestrates a self-reinforcing circuit connecting hypoxia inducible factor 1α-dependent signalling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1 to govern intestinal stem cell fate.

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.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

In this work, a library of several hundred million compounds was computationally docked to a cryoEM structure of the orphan G protein-coupled receptor GPR139, leading to the discovery of a potent agonist with in vivo effects and insights into GPR139 signalling.

Metallic glasses can break ductility bottlenecks: 10% tensile plasticity with strain-hardening emerges from a synergy between relaxation-assisted and transformation-mediated deformation mechanisms, overcoming a long-standing challenge in metallic glasses.

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.

Anti-TSLP biologics have shown promise for the clinical treatment of type 2 respiratory disease. Here the authors present a clinical trial of CM326, a monoclonal antibody against TSLP, and show the clinical effects in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), who present with type 2-dominant inflammation.

A cross-ancestry GWAS meta-analyses of brainstem structures identify 713 associations. It reveals shared/distinct genetic architectures across ancestries/substructures and overlaps with neuropsychiatric disorders and physiological functions.

Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate. Through integrated laboratory and clinical studies, the authors identify significant ERBB2 (the gene that encodes the HER2 protein) mutational heterogeneity in patients with urothelial cancer and co-mutation and amplification of ERBB2 as a potential biomarker of exceptional response to T-DXd.