The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4-6. Through SSB1-mediated recognition of single-stranded DNA, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS-INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.

Lead (Pb) halide perovskite light-emitting diodes (PeLEDs) have demonstrated extraordinary optoelectronic performance1-3. However, potential toxicity issues with Pb4,5 mean that removing Pb from the best-performing PeLEDs-without compromising their excellent external quantum efficiencies (EQEs)-remains a challenge. Here we report a tautomeric mixture coordination-induced electron localization strategy to stabilize Pb-free TEA2SnI4 (TEAI, 2-thiophenethylammonium iodide) perovskite by incorporating cyanuric acid (CA). We demonstrate that a crucial function of the coordination is to amplify electronic effects and even extend to Sn atoms without strong bonding with CA, due to the formation of H-bonded tautomeric dimer and trimer superstructures on the perovskite surface. This electron localization weakens adverse effects from Anderson localization and improves the ordering in crystal structure of TEA2SnI4. These factors give a two orders of magnitude reduction in nonradiative recombination capture coefficient and approximately 2-fold enhancement in exciton binding energy. Our Pb-free PeLED has an EQE of up to 20.29 per cent, representing a performance comparable to that of state-of-the-art Pb-containing PeLEDs6-12. We anticipate that these findings will provide insights into the stabilization of Sn(II) perovskites and further progress Pb-free perovskite applications.

Striatal dopamine and acetylcholine are essential for the selection and reinforcement of motor actions and decision-making1. In vitro studies have revealed an intrastriatal circuit in which acetylcholine, released by cholinergic interneurons (CINs), drives the release of dopamine, and dopamine, in turn, inhibits the activity of CINs through dopamine D2 receptors (D2Rs). Whether and how this circuit contributes to striatal function in vivo is largely unknown. Here, to define the role of this circuit in a living system, we monitored acetylcholine and dopamine signals in the ventrolateral striatum of mice performing a reward-based decision-making task. We establish that dopamine and acetylcholine exhibit multiphasic and anticorrelated transients that are modulated by decision history and reward outcome. Dopamine dynamics and reward encoding do not require the release of acetylcholine by CINs. However, dopamine inhibits acetylcholine transients in a D2R-dependent manner, and loss of this regulation impairs decision-making. To determine how other striatal inputs shape acetylcholine signals, we assessed the contribution of cortical and thalamic projections, and found that glutamate release from both sources is required for acetylcholine release. Altogether, we uncover a dynamic relationship between dopamine and acetylcholine during decision-making, and reveal multiple modes of CIN regulation. These findings deepen our understanding of the neurochemical basis of decision-making and behaviour.

External rewards such as food and money are potent modifiers of behaviour1,2. Pioneering studies established that these salient sensory stimuli briefly interrupt the tonic discharge of neurons that produce the neuromodulators dopamine (DA) and acetylcholine (ACh): midbrain DA neurons (DANs) fire a burst of action potentials that broadly elevates DA in the striatum3,4 at the same time that striatal cholinergic interneurons (CINs) produce a characteristic pause in firing5,6. These phasic responses are thought to create unique, temporally limited conditions that motivate action and promote learning7-11. However, the dynamics of DA and ACh outside explicitly rewarded situations remain poorly understood. Here we show that extracellular DA and ACh levels fluctuate spontaneously and periodically at a frequency of approximately 2 Hz in the dorsal striatum of mice and maintain the same temporal relationship relative to one another as that evoked by reward. We show that this neuromodulatory coordination does not arise from direct interactions between DA and ACh within the striatum. Instead, we provide evidence that periodic fluctuations in striatal DA are inherited from midbrain DANs, while striatal ACh transients are driven by glutamatergic inputs, which act to locally synchronize the spiking of CINs. Together, our findings show that striatal neuromodulatory dynamics are autonomously organized by distributed extra-striatal afferents. The dominance of intrinsic rhythms in DA and ACh offers new insights for explaining how reward-associated neural dynamics emerge and how the brain motivates action and promotes learning from within.

Coral reef ecosystems are being fundamentally restructured by local human impacts and climate-driven marine heatwaves that trigger mass coral bleaching and mortality1. Reducing local impacts can increase reef resistance to and recovery from bleaching2. However, resource managers lack clear advice on targeted actions that best support coral reefs under climate change3 and sector-based governance means most land- and sea-based management efforts remain siloed4. Here we combine surveys of reef change with a unique 20-year time series of land-sea human impacts that encompassed an unprecedented marine heatwave in Hawai'i. Reefs with increased herbivorous fish populations and reduced land-based impacts, such as wastewater pollution and urban runoff, had positive coral cover trajectories predisturbance. These reefs also experienced a modest reduction in coral mortality following severe heat stress compared to reefs with reduced fish populations and enhanced land-based impacts. Scenario modelling indicated that simultaneously reducing land-sea human impacts results in a three- to sixfold greater probability of a reef having high reef-builder cover four years postdisturbance than if either occurred in isolation. International efforts to protect 30% of Earth's land and ocean ecosystems by 2030 are underway5. Our results reveal that integrated land-sea management could help achieve coastal ocean conservation goals and provide coral reefs with the best opportunity to persist in our changing climate.

Plywood is widely used in construction, such as for flooring and interior walls, as well as in the manufacture of household items such as furniture and cabinets. Such items are made of wood veneers that are bonded together with adhesives such as urea-formaldehyde and phenol-formaldehyde resins1,2. Researchers in academia and industry have long aimed to synthesize lignin-phenol-formaldehyde resin adhesives using biomass-derived lignin, a phenolic polymer that can be used to substitute the petroleum-derived phenol3-6. However, lignin-phenol-formaldehyde resin adhesives are less attractive to plywood manufacturers than urea-formaldehyde and phenol-formaldehyde resins owing to their appearance and cost. Here we report a simple and practical strategy for preparing lignin-based wood adhesives from lignocellulosic biomass. Our strategy involves separation of uncondensed or slightly condensed lignins from biomass followed by direct application of a suspension of the lignin and water as an adhesive on wood veneers. Plywood products with superior performances could be prepared with such lignin adhesives at a wide range of hot-pressing temperatures, enabling the use of these adhesives as promising alternatives to traditional wood adhesives in different market segments. Mechanistic studies indicate that the adhesion mechanism of such lignin adhesives may involve softening of lignin by water, filling of vessels with softened lignin and crosslinking of lignins in adhesives with those in the cell wall.

Neptune-sized planets exhibit a wide range of compositions and densities, depending on factors related to their formation and evolution history, such as the distance from their host stars and atmospheric escape processes. They can vary from relatively low-density planets with thick hydrogen-helium atmospheres1,2 to higher-density planets with a substantial amount of water or a rocky interior with a thinner atmosphere, such as HD 95338 b (ref. 3), TOI-849 b (ref. 4) and TOI-2196 b (ref. 5). The discovery of exoplanets in the hot-Neptune desert6, a region close to the host stars with a deficit of Neptune-sized planets, provides insights into the formation and evolution of planetary systems, including the existence of this region itself. Here we show observations of the transiting planet TOI-1853 b, which has a radius of 3.46 ± 0.08 Earth radii and orbits a dwarf star every 1.24 days. This planet has a mass of 73.2 ± 2.7 Earth masses, almost twice that of any other Neptune-sized planet known so far, and a density of 9.7 ± 0.8 grams per cubic centimetre. These values place TOI-1853 b in the middle of the Neptunian desert and imply that heavy elements dominate its mass. The properties of TOI-1853 b present a puzzle for conventional theories of planetary formation and evolution, and could be the result of several proto-planet collisions or the final state of an initially high-eccentricity planet that migrated closer to its parent star.

Antibiotic binding sites are located in important domains of essential enzymes and have been extensively studied in the context of resistance mutations; however, their study is limited by positive selection. Using multiplex genome engineering1 to overcome this constraint, we generate and characterize a collection of 760 single-residue mutants encompassing the entire rifampicin binding site of Escherichia coli RNA polymerase (RNAP). By genetically mapping drug-enzyme interactions, we identify an alpha helix where mutations considerably enhance or disrupt rifampicin binding. We find mutations in this region that prolong antibiotic binding, converting rifampicin from a bacteriostatic to bactericidal drug by inducing lethal DNA breaks. The latter are replication dependent, indicating that rifampicin kills by causing detrimental transcription-replication conflicts at promoters. We also identify additional binding site mutations that greatly increase the speed of RNAP.Fast RNAP depletes the cell of nucleotides, alters cell sensitivity to different antibiotics and provides a cold growth advantage. Finally, by mapping natural rpoB sequence diversity, we discover that functional rifampicin binding site mutations that alter RNAP properties or confer drug resistance occur frequently in nature.

Social animals live and move through spaces shaped by the presence, motion and sensory cues of multiple other individuals1-6. Neural activity in the hippocampus is known to reflect spatial behaviour7-9 yet its study is lacking in such dynamic group settings, which are ubiquitous in natural environments. Here we studied hippocampal activity in groups of bats engaged in collective spatial behaviour. We find that, under spontaneous conditions, a robust spatial structure emerges at the group level whereby behaviour is anchored to specific locations, movement patterns and individual social preferences. Using wireless electrophysiological recordings from both stationary and flying bats, we find that many hippocampal neurons are tuned to key features of group dynamics. These include the presence or absence of a conspecific, but not typically of an object, at landing sites, shared spatial locations, individual identities and sensory signals that are broadcasted in the group setting. Finally, using wireless calcium imaging, we find that social responses are anatomically distributed and robustly represented at the population level. Combined, our findings reveal that hippocampal activity contains a rich representation of naturally emerging spatial behaviours in animal groups that could in turn support the complex feat of collective behaviour.

Graphitic electrode is commonly used in electrochemical reactions owing to its excellent in-plane conductivity, structural robustness and cost efficiency1,2. It serves as prime electrocatalyst support as well as a layered intercalation matrix2,3, with wide applications in energy conversion and storage1,4. Being the two-dimensional building block of graphite, graphene shares similar chemical properties with graphite1,2, and its unique physical and chemical properties offer more varieties and tunability for developing state-of-the-art graphitic devices5-7. Hence it serves as an ideal platform to investigate the microscopic structure and reaction kinetics at the graphitic-electrode interfaces. Unfortunately, graphene is susceptible to various extrinsic factors, such as substrate effect8-10, causing much confusion and controversy7,8,10,11. Hereby we have obtained centimetre-sized substrate-free monolayer graphene suspended on aqueous electrolyte surface with gate tunability. Using sum-frequency spectroscopy, here we show the structural evolution versus the gate voltage at the graphene-water interface. The hydrogen-bond network of water in the Stern layer is barely changed within the water-electrolysis window but undergoes notable change when switching on the electrochemical reactions. The dangling O-H bond protruding at the graphene-water interface disappears at the onset of the hydrogen evolution reaction, signifying a marked structural change on the topmost layer owing to excess intermediate species next to the electrode. The large-size suspended pristine graphene offers a new platform to unravel the microscopic processes at the graphitic-electrode interfaces.

According to twenty-first century climate-model projections, greenhouse warming will intensify rainfall variability and extremes across the globe1-4. However, verifying this prediction using observations has remained a substantial challenge owing to large natural rainfall fluctuations at regional scales3,4. Here we show that deep learning successfully detects the emerging climate-change signals in daily precipitation fields during the observed record. We trained a convolutional neural network (CNN)5 with daily precipitation fields and annual global mean surface air temperature data obtained from an ensemble of present-day and future climate-model simulations6. After applying the algorithm to the observational record, we found that the daily precipitation data represented an excellent predictor for the observed planetary warming, as they showed a clear deviation from natural variability since the mid-2010s. Furthermore, we analysed the deep-learning model with an explainable framework and observed that the precipitation variability of the weather timescale (period less than 10 days) over the tropical eastern Pacific and mid-latitude storm-track regions was most sensitive to anthropogenic warming. Our results highlight that, although the long-term shifts in annual mean precipitation remain indiscernible from the natural background variability, the impact of global warming on daily hydrological fluctuations has already emerged.

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain1 (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting.

The standard quantum limit bounds the precision of measurements that can be achieved by ensembles of uncorrelated particles. Fundamentally, this limit arises from the non-commuting nature of quantum mechanics, leading to the presence of fluctuations often referred to as quantum projection noise. Quantum metrology relies on the use of non-classical states of many-body systems to enhance the precision of measurements beyond the standard quantum limit1,2. To do so, one can reshape the quantum projection noise-a strategy known as squeezing3,4. In the context of many-body spin systems, one typically uses all-to-all interactions (for example, the one-axis twisting model4) between the constituents to generate the structured entanglement characteristic of spin squeezing5. Here we explore the prediction, motivated by recent theoretical work6-10, that short-range interactions-and in particular, the two-dimensional dipolar XY model-can also enable the realization of scalable spin squeezing. Working with a dipolar Rydberg quantum simulator of up to N = 100 atoms, we demonstrate that quench dynamics from a polarized initial state lead to spin squeezing that improves with increasing system size up to a maximum of -3.5 ± 0.3 dB (before correcting for detection errors, or roughly -5 ± 0.3 dB after correction). Finally, we present two independent refinements: first, using a multistep spin-squeezing protocol allows us to further enhance the squeezing by roughly 1 dB, and second, leveraging Floquet engineering to realize Heisenberg interactions, we demonstrate the ability to extend the lifetime of the squeezed state by freezing its dynamics.

California has experienced enhanced extreme wildfire behaviour in recent years1-3, leading to substantial loss of life and property4,5. Some portion of the change in wildfire behaviour is attributable to anthropogenic climate warming, but formally quantifying this contribution is difficult because of numerous confounding factors6,7 and because wildfires are below the grid scale of global climate models. Here we use machine learning to quantify empirical relationships between temperature (as well as the influence of temperature on aridity) and the risk of extreme daily wildfire growth (>10,000 acres) in California and find that the influence of temperature on the risk is primarily mediated through its influence on fuel moisture. We use the uncovered relationships to estimate the changes in extreme daily wildfire growth risk under anthropogenic warming by subjecting historical fires from 2003 to 2020 to differing background climatological temperatures and aridity conditions. We find that the influence of anthropogenic warming on the risk of extreme daily wildfire growth varies appreciably on a fire-by-fire and day-by-day basis, depending on whether or not climate warming pushes conditions over certain thresholds of aridity, such as 1.5 kPa of vapour-pressure deficit and 10% dead fuel moisture. So far, anthropogenic warming has enhanced the aggregate expected frequency of extreme daily wildfire growth by 25% (5-95 range of 14-36%), on average, relative to preindustrial conditions. But for some fires, there was approximately no change, and for other fires, the enhancement has been as much as 461%. When historical fires are subjected to a range of projected end-of-century conditions, the aggregate expected frequency of extreme daily wildfire growth events increases by 59% (5-95 range of 47-71%) under a low SSP1-2.6 emissions scenario compared with an increase of 172% (5-95 range of 156-188%) under a very high SSP5-8.5 emissions scenario, relative to preindustrial conditions.

Seismometers are generally used by the research community to study local or distant earthquakes, but seismograms also contain critical observations from regional1,2 and global explosions3, which can be used to better understand conflicts and identify potential breaches of international law. Although seismic, infrasound and hydroacoustic technology is used by the International Monitoring System4 to monitor nuclear explosions as part of the Comprehensive Nuclear-Test-Ban Treaty, the detection and location of lower-yield military attacks requires a network of sensors much closer to the source of the explosions. Obtaining comprehensive and objective data that can be used to effectively monitor an active conflict zone therefore remains a substantial challenge. Here we show how seismic waves generated by explosions in northern Ukraine and recorded by a local network of seismometers can be used to automatically identify individual attacks in close to real time, providing an unprecedented view of an active conflict zone. Between February and November 2022, we observed more than 1,200 explosions from the Kyiv, Zhytomyr and Chernihiv provinces, providing accurate origin times, locations and magnitudes. We identify a range of seismoacoustic signals associated with various types of military attack, with the resulting catalogue of explosions far exceeding the number of publicly reported attacks. Our results demonstrate that seismic data can be an effective tool for objective monitoring of a continuing conflict, providing invaluable information about potential breaches of international law.

The control over quantum states in atomic systems has led to the most precise optical atomic clocks so far1-3. Their sensitivity is bounded at present by the standard quantum limit, a fundamental floor set by quantum mechanics for uncorrelated particles, which can-nevertheless-be overcome when operated with entangled particles. Yet demonstrating a quantum advantage in real-world sensors is extremely challenging. Here we illustrate a pathway for harnessing large-scale entanglement in an optical transition using 1D chains of up to 51 ions with interactions that decay as a power-law function of the ion separation. We show that our sensor can emulate many features of the one-axis-twisting (OAT) model, an iconic, fully connected model known to generate scalable squeezing4 and Greenberger-Horne-Zeilinger-like states5-8. The collective nature of the state manifests itself in the preservation of the total transverse magnetization, the reduced growth of the structure factor, that is, spin-wave excitations (SWE), at finite momenta, the generation of spin squeezing comparable with OAT (a Wineland parameter9,10 of -3.9 ± 0.3 dB for only N = 12 ions) and the development of non-Gaussian states in the form of multi-headed cat states in the Q-distribution. We demonstrate the metrological utility of the states in a Ramsey-type interferometer, in which we reduce the measurement uncertainty by -3.2 ± 0.5 dB below the standard quantum limit for N = 51 ions.

Neutral-atom arrays trapped in optical potentials are a powerful platform for studying quantum physics, combining precise single-particle control and detection with a range of tunable entangling interactions1-3. For example, these capabilities have been leveraged for state-of-the-art frequency metrology4,5 as well as microscopic studies of entangled many-particle states6-11. Here we combine these applications to realize spin squeezing-a widely studied operation for producing metrologically useful entanglement-in an optical atomic clock based on a programmable array of interacting optical qubits. In this demonstration of Rydberg-mediated squeezing with a neutral-atom optical clock, we generate states that have almost four decibels of metrological gain. In addition, we perform a synchronous frequency comparison between independent squeezed states and observe a fractional-frequency stability of 1.087(1) × 10-15 at one-second averaging time, which is 1.94(1) decibels below the standard quantum limit and reaches a fractional precision at the 10-17 level during a half-hour measurement. We further leverage the programmable control afforded by optical tweezer arrays to apply local phase shifts to explore spin squeezing in measurements that operate beyond the relative coherence time with the optical local oscillator. The realization of this spin-squeezing protocol in a programmable atom-array clock will enable a wide range of quantum-information-inspired techniques for optimal phase estimation and Heisenberg-limited optical atomic clocks12-16.

The formation of stars and planets is accompanied not only by the build-up of matter, i.e., accretion, but also by its expulsion in the form of highly supersonic jets that can stretch for several parsecs1,2. As accretion and jet activity are correlated and because young stars acquire most of their mass rapidly early on, the most powerful jets are associated with the youngest protostars3. This period, however, coincides with the time when the protostar and its surroundings are hidden behind many magnitudes of visual extinction. Millimetre interferometers can probe this stage but only for the coolest components3. No information is provided on the hottest ( > 1000 K) constituents of the jet, i. e. the atomic, ionized, and high temperature molecular gas that are thought to make up the jet's backbone. Can we detect such a high temperature spine and what is it made up of? Here we report near-infrared JWST observations of Herbig-Haro 211, an outflow from an analogue of our Sun when it was at most a few times 104 years old. These reveal copious emission from hot molecules explaining the origin of the so-called "Green Fuzzies"4-7 discovered nearly two decades ago by the Spitzer Space Telescope8. This outflow is found to be propagating slowly in comparison to its more evolved counterparts and, surprisingly, almost no trace of atomic or ionized emission is seen suggesting its spine is almost purely molecular.

Privileged chiral catalysts-those that share common structural features and are enantioselective across a range of reactions-continue to transform the chemical-research landscape1. In recent years, new reactivity modes have been achieved through excited-state catalysis, processes activated by light, but it is unclear if the selectivity of ground-state privileged catalysts can be matched. Although the interception of photogenerated intermediates by ground-state cycles has partially addressed this challenge2, single, chiral photocatalysts that simultaneously regulate reactivity and selectivity are conspicuously scarce3. So far, precision donor-acceptor recognition motifs remain crucial in enantioselective photocatalyst design4. Here we show that chiral Al-salen complexes, which have well-defined photophysical properties, can be used for the efficient photochemical deracemization5 of cyclopropyl ketones (up to 98:2 enantiomeric ratio (e.r.)). Irradiation at λ = 400 nm (violet light) augments the reactivity of the commercial catalyst to enable reactivity and enantioselectivity to be regulated simultaneously. This circumvents the need for tailored catalyst-substrate recognition motifs. It is predicted that this study will stimulate a re-evaluation of many venerable (ground-state) chiral catalysts in excited-state processes, ultimately leading to the identification of candidates that may be considered 'privileged' in both reactivity models.

The Pacific Walker circulation (PWC) has an outsized influence on weather and climate worldwide. Yet the PWC response to external forcings is unclear1,2, with empirical data and model simulations often disagreeing on the magnitude and sign of these responses3. Most climate models predict that the PWC will ultimately weaken in response to global warming4. However, the PWC strengthened from 1992 to 2011, suggesting a significant role for anthropogenic and/or volcanic aerosol forcing5, or internal variability. Here we use a new annually resolved, multi-method, palaeoproxy-derived PWC reconstruction ensemble (1200-2000) to show that the 1992-2011 PWC strengthening is anomalous but not unprecedented in the context of the past 800 years. The 1992-2011 PWC strengthening was unlikely to have been a consequence of volcanic forcing and may therefore have resulted from anthropogenic aerosol forcing or natural variability. We find no significant industrial-era (1850-2000) PWC trend, contrasting the PWC weakening simulated by most climate models3. However, an industrial-era shift to lower-frequency variability suggests a subtle anthropogenic influence. The reconstruction also suggests that volcanic eruptions trigger El Niño-like PWC weakening, similar to the response simulated by climate models.

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions.

Electrochemical synthesis can provide more sustainable routes to industrial chemicals1-3. Electrosynthetic oxidations often may be performed "reagent-free", generating hydrogen (H2) derived from the substrate as the sole byproduct at the counter electrode. Electrosynthetic reductions, however, require an external source of electrons. Sacrificial metal anodes are commonly used for small-scale applications4, but more sustainable options are needed at large scale. Anodic water oxidation is an especially appealing option1,5,6, but many reductions require anhydrous, air-free reaction conditions. In such cases, H2 represents an ideal alternative, motivating the growing interest in the electrochemical hydrogen oxidation reaction (HOR) under non-aqueous conditions7-12. Here, we report a mediated H2 anode that achieves indirect electrochemical oxidation of H2 by pairing thermal catalytic hydrogenation of an anthraquinone mediator with electrochemical oxidation of the anthrahydroquinone. This quinone-mediated H2 anode is used to support nickel-catalyzed cross-electrophile coupling (XEC), a reaction class gaining widespread adoption within the pharmaceutical industry13-15. Initial validation of this method in small-scale batch reactions is followed by adaptation to a recirculating flow reactor that enables hectogram-scale synthesis of a pharmaceutical intermediate. The mediated H2 anode technology disclosed here offers a general strategy to support H2-driven electrosynthetic reductions.

The integer quantum anomalous Hall (QAH) effect is a lattice analog of the quantum Hall effect at zero magnetic field1-3. This striking phenomenon occurs in systems with topologically nontrivial bands and spontaneous time-reversal symmetry breaking. Discovery of its fractional counterpart in the presence of strong electron correlations, i.e., the fractional quantum anomalous Hall (FQAH) effect4-7, would open a new chapter in condensed matter physics. Here, we report direct observation of both integer and fractional QAH effects in electrical measurements on twisted bilayer MoTe2. At zero magnetic field, near filling factor [Formula: see text] (one hole per moiré unit cell) we see an integer QAH plateau in the Hall resistance Rxy quantized to [Formula: see text] while longitudinal resistance Rxx vanishes. Remarkably, at [Formula: see text] and [Formula: see text] we see plateau features in Rxy at [Formula: see text] and [Formula: see text], respectively, while Rxx remains small. All features shift linearly versus applied magnetic field with slopes matching the corresponding Chern numbers [Formula: see text], [Formula: see text], and [Formula: see text], precisely as expected for integer and fractional QAH states. Additionally, at zero magnetic field, Rxy is approximately 2[Formula: see text] near half filling ([Formula: see text]) and varies linearly as [Formula: see text] is tuned. This behavior resembles that of the composite Fermi liquid in the half-filled lowest Landau level of a two-dimensional electron gas at high magnetic field8-14. Direct observation of the FQAH and associated effects paves the way for researching charge fractionalization and anyonic statistics at zero magnetic field.

Disruption of the lung endothelial-epithelial cell barrier following respiratory virus infection causes cell and fluid accumulation in the air spaces and compromises vital gas exchange function1. Endothelial dysfunction can exacerbate tissue damage2,3, yet it is unclear whether the lung endothelium promotes host resistance against viral pathogens. Here we show that the environmental sensor aryl hydrocarbon receptor (AHR) is highly active in lung endothelial cells and protects against influenza-induced lung vascular leakage. Loss of AHR in endothelia exacerbates lung damage and promotes the infiltration of red blood cells and leukocytes into alveolar air spaces. Moreover, barrier protection is compromised and host susceptibility to secondary bacterial infections is increased when endothelial AHR is missing. AHR engages tissue-protective transcriptional networks in endothelia, including the vasoactive apelin-APJ peptide system4, to prevent a dysplastic and apoptotic response in airway epithelial cells. Finally, we show that protective AHR signalling in lung endothelial cells is dampened by the infection itself. Maintenance of protective AHR function requires a diet enriched in naturally occurring AHR ligands, which activate disease tolerance pathways in lung endothelia to prevent tissue damage. Our findings demonstrate the importance of endothelial function in lung barrier immunity. We identify a gut-lung axis that affects lung damage following encounters with viral pathogens, linking dietary composition and intake to host fitness and inter-individual variations in disease outcome.

Methane (CH4) is a potent greenhouse gas and its concentrations have tripled in the atmosphere since the industrial revolution. There is evidence that global warming has increased CH4 emissions from freshwater ecosystems1,2, providing positive feedback to the global climate. Yet for rivers and streams, the controls and the magnitude of CH4 emissions remain highly uncertain3,4. Here we report a spatially explicit global estimate of CH4 emissions from running waters, accounting for 27.9 (16.7-39.7) Tg CH4 per year and roughly equal in magnitude to those of other freshwater systems5,6. Riverine CH4 emissions are not strongly temperature dependent, with low average activation energy (EM = 0.14 eV) compared with that of lakes and wetlands (EM = 0.96 eV)1. By contrast, global patterns of emissions are characterized by large fluxes in high- and low-latitude settings as well as in human-dominated environments. These patterns are explained by edaphic and climate features that are linked to anoxia in and near fluvial habitats, including a high supply of organic matter and water saturation in hydrologically connected soils. Our results highlight the importance of land-water connections in regulating CH4 supply to running waters, which is vulnerable not only to direct human modifications but also to several climate change responses on land.

Endothelial cells line the blood and lymphatic vasculature, and act as an essential physical barrier, control nutrient transport, facilitate tissue immunosurveillance and coordinate angiogenesis and lymphangiogenesis1,2. In the intestine, dietary and microbial cues are particularly important in the regulation of organ homeostasis. However, whether enteric endothelial cells actively sense and integrate such signals is currently unknown. Here we show that the aryl hydrocarbon receptor (AHR) acts as a critical node for endothelial cell sensing of dietary metabolites in adult mice and human primary endothelial cells. We first established a comprehensive single-cell endothelial atlas of the mouse small intestine, uncovering the cellular complexity and functional heterogeneity of blood and lymphatic endothelial cells. Analyses of AHR-mediated responses at single-cell resolution identified tissue-protective transcriptional signatures and regulatory networks promoting cellular quiescence and vascular normalcy at steady state. Endothelial AHR deficiency in adult mice resulted in dysregulated inflammatory responses and the initiation of proliferative pathways. Furthermore, endothelial sensing of dietary AHR ligands was required for optimal protection against enteric infection. In human endothelial cells, AHR signalling promoted quiescence and restrained activation by inflammatory mediators. Together, our data provide a comprehensive dissection of the effect of environmental sensing across the spectrum of enteric endothelia, demonstrating that endothelial AHR signalling integrates dietary cues to maintain tissue homeostasis by promoting endothelial cell quiescence and vascular normalcy.

During the first 500 million years of cosmic history, the first stars and galaxies formed, seeding the Universe with heavy elements and eventually reionizing the intergalactic medium1-3. Observations with the James Webb Space Telescope (JWST) have uncovered a surprisingly high abundance of candidates for early star-forming galaxies, with distances (redshifts, z), estimated from multiband photometry, as large as z ≈ 16, far beyond pre-JWST limits4-9. Although such photometric redshifts are generally robust, they can suffer from degeneracies and occasionally catastrophic errors. Spectroscopic measurements are required to validate these sources and to reliably quantify physical properties that can constrain galaxy formation models and cosmology10. Here we present JWST spectroscopy that confirms redshifts for two very luminous galaxies with z > 11, and also demonstrates that another candidate with suggested z ≈ 16 instead has z = 4.9, with an unusual combination of nebular line emission and dust reddening that mimics the colours expected for much more distant objects. These results reinforce evidence for the early, rapid formation of remarkably luminous galaxies while also highlighting the necessity of spectroscopic verification. The large abundance of bright, early galaxies may indicate shortcomings in current galaxy formation models or deviations from physical properties (such as the stellar initial mass function) that are generally believed to hold at later times.

The presequence translocase of the mitochondrial inner membrane (TIM23) represents the major route for the import of nuclear-encoded proteins into mitochondria1,2. About 60% of more than 1,000 different mitochondrial proteins are synthesized with amino-terminal targeting signals, termed presequences, which form positively charged amphiphilic α-helices3,4. TIM23 sorts the presequence proteins into the inner membrane or matrix. Various views, including regulatory and coupling functions, have been reported on the essential TIM23 subunit Tim17 (refs. 5-7). Here we mapped the interaction of Tim17 with matrix-targeted and inner membrane-sorted preproteins during translocation in the native membrane environment. We show that Tim17 contains conserved negative charges close to the intermembrane space side of the bilayer, which are essential to initiate presequence protein translocation along a distinct transmembrane cavity of Tim17 for both classes of preproteins. The amphiphilic character of mitochondrial presequences directly matches this Tim17-dependent translocation mechanism. This mechanism permits direct lateral release of transmembrane segments of inner membrane-sorted precursors into the inner membrane.