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Light and redox switches are of interest for responsive materials, actuators and robotics. Here the authors integrated a redox- and photoresponsive switch into a polymer hydrogel enabling reversible redox-switching with high spatio-temporal precision.

Mutations in the insulin receptor cause severe insulin resistance, but their functional impact is often unclear. Here, the authors map ~14,000 receptor variants, linking molecular defects to disease and highlighting variants responsive to therapeutic activation.

McGeachan et al. observe oligomeric tau in synapses from individuals with progressive supranuclear palsy and provide evidence that tau pathology may spread through the brain via synapses.

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.

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.

Understanding synapse loss in Alzheimer’s disease has been hampered by a lack of human model systems. Here, the authors show that manipulation of physiological or pathological Aβ has differing effects on synapses in live human brain slice cultures.

Long-wavelength luminescence from boron-based cations is typically hindered by both intrinsic instability and pronounced non-radiative decay. Now a triadic design that integrates a non-Kekulé polycyclic aromatic hydrocarbon framework, a charge-localizing carbodicarbene ligand and counterion-directed assembly enables stable borenium ions with tunable red-to-near-infrared emission in the solid state.

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.

Hunter et al. use RNA labelling to investigate RNA transfer between organs in mice. They show that RNA potentially moves en masse from liver to kidney and that this movement is augmented in acute liver injury, although the physiological relevance of the phenomenon is not yet known.

Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.

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).

Photoactive transition metal complexes usually feature 4d6 and 5d6 precious metals with charge transfer excited state lifetimes exceeding hundreds of nanoseconds, while complexes with earth abundant 3d6 metals exhibit lifetimes of less than 1–2 ns. Here, the authors report a tetracarbene manganese(I) complex with an excited state lifetime of 190 ns.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

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.

A complementary analysis of DESI DR2 distance measurements along with supernova and CMB data shows consistent, moderate evidence that dark energy changes over time rather than behaving as a simple cosmological constant.

Smoking remains a leading cause of preventable death and disease. Here, the authors explore the link between smoking and DNA methylation using arrays and next generation sequencing, and develop mCigarette, an epigenetic biomarker of smoking.

Medical predictive analytics can enhance quality improvement, clinical research, and patient care. D-CLEF, a privacy-preserving model, integrates patient data across centers and performs comparably to centralized models, enabling collaboration without sharing patient records.

The complexity of epithelial cell states in the fibrotic niche in the context of chronic kidney disease remains incompletely understood. Here the authors integrate snRNA and ATAC-seq with high-plex single-cell molecular imaging to generate a spatially-revolved multiomic atlas of human kidney disease.

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.

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.

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

Pressure overload in the heart, such as from aortic stenosis, triggers early molecular changes before visible damage occurs. Here, the authors show that combining proteomics, transcriptomics, and genetic data reveals key drivers of heart failure, highlighting potential targets for treatment.

The number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

GABAB receptors contribute to complex inhibition that regulates cortical neurons in a translationally relevant manner over adult life. Here, authors show stronger presynaptic inhibition in humans than rats, and a role for GABAB receptors in the anti-seizure profile of levetiracetam.

Brain age gaps (BAGs) highlight deviations from healthy brain aging, yet their biophysical underpinnings in aging and dementia are not well understood. Here, the authors use EEG connectivity and generative modeling across diverse populations to reveal that BAGs are influenced by geography, income, sex and education, with implications for understanding accelerated aging and dementia.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

X chromosomes evolve faster than autosomes, but confounding factors make this a difficult phenomenon to study. Utilising the unusual sex determination system of Sciaridae flies, this study finds a slower evolution of the X chromosomes which appears to be driven by strong purifying selection.

The molecular classification of endometroid ovarian carcinomas (EnOC) has not been established, preventing the development of stratified therapeutic approaches. Here the authors characterise the molecular landscape of EnOC by whole exome sequencing, identifying clinically distinct disease subtypes.

A rhynchocephalian skeleton around 3–7 million years older than the oldest currently known lepidosaur fossil provides important insight into the origin of lizards and snakes.

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

Bone marrow adipose tissue (BMAT) comprises over 10% of total fat mass but its systemic metabolic role is unclear. Here, the authors show that BMAT glucose uptake is not insulin or cold responsive; however, BMAT basal glucose uptake is higher than in white adipose tissue or skeletal muscle, underscoring BMAT’s potential to influence systemic glucose homeostasis.

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.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

Suchacki et al. show that serotonin suppresses human brown adipose tissue (BAT) activation, and that inhibition of the serotonin transporter (SERT) potentiates the suppressive action of extracellular serotonin on BAT by preventing serotonin uptake.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

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.

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.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, blood protein markers of brain health are integrated with omics data to reveal DNA methylation differences that associate with these protein markers.

Quantum low-density parity-check (QLDPC) codes offer lower overhead than topological quantum error-correcting codes, but decoding remains a key challenge for scalable fault-tolerant quantum computing. This work introduces a highly parallelizable decoding algorithm for QLDPC codes that matches the accuracy of leading decoders while enabling significantly improved scalability.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.