Quantum simulations of many-body systems are among the most promising applications of quantum computers1. In particular, models based on strongly correlated fermions are central to our understanding of quantum chemistry and materials problems2, and can lead to exotic, topological phases of matter3,4. However, owing to the non-local nature of fermions, such models are challenging to simulate with qubit devices5. Here we realize a digital quantum simulation architecture for two-dimensional fermionic systems based on reconfigurable atom arrays6. We utilize a fermion-to-qubit mapping based on Kitaev's model on a honeycomb lattice3, in which fermionic statistics are encoded using long-range entangled states7. We prepare these states efficiently using measurement8 and feedforward9, realize subsequent fermionic evolution through Floquet engineering10,11 with tunable entangling gates12 interspersed with atom rearrangement, and improve results with built-in error detection. Leveraging this fermion description of the Kitaev spin model, we efficiently prepare topological states across its complex phase diagram13 and verify the non-Abelian spin-liquid phase3 by evaluating an odd Chern number14,15. We further explore this two-dimensional fermion system by realizing tunable dynamics and directly probing fermion exchange statistics. Finally, we simulate strong interactions and study the dynamics of the Fermi-Hubbard model on a square lattice. These results pave the way for digital quantum simulations of complex fermionic systems for materials science, chemistry16 and high-energy physics17.

Out-of-equilibrium phases in many-body systems constitute a new paradigm in quantum matter-they exhibit dynamical properties that may otherwise be forbidden by equilibrium thermodynamics. Among these non-equilibrium phases are periodically driven (Floquet) systems1-5, which are generically difficult to simulate classically because of their high entanglement. Here we realize a Floquet topologically ordered state theoretically proposed in ref. 6, on an array of superconducting qubits. We image the characteristic dynamics of its chiral edge modes and characterize its emergent anyonic excitations. Devising an interferometric algorithm allows us to introduce and measure a bulk topological invariant to probe the dynamical transmutation of anyons for system sizes up to 58 qubits. Our work demonstrates that quantum processors can provide key insights into the thus-far largely unexplored landscape of highly entangled non-equilibrium phases of matter.

Globular clusters (GCs) are among the oldest and densest stellar systems in the Universe, yet how they form remains a mystery1. Here we present a suite of cosmological simulations in which both dark-matter-free GCs and dark-matter-rich dwarf galaxies naturally emerge in the Standard Cosmology. We show that these objects inhabit distinct locations in the size-luminosity plane and that they have similar ages, age spread, metallicity and metallicity spread to globulars and dwarfs in the nearby Universe. About half of our simulated globulars form by means of regular star formation near the centres of their host dwarf, with the rest forming further out, triggered by mergers. The latter are more tidally isolated and more likely to survive to the present day. Finally, our simulations predict the existence of a new class of object that we call 'globular-cluster-like dwarfs' (GCDs). These form from a single, self-quenching, star-formation event in low-mass dark-matter halos at high redshift and have observational properties intermediate between globulars and dwarfs. We identify several dwarfs in our Galaxy, such as Reticulum II (refs. 2-4), that could be in this new class. If so, they promise unprecedented constraints on dark-matter models and new sites to search for metal-free stars.

Extreme event attribution assesses how climate change affected climate extremes, but typically focuses on single events1-4. Furthermore, these attributions rarely quantify the extent to which anthropogenic actors have contributed to these events5,6. Here we show that climate change made 213 historical heatwaves reported over 2000-2023 more likely and more intense, to which each of the 180 carbon majors (fossil fuel and cement producers) substantially contributed. This work relies on the expansion of a well-established event-based framework1. Owing to global warming since 1850-1900, the median of the heatwaves during 2000-2009 became about 20 times more likely, and about 200 times more likely during 2010-2019. Overall, one-quarter of these events were virtually impossible without climate change. The emissions of the carbon majors contribute to half the increase in heatwave intensity since 1850-1900. Depending on the carbon major, their individual contribution is high enough to enable the occurrence of 16-53 heatwaves that would have been virtually impossible in a preindustrial climate. We, therefore, establish that the influence of climate change on heatwaves has increased, and that all carbon majors, even the smaller ones, contributed substantially to the occurrence of heatwaves. Our results contribute to filling the evidentiary gap to establish accountability of historical climate extremes7,8.

The Perseverance rover has explored and sampled igneous and sedimentary rocks within Jezero Crater to characterize early Martian geological processes and habitability and search for potential biosignatures1-7. Upon entering Neretva Vallis, on Jezero Crater's western edge8, Perseverance investigated distinctive mudstone and conglomerate outcrops of the Bright Angel formation. Here we report a detailed geological, petrographic and geochemical survey of these rocks and show that organic-carbon-bearing mudstones in the Bright Angel formation contain submillimetre-scale nodules and millimetre-scale reaction fronts enriched in ferrous iron phosphate and sulfide minerals, likely vivianite and greigite, respectively. This organic carbon appears to have participated in post-depositional redox reactions that produced the observed iron-phosphate and iron-sulfide minerals. Geological context and petrography indicate that these reactions occurred at low temperatures. Within this context, we review the various pathways by which redox reactions that involve organic matter can produce the observed suite of iron-, sulfur- and phosphorus-bearing minerals in laboratory and natural environments on Earth. Ultimately, we conclude that analysis of the core sample collected from this unit using high-sensitivity instrumentation on Earth will enable the measurements required to determine the origin of the minerals, organics and textures it contains.

Cancer-associated muscle wasting is associated with poor clinical outcomes1, but its underlying biology is largely uncharted in humans2. Unbiased analysis of the RNAome (coding and non-coding RNAs) with unsupervised clustering using integrative non-negative matrix factorization3 provides a means of identifying distinct molecular subtypes and was applied here to muscle of patients with colorectal or pancreatic cancer. Rectus abdominis biopsies from 84 patients were profiled using high-throughput next-generation sequencing. Integrative non-negative matrix factorization with stringent quality metrics for clustering identified two highly coherent molecular subtypes within muscle of patients with cancer. Patients with subtype 1 (versus subtype 2) showed clinical manifestations of cachexia: high-grade weight loss, low muscle mass, atrophy of type IIA and type IIX muscle fibres, and reduced survival. On the basis of differential expression between the subtypes, we identified biological processes that may contribute to cancer-associated loss of muscle mass and function, including altered posttranscriptional regulation and perturbation of neuronal systems; cytokine storm and cellular immune response; pathways related to extracellular matrix; and metabolic abnormalities spanning xenobiotic metabolism, haemostasis, signal transduction, embryonic and/or pluripotent stem cells, and amino acid metabolism. Differential expression between subtypes indicated the involvement of multiple intertwined higher-order gene regulatory networks, suggesting that network interactions of (hub) long non-coding RNAs, microRNAs and mRNAs could represent targets for future research.

Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate1-3. Recent evidence has suggested that innervation has an important role in the development and progression of several types of cancer4,5. Cancer-to-neuron synapses have been reported in gliomas6,7, but whether peripheral tumours can form such structures is unknown. Here we show that SCLC cells can form functional synapses and receive synaptic transmission. Using in vivo insertional mutagenesis screening in conjunction with cross-species genomic and transcriptomic validation, we identified neuronal, synaptic and glutamatergic signalling gene sets in mouse and human SCLC. Further experiments revealed the ability of SCLC cells to form synaptic structures with neurons in vitro and in vivo. Electrophysiology and optogenetic experiments confirmed that cancer cells can receive NMDA receptor- and GABAA receptor-mediated synaptic inputs. Fitting with a potential oncogenic role of neuron-SCLC interactions, we showed that SCLC cells derive a proliferation advantage when co-cultured with vagal sensory or cortical neurons. Moreover, inhibition of glutamate signalling had therapeutic efficacy in an autochthonous mouse model of SCLC. Therefore, following malignant transformation, SCLC cells seem to hijack synaptic signalling to promote tumour growth, thereby exposing a new route for therapeutic intervention.

Smoke from extreme wildfires in Canada adversely affected air quality in many regions in 20231,2. Here we use satellite observations, machine learning and a chemical transport model to quantify global and regional PM2.5 (particulate matter less than 2.5 μm in diameter) exposure and human health impacts related to the 2023 Canadian wildfires. We find that the fires increased annual PM2.5 exposure worldwide by 0.17 μg m-3 (95% confidence interval, 0.09-0.26 μg m-3). North America had the largest increase in annual mean exposure (1.08 μg m-3; 0.82-1.34 μg m-3), but there were also increases in Europe (0.41 μg m-3; 0.32-0.50 μg m-3) owing to long-range transport. Annual mean PM2.5 exposure in Canada increased by 3.82 μg m-3 (3.00-4.64 μg m-3). In the USA, the contribution of the Canadian fires to increased PM2.5 was 1.49 μg m-3 (1.22-1.77 μg m-3), four times as large as the contribution from the 2023 wildfires originating in the USA. We find that 354 million (277-421 million) people in North America and Europe were exposed to daily PM2.5 air pollution caused by Canadian wildfires in 2023. We estimate that 5,400 (3,400-7,400) acute deaths in North America and 64,300 (37,800-90,900) chronic deaths in North America and Europe were attributable to PM2.5 exposure to the 2023 Canadian wildfires. Our results highlight the far-reaching PM2.5 pollution and health burden that large wildfires can have in a single year.

Monocyte-derived macrophages (mo-macs) often drive immunosuppression in the tumour microenvironment (TME)1 and tumour-enhanced myelopoiesis in the bone marrow fuels these populations2. Here we performed paired transcriptome and chromatin accessibility analysis over the continuum of myeloid progenitors, circulating monocytes and tumour-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that lung tumours prime accessibility for Nfe2l2 (NRF2) in bone marrow myeloid progenitors as a cytoprotective response to oxidative stress, enhancing myelopoiesis while dampening interferon response and promoting immunosuppression. NRF2 activity is amplified during monocyte differentiation into mo-macs in the TME to regulate stress and drive immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced the survival and immunosuppression of mo-macs in the TME, restoring natural killer and T cell anti-tumour immunity and enhancing checkpoint blockade efficacy. Our findings identify a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the lung TME and highlight the potential of early interventions to reprogram macrophage fate for improved immunotherapy outcomes.

Carbonaceous asteroids are the source of the most primitive meteorites1 and represent leftover planetesimals that formed from ice and dust in the outer Solar System and may have delivered volatiles to the terrestrial planets2-5. Understanding the aqueous activity of asteroids is key to deciphering their thermal, chemical and orbital evolution, with implications for the origin of water on the terrestrial planets. Analyses of the objects, in particular pristine samples returned from asteroid Ryugu, have provided detailed information on fluid-rock interactions within a few million years after parent-body formation6-11. However, the long-term fate of asteroidal water remains poorly understood. Here we present evidence for fluid flow in a carbonaceous asteroid more than 1 billion years after formation, based on the 176Lu-176Hf decay systematics of Ryugu samples, which reflect late lutetium mobilization. Such late fluid flow was probably triggered by an impact that generated heat for ice melting and opened rock fractures for fluid migration. This contrasts the early aqueous activity powered by short-lived radioactive decay, with limited fluid flow and little elemental fractionation12. Our results imply that carbonaceous planetesimals accreted by the terrestrial planets could have retained not only hydrous minerals but also aqueous water, leading to an upwards revision of the inventory of their water delivery by a factor of two to three.

Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth through paracrine mechanisms1 and by electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses2,3. Outside of the central nervous system, innervation of tumours such as prostate, head and neck, breast, pancreatic, and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression4-12. However, the extent to which the nervous system regulates small cell lung cancer (SCLC) progression, either in the lung or when growing within the brain, is less well understood. SCLC is a lethal high-grade neuroendocrine tumour that exhibits a strong propensity to metastasize to the brain. Here we demonstrate that in the lung, vagus nerve transection markedly inhibits primary lung tumour development and progression, highlighting a critical role for innervation in SCLC growth. In the brain, SCLC cells co-opt neuronal activity-regulated mechanisms to stimulate growth and progression. Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity each drive proliferation of SCLC in the brain through paracrine and synaptic neuron-cancer interactions. SCLC cells form bona fide neuron-to-SCLC synapses and exhibit depolarizing currents with consequent calcium transients in response to neuronal activity; such SCLC cell membrane depolarization is sufficient to promote the growth of intracranial tumours. Together, these findings illustrate that neuronal activity has a crucial role in dictating SCLC pathogenesis.

Bacteriophages are the most abundant entities on earth and exhibit vast genetic and phenotypic diversity. Exploitation of this largely unexplored molecular space requires identification and functional characterization of genes that act at the phage-host interface. So far, this has been restricted to few model phage-host systems that are amenable to genetic manipulation. Here, to overcome this limitation, we introduce a non-genetic mRNA targeting approach using exogenous delivery of programmable antisense oligomers to silence genes of DNA and RNA phages. A systematic knockdown screen of core and accessory genes of the nucleus-forming jumbo phage ΦKZ, coupled to RNA-sequencing and microscopy analyses, reveals previously unrecognized proteins that are essential for phage propagation and that, upon silencing, elicit distinct phenotypes at the level of the phage and host response. One of these factors is the RNase H-like protein ΦKZ155 (also known as Nlp2), which acts at a major decision point during infection, linking the formation of the protective phage nucleus to phage genome amplification. This non-genetic antisense oligomer-based gene silencing method promises to be a versatile tool for molecular discovery in phage biology, will help to elucidate defence and anti-defence mechanisms in non-model phage-host pairs, and offers potential for optimizing phage therapy and biotechnological procedures.

The human stomach features distinct, regionalized functionalities along the anterior-posterior axis1,2. Historically, studies on stomach patterning have used animal models to identify the underlying principles3-7. Recently, human pluripotent stem (hPS)-cell-based gastric organoids for modelling domain-specific development of the fundic and antral epithelium are emerging8-10. However, recapitulating self-organized fundic-antral patterning in early stomach organogenesis remains challenging, presenting a considerable barrier for advancing knowledge of stomach organogenesis. Here we report human gastroids-a self-organized multilineage gastric organoid derived from hPS cells-to model gastric fundic-antral patterning in vitro. Through multi-germ-layer co-development, we generate gastroids that feature an epithelial chamber with bipolar fundic-antral patterning, annexed with neural populations near the fundic domain while enveloped by mesenchymal cells, therefore showing molecular, cellular, structural and anatomical similarity to stomach development in vivo. Non-endodermal cells, especially neural populations, function as a critical signalling centre to instruct fundic-antral patterning in gastroids through WNT-mediated crosstalk. Single-cell transcriptomic profiling and genetic silencing further reveal NR2F2 as a key mediator of fundic-antral patterning in gastroid development. This study reveals a principle for instructing gastric patterning and provides a higher-fidelity platform for advancing knowledge of stomach organogenesis and gastric organoid development.

Controlling spin currents, that is, the flow of spin angular momentum, in small magnetic devices, is the principal objective of spin electronics, a main contender for future energy-efficient information technologies1,2. A pure spin current has never been measured directly because the associated electric stray fields and/or shifts in the non-equilibrium spin-dependent distribution functions are too small for conventional experimental detection methods optimized for charge transport3,4. Here we report that resonant inelastic X-ray scattering (RIXS) can bridge this gap by measuring the spin current carried by magnons-the quanta of the spin wave excitations of the magnetic order-in the presence of temperature gradients across a magnetic insulator. This is possible due to the sensitivity of the momentum- and energy-resolved RIXS intensity to minute changes in the magnon distribution under non-equilibrium conditions. We use the Boltzmann equation in the relaxation time approximation to extract transport parameters, such as the magnon lifetime at finite momentum, essential for the realization of magnon spintronics.

Epithelial cells work collectively to provide a protective barrier, yet they turn over rapidly through cell division and death. If the numbers of dividing and dying cells do not match, the barrier can vanish, or tumours can form. Mechanical forces through the stretch-activated ion channel Piezo1 link both of the processes; stretch promotes cell division, whereas crowding triggers live cells to extrude and then die1,2. However, it was not clear what selects a given crowded cell for extrusion. Here we show that the crowded cells with the least energy and membrane potential are selected for extrusion. Crowding triggers sodium (Na+) entry through the epithelial Na+ channel (ENaC), which depolarizes cells. While those with sufficient energy repolarize, those with limited ATP remain depolarized, which, in turn, triggers water egress through the voltage-gated potassium (K+) channels Kv1.1 and Kv1.2 and the chloride (Cl-) channel SWELL1. Transient water loss causes cell shrinkage, amplifying crowding to activate crowding-induced live cell extrusion. Thus, our findings suggest that ENaC acts as a tension sensor that probes for cells with the least energy to extrude and die, possibly damping inadvertent crowding activation of Piezo1 in background cells. We reveal crowding-sensing mechanisms upstream of Piezo1 that highlight water regulation and ion channels as key regulators of epithelial cell turnover.

Amino acids (AAs) have a long history of being used as stabilizers for biological media1. For example, they are important components in biomedical formulations. The effect of AAs on biological systems is also starting to be appreciated. For example, it is believed that water-stressed cells increase the levels of AAs to prevent protein aggregation2. Several hypotheses have been put forward regarding their function, ranging from water-structuring3 to hydrotropic4 to specific effects such as stabilization against misfolding, yet it is not known whether their stabilizing function is protein specific or a generic colloidal property. Here we deduce that AAs possess a new and broad colloidal property: they stabilize patchy nanoscale colloids by adsorbing onto their surfaces through weak interactions. We demonstrate this general property by careful experimental evaluation of the stabilizing effect of AAs on dispersions of various proteins, plasmid DNA and non-biological nanoparticles. Furthermore, we develop a theoretical framework that captures this phenomenon and experimentally corroborate several new broad theoretical implications that apply beyond AAs. In vivo experiments further demonstrate that the addition of 1 M proline to insulin doubles its bioavailability in blood. Overall, our results indicate that the role of small molecules is as important as that of ionic strength and should always be reported in biophysics experiments.

The Lepidosauria is the most species-rich group of land-dwelling vertebrates. The group includes around 12,000 species of lizards and snakes (Squamata) and one species of Rhynchocephalia, the tuatara Sphenodon punctatus from New Zealand1. Squamates owe their success to their generally small size, but also to their highly mobile skull that enables them to manipulate large prey. These key features of lizard and snake skulls are not seen in Sphenodon, which makes it important to understand the nature of their common ancestor. Lepidosaurs originated in the Triassic 252-201 million years ago, but confusion has arisen because of incomplete fossils, many of which are generalized lepidosauromorphs, neither squamates nor rhynchocephalians2-5. Here we report a reasonably complete skull and skeleton of a definitive rhynchocephalian from the Middle Triassic (Anisian) Helsby Sandstone Formation of Devon, UK that is around 3-7 million years older than the oldest currently known lepidosaur. The new species shows, as predicted, a non-mobile skull but an open lower temporal bar and no large palatine teeth, and it seems to have been a specialized feeder on insects. This specimen helps us understand the initial diversification of Lepidosauria as part of the Triassic Revolution, when modern-style terrestrial ecosystems emerged.

As a key mitochondrial Ca2+ transporter, NCLX regulates intracellular Ca2+ signalling and vital mitochondrial processes1-3. The importance of NCLX in cardiac and nervous-system physiology is reflected by acute heart failure and neurodegenerative disorders caused by its malfunction4-9. Despite substantial advances in the field, the transport mechanisms of NCLX remain unclear. Here we report the cryo-electron microscopy structures of NCLX, revealing its architecture, assembly, major conformational states and a previously undescribed mechanism for alternating access. Functional analyses further reveal an unexpected transport function of NCLX as a H+/Ca2+ exchanger, rather than as a Na+/Ca2+ exchanger as widely believed1. These findings provide critical insights into mitochondrial Ca2+ homeostasis and signalling, offering clues for developing therapies to treat diseases related to abnormal mitochondrial Ca2+.

Antigen-induced clustering of cell surface receptors, including T cell receptors and Fc receptors, represents a widespread mechanism in cell signalling activation1,2. However, most naturally occurring antigens, such as tumour-associated antigens, stimulate limited receptor clustering and on-target responses owing to insufficient density3-5. Here we repurpose proximity labelling6, a method used to biotinylate and identify spatially proximal proteins, to amplify designed probes as synthetic antigen clusters on the cell surface. We develop an in vivo proximity-labelling technology controlled by either red light or ultrasound to covalently tag fluorescein probes at high density near a target antigen. Using T cell receptors as an example, we demonstrate that the amplified fluorescein effectively clusters and directs a fluorescein-binding bispecific T cell engager to induce enhanced T cell activation and cytotoxicity. Noninvasive, tissue-selective labelling in multiple syngeneic mouse tumour models produces potent immune responses that rapidly eradicate treated tumours. Efficient cell lysis further promotes epitope spreading to induce systemic immunity against untreated distal lesions and immune memory against rechallenge. Thus, proximity-labelling chemistry holds promise as a generalized strategy to manipulate antigen-dependent receptor function and cell states.