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Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

The contribution of genetic factors to the tumour immune microenvironment (TIME) remains to be investigated. Here, the authors suggest the role of TIME eQTLs for target genes involved in reversing immune suppressive features.

It remains to be seen if high-T_c superconductors rely on similar Fermi-surface instabilities as their BCS counterparts. Miao et al. study the high-T_c compound LiFe_1−xCo_xAs with high-resolution ARPES and find a robust gap with Co doping that suggests the order parameter is not tied to such instabilities.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Small-conductance Ca²⁺ -activated K⁺ (K_Ca2.1-K_Ca2.3) channels modulate neuronal and cardiac excitability. Here, authors report cryo-EM structures of the K_Ca2.2 channel, providing a basis for understanding the small unitary conductance and pharmacology of K_Ca2.x channels.

Heterostructure interfaces have physical properties distinct from bulk materials, providing the basis for many electronic devices. Miao et al. propose a spin ice heterostructure that can host a two-dimensional gas of emergent magnetic monopoles with a net magnetic charge.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

Atmospheric dryness is increasing as air temperatures rise because of climate change. This Review explores temporal trends and spatial heterogeneity in global atmospheric dryness and the implications for plant growth, productivity and terrestrial carbon cycling.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

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.

The interplay between magnetism and charge density wave in the kagome magnet FeGe is under debate. By using elastic and inelastic X-ray scattering, angle-resolved photoemission spectroscopy, and first principles calculations, Miao et al. propose that the charge density wave is stabilized by spin-phonon coupling.

The understanding of charge density wave (CDW) correlations in cuprate superconductors remains hampered due to the lack of scattering phase information. Here, Chen et al. discover a reproducible CDW domain memory effect upon repeated cycling to temperatures well above the CDW ordering temperature.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

An analysis of data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920–2024) shows spatiotemporal transitions across epidemiologic stages 1 to 3 of inflammatory bowel disease, and models stage 4 progression.

Colour code on a superconducting qubit quantum processor is demonstrated, reporting above-breakeven performance and logical error scaling with increased code size by a factor of 1.56 moving from distance-3 to distance-5 code.

The emergence of large language models has the potential to transform healthcare. Here, the authors show that, when providing clinical recommendations, these models perform poorly compared to physicians and are overly cautious in their decisions.

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases such as chronic kidney disease (CKD). Here, the authors perform a sex-stratified, cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits, with results including identification of four novel loci associated with the CKD-defining trait eGFR.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

In this Roadmap, Aggarwal and colleagues summarize current research and knowledge gaps on the relationship between sleep, circadian rhythms and cardiovascular resilience; highlight potential therapeutic targets and interventions for optimizing sleep and circadian rhythms to improve cardiovascular function and prevent disease; and outline research directions and opportunities, emphasizing the need for multidisciplinary collaboration.

The authors experimentally realize the control of the topological charge of magnetic skyrmionic structures at room temperature in a Dzyaloshinskii-Moriya interaction (DMI) platform with spatially alternating signs. By modifying the DMI energy landscape through chemisorbed oxygen, a magnetic topological transition is realized.

In the IMpower151 trial, the drug combination previously shown to be effective in the IMpower150 trial was not significantly effective in a Chinese population.

In a quantum simulation of a (2+1)D lattice gauge theory using a superconducting quantum processor, the dynamics of strings reveal the transition from deconfined to confined excitations as the effective electric field is increased.

A hybrid analogue–digital quantum simulator is used to demonstrate beyond-classical performance in benchmarking experiments and to study thermalization phenomena in an XY quantum magnet, including the breakdown of Kibble–Zurek scaling predictions and signatures of the Kosterlitz–Thouless phase transition.

High-resolution observations reveal fibril motions in the chromospheric umbra of a sunspot, providing a potential energy source for coronal heating.

Myeloid cells are implicated in the innate immune and inflammatory response during infection with Chlamydia trachomatis. Here the authors show the evasion of the neutrophil response to infection and concomitant induction of sterile immunity via the purinergic P2X7 receptor.

A variety of metal electrodes can be deposited on a graphene substrate, delaminated and transferred onto two-dimensional semiconductors to form high-quality metal–semiconductor interfaces.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Antisymmetric exchange, or the Dzyaloshinskii-Moriya interaction, has been a topic intense study in recent years, due to its critical role in stabilizing topological spin-textures such as Skyrmions. Here, using a combination of point group analysis and spin polarized electron microscopy Niu et al demonstrate the existence of an out-of-plane Dzyaloshinskii-Moriya interaction, which was hitherto unobserved.

Analysis of medulloblastomas in humans and mice shows that the functional consequences of ZIC1 mutations are exquisitely dependent on the cells of origin that give rise to different subgroups of medulloblastoma.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

Autonomic dysfunction is a feature of some α-synucleinopathies, but there are no models of pure autonomic dysfunction associated with α-synuclein. Here the authors describe a mouse model of pure autonomic dysfunction without motor dysfunciton by injection of pre-formed fibrils of α-synuclein to the stellate and celiac ganglia.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum samples from three independent immunotherapy trials and found the serum kynurenine/tryptophan ratio increases to be associated with worse overall survival.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Delivering therapeutics to the brain is challenging because of the hard-to-cross blood–brain barrier. Here, the authors show that HER3, which is expressed on the surface of many metastatic tumours, is associated with the brain endothelium and can drive accumulation of HER3-targeted nanoparticles within the brain, for therapy against HER3-positive tumours.

Cycloaddition reactions are among the most useful reactions in chemical synthesis, but biosynthetic enzymes with 2 + 2 cyclase activity have yet to be observed. Now it is shown that a β-barrel-fold protein catalyses competitive 2 + 2 and 4 + 2 cycloaddition reactions. This protein can be engineered to preferentially produce the exo-2 + 2, exo-4 + 2 or endo-4 + 2 product.

By implementing random circuit sampling, experimental and theoretical results establish the existence of transitions to a stable, computationally complex phase that is reachable with current quantum processors.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Caspase-7 cleaves and activates acid sphingomyelinase (ASM), which promotes the repair of gasdermin pores and thereby delays pore-driven lysis to allow other processes such as extrusion or apoptosis to occur before cell death.

Promoting more bone growth is of keen interest in the treatment of osteoporosis, and preventing the degradation of S1P offers a new therapeutic avenue for this approach.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Here the authors show the structures of single-pass transmembrane receptor guanylyl cyclase in both apo and hormone-bound states, advancing our understanding of cross-membrane signaling by single-pass transmembrane receptors.

Su et al. report cryo-EM structures of β₁-adrenergic receptor, Gs and ligands of different efficacies. These complexes have similar overall architecture, but with local conformational differences and different stabilities.

To trace the sources of Black Carbon being transported into the Tibetan Plateau is crucial for guiding an effective mitigation strategy. Here the authors utilized the adjoint of the Goddard Earth Observing System-Chem model and find that international trade aggravates the BC pollution over the HTP glacier regions and may cause significant climate change.