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A large cross-population atlas of gene–environment interactions reveals how age, sex and lifestyle shape genetic effects, heritability, prediction accuracy and disease biology, with implications for personalized medicine and drug development.

A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Lee et al. show that Ca²⁺ triggers condensates enriched with PDIA6, an ER-resident disulfide isomerase and chaperone, along with other protein disulfide isomerase family proteins and some chaperones that in turn enhance folding of proinsulin.

Desmoplastic stroma is a hallmark of aggressive colorectal cancer. Matrix cancer-associated fibroblasts derived THBS2 establishes a fibrotic, immune-exclusionary barrier that limits CD8⁺ T cell infiltration, while its inhibition restores CXCR3-mediated T cell recruitment and enhances response to immune checkpoint blockade.

Sekiya and colleagues identify that, in response to reductive metabolism, CtBP2 is secreted via exosomes and regulates metabolism in recipient cells via CYB5R3 and AMPK. Exosomal CtBP2 administration extends lifespan and healthspan in aged mice, and serum levels of CtBP2 decline with age in humans.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

COVID-19 severity is linked to microthrombus formation. Here, using an in vivo two-photon imaging technique in mice and human scRNA-Seq data, the authors show increased adhesion molecules on vascular neutrophils leading to platelet aggregation and reduced lung perfusion.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

By using three silicon spin qubits to construct a phase-correcting code, quantum error correction is implemented and protection of the three-qubit state against any phase-flip error on one of the three qubits is demonstrated.

Here the authors reveal that oncoprotein DEK binds the nucleosome, colocalizes with H3 K27 trimethylation and stimulates Polycomb repressive complex 2 methyltransferase through chromatin compaction, as revealed by the cryo-electron microscopy structures of nucleosome-bound DEK.

Poor access to suitable light-sheet microscopes remains a big obstacle for many end-users in biomedical research. Here, the authors present descSPIM, a low-cost, low-expertise light-sheet microscope for routine 3D imaging of cleared samples.

Water intake is critical to our life, and the subfornical organ in the brain involved in the control of this behavior. Here, the authors reveal that two distinct groups of CCK-producing neurons in the SFO suppress water intake according to the physiological condition or water-intake stimulus.

At low temperatures, the orbital degrees of freedom in insulating magnets normally do not fluctuate, leaving only magnetic behaviour. Measurements now suggest that in Pr₂Zr₂O₇, it is possible to reach a quantum regime of coupled spin–orbital dynamics.

Quantum control on an isotopically enriched Si spin qubit is demonstrated with ultrahigh gate fidelities and long coherence times —  even in the presence of sizeable charge noise.

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.

In quantum chromodynamics, the condensation of quark–antiquark pairs breaks the chiral symmetry of vacuum. Experiments with pionic tin atoms demonstrate that the symmetry is partially restored at high densities.

MraY (phospho-N-acetylmuramoyl-pentapeptide-transferase) inhibitory natural products are attractive candidates for the development of agents to combat antimicrobial-resistant bacteria, but their properties need to be improved by structural optimization which is challenging. Here, the authors develop a strategy for a comprehensive in situ evaluation of the build-up library, which enables streamlining of the preparation of the analogue library and direct assessment of its biological activities.

In land plants, the Ia and IIIb basic helix–loop–helix (Ia-IIIb bHLH) module regulates stomatal development. This study shows that a Ia-IIIb bHLH heterodimer, MpSETA-MpICE2, regulates seta formation in Marchantia and suggests a common mechanism underlying stomata and setae formation.

The role of cortical PV neurons in the regulation of sleep architecture and homeostatic sleep rebound is not fully understood. Here, the authors show that CaMKII-mediated control of cortical parvalbumin-neuron activity regulates the homeostatic sleep rebound in mice.

The gastric H⁺,K⁺-ATPase is a proton pump that creates the acidic environment of the stomach lumen, maintaining high proton gradient across the gastric mucosa cell membrane. Here, structural analysis of rationally designed H⁺,K⁺-ATPase mutants provides insight into this and other P-type ATPases cation binding stoichiometry and mechanisms.

Checkpoint blockade is effective in only a subset of patients; therefore, biomarkers that can predict efficacy would be clinically highly valuable. Nishkawa and colleagues develop a biomarker based on PD-1 positivity of effector and regulatory T cells in the tumor microenvironment that accurately predicts the effectiveness of checkpoint blockade in patients.

Stress-independent autophagy is less understood than stress-induced autophagy and is important for thymic self-tolerance. Here the authors show that a mitochondrial protein C15ORF48 is important for stress-independent autophagy and alters glutathione metabolism and C15orf48 knockout mice develop autoimmunity and changes to thymic epithelial cells.

A genome-wide CRISPR knockout screen in eHAP cells using ATAC-see to fluorescently label chromatin identifies novel regulators of accessibility, such as the transcription factor TFDP1 via regulation of canonical histone expression.

Optics used for X-ray focusing suffer from wavelength dependent effects like chromatic aberration. Here the authors demonstrate fabrication of a ultracompact Kirkpatrick-Baez mirror and use it for achromatic focusing to 20 nm spot for the soft X-ray at 2-keV photon energy.

Breathing might be crucial for cognition during both offline and online brain states. Here, the authors show that temporal apnea induced by activating the PreBötzinger complex during memory formation resulted in memory impairments.

Nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme for NAD synthesis, has been proposed as a potential target for cancer therapy. Here, the authors show synthetic lethality when combining NAMPT inhibition with Niacin restriction in neuroendocrine-type cancer.

Chemogenetic inactivation of the subthalamic nucleus in monkeys increases spike train variability in the pallidum and prolongs movement time, suggesting its role in stabilizing pallidal spike trains to achieve stable motor control.

A coherent quantum link between distant quantum processors is desirable for scaling up of quantum computation. Noiri et al. demonstrate a strategy to link distant quantum processors in silicon, by implementing a shuttling-based two-qubit gate between spin qubits in a Si/SiGe triple quantum dot.

Tamagawa, Fujii et al. demonstrate that squamous differentiation in human pancreatic cancer can be attributed to TP63-mediated lineage conversion and epigenetic reprogramming that depends upon a hypoxic and Wnt-defective niche.

Experiments in mouse models and histology of human head and neck squamous cell carcinomas show that TIMP1-mediated periosteal thickening in proximity to tumours acts as a barrier to cancer invasion of the bone.

Mouse induced pluripotent stem cells derived from differentiated fibroblasts could be converted from male (XY) to female (XX), resulting in cells that could form oocytes and give rise to offspring after fertilization.

The SMART (MLKL-activation reporter) system FRET biosensor allows for necroptosis assessment in primary cells and in a mouse model of cisplatininduced AKI.

Single- and two-qubit gate fidelities above the fault-tolerance threshold for quantum computation are demonstrated in silicon quantum dots by fast electrical control using a micromagnet-induced gradient field and tunable coupling.

How enhancers transition from a hypoacetylated primed state to a hyperacetylated-active state in response to differentiation stimuli is incompletely understood. Here the authors show that SETD5 forms a complex with NCoR-HDAC3 co-repressor to prevent histone acetylation of master adipogenic gene enhancers, while SETD5 degradation triggers enhancer hyperacetylation and transition to active state.