Physics

Antigenic variation, using large genomic repertoires of antigen-encoding genes, allows pathogens to evade host antibody. Many pathogens, including the African trypanosome Trypanosoma brucei, extend their antigenic repertoire through genomic diversification. Although evidence suggests that T. brucei depends on the generation of new variant surface glycoprotein (VSG) genes to maintain a chronic infection^1-4, a lack of experimentally tractable tools for studying this process has obscured its underlying mechanisms. Here we present a highly sensitive targeted sequencing approach for measuring VSG diversification. Using this method, we demonstrate that a Cas9-induced DNA double-strand break within the VSG coding sequence can induce RAD51- and BRCA2-dependent VSG recombination with patterns identical to those observed during infection. These newly generated VSGs are antigenically distinct from parental clones and thus capable of facilitating immune evasion. Together, these results provide insight into the mechanisms of VSG diversification and an experimental framework for studying the evolution of antigen repertoires in pathogenic microorganisms.

The placenta — a temporary organ of the offspring — attaches to the mother’s uterus, from which it taps a blood supply. A high-resolution map of individual cells at this junction now reveals some of the specific cell–cell interactions involved and pinpoints cell types that are vulnerable in common pregnancy complications. A study of the placental–uterine connection has characterized known and previously unknown cell types and states.

Quantum simulations of electronic structure and strongly correlated quantum phases are among the most promising applications of quantum computing. These computations benefit from native fermionic encodings^1,2, enforcing fermionic statistics and conservation laws such as particle number and magnetization³ independent of gate errors. While ultracold atoms in optical lattices have become established as powerful analogue simulators of strongly correlated fermionic matter^4-7, neutral-atom platforms have concurrently emerged as versatile, scalable architectures for spin-based digital quantum computation⁸. Unifying these capabilities requires high-fidelity motionally coherent gates for fermionic atoms^9-11, similar to collisional gates in bosonic systems^12,13, paving the way for programmable fermionic quantum processors. Here we demonstrate collisional entangling gates with fidelities up to 99.75(6)% and Bell-state lifetimes exceeding 10 s, realized by means of controlled interactions of fermionic atoms in an optical superlattice. Using quantum gas microscopy¹⁴, we microscopically characterize spin-exchange and pair-tunnelling gates and realize a robust composite pair-exchange gate, a key building block for quantum chemistry simulations^3,15. Our results establish controlled collisions in optical lattices as a competitive and complementary route to high entangling gate fidelities in neutral-atom quantum computers. Operating intrinsically with fermions, this capability naturally extends to many-qubit architectures, in which fermionic statistics become relevant, enabling complex state preparation and advanced readout^16-19 in scalable analogue-digital hybrid quantum simulators. Combined with local addressing^20,21, these gates mark a crucial step towards a fully digital fermionic quantum computer based on controlled motion and entanglement of neutral atoms.

Artificial light at night (ALAN) marks the global impact of humanity^1,2. Yet, our understanding of its true ebb and flow has been limited, often based on temporally aggregated satellite data that obscure finer dynamics. Here, using daily night-time satellite imagery³ and a continuous change detection approach^4,5, we created global maps of high-frequency ALAN dynamics (2014-2022). Our findings challenge the prevailing perspective that changes in light radiance are largely gradual and unidirectional. Instead, the nightlights of Earth are surprisingly dynamic, characterized by frequent and coexisting brightening and dimming. On average, each location experiencing change underwent 6.6 distinct shifts over the 9 years. Driven by this volatility, the cumulative area of total ALAN change comprised 2.05 million km² of abrupt changes and 19.04 million km² of gradual changes. Brightening contributed a radiance increase equivalent to 34% of the 2014 global baseline, whereas dimming offset this by 18%. Notably, both brightening and dimming have markedly intensified over the past decade. This evidence of increasing volatility in human night-time activity provides an important dynamic dimension for understanding urban evolution, energy transitions, policy impacts and ecological consequences of rapidly changing illuminated nights.

Recently, de novo variants in an 18-nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder that is predicted to affect tens of thousands of individuals worldwide^1,2. RNU4-2 is a non-protein-coding gene that is transcribed into the U4 small nuclear RNA component of the major spliceosome³. ReNU syndrome variants disrupt spliceosome function and alter 5' splice site selection^1,4. Here we performed saturation genome editing (SGE) of RNU4-2 to identify the functional and clinical impact of variants across the entire gene. The resulting SGE function scores, derived from variants' effects on cell fitness, discriminate ReNU syndrome variants from those observed in the population and markedly outperform in silico variant effect prediction. Using these data, we redefine the ReNU syndrome critical region at single-nucleotide resolution, resolve variant pathogenicity for variants of uncertain significance and show that SGE function scores delineate variants by phenotypic severity and the extent of observed splicing disruption. Furthermore, we identify variants affecting function in regions of RNU4-2 that are critical for interactions with other spliceosome components. We show that these variants cause a new recessive neurodevelopmental disorder that is distinct from ReNU syndrome. Together, this work defines the landscape of variant function across RNU4-2, providing critical insights for both diagnosis and therapeutic development.

The UN Decade on Ecosystem Restoration aims to stop biodiversity losses¹. Approximately 60% of tropical forests have already been lost or severely degraded², making restoration essential to achieve conservation goals. Recovery trajectories of trees have been studied intensively^3,4, but a comprehensive understanding of biodiversity recovery is lacking. Here we analyse recovery trajectories across trophic levels including 16 taxonomic groups from three kingdoms in a lowland tropical forest by investigating resistance to perturbation, recovery times and return rates to old-growth forest conditions. Abundance and diversity regained more than 90% and composition approximately 75% similarity to old-growth forests within 30 years, but full recovery takes several decades. Mobile animal communities acting as seed dispersers or pollinators had high resistance levels and recovered faster than trees or tree seedlings. Return rates contributed 1-2.5 times more than resistance to the recovery times of species composition. Taxon-specific recovery times could not be explained by simple mechanisms (life-history strategies, trophic level or mobility). We show the enormous potential of protecting naturally recovering secondary forests to stop and reverse biodiversity losses.

Cell-type-specific promoters are used in gene therapy to restrict expression of the therapeutic payload. However, these promoters often have suboptimal strength, selectivity and size. Here, leveraging recent insights into the function of enhancers, we developed synthetic super-enhancers (SSEs) by assembling functionally validated enhancer fragments into multipart arrays. Focusing on the core SOX2-driven and SOX9-driven transcriptional regulatory network in glioblastoma stem cells (GSCs)¹, we engineered SSEs with robust activity and high selectivity. Single-cell profiling, biochemical analyses and genome-binding data indicated that SSEs integrate neurodevelopmental and signalling-state transcription factors to trigger the formation of large multimeric complexes of transcription factors. Moreover, GSC-selective expression of a combination of cytotoxic (HSV-TK and ganciclovir) and immunomodulatory (IL-12) payloads, delivered using adeno-associated virus vectors, as a single treatment led to curative outcomes in a mouse model of aggressive glioblastoma. Notably, IL-12 induced an immunological memory that prevented tumour recurrence. The activity and selectivity of the adeno-associated virus and SSE were validated using primary human glioblastoma tissue and normal cortex samples. In summary, SSEs harness the unique core transcriptional programs that define the GSC phenotype and enable precision immune activation. This approach may have broader applications in other contexts when precise control of transgene expression in specific cell states is necessary.

In the standard model of particle physics, the masses of the W and Z bosons, the carriers of the weak interaction, are uniquely related. A precise determination of their masses is important because quantum loops of heavy, undiscovered particles could modify this relationship. Although the Z mass is known to the remarkable precision of 22 parts per million (2.0 MeV), the W mass is known much less precisely. A global fit to measured electroweak observables predicts the W mass with 6 MeV uncertainty^1-3. Reaching a comparable experimental precision would be a sensitive and fundamental test of the standard model, made even more urgent by a recent challenge to the global fit prediction by a measurement from the CDF Collaboration at the Fermilab Tevatron collider⁴. Here we report the measurement of the W mass by the CMS Collaboration at the CERN Large Hadron Collider, based on a large data sample of W → μν events collected in 2016 at the proton-proton collision energy of 13 TeV. The measurement exploits a high-granularity maximum likelihood fit to the kinematic properties of muons produced in W decays. By combining an accurate determination of experimental effects with marked in situ constraints of theoretical inputs, we reach a precise measurement of the W mass, of 80,360.2 ± 9.9 MeV, in agreement with the standard model prediction.

The development of glucagon-like peptide 1 (GLP1) receptor agonists, including semaglutide and tirzepatide, has transformed the clinical management of overweight and obesity. However, substantial inter-person variability exists in both weight loss efficacy and the incidence of side effects¹. To investigate the genetic basis of this variability, here we conduct a genome-wide association study of self-reported weight loss and treatment-related side effects in 27,885 people following GLP1 receptor agonist therapy. We identify a missense variant in GLP1R that is associated significantly with increased efficacy of GLP1 medications (P = 2.9 × 10^-10), with an additional -0.76 kg of weight loss expected per copy of the effect allele. Furthermore, we identify associations linking variation in both GLP1R and GIPR to GLP1 medication-related nausea or vomiting, with the GIPR association being restricted to people using tirzepatide. We incorporate these findings into a broader model of GLP1 medication response, and demonstrate the ability to stratify patients by efficacy and side effect risk. These findings provide direct genetic evidence that variation in the drug target genes contributes to inter-person variability in response and lay the foundation for precision medicine approaches in the treatment of obesity.

Dynamic surface reconstruction critically governs the performance and durability of oxide-based electrocatalysts for the oxygen evolution reaction (OER), yet controlling this process under operating conditions remains challenging. Here, we demonstrate that lattice strain regulates the extent of surface reconstruction in perovskite oxides by modulating the redox behavior of lattice nickel (Ni). Using epitaxial LaNiO₃ (LNO) thin films as a model system, we show that strain-induced changes in Ni-oxygen(O) bond length systematically tune the reducibility of Ni³⁺, thereby controlling the degree of surface reconstruction. Tensile strain enhances Ni reducibility, promotes Ni (oxy)hydroxide formation, and results in a nearly order-of-magnitude increase in reconstruction compared to compressive strain. Under OER conditions in iron (Fe)-containing alkaline electrolytes, tensile-strained LNO exhibits a 5.7-fold enhancement in activity due to synergistic interactions between Fe species and the reconstructed Ni-based surface. By extending this concept to powder-type catalysts through isovalent doping, we demonstrate that modulation of the Ni-O bond length through Scandium (Sc) doping induces comparable surface reconstruction behavior and catalyst activity, thereby confirming the scalability of this approach. These results identify metal-oxygen bond length as a general design parameter for tuning dynamic surface reconstruction and catalytic activity in perovskite oxide electrocatalysts.

The persistent burden of respiratory viruses requires rapid, simple, and robust screening and environmental surveillance technologies that enable widespread and frequent testing. Importantly, these technologies should be based on infectivity-relevant signals, as RNA detection alone has limited correlation with transmission risk. Here, we present a membrane fusion-mediated platform that autonomously detects viruses by recapitulating the native viral entry mechanism. Fusogenic vesicles selectively fuse with fusion-competent viral particles, triggering encapsulated CRISPR-Cas13a components to generate fluorescent signals upon recognition of the released viral RNA. Through an autonomous workflow and accelerated signal generation within a confined vesicle, our platform achieves one-step detection of viruses within 2 min. The assay robustly detects three major respiratory viruses, with analytical sensitivities down to 5 TCID₅₀/mL for RSV and 50 TCID₅₀/mL for SARS-CoV-2 and IAV. Clinical validation with 100 nasopharyngeal samples achieved 91.7% sensitivity. Remarkably, the sprayable format enables large-area surveillance of surface contamination-like luminol revealing hidden bloodstains, it makes invisible viral threats visible. This approach establishes an intuitive real-time detection platform, extending beyond clinical specimens to encompass environmental threats.

Seawater electrolysis for green hydrogen is severely limited by the competing chloride oxidation reaction (ClOR) and the sluggish kinetics of oxygen evolution reaction (OER). This study introduces a lattice renormalization strategy to direct the reconstruction of Co-Mo-O catalysts in alkaline electrolyte, effectively shifting the OER pathway from the traditional adsorbate evolution mechanism (AEM) to the more efficient lattice oxygen mechanism (LOM). Selective Mo leaching induces the construction of a CoOOH/Co(OH)₂ with a stable Co³⁺-O-Co²⁺ electron-withdrawing chain, which significantly enhances Co-O covalency and activates lattice oxygen. The optimized catalyst, r-CoO_xH_y@NF, achieves low overpotentials of 330 and 380 mV at 500 and 1000 mA cm^- ² in simulated alkaline seawater, respectively. When configured into a membrane electrode assembly (MEA) electrolyzer, the system attains a low cell voltage of 1.66 V at 1.0 A cm^- ² for 480 h. In situ characterization and theoretical analysis reveal a "lattice oxygen-hydrogen-bonding network" synergy, where dynamically evolving hydrogen-bonding network at the interface not only facilitates rapid proton transfer but also electronically modulates the lattice oxygen orbitals via polarization effects, with stabilizing the LOM pathway and conferring superior chloride resistance. This work underscores the pivotal role of metal-ligand covalency and interfacial microenvironment in steering reconstruction pathways for industrial seawater splitting.

Normal mitochondrial function in stem cells is essential for effective bone regeneration, with mitochondrial complex IV (cytochrome c oxidase, CcO) playing a crucial role in sustaining electron transport chain activity and ATP synthesis. To address mitochondrial dysfunction associated with bone defects, we developed a dendritic mesoporous silica nanoparticle (DMSN)-based, CcO-mimetic nanozyme, named triphenylphosphonium (TPP)-DMSN-Fe/Cu. The nanozyme incorporated iron and copper single atoms to mimic the catalytic center of CcO and is modified with the mitochondria-targeting agent TPP. In vitro, TPP-DMSN-Fe/Cu nanozymes colocalized with mitochondria and enhanced mitochondrial function, effectively regulating cellular energy metabolism and promoting stem cell osteogenesis. In vivo, TPP-DMSN-Fe/Cu nanozymes resulted in significantly enhanced bone regeneration compared to the control, resulting in a 177% increase in bone volume and a 12% increase in mineral density at critical-sized bone defects in rats after 4 weeks of treatment. Taken together, these findings demonstrate that bioinspired, mitochondria-targeting TPP-DMSN-Fe/Cu nanozymes hold strong promise for accelerating bone regeneration via regulating cellular energy metabolism.

As a sustainable cathode material for sodium-ion batteries, Na₄MnFe(PO₄)₃ (NMFP) is prized for high theoretical operating voltage and cost-effectiveness. However, its practical electrochemical activity is notoriously poor, contradicting theoretical predictions. Here, we reveal that this inactivity stems primarily from Mott localization, driven by strong electron correlations within the high-spin 3d⁵ electronic configuration (t_2g ³e_g ²) of Mn²⁺ and Fe³⁺. This symmetric, half-filled state leads to pronounced charge localization, severely suppressing the intrinsic redox activity. To address this limitation, we devised a symmetry-breaking reconstruction strategy which reorganizes the spin ordering to promote electron delocalization and activates multiple redox couples (Mn⁴⁺/Mn³⁺, Mn³⁺/Mn²⁺, and Fe³⁺/Fe²⁺). More critically, induce a novel "Na2 dp Na1" migration path for Na⁺, with a remarkably lower energy barrier than those of conventional paths (0.39 vs. 0.98 eV). Consequently, the engineered Na₄Mn_0.5Fe_0.5Cr_0.5Ti_0.5(PO₄)₃ delivers 138.84 mAh g^-1 at 0.1C, which represents a 12.74-fold breakthrough over the pristine NMFP (10.9 mAh g^-1). Our findings elucidate symmetry-breaking as a critical route for activating Mott-localized states in polyanionic frameworks and establish a new paradigm for designing redox-active and sustainable cathode materials.

Polymer brush–gold nanoparticle (AuNP) hybrids have attracted considerable attention because the structural flexibility of polymer brushes complements the geometry-dependent plasmonic properties of AuNPs. When AuNPs are brought into close proximity, coupling between their localized surface plasmon resonance (LSPR) modes alters their electronic and optical characteristics, enabling the design of tunable plasmonic materials. Among various hybrid systems, precise control over the plasmonic responses of anisotropic AuNPs such as gold nanorods (AuNRs) remains challenging due to their increased structural and orientation-dependent complexity. Integrating AuNRs with polymer brushes offers additional tunability arising from the anisotropic shape of the nanorods, including orientation- and arrangement-dependent optical behavior. In this study, we demonstrate plasmonic modulation of AuNRs through structural regulation of poly(styrenesulfonate) (PSS) brushes. Drastic yet reversible orientation changes of AuNRs were achieved by compressing the PSS brushes using poor solvents. Furthermore, distinct plasmonic responses were observed depending on the assembled structures of tilted AuNRs within the brushes, reflecting different morphological states of the brush matrix under external stimuli. The brush–nanorod hybrids, which enable controllable orientation and assembly of AuNRs, exhibit tunable optical properties and hold promise for applications in colorimetric, optoelectronic, and plasmonic devices.

Surface engineering has produced remarkable advances in green- and red-light-emitting CsPbX3 (X = Br, I) nanocrystals. However, realizing efficient and stable blue-light emission from the higher-bandgap CsPbCl3 remains challenging due to its intrinsically defect-prone nature. This work computationally screens diverse X-type ligands to establish rational design principles for effectively passivating the trap-forming halide vacancies in CsPbCl3 nanocrystals. The multidentate anionic oxygen donors from phosphonic, sulfonic, and carboxylic acids passivate undercoordinated Pb sites with strong, stable binding. Out of these, electronic structure analyses identify 16 ligands that eliminate midgap defect states and restore a clean bandgap in CsPbCl3 nanocrystals. Such surface passivation not only removes trap states but also restores delocalized band edges, leading to the desired shortened radiative lifetimes. The fast radiative process suggests enhanced blue light emission from these passivated CsPbCl3 nanocrystals. Crucially, the effective passivation does not depend solely on the headgroup but is equally dictated by the molecular backbone and substituents. While the aliphatic chains in the ligand backbone promote a clean bandgap, π-conjugated aromatic moieties often introduce in-gap molecular states. Moreover, bulky ligand tails introduce steric hindrance, weakening adsorption energies despite an optimal binding headgroup. Overall, our findings outline a roadmap to achieve high-efficiency blue light emission from CsPbCl3 nanocrystals through strategic ligand engineering.

Electron beam melting (EBM) is an additive manufacturing technology that can process materials and manufacture components otherwise impossible or uneconomical. However, defects, including porosity and surface irregularities, are widely reported in EBM-built components, and their formation mechanisms are not fully understood. Here, using in-situ high-speed synchrotron X-ray imaging, we reveal that bubble explosions in Al6061 during EBM induce melt pool instabilities contributing to defect formation. The melt pool and keyhole evolve through three stages: (1) initial formation of a melt pool, (2) subsurface bubble formation and explosion, and (3) periodic keyhole oscillation. During scanning, periodic bubble explosions can eject molten liquid as spatters and disturb the vapor depression and melt pool, contributing to surface humping, that may trigger lack-of-fusion defects in subsequent layers. The physical insights we report could provide guidance for EBM machine development, process innovation, alloy design and model development.

Bacterial therapeutics hold great promise for cancer treatment by targeting oxygen-poor tumor regions and complementing existing therapies. However, current approaches often struggle with safety concerns and complex engineering. Developing a safe, effective delivery platform relying entirely on natural bacterial biosynthesis remains a challenge. Here we show that attenuated Serratia marcescens serves as a powerful biohybrid platform for cancer therapy by leveraging its natural biosynthesis of prodigiosin, a photosensitive pigment. We engineer S. marcescens to yield high prodigiosin levels, which exhibit strong intrinsic anti-cancer activity and near-infrared photosensitivity. In female mouse models of melanoma and colorectal cancer, this platform triggers robust systemic immune responses, including enhanced T cell recruitment and long-term memory against tumor recurrence. Furthermore, the bacteria induces tumor cell death via mitophagy, while photothermal properties of prodigiosin enables rapid, light-controlled bacterial clearance post-treatment. These findings establish S. marcescens as a versatile, self-regulating biosynthetic platform for precise and safe cancer immunotherapy.

Pathological neovascularization and vascular leakage are central drivers of many sight-threatening diseases. While strategies targeting vascular endothelial growth factor (VEGF) have improved clinical outcomes, many patients do not benefit from the treatment, highlighting the need for alternative therapeutic strategies. Two independent vitreous proteomics studies in patients with proliferative diabetic retinopathy (PDR) reveal a significant reduction in Frizzled-related Protein (FRZB), a finding recapitulated in preclinical models of ocular angiogenesis. Here, we show that loss of Frzb exacerbates ocular angiogenesis, whereas therapeutic delivery of Fc-recombinant FRZB or its netrin-related motif (NTR) robustly suppresses and reverses ocular angiogenesis across various preclinical models. Fc-NTR acts additively with Aflibercept, supporting its potential as a combination therapy. Mechanistically, FRZB binds Caveolin-1 (CAV1), inhibits its phosphorylation at Tyr42, promotes retention of the TGFβ receptor ALK5, and enhances Smad2/3 signalling. These findings define FRZB as a potent suppressor of ocular angiogenesis and establish a promising therapeutic avenue.

The human cortical functional hierarchy, spanning from primary sensorimotor to transmodal association regions, represents a fundamental principle of brain organisation. Here, we show lifespan changes in the sensorimotor-association (S-A) gradient in the cortical functional hierarchy using multimodal neuroimaging data from 33,247 participants aged 32 postmenstrual weeks to 80 years. We identify three critical neurodevelopmental milestones: initiation (third trimester to perinatal period), establishment (infancy to early childhood), and expansion-stabilisation (late childhood to adulthood). Pronounced gradient changes are predominantly observed during the first decade, with continued refinement extending into mid-adulthood. Spatiotemporally heterogeneous growth patterns in functional gradients align with evolutionary hierarchies, segregation-integration dynamics, structural maturation, and cognitive spectrum development, proceeding along a dominant S-A growth axis. These findings establish a unified neurodevelopmental framework that links connectome gradient dynamics to multifaceted functional and structural properties, advancing our understanding of cortical hierarchy maturation across the lifespan.

Electrically modulated metasurfaces manipulate light fields but suffer from high operating voltages, low tuning sensitivity, and a reliance on telecommunication bands, limiting their applications in light communication (LC). Here, we demonstrate electrically modulated plasmonic metasurfaces that enable continuous and reversible wavelength modulation with a tuning sensitivity up to ~ 1 nm/V at a CMOS-compatible voltage below 5 V. These metasurfaces consist of dimethyl sulfoxide (DMSO) immersed metal nanoparticle lattices and Au electrodes on transparent conductive oxide (TCO)/quartz substrate. Through simulations and experiments, we reveal that the wavelength shift is synergistically governed by the refractive index variation of the DMSO superstrate and the Seebeck effect of the TCO layer, which is further amplified by the lattice mode. Further, we propose two LC applications of these tunable metasurfaces: single-mode spectral shifting for image information transmission and multimode spectral shifts for a 1×3 encoder. The device paves the way for applying metasurfaces in optical communication and optoelectronic circuits.