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Using inbred medaka strains, the authors mapped 59 genetic loci linked to heart rate. Gene editing validated conserved genes affecting heart rate and morphology, highlighting the power of isogenic strains in uncovering mechanisms of cardiac traits and disease.

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.

RORγt⁺ antigen-presenting cells (APC) are playing a role in the generation of oral tolerance via their interaction with regulatory T cells recognising dietary and commensal bacterial antigens. Here authors show that a cis transcriptional regulatory element is responsible for RORγt specifically in APCs through interaction with RUNX3 and formation of chromatin loops, which determines a transcriptional program that distinguishes these oral tolerance mediating APCs from RORγt⁺ T cells.

This study identifies ANTXR2 as the cellular receptor for Clostridium perfringens toxin NetF and determines its structure bound to the toxin using cryo-EM, revealing a distinct lateral binding mechanism that facilitates membrane pore formation.

Mass spectrometry is a cornerstone of untargeted metabolomics, but comparisons across ionization modes have remained a substantial challenge due to the distinct fragmentation patterns produced by each polarity. Here, the authors present MS2DeepScore 2.0, a machine learning-based model to predict chemical similarity between mass fragmentation spectra, which works both between different and the same ionization modes.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

By generating whole genomes of 150 participants representing 12 Khoe-San click-speaking groups, the authors, reveal over 1.3 million unknown DNA variants, distinct San and here described Damara genetic trajectories, while achieving century-long global predominance.

Florets of indica rice open earlier than japonica rice, hindering utilization of the cross subspecies heterosis. Here, the authors show that an OsMYB8-OsJAR1 module regulates diurnal floret opening time divergences between the two subspecies.

In this work, authors use whole genome tracking in a neonatal intensive care unit to reveal a strong link between Staphylococcus aureus colonization and invasive infection, pinpointing critical new targets for infection prevention in high-risk infants.

The authors show that plasma AT(N) biomarkers can distinguish Alzheimer’s disease and frontotemporal lobar degeneration in diverse Latin American populations. Using machine learning and integrating neuroimaging, significant diagnostic accuracy was achieved, enhancing clinical assessments of these conditions in Latin America.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

Lamin A/C in the nuclear lamina is identified as a regulator of cysteine catabolic flux, necessary for cell fate decisions and function.

This study shows that WDR5 remodels NANOG condensates to control transcriptional programs. Disrupting their interaction compromises stem cell identity and suppresses leukemia stem cell expansion.

Long COVID is associated with challenges in energy management, with limited interventions available. In this study, a just-in-time app-based energy management intervention for long COVID did not reduce postexertional malaise compared to usual care, though both groups improved over time, showing the approach was safe but not effective.

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.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

This paper uses multiomics to profile a large cohort of meningioma samples to highlight the role of the tumor microenvironment in driving the epigenetic changes underpinning tumor classification and prediction of outcome.

This multidisciplinary response to investigate the large outbreak of unknown febrile illness in the Panzi Health Zone in the Democratic Republic of the Congo in late 2024 suggests that the outbreak was largely associated with malarial cases and concurrent viral respiratory infections.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

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.

Mangrove ecosystems are facing severe climate threats. However, this study shows that strategically expanding protected areas to include the most climate-resilient sites can safeguard biodiversity and ecosystem services for the future, and this can be achieved with only a modest increase in protected area.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Humans alter the daily timing of animal activity, potentially reshaping predator–prey interactions. This meta-analysis reveals that larger species tend to “lose” under human disturbance, with large predators overlapping less with their prey, and large prey overlapping more with their predators.

Intermittent fasting (IF) has been recognized as a potential cancer therapeutic approach but its effect on tumor growth is limited. This study demonstrates that response to IF varies between glioblastoma subtypes, with IF specifically inhibiting Tp53-driven glioblastoma due to a reshaping of the gut microbiota and subsequent altered methionine metabolism suppressing TGF- β signaling.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Machine learning is used to understand emissions of the potent greenhouse gas nitrous oxide from the Southern Ocean. Low-pressure storms are found to drive emissions, leading to a revised picture of marine greenhouse gas cycling

In vitro methods for thymic organoid cultures are useful to examine requirements for T cell development and for generating large numbers of cells for therapeutic purposes. Here the authors use human induced pluripotent stem cells, differentiate these into thymic epithelial organoid cultures and utilise haematopoietic progenitors to show development of T cells in vitro.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

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.

Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

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

Single iron atoms on nitrogen-doped carbon catalysts are a promising alternative to platinum for the oxygen reduction reaction on fuel cell cathodes, but commonly suffer from low stability. Here an in situ chemical vapour deposition synthetic approach is presented, enabling high iron active site dispersion and reducing surface porosity, which mitigates demetallation and carbon corrosion, ensuring high activity and stability.

Using the single-cell Deep Visual Proteomics technique, the authors develop a resource providing spatially resolved proteomic analysis of individual cells in human liver tissue.

In the adrenal cortex, cholesterol used for steroid production is stored in lipid droplets. The authors demonstrate here the importance of the transcription factor HHEX in maintaining glucocorticoid levels and protecting lipid droplets from androgen-induced lipid depletion.

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.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

In a study of four brain-dead human decedents, extracorporeal liver cross-circulation using genetically modified pig livers provides essential hepatic functions, supporting the feasibility of this approach for temporary liver support as a bridge to organ transplantation.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

GATA6 maintains epithelial traits and limits EMT in pancreatic cancer. Combined MEK and HDAC inhibition restores GATA6+ tumor cells, boosting MHCI expression and CD8+ T cellmediated anti-tumor immunity.

Cell fate transitions rely on dynamic regulatory programs that RNA velocity often blurs. Here, the authors show that MoFlow integrates multi-omic data to infer locally adaptive, single-cell-resolved velocities that illuminate fine-scale regulatory dynamics.

The famous nebula Barnard 68 has been used as a giant cosmic-ray detector: cosmic-ray-excited vibrational H₂ emission has been observed by JWST, giving a direct measurement of the CR ionization rate.

The authors conduct a national inventory on individual tree carbon stocks in Rwanda using aerial imagery and deep learning. Most mapped trees are located in farmlands; new methods allow partitioning to any landscape categories, effective planning and optimization of carbon sequestration and the economic benefits of trees.

A distinctive population with high hunter-gatherer ancestry persisted 3,000 years later than in most European regions, contributing to later Lower Rhine–Meuse Bell Beaker users.