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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).

Mitochondrial respiration involves super-complexes whose assembly pathway is debated. Here, authors reveal structural intermediates showing that complex IV matures last, with HIGD2A acting as a placeholder before NDUFA4 completes respirasome assembly.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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.

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.

This study found higher RSV antibody levels were associated with lower RSV risk in children outside the hospital. An earlier rise in incidence and higher incidence rates were observed among children <5 years compared to older children and adults.

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.

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.

Previous studies have shown that cellular electrostatic interactions are influential. Here the authors use cryo-EM and steady-state kinetic studies to investigate electrostatic interactions between cytochrome (cyt.) c and the complex (C) III₂-IV supercomplex from S.cerevisiae at low salinity.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

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.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Reverse electron transport is the mechanism behind excess mitochondrial reactive oxygen species in the livers of obese mice, which has implications for developing therapeutics for fatty liver disease in humans.

Pneumococci can alternate between harmless and highly virulent forms. Here the authors show that such variation may be due to random rearrangements in a genetic locus encoding a restriction-modification system, resulting in epigenetic changes that affect expression of many genes.

Substrate preorganization is a ubiquitous concept in the active sites of natural enzymes and is linked to their intrinsic activity. In this study, a designed cleft in a synthetic supramolecular catalyst is shown to preorganize water, resulting in high water oxidation activity and distinct mechanistic changes.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

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.

The combination of transparency, small brain size and genetic access positions Danionella translucida as a promising model organism for functional imaging of neuronal circuits, especially during complex behaviors in adults.

Using a combination of cryo-electron microscopy, activity measurements and in vivo experiments, the authors show that decylubiquinone, an analogue of the mammalian electron carrier, ubiquinol, binds to and inhibits the CIII₂CIV₂ supercomplex from M. smegmatis, and inhibits growth of M. tuberculosis. This compound may thus represent a new therapeutic strategy to treat tuberculosis.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

The switch from glucose- to fatty acid-dependent metabolism in cardiomyocytes of newborn mice is governed by γ-linolenic acid in maternal milk, which binds to retinoid X receptors, thereby causing a transcription-dependent metabolic transition.

The obligate supercomplex from M. Tuberculosis has emerged as a promising drug target. Here the authors employ structural experiments, activity assays, and multiscale molecular simulations, to elucidate the mechanism of charge transfer in this enzyme.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

Dendritic cells play pivotal roles in the immune response to viral infection but are targeted by flaviviruses resulting in evasion of the host response. Here the authors show Zika but not Dengue virus limits the NF-κB response in monocyte derived dendritic cells diminishing their ability to activate T cells.

A new study shows the total global SOC stock of 1 m in the world’s tidal marshes to be 1.44 Pg C. On average, SOC in tidal marshes’ 0–30 cm and 30–100 cm soil layers are estimated at 83.1 Mg C ha⁻¹ and 185.3 Mg C ha⁻¹, respectively.

Na⁺ controls the function of the mitochondrial oxidative phosphorylation system and hypoxic redox signalling through an unexpected interaction with phospholipids.

Analyses of neuroimaging datasets from 5,306 participants across 15 countries found generally larger brain-age gaps in Latin American compared with non-Latin American populations, which were influenced by disparities in socioeconomic and health-related factors.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Changes in the expression of the RNA-binding protein HuR are common in several cancers. Here, the authors show that HuR regulates glutaminase mRNA metabolism in the context of breast cancer. This work reveals that dual inhibition of HuR and glutaminase may have therapeutic potential.

A new phylogenomic tree for butterflies is constructed using 391 genes from 2,300 species, representing 92% of genera. It suggests that butterflies originated around 100 million years ago in what is now the Americas and originally fed on Fabaceae.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

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

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Disruption of leukaemia inhibitory factor production from group 2 innate lymphoid cells prevents immune cells leaving the lungs to migrate to lymph nodes, leading to plasmacytoid dendritic cells becoming retained in the lungs following viral infection.

The small intestinal lamina propria is rich in innate lymphoid cells, which are important contributors of mucosal immunity. Here authors identify a small progenitor cell population that can develop into all types of innate lymphoid cells in their intestinal microenvironment but their developmental potential becomes more restricted when placed into other tissues, such as liver, lung or spleen.

Chalcopyrite, the main copper ore mineral, is usually formed at high temperatures, according to a study that shows that microbial processes might promote its low-temperature formation in acidic pit lake sediments, with implications for bioremediation and biomining.

Combined analysis of new genomic data from 116 ancient hunter-gatherer individuals together with previously published data provides insights into the genetic structure and demographic shifts of west Eurasian forager populations over a period of 30,000 years.

To understand the potential for seaweed as a Blue Carbon strategy, the authors quantify carbon burial under 20 globally distributed seaweed farms. They attribute an average of 1.06 ± 0.74 tCO₂e ha⁻¹ yr⁻¹ to seaweed farms, and show increased accumulation of carbon with farm age.

The authors show that pink1-mutant flies display intestinal dysfunction and that suppression of Relish, an innate immune response mediator, in the gut rescues mitochondrial dysfunction and cell death in the brain.

The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.