A lithium (Li)-metal anode paired with a high-nickel cathode is considered to be a combination that holds promise to surpass the 500 Wh kg-1 threshold1,2. Approaching such high energy density, electrolytes capable of stabilizing both anode and cathode interphases are of importance to secure safe and long-term cycling3,4. Although anion-derived inorganic interphases have shown remarkable success at the Li side5-7, developing intrinsic strategies to concurrently protect both electrodes remains a key challenge. Here we report a micro-emulsion strategy for electrolyte design that bypasses the Li+ solvation regulation and produces fluoride-rich interphases for both electrodes. Specifically, liquid-liquid interfacial tension between the micelles and carbonate solvents, rather than the electric field, propels the motion of fluorinated droplets towards the anode and the cathode. In this way, the interphase construction of both electrodes can be enhanced and decoupled from the solvation structure strategy. Through use of the micro-emulsion electrolyte, two pouch full cells with energy densities of 531 Wh kg-1 and 547 Wh kg-1 retain 81% and 79% of their capacity after 189 and 155 cycles, respectively. The introduction of liquid-liquid interfacial tension provides a perspective for interphase regulation and electrolyte design, and paves the way for the development of high-voltage Li-metal batteries.

Early detection of structural heart disease is critical to improving outcomes, but widespread screening remains limited by the cost and accessibility of imaging tools such as echocardiography1,2. Recent advances in machine learning applied to heart rhythm recordings have shown promise in identifying disease3,4, although previous work has been limited by development in narrow populations or targeting only select heart conditions5. Here we introduce a deep learning model, EchoNext, trained on more than 1 million heart rhythm and imaging records across a large and diverse health system to detect many forms of structural heart disease. The model demonstrated high diagnostic accuracy in internal and external validation, outperforming cardiologists in a controlled evaluation and showing consistent performance across different care settings and racial and/or ethnic groups. The models were prospectively evaluated in a clinical trial of patients without previous cardiac imaging, successfully identifying previously undiagnosed heart disease. These findings support the potential of artificial intelligence to expand access to heart disease screening at scale. To enable further development and transparency, we have publicly released model weights and a large, annotated dataset linking heart rhythm data to imaging-based diagnoses.

To gain a comprehensive, unbiased perspective on molecular changes in the brain that may underlie the need for sleep, we have characterized the transcriptomes of single cells isolated from rested and sleep-deprived flies. Here we report that transcripts upregulated after sleep deprivation, in sleep-control neurons projecting to the dorsal fan-shaped body1,2 (dFBNs) but not ubiquitously in the brain, encode almost exclusively proteins with roles in mitochondrial respiration and ATP synthesis. These gene expression changes are accompanied by mitochondrial fragmentation, enhanced mitophagy and an increase in the number of contacts between mitochondria and the endoplasmic reticulum, creating conduits3,4 for the replenishment of peroxidized lipids5. The morphological changes are reversible after recovery sleep and blunted by the installation of an electron overflow6,7 in the respiratory chain. Inducing or preventing mitochondrial fission or fusion8-13 in dFBNs alters sleep and the electrical properties of sleep-control cells in opposite directions: hyperfused mitochondria increase, whereas fragmented mitochondria decrease, neuronal excitability and sleep. ATP concentrations in dFBNs rise after enforced waking because of diminished ATP consumption during the arousal-mediated inhibition of these neurons14, which augments their mitochondrial electron leak7. Consistent with this view, uncoupling electron flux from ATP synthesis15 relieves the pressure to sleep, while exacerbating mismatches between electron supply and ATP demand (by powering ATP synthesis with a light-driven proton pump16) precipitates sleep. Sleep, like ageing17,18, may be an inescapable consequence of aerobic metabolism.

The Standard Model of particle physics-the theory of particles and interactions at the smallest scale-predicts that matter and antimatter interact differently due to violation of the combined symmetry of charge conjugation (C) and parity (P). Charge conjugation transforms particles into their antimatter particles, whereas the parity transformation inverts spatial coordinates. This prediction applies to both mesons, which consist of a quark and an antiquark, and baryons, which are composed of three quarks. However, despite having been discovered in various meson decays, CP violation has yet to be observed in baryons, the type of matter that makes up the observable Universe. Here we report a study of the decay of the beauty baryon Λ0b to the pK-π+π- final state, which proceeds through b → u or b → s quark-level transitions, and its CP-conjugated process, using data collected by the Large Hadron Collider beauty experiment1 at the European Organization for Nuclear Research (CERN). The results reveal significant asymmetries between the decay rates of the Λ0b baryon and its CP-conjugated antibaryon, providing, to our knowledge, the first observation of CP violation in baryon decays and demonstrating the different behaviours of baryons and antibaryons. In the Standard Model, CP violation arises from the Cabibbo-Kobayashi-Maskawa mechanism2, and new forces or particles beyond the Standard Model could provide further contributions. This discovery opens a new path in the search for physics beyond the Standard Model.

Non-antibiotic drugs can alter the composition of the gut microbiome1, but they have largely unknown implications for human health2. Here we examined how non-antibiotics affect the ability of gut commensals to resist colonization by enteropathogens3. We also developed an in vitro assay to assess enteropathogen growth in drug-perturbed microbial communities. Pathogenic Gammaproteobacteria were more resistant to non-antibiotics than commensals and their post-treatment expansion was potentiated. For 28% of the 53 drugs tested, the growth of Salmonella enterica subsp. enterica serovar Typhimurium. (S. Tm) in synthetic and human stool-derived communities was increased, and similar effects were observed for other enteropathogens. Non-antibiotics promoted pathogen proliferation by inhibiting the growth of commensals, altering microbial interactions and enhancing the ability of S. Tm to exploit metabolic niches. Drugs that promoted pathogen expansion in vitro increased the intestinal S. Tm load in mice. For the antihistamine terfenadine, drug-induced disruption of colonization resistance accelerated disease onset and increased inflammation caused by S. Tm. Our findings identify non-antibiotics as previously overlooked risk factors that may contribute to the development of enteric infections.

Liquids comprising two coexisting phases can form a range of stable and metastable states, including wetting films, droplets and threads1-3. Processes that permit rapid and reversible transformations between these morphologies, however, have been difficult to realize because physical properties required for rapid shape change (for example, low interfacial tension or viscosity) provide pathways for relaxation that result in short-lived states. Fully reversible formation of long-lived microdomain states would expand the palette of properties that can be accessed dynamically using biphasic liquids (for example, tunable optical metamaterials). Here we report the discovery of shape-shifting and bistable microdomains of a biphasic liquid system consisting of an isotropic oil and a liquid crystalline oil. The isotropic oil forms stable wetting films ('original' shape) between solid surfaces and an overlying liquid crystal phase, and, when exposed to a transient (<1 s) a.c. electric field at low frequency (10 Hz), transforms into long-lived (>24 h) spherical domains ('temporary' shape) stabilized by topological defects in the liquid crystal1,4,5. Subsequent application of an a.c. electric field of high frequency (1 kHz) triggers solitons to form in the liquid crystal6-8, creating kinetic pathways that lead to remarkably rapid (<3 s) coalescence of the dispersed spherical domains and recovery of the original shape (wetting film)1,8,9. We show rapid and reversible switching between distinct optical states of the biphasic system, with each state persisting without continuous application of the field, thus providing a combination of optical properties long sought in thin liquid films10-17. The fully reversible and long-lived emulsion formation reported here appears promising for materials synthesis, microchemical systems and tunable optical metamaterials (for example, to control visibility and transmittance of light through windows)17-21.

The synthesis of enantiopure compounds is a central focus in organic chemistry owing to the prevalence of chiral centres in biological systems and the impact of homochirality on molecular properties. With growing recognition of electrochemistry as a powerful tool to improve the scope and sustainability of organic synthesis1, increasing efforts have been directed towards developing asymmetric electrocatalytic reactions to access challenging chiral molecules2-4. However, many useful electrochemical reactions rely on direct electrolysis without a catalyst, making them inherently difficult to render enantioselective. Supporting electrolytes are integral to electrochemical systems and, in addition to ensuring sufficient solution conductivity, they can influence the rate and selectivity of electrochemical transformations5. Chiral supporting electrolytes can mediate asymmetric reactions via direct electrolysis, but their use in organic electrosynthesis remains largely unexplored6,7. Here we describe the use of substoichiometric chiral phosphate salts as supporting electrolytes to facilitate the oxidation of racemic trivalent phosphines to afford enantioenriched phosphine oxides. Our approach relies on a dynamic-kinetic-resolution strategy that exploits the rapid pyramidal inversion of an anodically generated phosphoniumyl radical cation8, while a high concentration of chiral phosphate at the electrode-electrolyte interface9,10 enhances enantioselective control during rate-limiting nucleophilic addition. Our results highlight the promise of chiral supporting electrolytes for promoting radical-ion-mediated asymmetric transformations.

The metabolic activity of soil microbiomes has a central role in global nutrient cycles1. Understanding how soil metabolic activity responds to climate-driven environmental perturbations is a key challenge2,3. However, the ecological, spatial and chemical complexity of soils4-6 impedes understanding how these communities respond to perturbations. Here we address this complexity by combining dynamic measurements of respiratory nitrate metabolism7 with modelling to reveal functional regimes that define soil responses to environmental change. Measurements across more than 1,500 soil microcosms subjected to pH perturbations8,9 reveal regimes in which distinct mechanisms govern metabolite dynamics. A minimal model with two parameters, biomass activity and growth-limiting nutrient availability, predicts nitrate utilization dynamics across soils and pH perturbations. Parameter shifts under perturbation reveal three functional regimes, each linked to distinct mechanisms: (1) an acidic regime marked by cell death and suppressed metabolism; (2) a nutrient-limited regime in which dominant taxa exploit matrix-released nutrients; and (3) a resurgent growth regime driven by exponential growth of rare taxa in nutrient-rich conditions. We validated these model-derived mechanisms with nutrient measurements, amendment experiments, sequencing and isolate studies. Additional experiments and meta-analyses suggest that functional regimes are widespread in pH-perturbed soils.

With their superficially shark-like appearance, the Mesozoic ichthyosaurs provide a classic illustration of major morphological adaptations in an ancestrally terrestrial tetrapod lineage following the invasion of marine habitats1-3. Much of what is known about ichthyosaur soft tissues derives from specimens with body outlines4-6. However, despite offering insights into aspects of biology that are otherwise difficult to envisage from skeletal evidence alone (such as the presence of a crescentic fluke), information on their soft parts has hitherto been limited to a taxonomically narrow sample of small- to dolphin-sized animals2,4-6. Here we report the discovery of a metre-long front flipper of the large-bodied Jurassic ichthyosaur Temnodontosaurus, including unique details of its soft-tissue anatomy. In addition to revealing a wing-like planform, the fossil preserves a serrated trailing edge that is reinforced by novel cartilaginous integumental elements, herein denominated chondroderms. We also document chordwise-parallel skin ornamentations and a protracted fleshy distal tip that presumably acted like a flexible winglet in life. By integrating morphological and numerical data, we show that the observed features probably provided hydroacoustic benefits, and conclude that the visually guided7,8 Temnodontosaurus relied on stealth while hunting in dim-lit pelagic environments. This unexpected combination of control surface modifications represents a previously unrecognized mode of concealment, and underscores the importance of soft-tissue fossils when inferring aspects of palaeoethology and predator-prey palaeoecology.

In microbial communities, viruses compete for host cells and have evolved diverse mechanisms to inhibit competitors. One strategy is superinfection exclusion, whereby an established viral infection prevents a secondary infection of the same cell1. This phenomenon has been shown to have an important role in the spread of eukaryotic viruses. Here we determine that superinfection exclusion proteins in bacterial viruses (bacteriophages, hereafter phages) perform a similar role, promoting viral spread through the bacterial community. We characterize a phage protein that alters the dynamics of a common phage receptor, the type IV pilus. This protein, known as Zip, does not abrogate pilus activity, but fine-tunes it, providing a strong phage defence without a fitness cost. Notably, Zip also prevents internalization and destruction of newly released phage progeny, a phenomenon that we call the anti-Kronos effect after the Greek god who consumed his offspring. Zip activity promotes the accumulation of free phages in bacterial lysogen communities, thereby enhancing viral spread. We further demonstrate that the anti-Kronos effect is conserved across diverse prophage-encoded superinfection exclusion systems. Our results identify the mechanistic basis of a superinfection exclusion system that safeguards phage progeny and provide insights into the conservation of viral defence mechanisms among bacterial and eukaryotic systems.

Living biological systems rely on the continuous operation of chemical reaction networks. These networks sustain out-of-equilibrium regimes in which chemical energy is continually converted into controlled mechanical work and motion1-3. Out-of-equilibrium reaction networks have also enabled the design and successful development of artificial autonomously operating molecular machines4,5, in which networks comprising pairs of formally-but non-microscopically-reverse reaction pathways drive controlled motion at the molecular level. In biological systems, the concurrent operation of several reaction pathways is enabled by the chemoselectivity of enzymes and their cofactors, and nature's dissipative reaction networks involve several classes of reactions. By contrast, the reactivity that has been harnessed to develop chemical reaction networks in pursuit of artificial molecular machines is limited to a single reaction type. Only a small number of synthetic systems exhibit chemically fuelled continuous controlled molecular-level motion6-8 and all exploit the same class of acylation-hydrolysis reaction. Here we show that a redox reaction network, comprising concurrent oxidation and reduction pathways, can drive chemically fuelled continuous autonomous unidirectional motion about a C-C bond in a structurally simple synthetic molecular motor based on an achiral biphenyl. The combined use of an oxidant and reductant as fuels and the directionality of the motor are both enabled by exploiting the enantioselectivity and functional separation of reactivity inherent to enzyme catalysis.

Most people in the USA manage their health by taking at least one prescription drug, and drugs classified as non-antibiotics can adversely affect the gut microbiome and disrupt intestinal homeostasis1,2. Here we identify medications that are associated with an increased risk of gastrointestinal infections across a population cohort of more than one million individuals monitored over 15 years. Notably, the cardiac glycoside digoxin and other drugs identified in this epidemiological study are sufficient to alter the composition of the microbiome and the risk of infection with Salmonella enterica subsp. enterica serovar Typhimurium (S. Tm) in mice. The effect of digoxin treatment on S. Tm infection is transmissible through the microbiome, and characterization of this interaction highlights a digoxin-responsive β-defensin that alters the microbiome composition and consequent immune surveillance of the invading pathogen. Combining epidemiological and experimental approaches thus provides an opportunity to uncover drug-host-microbiome-pathogen interactions that increase the risk of infections in humans.

Tumour necrosis is associated with poor prognosis in cancer1,2 and is thought to occur passively when tumour growth outpaces nutrient supply. Here we report, however, that neutrophils actively induce tumour necrosis. In multiple cancer mouse models, we found a tumour-elicited Ly6GHighLy6CLow neutrophil population that was unable to extravasate in response to inflammatory challenges but formed neutrophil extracellular traps (NETs) more efficiently than classical Ly6GHighLy6CHigh neutrophils. The presence of these 'vascular-restricted' neutrophils correlated with the appearance of a 'pleomorphic' necrotic architecture in mice. In tumours with pleomorphic necrosis, we found intravascular aggregates of neutrophils and NETs that caused occlusion of the tumour vasculature, driving hypoxia and necrosis of downstream vascular beds. Furthermore, we found that cancer cells adjacent to these necrotic regions (that is, in 'perinecrotic' areas) underwent epithelial-to-mesenchymal transition, explaining the paradoxical metastasis-enhancing effect of tumour necrosis. Blocking NET formation genetically or pharmacologically reduced the extent of tumour necrosis and lung metastasis. Thus, by showing that NETs drive vascular occlusion, pleomorphic necrosis and metastasis, we demonstrate that tumour necrosis is not necessarily a passive byproduct of tumour growth and that it can be blocked to reduce metastatic spread.

Atherosclerosis is the main underlying cause of cardiovascular diseases. Its prevention is based on the detection and treatment of traditional cardiovascular risk factors1. However, individuals at risk for early vascular disease often remain unidentified2. Recent research has identified new molecules in the pathophysiology of atherosclerosis3, highlighting the need for alternative disease biomarkers and therapeutic targets to improve early diagnosis and therapy efficacy. Here, we observed that imidazole propionate (ImP), produced by microorganisms, is associated with the extent of atherosclerosis in mice and in two independent human cohorts. Furthermore, ImP administration to atherosclerosis-prone mice fed with chow diet was sufficient to induce atherosclerosis without altering the lipid profile, and was linked to activation of both systemic and local innate and adaptive immunity and inflammation. Specifically, we found that ImP caused atherosclerosis through the imidazoline-1 receptor (I1R, also known as nischarin) in myeloid cells. Blocking this ImP-I1R axis inhibited the development of atherosclerosis induced by ImP or high-cholesterol diet in mice. Identification of the strong association of ImP with active atherosclerosis and the contribution of the ImP-I1R axis to disease progression opens new avenues for improving the early diagnosis and personalized therapy of atherosclerosis.

Hybridized matter-photon excitations in hyperbolic crystals-anisotropic materials characterized by permittivity tensor components with opposite sign-have attracted substantial attention owing to their strong light-matter interactions in the form of hyperbolic polaritons1-3. However, these phenomena have been restricted to hyperbolic crystals, whose optical responses are confined to fixed spectral regions and lack tunability, thereby limiting their broader applicability4,5. Here we demonstrate the emergence of hyperbolic surface phonon polaritons in a non-hyperbolic yttrium vanadate (YVO4) crystal. Using real-space nanoimaging combined with theoretical analyses, we visualize hyperbolic wavefronts of surface phonon polaritons on YVO4 crystal surfaces within its non-hyperbolic frequency range, where the permittivity tensor components of the material have the same negative sign. Furthermore, by varying the temperature from room temperature to cryogenic levels, we realize in situ manipulation of polariton dispersions, enabling a topological transition from hyperbolic to canalization and eventually to the elliptic regime. This temperature-controlled dispersion engineering not only provides precise control over polariton topology but also modulates their wavelength and group velocity, showing remarkable sensitivity alongside low-loss, long-range propagation. These findings extend the realm of hyperbolic nano-optics by removing the reliance on hyperbolic crystals, unlocking opportunities for applications in negative refraction6-10, superlensing11,12, polaritonic chemistry13, integrated photonics14-16 and beyond.

Birds have a sex chromosome system in which females are heterogametic (ZW) and males are homogametic (ZZ)1. The differentiation of avian sex chromosomes from ancestral autosomes entails the loss of most genes from the W chromosome during evolution1,2. However, the extent to which mechanisms evolved that counterbalance this substantial reduction in female gene dosage remains unclear. Here we report functional in vivo and evolutionary analyses of a Z-linked microRNA (miR-2954) with strong male-biased expression, previously proposed to mediate avian sex chromosome dosage compensation3. We knocked out miR-2954 in chicken, which resulted in early embryonic lethality in homozygous knockout males, probably driven by specific upregulation of dosage-sensitive Z-linked target genes. Evolutionary gene expression analyses further revealed that these dosage-sensitive target genes underwent both transcriptional and translational upregulation on the single Z in female birds. Altogether, this work unveils a scenario in which evolutionary pressures following W gene loss drove transcriptional and translational upregulation of dosage-sensitive Z-linked genes in females but also their transcriptional upregulation in males. The resulting excess of transcripts in males, resulting from the combined activity of two upregulated dosage-sensitive Z gene copies, was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution. This study uncovered a unique sex chromosome dosage compensation system in birds, in which a microRNA has become essential for male survival.

Whole-genome doubling (WGD) is a common feature of human cancers and is linked to tumour progression, drug resistance, and metastasis1-6. Here we examine the impact of WGD on somatic evolution and immune evasion at single-cell resolution in patient tumours. Using single-cell whole-genome sequencing, we analysed 70 high-grade serous ovarian cancer samples from 41 patients (30,260 tumour genomes) and observed near-ubiquitous evidence that WGD is an ongoing mutational process. WGD was associated with increased cell-cell diversity and higher rates of chromosomal missegregation and consequent micronucleation. We developed a mutation-based WGD timing method called doubleTime to delineate specific modes by which WGD can drive tumour evolution, including early fixation followed by considerable diversification, multiple parallel WGD events on a pre-existing background of copy-number diversity, and evolutionarily late WGD in small clones and individual cells. Furthermore, using matched single-cell RNA sequencing and high-resolution immunofluorescence microscopy, we found that inflammatory signalling and cGAS-STING pathway activation result from ongoing chromosomal instability, but this is restricted to predominantly diploid tumours (WGD-low). By contrast, predominantly WGD tumours (WGD-high), despite increased missegregation, exhibited cell-cycle dysregulation, STING1 repression, and immunosuppressive phenotypic states. Together, these findings establish WGD as an ongoing mutational process that promotes evolvability and dysregulated immunity in high-grade serous ovarian cancer.