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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.

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.

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.

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.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

Zhang et al. examine associations between wildfire-specific PM_2.5 and emergency department visits for mental disorders in children across 845 communities in Australia, Brazil and Canada over a 15-year period.

A photochemical regeneration strategy achieves repeated capture and release of diverse precious metals by integrating a phenol–quinone redox cycle into a nanocarbon aerogel scaffold, offering a practical and sustainable pathway for metal recovery.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

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.

As presented at the ESMO Congress 2025: Results of the phase 2/3 AGITG DYNAMIC-III trial show that de-escalated chemotherapy based on ctDNA-negative status in patients with stage III colon cancer did not meet non-inferiority for 3-year recurrence-free survival when compared to standard of care, although it enables better informed treatment decisions.

By combining satellite observations with ground-based data and expert validation, this analysis demonstrates considerable misestimation of grassland extent and thereby carbon stock estimates in previous global assessments based on remote sensing.

Successful human-AI collaboration could greatly contribute to breast cancer mammographic screening. Here, the authors use a large-scale retrospective mammography dataset to simulate and compare five plausible AI-integrated screening pathways, finding optimal ways in which human-AI collaboration could be implemented in real-world settings.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Mountains, with their sharp climatic contrasts, are emblematic of climate-driven species movement and, ultimately, loss. Here, we argue that these same contrasts make mountains powerful natural laboratories for discovering the mechanisms that underlie biological change.

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.

Detection of hot intracluster gas in SPT2349−56 with the Atacama Large Millimeter/submillimeter Array provides new insights into early cluster formation.

Man-made ammonia emissions have harmful effects on human health and ecosystems, yet global mitigation strategies remain underexploited. A study now finds that emissions could be halved cost-effectively by 2050 through targeted and prioritized measures, with benefits far outweighing costs.

This study applies a global food and land system modelling framework to quantify the impact of 23 food system measures on 15 outcome indicators related to public health, the environment, social inclusion and the economy—from today until 2050.

A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

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.

The extreme hot and dry conditions of 2023 reduced soil respiration and enhanced net forest carbon sequestration in Canada, offsetting wildfire emissions, according to satellite-based and in situ observations of CO₂ fluxes.

Pretreatment is a prerequisite to recycle spent lithium-ion batteries (LIBs) and advance resource circularity, but its impacts on the overall performance and environmental footprint of LIBs recycling are poorly understood. This study develops unit-level models to address this knowledge gap.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

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.

Halving nitrogen waste could help meet a broad array of Sustainable Development Goals, with associated societal benefits topping US$1.3 trillion, according to an integrated assessment framework that evaluates cost-effectiveness and environmental impacts.

The early postnatal roles of dendrite-targeting interneurons in primary visual cortex (V1) remain elusive. Here, the authors find that somatostatin interneurons in mouse V1 exhibit a uniquely delayed developmental trajectory for innervation and sensory responses, highlighting a window for the emergence of a key mechanism for normalization in cortical circuits.

The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.

Insulin signaling plays a crucial role in coordinating skeletal development with whole‑body energy metabolism. Here, the authors use phosphoproteomics to show insulin-signaling rewiring in aged, insulin-resistant bone and identify defective phosphorylation of AFF4 as a key mechanism for regulating gene-specific transcriptional activation.

Although N₂O emissions from wastewater treatment plants have been studied extensively, emissions of NH₃ have been largely considered irrelevant. Analysis of such emissions from a sludge drying pan, a commonly used method, shows that NH₃ emissions are in fact substantial and should not be overlooked.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

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.

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.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

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.

During SARS-CoV-2 infection caspase-8 fuels harmful inflammation independent of apoptosis. Genetic loss of caspase-8 reduces cytokine levels, lowers viral load and mitigates disease severity, revealing non-apoptotic caspase-8 as a key driver of severe COVID-19.

A mix-and-go system enables the rapid prototyping of antibody formulations, allowing control of their orientation on the surface of LNPs for specific cell targeting, significantly improving the ex vivo and in vivo deliveries of mRNA.