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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.

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.

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.

The detection of forsterite and enstatite emissions in EC 53 during accretion bursts marks one of the first pieces of direct evidence of in situ silicate crystallization in young stars.

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.

The circuitry underpinning visuomotor behaviors in flies is poorly understood. Here, the authors show that the underlying computations require bilateral electrical coupling to control turning dynamics and direction for effective course control.

This study associates p53 loss and brain metastasis in breast cancer. Mechanistically, p53-null tumors recruit astrocytes that provide substrates for enhanced fatty acid synthesis via upregulated SCD1 expression, representing a targetable axis in the disease.

Engineering polymerases to synthesize alternative genetic polymers remains a challenging problem in synthetic biology. Using DNA shuffling and droplet microfluidics, the current study provides a short evolutionary path from a DNA polymerase to one with robust RNA-synthesizing activity.

Comparative genomics and high-resolution mass spectrometry reveal the biosynthetic gene clusters, and vast chemical diversity of natural products that they encode, in Photorhabdus and Xenorhabdus, bacteria that interact with hosts as symbionts and entomopathogens.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

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.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

This work introduces a bilevel optimization framework that discovers optimal reward functions for embodied reinforcement learning agents through a mechanism called regret minimization. The approach accelerates policy optimization and enhances adaptability across diverse tasks.

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.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

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.

Here the authors dissect the developmental and functional relationship between tumor-responsive cytotoxic T cells in the tumor versus the tumor-draining lymph nodes (tdLNs), finding that stem-like T_PEX cells dependent on MYB in the tdLNs are required for CD8⁺ T cell tumor infiltration and ICB responses.

Antimicrobial resistance genes that have been mobilized between bacterial species represent a subset of the naturally occurring resistome. Here, the authors compare the abundance, diversity and geographical patterns of acquired resistance genes with latent resistance genes in global sewage metagenomes.

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.

Toll-like receptor 7 (TLR7) normally recognizes exogenous single-stranded RNA for the activation of innate immunity. Here the authors show that TLR7 may also contribute, via the modulation of mast cell functions, to experimental, cigarette smoke-induced mouse models of emphysema, thereby hinting TLR7 as a potential therapeutic target for human lung inflammation.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Aqueous zinc–iodine batteries offer an inexpensive, safe technology for energy storage, but using inactive host materials limits the energy density and polyiodide shuttling reduces cycling lifetimes. Now it has been shown that integrating electroactive ferrocene into cathodes offers additional capacity to enhance energy density and enables shuttle-free operation.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

Here the authors develop CRISPR–ChIP to enable the identification of factors required for chromatin regulation. Using this new method, they unveil a functional partitioning of H3K79 methylation into two distinct regulatory units, with important implications in MLL leukemia.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

We analyse a global dataset of genomic DNA sequences for Ophiuroidea to gain an understanding of phylogenetic divergence and biotic movement across oceans, finding phylogentically divergent faunas at shelf depths but greater connectivity of species at deep-sea depths.

Hillside urbanization rises as cities exhaust flat land, threatening sensitive ecosystems. Mapping of 11.65 Mha added since 2000 reveals that 35% of them are in critical areas, fragmenting habitats and endangering 70% of globally threatened species.

Here, the authors characterize two distinct T_reg cell populations in the visceral adipose tissue of lean and high-fat diet-fed mice. ST2⁺ T_reg cells are dominant in male mice and are transcriptionally driven by GATA3 and PPARγ, regulators that limit the differentiation of the more female-dominant population of CXCR3⁺ T_reg cells that are T-bet dependent. Functional distinctions are also evident in glucose tolerance and adipose inflammation.

Group 2 innate lymphoid cells (ILC2s) are generally considered to have pro-tumor functions. However, Belz and colleagues demonstrate that ILC2s have anti-melanoma effects due to their high production of the inflammatory cytokine granulocyte-macrophage colony-stimulating factor in the tumor microenvironment.

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.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Modern communication networks must balance efficiency with user privacy. Here, authors develop a privacy-preserving interpretable Bayesian framework that enables network optimization using only aggregated data, without compromising individual user information.

An analysis based on data from the Global Dietary Database shows mean animal-sourced food intakes among children and adolescents increased modestly from 1990 to two portions per day in 2018, but remain low in sub-Saharan Africa, India and Bangladesh.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Experiments in mice show that the perineural net has a key role in metabolic disease by controlling insulin access to neurons in the arcuate nucleus of the hypothalamus.

Dietary quality is reported at the global, regional and national level across 185 countries. Though diet quality increased modestly since 1990 at the global level, in South Asia and Sub-Saharan Africa it did not improve. In some regions, children’s dietary quality is lower than that of adults.

As research on human kidney models differentiated directly from human pluripotent stem cells continues to advance rapidly, this Review examines current protocols used in the field, as well as discusses potential caveats and limitations when using these approaches for drug screening, disease modelling and tissue engineering.

Cell-type-resolved spatial proteomics of the skin from patients with toxic epidermal necrolysis reveals that it is driven by JAK/STAT signaling, leading to successful treatment of this potentially fatal condition in patients using JAK inhibitors.

A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

Modeling analysis from the Global Dietary Database estimated that 70% of new global cases of type 2 diabetes are attributable to suboptimal intake of 11 dietary factors, with substantial differences in dietary risks across world regions and nations.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Targeted re-sequencing of 890 diverse accessions of hexaploid and tetraploid wheat identifies regions showing the signals of wild emmer introgression, thus suggesting that historic wild-relative gene flow shaped modern bread wheat's adaptive diversity.

The common form of salt has a 1:1 ratio of Na⁺ and Cl⁻; however, species that deviate from this can be found under extreme conditions, such as high pressure. Now, as a result of cation–π interactions that promote ion–surface adsorption, Na₂Cl and Na₃Cl have been observed as two-dimensional crystals on graphene at ambient conditions.

Visceral adipose tissue contains populations of regulatory T cells that exhibit sexual dimorphism, determined by the surrounding niche, and differ between male and female mice in terms of cell number, phenotype, transcriptional landscape and chromatin accessibility.