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The amount of carbon dioxide in the atmosphere declined as the Earth entered the last glacial period. Estimates of deep carbonate ion concentrations suggest that a substantial amount of carbon was sequestered in the deep Atlantic Ocean.

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.

Here the authors show how the DNA-sensing cGAS–STING pathway activates NF-κB and inflammatory gene expression with delayed kinetics via post-Golgi endolysosomal signaling.

The mysteries behind immune aging and its related inflammation are being unmasked. Jin et al. reveal that the defective turnover of damaged mitochondria in CD4⁺ T cells from older individuals results in the exacerbated secretion of mitochondrial DNA, which fuels inflammaging and impairs immune responses.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

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

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

α,α-Dideutero carboxylic acids are common precursors for isotopically labelled molecules; however, their synthesis often requires high temperatures with strong bases or precious metals. Now, the α-deuteration of carboxylic acids has been developed under mild conditions using a ternary catalyst system of K₂CO₃, pivalic anhydride and 4-dimethylaminopyridine.

Low modulus materials that can change shape in response to external stimuli are promising for a wide range of applications. The authors here introduce a shape-reprogrammable construct, based on liquid metal microfluidic networks and electromagnetic actuation, that supports a unique collection of capabilities.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

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.

Antibiotic contamination has become a global challenge. Here, authors develop a retrievable and recyclable microalgae hydrogel network system, which can achieve efficient degradation of antibiotics over a wide range of concentrations.

Primordazine inhibits poly(A)-tail-independent noncanonical translation (PAINT) in early zebrafish embryos and in mammalian cells under select conditions, an effect mediated by deadenylated 3ʹ UTRs that results in ablation of primordial germ cells.

Here the authors report asperigimycins, fungal ribosomally synthesized and post-translationally modified peptides with a heptacyclic scaffold. After chemically modifying them for nanomolar anticancer activity, CRISPR screening identifies SLC46A3 as a key transporter for their uptake in cells.

LiTi₂O₄is the only known spinel oxide superconductor, but systematic investigations of its transport properties have been lacking so far. Here, the authors' analyses detect an unusual magnetoresistance, revealing spin-orbit fluctuations similar to those in high-temperature superconductors.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Crystalline dispersoids are commonly used to strengthen metals by obstructing dislocation movement, but this often comes at the cost of ductility. Here, the authors demonstrate that amorphous nanoparticles, introduced via additive manufacturing, enhance both the tensile strength and fatigue resistance of metallic materials.

We establish a spin nematic phase in the square-lattice iridate Sr₂IrO₄ and find a complete breakdown of coherent magnon excitations at short-wavelength scales, suggesting a many-body quantum entanglement in the antiferromagnetic state.

A consensus genome-scale gene regulatory network reconstruction allows dissection of the transcriptional regulation of microalgal responses to light and carbon availability and discovery of novel regulators of photoprotection and CO₂ acquisition.

The sensitivity of mesothelioma to the treatment of immune checkpoint blockade remains elusive. Here this group reports a double blind, placebo-controlled, randomized phase III trial of PD1 inhibitor (Nivolumab) on 332 patients with relapsed mesothelioma, and to uncover determinants of efficacy.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

The response of the body to drugs follows complex dynamical processes that can be difficult to predict. Lu and colleagues combine a neural network approach with pharmacokinetic/pharmacodynamic modelling to learn these complex dynamics.

Despite having many similarities with graphene, single-layer boron nitride has a very large bandgap. Now, single-layer hybrids consisting of a blend of domains of boron nitride and graphene have been synthesized. By varying the percentage of boron nitride it is possible to tune the electronic properties, which is a very promising development for potential devices.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.

p53 regulates signalling pathways involved in metabolic homeostasis. Here the authors show that O-GlcNAcylation of p53 in the liver plays a key role in the physiological regulation of glucose homeostasis, potentially via controlling the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Structural studies of the itch receptors MRGPRX2 and MRGPRX4 in complex with endogenous and synthetic ligands provide a basis for the development of therapeutic compounds for pain, itch and mast cell-mediated hypersensitivity.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Exploratory biomarker analyses of the phase 3 CheckMate 649 trial show that in patients with advanced gastroesophageal cancer, KRAS alterations were associated with greater overall survival (OS) benefit when treated with nivolumab plus chemotherapy vs chemotherapy alone, whereas high regulatory T-cell signatures were associated with greater OS benefit when treated with nivolumab plus ipilimumab.

Polyunsaturated fatty acids (PUFAs) are attracting considerable interest because of their diverse structures and properties. Now a method to access a wide array of PUFAs by full solid-phase synthesis has been developed and used to discover an anti-inflammatory fatty acid.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Soil biodiversity is poorly studied compared to aboveground biodiversity, but is an important driver of ecosystem functioning. This Review discusses advances in research into the relationships between soil biodiversity and ecosystem functioning, highlighting that integrative and causal study approaches will be needed to fill the gaps in our understanding.

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.