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Most H₂ used in the chemical industry is derived from fossil fuels. Now it has been shown that coupling native microbial H₂ pathways with engineered alkene biosynthesis and membrane-bound Pd catalysis enables biocompatible hydrogenation of metabolic intermediates in living bacteria. This hybrid chemo-microbial platform supports the carbon-negative synthesis of industrial chemicals from waste-derived feedstocks.

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.

Neoantigen-based adoptive T cell therapies represent a personalized approach for cancer immunotherapy. Here the authors describe NEO-STIM, an ex vivo T cell induction platform to STIMulate peripheral blood T cells to generate responses against tumor NEOantigens.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

The SONAR trial showed that the endothelin receptor antagonist atrasentan improves kidney outcomes in patients with type 2 diabetes and chronic kidney disease, though individual responses varied. Here the authors report exploratory analyses of the SONAR trial that identify urinary clusterin as a potential predictor of kidney disease progression and response atrasentan in type 2 diabetes.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Glioblastoma is characterised by high levels of intratumoural heterogeneity and plasticity, hindering treatment. Here, the authors develop an analytical framework, scFOCAL, to predict the sensitivity of glioblastoma cell subpopulations to therapies based on reversal of disease transcriptional signatures to identify synergistic therapeutic combinations.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

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.

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.

Pangenomic and epidemiological analyses reveal a genetic shift in U.S. Salmonella Hadar populations during 2019–20, driven by expansion of a lineage carrying a prophage-like element that likely arose in commercial poultry and spread to backyard flocks.

This paper develops the Risk Analysis – Perception framework to analyze a national survey and public health metrics for public perceptions of extreme heat risk in the US, finding substantial misalignments between assessed and perceived risk.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

An implantable vagus nerve-targeted device safely reduces disease activity and joint damage in rheumatoid arthritis, offering a new nondrug treatment for patients who do not respond to or cannot tolerate medication.

Coagulase-negative staphylococci secrete natural products that prevent pathogen colonization. Here, the authors identify hominicin, a daptide bacteriocin produced by Staphylococcus hominis that has antimicrobial activity against a skin pathogen.

Guided by density functional theory, a commercially viable refractory alloy is developed, which exhibits excellent room-temperature ductility and strength, and high strength at elevated temperatures.

Geochemical data from zircons show that subduction-like processes were operating contemporaneously with stagnant-lid-like processes at different locations as early as 4.4 billion years ago on the Hadean Earth.

Byg et al. examine whether psychiatric genetic risk interacts with early nutrition to influence child behaviour in pre-adulthood measured using the repeated Child Behaviour Checklist (CBCL). They find nutrition in early life and psychiatric genetic risk may interact to determine longer term child behaviour.

The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

Effective early detection and intervention strategies for lung cancer are urgently needed. The authors of this Review summarize the current state of lung cancer screening and provide future directions for optimal implementation, including biomarker development. They also discuss precancer interception strategies that could transform both lung cancer prevention and early intervention.

The parent diphosphene molecule is of fundamental interest, but its reactive nature renders it challenging to isolate, and current metal-stabilized derivatives are limited to complexes of p-/d-metals. Here, the authors introduce f-element diphosphene complexes, adding to f-element diazenes that were first reported over thirty years ago.

The cytochrome bc₁ oxidase of Mycobacterium tuberculosis is a potential target in the fight against tuberculosis. Here, the authors evaluate the potential of cytochrome bc₁ inhibitors as partner drugs in tuberculosis treatment regimens.

We report the outcome of an international optical observation campaign of a prototype constellation satellite, AST SpaceMobile’s BlueWalker 3, which features a 64.3 m² phased-array antenna and a launch vehicle adaptor.

Solid contacts on a microscopic level are widely described by a classical contact mechanics theory. Here Styleet al.show that this theory breaks down when a small particle adheres to a soft surface where a fluid-like behaviour is observed because of the predominant role played by surface tension.

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.