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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).

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

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.

Mirusviruses were detected in metagenomic datasets, but little is known about how they infect their hosts. Here, the authors characterize mirusviruses in the marine protist Aurantiochytrium, detecting virions, viral genes and proteins, and establishing this as a valuable model system.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

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.

The phloem is the system of ‘blood vessels’ that translocates carbohydrates from the leaves to different plant organs. Here, using new structural imaging and pressure measuring tools, the researchers show interesting phloem structural changes that ensure a passive transport mechanism in tall trees.

CAR T cell immunotherapy for paediatric solid and brain tumours is constrained by the availability of targetable antigens. Here, the authors investigate the landscape of cancer-specific exons as potential targets by analysing 1,532 RNAseq datasets from 16 types of paediatric solid and brain tumours.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Holistic indicator frameworks are needed to track food systems transformation. This Analysis shows the application of a framework recently developed by the Food Systems Countdown Initiative to all UN member states, revealing current status, data gaps and priority actions.

Consuming the milk of other species is a unique adaptation of Homo sapiens. Here, the authors carry out proteomic analysis of dental calculus of 41 ancient individuals from Sudan and Kenya, indicating milk consumption occurred as soon as herding spread into eastern Africa.

Ground- and satellite-based air pollution data from 2000 to 2022 quantify the contribution of wildfire smoke to stagnation or reversal in PM_2.5 concentration trends, showing that this contribution will grow as the climate continues to warm.

Extracellular vesicles secreted by cells play a crucial role in cellular communication. Here, the authors identify a functional BK channel in extracellular vesicle membranes and establish its role in preserving vesicle integrity, K+ homeostasis, and physiological function.

This study presents the first annual update of the indicator framework developed by the Food Systems Countdown Initiative, published in Nature Food in 2023. Almost half of all indicators show some desirable trends. Governance and resilience indicators were revealed as the most connected across themes, constituting entry points for transformative change.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Human disease mutations affect protein–protein interfaces in a three-dimensional structurally resolved interaction network. Predicted oncoPPIs in cancer correlate with survival and drug sensitivity, and affect growth in vitro, supporting their relevance to disease pathogenesis.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Disease signatures in high-dimensional biomedical data are detected with a visualization algorithm.

Multitrait genome-wide analysis of glaucoma and related phenotypes identifies new risk loci and enables development of a polygenic risk score to predict disease susceptibility and key clinical outcomes.

The PI3K/Akt/mTOR pathway has been previously implicated in fibrosis and a pan-PI3K/mTOR inhibitor is currently under clinical evaluation for the treatment of IPF. Here the authors show that the mTORC1/4E-BP1 axis is critical for TGF-β1-induced fibrogenesis in in vitro and ex vivo models and that canonical PI3K/Akt signalling is dispensable.

Single-cell sequencing approaches need to balance sensitivity, throughput and experimental complexity. Here the authors combine droplet-based microfluidics and combinatorial indexing to develop OAK, a versatile method for ultra-high throughput single-cell multiomic profiling.

Climate threats to iconic places may arouse public concern and protective sentiment. This study shows that mass coral bleaching influenced sentiments, threat perceptions and values associated with the Great Barrier Reef and climate change attitudes in Australian and international tourists.

Genome-scale CRISPR–Cas9-based synthetic lethality screens identify PKMYT1 as a potential therapeutic target in tumours with CCNE1 amplification.

Whole-exome sequencing in a large autism study identifies over 100 autosomal genes that are likely to affect risk for the disorder; these genes, which show unusual evolutionary constraint against mutations, carry de novo loss-of-function mutations in over 5% of autistic subjects and many function in synaptic, transcriptional and chromatin-remodelling pathways.

Single-nucleus RNA-sequencing analyses of brain from humans, macaques, marmosets, mice and ferrets reveal diverse ways that interneuron populations have changed during evolution.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Conventional microscopy is unable to correlate nanoscale properties of metal halide perovskites with the performance of solar cells. Frohna et al. present a multimodal operando microscopy toolkit as a diagnostic tool to address the issue.

Neuroblastoma (NB) is often driven by MYCN amplification. Here, the authors show that the most frequent genetic lesion, gain of 17q21-ter in NB leads to overexpression of ALYREF, which forms a complex with MYCN, regulating MYCN stability via the deubiquitinating enzyme, USP3.

The bicyclic azetidines, a class of potent, well-tolerated antimalarial compounds that is active against multiple stages of the Plasmodium life-cycle, has been discovered following screens against libraries of compounds reminiscent of natural products.

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

Behavioural studies and neural recordings in mice show that virgin mice can acquire maternal behaviour through an oxytocin-dependent mechanism.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

Although the gain in chromosome 17q21-ter is commonly associated with neuroblastoma, it is not clear which gene of this region mediates tumorigenesis. Here, the authors are showing that JMJD6, which locates in that region, is a neuroblastoma tumorigenic factor.

Burke et al. show that smoke exposure is associated with behavioural changes and worsening sentiment, with important differences by income. They document substantial infiltration of smoke into homes, suggesting that current policy reliance on self-protection could be ineffective.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

To limit warming, a rapid reduction in coal use is needed. Early retirement of coal power plants by members of the Powering Past Coal Alliance, which includes mainly wealthy countries that use little coal, would have a modest climate impact. Prospects for expanding the Alliance are examined.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Jones et al. examine the generalizability of the valence–dominance model of social judgements of faces in 41 countries across 11 world regions. They find evidence of both generalizability and variation, depending on the analytical method.