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Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Pathological neovascularization is a leading cause of vision loss. In this study, the authors identify FRZB and its NTR domain as suppressors of ocular angiogenesis. FRZB prevents CAV1 phosphorylation at Tyr42 which enhances downstream TGFβ signaling via ALK5 retention.

AlphaFold’s success in protein structure predictions has led to similar attempts to predict interactomes. Here, the authors demonstrate that AI-based screens are very limited in discovering truly novel interactions compared to experimental screens, exposing open challenges in interaction prediction.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Maize cultivar evolution boosts maize yield, yet the response pattern of maize to extreme climates is unclear. This study clarifies the synergy and trade-off mechanisms underlying the increase of yield per unit area and adaptation to extreme climates.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

Organo-electrocatalysts that can be used for both inorganic and organic conversions have been reported, ranging from laboratory-scale to large-scale reactions. This work demonstrates the application of a range of amide-based catalysts on electrodes to drive various reactions, including the chlorine evolution reaction and other chlorine-related organic transformations.

A single-cell multiomic atlas of the human maternal–fetal interface across pregnancy reveals cell types, states and spatial niches, developmental tissue architectures and transcriptional programmes, and identifies cell types with roles in pre-eclampsia, spontaneous preterm birth and miscarriage.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

The Human Development Multiomic Atlas catalogues single-cell accessibility and gene expression data from human fetal cells across 12 organs, enabling the inference of syntactic rules for motifs that govern cell-type-specific transcription factor binding and chromatin accessibility during human development.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

Predicting antimicrobial resistance from bacterial genomic data is challenging. Here, the authors introduce AMR-GNN, a graph neural network that integrates multiple genomic representations to improve prediction, reduce clonal bias, and identify biomarkers.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

The transcription factor ATF4 is shown to regulate double-stranded DNA repair within vulnerable CUX2⁺ upper-layer 2/3 cortical neurons, enabling their survival during development.

Genetic analyses in more than 15,000 individuals from across the Americas, including individuals with autism and family members, define the genetic landscape of autism in Latin American populations and identify significant overlap with other ancestries.

DNA hybridisation thermodynamics parameters underlie rational design of oligonucleotides for diagnostics and nanotechnology. Here, the authors present an accurate method to measure the free energy of a given DNA structure at specific temperature and buffer conditions.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

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.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

A fully automated methodology based on rubrics capturing a broad range of cognitive and intellectual demands is illustrated using LLMs and tasks, demonstrating a new way to evaluate the capabilities of AI systems and anticipate their performance.

A multimodal organic electrochemical transistor array enables picomolar dopamine sensing, high-bandwidth electroencephalography acquisition and on-device seizure classification within one flexible bioelectronic platform.

A transmission model, integrating trial-derived prophylaxis efficacy and behavioural factors such as screening frequency and intervention uptake and adherence, evaluates different enrolment programmes for doxycycline post-exposure prophylaxis in terms of their potential effects on syphilis incidence, using data and indications from Singapore and England.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

In a phase 1b trial, patients with treatment-naive metastatic pancreatic adenocarcinoma received the CD73 inhibitor quemliclustat plus gemcitabine and nabpaclitaxel with or without the anti-PD1 antibody zimberelimab, showing encouraging clinical response rates and survival in quemliclustat-treated patients.

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

Host cell protein degradation machinery including the lysosome is involved in the processing and degradation of protein antigens. Here the authors develop lysosomal targeting vaccine approaches and test these in murine models of influenza infection.

Fabrication of single liquid-metal fibers is challenged by their limited surface area, thus restricting its functional deployment in soft electronic systems. Here, the authors develop a scalable, solution-deposition strategy for stretchable, multifunctional 1D liquid-metal-based bioelectronic fibers.

A study of reproducibility in a stratified random sample of 600 papers published from 2009 to 2018 in 62 journals spanning the social and behavioural sciences finds higher reproducibility among more recent papers and papers from journals that require data sharing.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

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.

The fluorescence-based protein assembly platform GEMINI is able to record the history of individual cells by leveraging a computationally designed protein assembly as an intracellular memory device.

Analyses of biobank data show that human variation such as age, sex and genetics, particularly at the major histocompatibility complex locus, is associated with viral abundance and supports a causal link between abundance of Epstein–Barr virus and Hodgkin’s lymphoma.

The study shows that label-free nanofluidic scattering microscopy combined with an AI vision transformer can measure the mass and size of single biomolecules down to 6 kDa (1.5 nm), as demonstrated on the example of insulin.

Electroreduction of CO on copper is notable for enabling C–C coupling, but a fundamental understanding of what drives product selectivity is lacking. Here a series of well-defined copper nanocrystals with tunable shape and size are used to control product selectivity, with strain identified as a major factor in n-propanol formation.

Producing valuable hydrocarbons electrochemically from carbon monoxide (CO) is an energy-efficient pathway, but reliance on costly pure CO as a feedstock limits its economic viability. This article shows that abundant CO-rich syngas can be directly used to synthesize ethylene.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

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.

Homogeneous catalytic hydroboration represents a valuable strategy for the synthesis of alcohols but reports which employ iron-based catalysts are somewhat limited. Here, the authors report an iron metalloborane complex as an efficient pre-catalyst for hydroboration of ketones, cyclic esters and CO₂ with mild conditions.

INSTALL overcomes fundamental challenges for DNA delivery and integration methods by synergizing immune-stealth nucleic acids with recombinases to enable kilobase-scale integration strategies without viral vectors.

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.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Data from cryogenic electron microscopy combined with hydrogen–deuterium exchange mass spectrometry inform a mechanism for cold-evoked activation of the TRPM8 channel, providing a structural and energetic framework to explain cold sensitivity.

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

A pangenome reference for the phenotypically diverse crop sorghum aims to help accelerate future efforts to breed crops that are better adapted to changing environments.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.