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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).

An implementation trial conducted across 60 schools in Rwanda found that CyberRwanda, a digital, school-based intervention, did not affect the primary outcomes of modern contraceptive use, childbearing and HIV testing among adolescents but was associated with higher contraceptive use among sexually active participants.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

A seven-week school-based field experiment shows that social-rewards schemes increase physical activity in preadolescents, with girls being more receptive to reciprocal and boys to team rewarding schemes.

Surface acoustic waves have previously been used, in conjunction with electric currents and assisting magnetic fields, to manipulate magnetization. Here, Rivelles, Yanes, and coauthors succeed in driving magnetic domain walls solely with surface acoustic waves, an important milestone in acoustically controlled spintronic devices.’

In a phase 3 trial for Huntington’s disease, pridopidine did not meet its primary endpoints but was safe and favored in some prespecified subgroup analyses.

Norovirus genotype GII.17 has been linked with a recent increase in cases in Europe and the Americas. Here, the authors investigate the genetic diversity and mutational patterns, and phenotypic differences associated with the recent circulating strain.

Single-cell transcriptomic analyses of Plasmodium falciparum and Anopheles gambiae reveal key developmental stages, processes and factors in parasite–mosquito interactions and identify potential targets for blocking malaria transmission.

Whether mRNA SARS-CoV-2 vaccines promote T cells within the nasal mucosa of vaccine recipients is not known. Here the authors show that after mRNA SARS-CoV-2 vaccination, antigen specific T cells can be measured in the nasal mucosa and that these T cells may be localised to respond to a subsequent virus infection.

Clinical trial registration NCT04713163

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

The role of wild and domesticated animals on alpine ecosystems is unclear. Here, the authors use sedaDNA from 14 European alpine lakes to demonstrate a positive association between wild and domesticated animal and plant diversity through the past 14 thousand years.

Doxycycline post-exposure prophylaxis is recommended in the United States for populations at risk of bacterial sexually transmitted infections, but there is concern about development of antimicrobial resistance. Here, the authors use insurance claims data to estimate the potential impacts of the policy on antimicrobial consumption.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

Across 13 longitudinal studies (3,737 adults), the authors show that brain atrophy parallels memory loss, with a stronger coupling in later life. APOE ε4 increases decline, yet genetic risk does not modify the brain–memory relationship.

Quantifying genomic aberrations resulting from designer nucleases activity is essential for gene therapy clinical translation. Here, the authors present a modular digital PCR technique that profiles DNA repair precision and cut-repair cycles at the edited loci, exposing current evaluation biases.

While several advancements have been made in the use of on-demand solid-state quantum emitters for quantum communication, using them to realise a quantum relay among remote parties had not been realised so far. Here, the authors fill this gap by realising all-photonic quantum state teleportation with photons generated by distinct remote quantum dots.

Through an epigenome-wide blood analysis in children of mothers with or without type 1 diabetes, the authors identify epigenetic modifications of type 1 diabetes susceptibility loci through which maternal type 1 diabetes may protect from islet autoimmunity in offspring.

A potential origin of homochirality in living organisms is the parity-violating energy difference between enantiomers. Here, the authors realize a technique to control rotational states of chiral molecules using microwave and ultraviolet radiation.

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.

Whole-genome sequencing and mutational signature analysis of 265 head and neck cancer samples collected from eight different countries provide insight into the vital contribution of tobacco smoke in disease etiology.

Merghoub, Wolchok and colleagues reveal a role of the extracellular matrix protein thrombospondin-1 (TSP-1) and CD47 in promoting T cell exhaustion during tumor progression in mice and humans.

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.

This work uses gene expression and single cell analyses to group extrapulmonary tuberculosis patients into three immune types, revealing immune pathways driving pathogenesis and markers that could improve diagnosis and guide tailored treatments.

SARS-CoV-2 vaccination has shown reduced efficacy in patients with haematological malignancies. Here, the authors show that a third vaccine is able to enhance SARS-CoV-2 antibody responses in most cases in a cohort of 381 patients with haematological malignancies.

Anandasabapathy and colleagues show that the inhibitory receptor PD-1 impacts the specification of tissue-resident memory T cells in the skin.

The regulatory landscape controlling Hoxd gene expression in tetrapod digit development was probably co-opted from a pre-existing cloacal regulatory mechanism, as evidenced by the effects of genetic deletion experiments in zebrafish fin, cloaca and mouse urogenital development.

In skeletal muscle mitochondria, CRL5^Ozz and Alix regulate the levels of the ATP transporter Slc25A4; loss of either protein in mice alters Slc25A4, causing mitochondrial defects, metabolic changes, and a shift from oxidative to glycolytic fibers.

Living plant collections hold an immense wealth of plant diversity and have critical educational, scientific and conservation roles. This Perspective examines current data management practices of living collections and advocates for higher data standards and a robust and inclusive global data ecosystem.

Creative experiences such as dance, music, drawing, and strategy video games might preserve brain health. The authors show that regular practice or short training in these activities is linked to brains that look younger and work more efficiently.

How do low-mass binaries age? Astronomers have constrained a tight, circular orbit of a close-in companion around a dying giant star, raising new questions about how tidal forces shape binary orbits in the final phases of stellar evolution.

Ecological effects, such as disturbances, have a spatial dimension, but what influences their spatial propagation is not fully understood. Here, the authors find generalist and widespread species are key to propagating effects spatially, mediated by landscape characteristics and species provenance.

Demystifying the spawning strategies of fish can help us understand their evolutionary drivers and better inform fisheries management. This study reveals the spawning strategies of pelagic fish, showing that the benefits of co-located spawning across time and space outweigh the potential drawbacks.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Rider, Grantham, Smith, Watson et al. integrate multiomic data from patients with psoriasis using dimensionality reduction and machine learning techniques. This approach identifies biological relationships between genetic background, clinical features and disease severity, providing insight into disease variability across individuals.

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.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Using two wavelengths to activate different photoreactions in a resin system has attracted attention in the scientific community. Here, the authors use wavelength orthogonal photochemistry to spatially control the curing kinetics of a thiol-ene photopolymerization reaction.

Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

The phosphoethanolamine modified cellulose in E. colibiofilms has revealed that polysaccharide functionalization alters the biofilm properties. Here, the authors show a model system to explore the role of phosphoethanolamine and other unnatural modifications on the properties of the biofilm-inspired assemblies.

Köhler et al. present the crystal structure of fungal tRNA ligase Trl1-LIG bound to an activated RNA substrate, providing key insights into conserved substrate binding and activation, enzyme specificity and a tRNA substrate coordination model.

Across 27 countries, Većkalov and Geiger et al. find that scientific consensus messaging on climate change is an effective, non-polarizing tool for changing misperceptions, beliefs and worry but not support for public action.

A study of dependencies associated with cancer-causing mutations has identified a small molecule that binds to SHOC2 and inhibits RAS signalling in cells carrying NRAS Q61 mutations, a common oncogenic driver in melanoma.

SIRT1-driven deacetylation of the MED1 subunit of the Mediator complex under stress modifies gene expression by enhancing RNA polymerase II action, promoting survival and growth of estrogen-receptor-positive breast cancer cells.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

Head and neck cancer patients could greatly benefit from personalised treatment, but a lack of large public datasets hampers this potential. Here, the authors present HANCOCK, a multimodal dataset that integrates demographical, clinical, and histopathological data for 763 head and neck cancer patients that empowers machine learning models for clinical outcome prediction.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

Epstein–Barr virus infection generates a neuroinvasive B cell subset, which recruits activated T cells to the central nervous system, promoting multiple sclerosis.

Analyses of the exposomes of populations across 40 countries found global disparities in healthy aging attributed to diverse biological, socioeconomic and political factors, with accelerated aging seen in populations from Egypt, South Africa, and Latin American and Caribbean regions.