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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).

The microscopic pairing mechanism in high-temperature superconductors remains debated. Here, the authors offer a new perspective on this problem by proposing that the strong pairing in Fermi-Hubbard type models relevant to cuprates is driven by a Feshbach resonance, which enhances interactions between doped holes.

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.

Watt, Dauber, Szkop and colleagues find that H3K4me3 remodels 5′UTR selection in hypoxia and that this process is independent of HIF-1 transcriptional mechanisms.

This study explores the genetic structure of hepatitis C virus outbreaks in rural U.S communities affected by the opioid crisis. Analysis of intra-host viral populations from 692 participants reveals hidden transmission networks.

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.

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 large brain imaging study of over 2000 people worldwide shows that fear conditioning engages brain regions linked to emotion and attention, with differences in individuals with anxiety or depression and strong influences from task design.

The magnitude of greenhouse gas emissions from land use change on tropical peatlands is unclear. Here, the authors measure greenhouse gas fluxes throughout the conversion from peat swamp forest to oil palm plantation, and estimate the contribution to regional and global emissions.

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.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

In this work, the authors present structural and functional evidence of lipid exchange within the gram-negative Mla pathway, broadening our understanding of lipid transport in bacteria and providing insight into the mechanism of a unique ABC transporter.

Respiratory complex I is pivotal for cellular energy conversion. Here, the authors present the structure of complex I from the α-proteobacterium Paracoccus denitrificans, revealing the elements that stabilise the closed state and completing P. denitrificans complex I as a unified platform for combining structure, function and genetics in mechanistic studies.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Trained on 1.5 million whole-slide images from 100,000 patients, a pathology foundation model is shown to improve performance of specialized models in detection of rare cancers.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Using cryo-EM, Chung et al. investigate conformational states of mammalian respiratory complex I to reveal an ubiquinone-10 molecule occupying the full length of the Q-binding channel. Molecular dynamics simulations suggest how the charge states of key residues influence the substrate binding pose.

Mirchandani and colleagues show that tissue hypoxia alters the number and phenotype of circulating monocytes and their differentiation into lung macrophages, with important implications for the resolution of inflammation in the lung.

The effects of including the chemical industry in the existing Carbon Border Adjustment Mechanism of the European Union are unclear. A study finds that the current framework covers only half of key chemical emissions, urging the addition of fossil feedstocks and tougher default rules to boost efficacy.

An insertion of an Alu element into an intron of the TBXT gene is identified as a genetic mechanism of tail-loss evolution in humans and apes, with implications for human health today.

A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection.

Synapses are surrounded by an extracellular matrix (ECM) of extremely long-lived proteins that is thought to only be remodeled by proteolysis and de novo synthesis. Here, the authors show an alternative molecular recycling mechanism that occurs for the key ECM protein Tenascin-R.

Genome-wide association analyses identify 301 new loci influencing bone mineral density and 13 loci influencing fracture risk. Integrative analyses of epigenomic data and mouse knockout phenotypes provide additional insights into osteoporosis pathophysiology.

Pseudomonas putida is becoming a host of choice for the valorization of lignocellulosic substrates. Here, the authors provide insight into the adaptation of this bacterium to the non-native substrate D-xylose, enabled by metabolic engineering and adaptive laboratory evolution.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

A large-scale metagenomic analysis of plant and mammal environmental DNA reveals complex ecological changes across the circumpolar region over the past 50,000 years, as biota responded to changing climates, culminating in the postglacial extinction of large mammals and emergence of modern ecosystems.

Despite prior concerns regarding potential adverse effects, a 23-h fasting regimen mitigates metabolic abnormalities observed in Pcca-mutated mice by reducing propionate production from the microbiome and  enhancing propionyl-CoA disposal for gluconeogenesis and fatty acid oxidation to acetyl-CoA.

Matthew Brown, Peter Donnelly and colleagues report results of a genome-wide association meta-analysis and follow-up study of ankylosing spondylitis. They identify three new risk variants and report a genetic interaction between ERAP1 and HLA-B27, implicating aberrant peptide handling in the pathophysiology of this disease.

In the early embryo, Cas9 expressed in the female germline induces double-stranded breaks that are corrected by homology-directed repair, biasing inheritance of a desired allele in mice.

Building soil health and manipulating the soil microbiome, alongside targeted plant breeding that prioritizes preferential root architectural development, hold the key to the future success of regenerative agriculture. Greater integration is needed between disciplines focused on the rhizosphere scale with plant, microbiome and soil scientists working at the wider farm scale.