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Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Self-assembled multidomain supramolecular peptide hydrogels that engage in dynamic covalent bonding with small-molecule drugs and biologics are shown to offer sustained release, extend the activity, and maintain safe and potent drug levels in vivo.

During ageing, S-adenosylmethionine (SAM) is depleted from muscle stem cells (MuSCs) because of increased synthesis of the polyamine spermidine, leading to loss of heterochromatin and dysfunction of MuSCs. SAM restoration rescues the mouse MuSC defects.

Lineage tracing in mice identifies a subpopulation of basal cells that express Tmprss2 and Nkx3 as the origin of ERG-driven prostate cancer. Upon expansion, these cells show an enrichment for STAT3 chromatin binding and elevated expression of KMT2A and DOT1L as dependencies for ERG oncogenicity.

Changes in the microenvironment of the aged lung relative to younger lung tissue can lead to the reactivation of dormant melanoma cells through a mechanism that involves a decrease in WNT5A and AXL signalling and an increase in MERTK.

Brett et al. demonstrate that voluntary exercise improves quiescent muscle stem cell (MuSC) function and regenerative capacity in old but not young mice through exercise-induced upregulation of Cyclin D1 and repression of TGF-β activity in quiescent MuSCs.

The endosomal retrieval subdomain organizes recycling of endocytosed proteins. Here, using proximity proteomics, the authors reveal that this recycling subdomain regulates switching of specific RAB GTPases, a feature likely important in neuroprotection.

This study reports on biologically sourced polymuconate polymers with weakened C–C backbone bonds, designed for closed-loop chemical recycling to monomers. Synthesized via free-radical polymerization, these materials achieve tunable mechanical properties comparable to those of commercial plastics. A techno-economic analysis shows that recycling significantly reduces costs and environmental impacts, enhancing the competitiveness of these polymers in the sustainable plastics market.

The discovery of 2023 KQ₁₄, a Sedna-like object with a perihelion of 66 au, fills a gap in the known population. Its orbit does not align with other Sedna-like objects, shedding light on the diversity and dynamical history of the outer Solar System.

Many rare high-impact variants have been associated with disease, but the origins and functional impact are not always explored. Here, the authors trace the ancestry of a rare high impact atrial fibrillation allele in KCNQ1, and use iPSC-derived cardiomyocytes to characterize the effect of the allele.

Degradable thermoset multimaterials can be synthesized from a commercially accessible, biosourced monomer using orthogonal polymerizations in a single pot; after selective degredation, the resulting small molecules can be repolymerized.

A long- and short-read barley pan-transcriptome assembled from 20 diverse barley genotypes offers insights into genotype- and tissue-dependent gene expression and function.

Genomic innovation in plant defense is explored by the authors who uncover the genome-wide hijacking of the albumin-1 gene family by biocidal cyclic peptides called cyclotides, and recruitment of asparaginyl endopeptidases for peptide cyclization.

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.

The epidemiology, risk factors, causes, treatment and outcomes of intracerebral haemorrhage (ICH) in young adults (aged ∼18–50 years) can differ markedly from those in elderly patients with ICH. Challenges in this setting include high early mortality and long-term mortality as well as long-term disability and ICH recurrence in survivors.

This study estimates the reproductive potential of fish in globally distributed coral reef sites. The results show substantial gains in reproductive potential can be achieved through the 30 × 30 conservation target, particularly for the important fisheries family, Serranidae, demonstrating the possible benefit of protection to population replenishment.

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).

On the Moon, extensional tectonic features have only been observed close to the influence of the mare basalt-filled basins and floor-fractured craters. Analysis of Lunar Reconnaissance Orbiter Camera images reveals several potentially very young extensional tectonic features in the farside highlands, implying that extensional stresses may locally exceed compressional ones.

Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

The Earth co-orbital asteroid Kamo‘oalewa, which is a target of the Chinese Tianwen-2 mission, may have a lunar origin instead of an asteroidal one. Dynamical constraints from numerical simulations suggest that it could be an escaping fragment from the lunar Giordano Bruno crater.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

A century ago this month, Frederick Soddy described and named isotopes in the pages of Nature. Brett F. Thornton and Shawn C. Burdette discuss how chemists have viewed and used isotopes since then — either as chemically identical or chemically distinct species as the need required and technology allowed.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Homotrimeric DARPin molecules neutralize SARS-CoV-2 variants of concern by targeting a critical ACE2-binding interface.

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.

Patients with Acute myeloid leukemia (AML) who do not respond to standard chemotherapy have limited treatment options. Here, the authors show that high expression of the gene TNFAIP3/A20 in AML cells contributes to chemotherapy resistance by blocking a type of cell death called necroptosis.

Non-equilibrium systems of immiscible liquids have significant potential to advance different technologies, but control over morphology or functionality remains unexplored. Here, the authors demonstrate an all-liquid fluidic device by exploiting surfactant assemblies to produce a semi-permeable membrane between the liquids.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

Estimating health burden of air pollution against the background of population aging is of significance for achieving Sustainable Development Goal 3.9. Here, the authors show that population aging is expected to be the leading contributor to increased deaths attributable to PM2.5 in China by 2035, which will counter the positive gains achieved by improvements in air pollution and healthcare.

Pertussis immunisation for pregnant women has been introduced to protect newborns, but immunological evidence suggests that this lessens subsequent infant immune response to vaccination. Here, the authors assess the epidemiological impacts of both consequences of maternal immunisation on infant infection.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

In mouse experiments and in clinical trials in humans, boosting with Omicron-specific mRNA following immunization with Wuhan-1 spike mRNA results in immune responses focused on conserved rather than variant-specific epitopes.

Using a global dataset of traded species, it is found that the highest levels of traded phylogenetic and functional diversity are from tropical regions, where high numbers of evolutionary distinct and globally endangered species occur.

Environmental enteropathy is a disorder of the small intestine that contributes to the persistence of childhood malnutrition worldwide. Here, Brownet al. show in mice that early-life malnourishment, in combination with exposure to commensal bacteria, remodels the small intestine to resemble features of the disease.

Here, using participants in the CHILD birth cohort, the authors reveal that impaired 1-year microbiota maturation may be universal to 5-year pediatric allergies, mediated by functional and metabolic imbalances of compromised mucous integrity, elevated oxidative activity, decreased fermentation, and elevated trace amines.