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Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Tight regulation of inflammasome assembly and activation is essential for controlling chronic inflammation and preventing the emergence of inflammatory pathologies. Here, the authors identify the E3 ubiquitin ligase TRIM21 as a regulator of ASC polymerization and ASC particle release during pyroptosis. Importantly, they identify the presence of TRIM21+/ASC+ particles and anti-TRIM21 autoantibodies in mouse models and human patients, linking inflammasome-driven inflammation to systemic autoimmunity.

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.

Here, authors show that pneumococcal vaccine serotype persistence is associated with replacement by lineages of the same serotype with reduced capsule, antibody binding and virulence. Considering factors beyond serotype alone is important when evaluating vaccine impact.

Gene editing technologies enable precise DNA modifications but remain limited by efficiency, precision of intended edits, and flexibility. Here, authors develop chimeric oligonucleotide-directed and Cas polymerase-based systems that enhance programmable gene correction across cells and embryos.

Mycobacterium tuberculosis owes its success partly to its ability to enter a ‘dormant’, non-replicative state, reactivating years or even decades after initial infection. In this work, authors find that a key alteration in a gene involved in this dormancy response has evolved, or is evolving, in parallel in human-adapted lineages across the globe.

Integration of data representing 35,120 brain scans from diverse global studies enables construction of reference charts that define normative microstructural and macrostructural properties across the human lifespan for research and clinical diagnosis.

SCCmec is a large mobile genetic element that confers resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus. Here, the authors show that biofilm growth conditions enhance the efficiency of natural transformation in S. aureus and allow the transfer of SCCmec to methicillin-sensitive strains.

This study challenges the paradigm that resistance mutations precede fitness compensatory adaptations, showing that pre-existing alterations in mycobacterial oxidative stress responses can prime rapid evolution of resistance without fitness costs.

Ribosomal Protein S15 (RPS15) is recurrently mutated in B-cell leukemia but its leukemogenic role remains unclear. Here, the authors establish mutant RPS15 as a cancer driver and reveal mechanisms by which these mutations induce translational defects, DNA damage and genomic instability that together promote leukemogenesis.

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.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

This resource leverages spatial and single-cell transcriptomics to investigate lncRNAs in cancer and reports 94,795 previously unannotated lncRNAs and new approaches to infer their functions.

It has been proposed that language meaning is represented throughout the cerebral cortex in a distributed ‘semantic system’, but little is known about the details of this network; here, voxel-wise modelling of functional MRI data collected while subjects listened to natural stories is used to create a detailed atlas that maps representations of word meaning in the human brain.

Snyder et al. analyze two population-based birth cohorts to test associations of newborn metabolite concentrations and childhood respiratory outcomes. C4, C10:1, C18:2, and citrulline are associated with early-life wheezing and asthma, with C18:2 specifically associated with increased non-allergic asthma risk.

Studies in vitro of protease mixtures modeling the oral cancer microenvironment elicit trafficking and signaling of PAR2, an oral cancer pain mediator, that is dictated by the relative potencies and efficacies of the proteases to cleave the receptor

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.

Analyses of snRNA genes in a French cohort of people with rare disorders, with validation through international collaboration, identify monoallelic and biallelic variants in RNU2-2 as frequent causes of neurodevelopmental disorders with epilepsy.

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.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Two individuals with KCNT1-related epileptic encephalopathy were treated with a KCNT1-targeting antisense oligonucleotide, leading to significant reductions in seizure frequency and intensity, but also the development of hydrocephalus.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

Computationally designing proteins with interfaces that bind small molecules has posed a long-standing challenge. Here, authors combine deep learning and physics-based approaches to design proteins that bind small molecules, and demonstrate their approach by designing a cortisol biosensor.

Age-related microbiome changes increase medium-chain fatty acid-producing bacteria, driving GPR84-mediated myeloid inflammation, impaired vagal signalling and hippocampal dysfunction; targeting this gut–brain pathway restores memory in aged mice.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Evo 2 is an artificial intelligence-based biological foundation model trained on 9 trillion DNA base pairs spanning all domains of life that predicts functional properties from genomic sequences and provides a rich generative model for researchers in biology.

Guardo et al. present machine learning models for identification of long COVID using health survey, genetic, and electronic health record data and compare to traditional methods using electronic health records alone. They find that multimodal machine learning practices have a stronger overall identification of long COVID.

The immunological events that correlate with latent Mycobacterium tuberculosis (Mtb) infection (LTBI) containment in immune suppressed hosts remain to be explored. The authors here show that CD8⁺ T cells are critical for BCG vaccination-induced prevention of Mtb dissemination in the absence of CD4⁺ T cells in a mouse model of contained tuberculosis.

Cytomegalovirus (CMV) seropositivity exacerbates immune complications in people living with HIV (PLHIV). Here, the authors utilize multi-omics and immune phenotyping data and show that CMV seropositivity induces pro-inflammatory cytokines and further identify FCRL6 as a potential biomarker for immune activation.

Genome-wide analysis coupled with long-read sequencing identifies a repeat expansion in GOLGA8A associated with high risk for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.

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.

Lea Hanemann explains how sealed cuvettes can be used to quantify the release of organic compounds from living mangrove roots.

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.

Photocatalysts for methane conversion can suffer from inefficient charge carrier diffusion, limiting their effectiveness. Here the authors exploit the insulator–metal transition in VO₂ to create an electronic phase junction, enhancing the non-oxidative conversion of methane into hydrogen, ethane and propane, with peak efficiency at the transition’s critical temperature.

Separate from its catalytic activity, b-carbonic anhydrase 4 binds directly the Cl- channel SLAC1 in Arabidopsis guard cells, promoting SLAC1 activity and stomatal responsiveness to CO2, and facilitating plant growth.

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.

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.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Individual supratentorial ependymoma tumour subgroups have two distinct progenitor-like cell states—neuroepithelial-like and embryonic-like—that are reminiscent of early human brain development and diverge in the extent of their neuronal or ependymal differentiation.

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.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.