Time-dependent drives hold promise for realizing non-equilibrium many-body phenomena that are absent in undriven systems1-3. Yet, drive-induced heating normally destabilizes the systems4,5, which can be parametrically suppressed in the high-frequency regime by using periodic (Floquet) drives6,7. It remains largely unknown to what extent highly controllable quantum simulators can suppress heating in non-periodically driven systems. Here, using the 78-qubit superconducting quantum processor, Chuang-tzu 2.0, we report the experimental observation of long-lived prethermal phases in many-body systems with tunable heating rates, driven by structured random protocols, characterized by n-multipolar temporal correlations. By measuring both the particle imbalance and subsystem entanglement entropy, we monitor the entire heating process over 1,000 driving cycles and observe the existence of the prethermal plateau. The prethermal lifetime is 'doubly tunable': one way by driving frequency, the other way by multipolar order; it grows algebraically with the frequency with the universal scaling exponent 2n + 1. Using quantum-state tomography on different subsystems, we demonstrate a non-uniform spatial entanglement distribution and observe a crossover from area-law to volume-law entanglement scaling. With 78 qubits and 137 couplers in a two-dimensional configuration, the entire far-from-equilibrium heating dynamics are beyond the reach of simulation using tensor-network numerical techniques. Our work highlights superconducting quantum processors as a powerful platform for exploring universal scaling laws and non-equilibrium phases of matter in driven systems in regimes where classical simulation faces formidable challenges.

One of the most remarkable properties associated with Bose-Einstein condensation (BEC) is superfluidity, in which the system exhibits zero viscosity and flows without dissipation. The superfluid phase has been observed in wide-ranging bosonic systems spanning naturally occurring quantum fluids, such as liquid helium, to engineered platforms such as bilayer excitons and cold atom systems1-4. Theoretical works have proposed that interactions could drive the BEC ground state into another exotic phase that simultaneously exhibits properties of both a crystalline solid and a superfluid-termed a supersolid5-8. Identifying a material system, however, that hosts the predicted BEC solid phase, driven purely by interactions and without imposing an external lattice potential, has remained unknown9-11. Here we report observation of a superfluid-to-insulator transition in the layer-imbalanced regime of bilayer magnetoexcitons. Mapping the transport behaviour of the bilayer condensate as a function of density and temperature suggests that the insulating phase is an ordered state of dilute excitons, stabilized by dipole interactions. The insulator melts into a recovered superfluid on increasing the temperature, which could indicate that the low-temperature solid is also a quantum coherent phase.

Early development across vertebrates and insects critically relies on robustly reorganizing the cytoplasm of fertilized eggs into individualized cells1,2. This intricate process is orchestrated by large microtubule structures that traverse the embryo, partitioning the cytoplasm into physically distinct and stable compartments3,4. Here, despite the robustness of embryonic development, we uncover an intrinsic instability in cytoplasmic partitioning driven by the microtubule cytoskeleton. By combining experiments in cytoplasmic extract and in vivo, we reveal that embryos circumvent this instability through two distinct mechanisms: either by matching the cell-cycle duration to the time needed for the instability to unfold or by limiting microtubule nucleation. These regulatory mechanisms give rise to two possible strategies to fill the cytoplasm, which we experimentally demonstrate in zebrafish and Drosophila embryos, respectively. In zebrafish embryos, unstable microtubule waves fill the geometry of the entire embryo from the first division. Conversely, in Drosophila embryos, stable microtubule asters resulting from reduced microtubule nucleation gradually fill the cytoplasm throughout multiple divisions. Our results indicate that the temporal control of microtubule dynamics could have driven the evolutionary emergence of species-specific mechanisms for effective cytoplasmic organization. Furthermore, our study unveils a fundamental synergy between physical instabilities and biological clocks, uncovering universal strategies for rapid, robust and efficient spatial ordering in biological systems.

Allergic diseases are caused by overexuberant type II immune responses mounted against environmental antigens1. The allergic state is typified by the presence of allergen-reactive immunoglobulin E (IgE), which triggers mast cell degranulation upon allergen encounter, manifesting in pruritis, oedema and, in severe cases, anaphylaxis. Over the past century, the prevalence of allergic diseases has increased markedly, suggesting that environmental rather than genetic factors are mediating this change2. Although many hypotheses connecting environment to allergy exist3-6, the biological mechanisms that underpin environmentally mediated protection from allergy are unknown. Here we show, using a mouse model of allergic disease, that exposure to immunostimulatory environments generated cross-reactive adaptive immune memory, which tracked with obstructed type II immune responses upon allergen exposure. We found that engagement of cross-reactive adaptive immunity protected against future allergic sensitization and suppressed established allergic responses. Cross-reactivity in a tolerogenic context also prevented allergy, with the effect extending across antigenically complex exposures even at low protein sequence similarity. Our findings demonstrate a mechanistic relationship between environment and allergy, with general implications for adaptive immune function in natural settings.

Solid-state thorium-229 (229Th) nuclear clocks1-5 are set to provide new opportunities for precision metrology and fundamental physics6-8. Taking advantage of inherent low sensitivity of a nuclear transition to its environment9, orders of magnitude more emitters can be hosted in a solid-state crystal compared with current optical lattice atomic clocks10. Furthermore, solid-state systems needing only simple thermal control11 are key to the development of field-deployable compact clocks. Here we explore and characterize the frequency reproducibility of the 229Th:CaF2 nuclear clock transition, a key performance metric for all clocks. We measure the transition linewidth and centre frequency as a function of the doping concentration, temperature and time. We report the concentration-dependent inhomogeneous linewidth of the nuclear transition, limited by the intrinsic host crystal12 properties. We determine an optimal working temperature for the 229Th:CaF2 nuclear clock at 196(5) K, at which the first-order thermal sensitivity vanishes. This would enable in situ temperature co-sensing using different quadrupole-split lines, reducing the temperature-induced systematic shift below the 10-18 fractional frequency uncertainty level. At 195 K, the reproducibility of the nuclear transition frequency is 220 Hz (fractionally 1.1 × 10-13) for two differently doped 229Th:CaF2 crystals over 7 months. These results form the foundation for understanding, controlling and harnessing the coherent nuclear excitation of 229Th in solid-state hosts and for their applications in constraining temporal variations of fundamental constants.

Cranial nerves densely innervate the heart and vasculature, with sensory neurons reporting on blood pressure, respiratory gases and tissue damage1. The roles of arterial baroreceptors in systemic physiology are well appreciated2, but the functions of vagal cardiac mechanoreceptors have been more difficult to parse, in part due to the closed-loop structure of the cardiovascular system. Here we use genetic tools in mice to identify a small group of neurons that are acutely sensitive to circulating blood volume and initiate a reflex that compensates for decreased filling of the heart in an upright posture and haemorrhage. Vagal PIEZO2 neurons form characteristic end-net endings in the heart, lower blood pressure in response to optogenetic stimulation and display blood-volume-dependent responses with every heartbeat that are time-locked to atrial and ventricular systole. Knockout of Piezo2 and/or ablation of PIEZO2 neurons in vagal ganglia eliminates this heartbeat-coupled nerve activity, causes orthostatic hypotension and compromises cardiovascular stability during trauma-induced blood loss. Together, these findings demonstrate that vagal mechanoreceptors monitor the cardiac cycle and initiate a blood-volume-dependent reflex that defends the constancy of circulation.

The invention of the laser transformed optics by providing intense, coherent light in the visible region, but extending this concept to X-rays has been hindered by a lack of suitable gain media and mirrors. Current hard X-ray free-electron laser (XFEL) facilities1-5 overcome this by amplifying shot noise from a high-peak-current electron bunch via self-amplified spontaneous emission6 in a single pass through long undulators, delivering very high brightness but with a noisy, multi-spiked temporal and spectral profile. Cavity-based XFELs (CBXFELs)7-9 were proposed to close this gap by recirculating spectrally filtered X-ray pulses in a Bragg-reflecting cavity synchronized to a high-repetition-rate electron beam. Here we show lasing with multi-pass gain at 6.952 keV in a 132.8-m round-trip diamond-based Bragg cavity10 at the European XFEL, matched to the 2.23-MHz bunch spacing of the superconducting accelerator5. Under stringent length and angular stability requirements, a ring-up in the cavity across successive bunches was observed, producing spectrally pure, microjoule-level pulses. This establishes the feasibility of CBXFELs in an accelerator environment and validates diamond Bragg optics for X-ray resonators. The demonstrated spectral purity opens a path to next-generation X-ray science, which demands highly coherent, stable sources.

Human genetic variation influences all aspects of our biology, including the oral cavity1-3, through which nutrients and microbes enter the body. Yet it is largely unknown which human genetic variants shape a person's oral microbiome and potentially promote its dysbiosis3-5. We characterized the oral microbiomes of 12,519 people by re-analysing whole-genome sequencing reads from previously sequenced saliva-derived DNA. Human genetic variation at 11 loci (10 new) associated with variation in oral microbiome composition. Several of these related to carbohydrate availability; the strongest association (P = 3.0 × 10-188) involved the common FUT2 W154X loss-of-function variant, which associated with the abundances of 58 bacterial species. Human host genetics also seemed to powerfully shape genetic variation in oral bacterial species: these 11 host genetic variants also associated with variation of gene dosages in 68 regions of bacterial genomes. Common, multi-allelic copy number variation of AMY1, which encodes salivary amylase, associated with oral microbiome composition (P = 1.5 × 10-53) and with dentures use in UK Biobank (P = 5.9 × 10-35, n = 418,039) but not with body mass index (P = 0.85), suggesting that salivary amylase abundance impacts health by influencing the oral microbiome. Two other microbiome composition-associated loci, FUT2 and PITX1, also significantly associated with dentures risk, collectively nominating numerous host-microbial interactions that contribute to tooth decay.

Eukaryotic genome replication is surveyed by the S-phase checkpoint, which coordinates sequential origin activation to prevent the exhaustion of poorly defined, rate-limiting replisome components1-3. Here we show that excessive origin firing saturates chromatin-bound proliferating cell nuclear antigen (PCNA)-a sliding clamp for DNA polymerase processivity and Okazaki fragment processing4-thereby restricting further PCNA loading and lagging-strand synthesis when checkpoint control is lost. PCNA-associated factor 15 (PAF15) emerges as a dosage-sensitive regulator of this process5-9. During unperturbed S phase, the entire soluble PAF15 pool binds to chromatin, leaving no reserve to stabilize PCNA under conditions of excessive origin activation. PAF15 binds to PCNA specifically on the lagging strand through a high-affinity PIP motif and occupies the DNA-encircling channel, protecting the clamp and associated enzymes from premature unloading by the ATAD5-RFC complex. Conversely, overexpression of PAF15 or forced redistribution to the leading strand disrupts replisome progression and induces cell death. These detrimental effects are mitigated by Timeless-Claspin, which blocks PAF15-PCNA binding on the leading strand. E2F4-mediated repression fine-tunes PAF15 expression to ensure optimal dosage and strand specificity. These findings reveal a previously unrecognized replisome constraint: when PAF15-PCNA assemblies are exhausted, the S-phase checkpoint globally restricts origin activation, linking a strand-specific rate-limiting mechanism to global replication dynamics.

Vacuum ultraviolet (VUV, 100-200 nm) light sources are crucial for advanced spectroscopy, quantum research and semiconductor lithography1-3. Compared with conventional large-scale VUV generation technologies4-7, second-harmonic generation (SHG) through nonlinear optical (NLO) crystals8-10 is the simplest and most efficient method. However, the scarcity of suitable NLO crystals has constrained the production of VUV light through SHG: existing materials fail to meet phase-matching requirements, suffer from low conversion efficiency or have severe growth limitations11-19. In this study, we report the development of the fluorooxoborate crystal NH4B4O6F (abbreviated as ABF) as a promising material for VUV light generation. VUV devices with specific phase-matching angles were constructed, achieving a record 158.9-nm light through phase-matching SHG and a maximum nanosecond pulse energy of 4.8 mJ at 177.3 nm with a conversion efficiency of 5.9%. The enhanced NLO performance is attributed to optimized arrangements of fluorine-based units creating asymmetric sublattices. This work provides further material in the NLO field, with potential for applications in compact, high-power VUV lasers using ABF.

Pesticides are widely distributed in soils1-3, yet their effects on soil biodiversity remain poorly understood4-7. Here we examined the effects of 63 pesticides on soil archaea, bacteria, fungi, protists, nematodes, arthropods and key functional gene groups across 373 sites spanning woodlands, grasslands and croplands in 26 European countries. Pesticide residues were detected in 70% of sites and emerged as the second strongest driver of soil biodiversity patterns after soil properties. Our analysis further revealed organism- and function-specific patterns, emphasizing complex and widespread non-target effects on soil biodiversity. Pesticides altered microbial functions, including phosphorus and nitrogen cycling, and suppressed beneficial taxa, including arbuscular mycorrhizal fungi and bacterivore nematodes. Our findings highlight the need to integrate functional and taxonomic characteristics into future risk assessment methodology to safeguard soil biodiversity, a cornerstone of ecosystem functioning.

Optical control offers a non-contact, high-precision and ultrafast route to manipulating quantum material properties1-5. Fractional Chern ferromagnetic states in moiré superlattices are a promising platform by which to pursue topological quantum computing6-10, but an effective optical control protocol has remained elusive. Here we demonstrate robust optical switching of integer and fractional Chern ferromagnets in twisted molybdenum ditelluride (MoTe2) bilayers using continuous-wave circularly polarized light. Highly efficient optical manipulation of spin orientations in the topological ferromagnet regime is realized at zero field using a pump light power as low as 28 nW µm-2. Using this optically induced transition, we also demonstrate magnetic bistate cycling and spatially resolved writing of ferromagnetic domain walls. This work establishes a reliable and efficient optical control scheme for moiré Chern ferromagnets, paving the way for dissipationless spintronics and quantized Chern junction devices.

Bile acids (BAs) are crucial amphipathic surfactants that function as multifaceted regulators in various physiological processes, including nutrient absorption and distribution, lipid metabolism and inflammation1,2. The human organic solute transporter αβ (OSTα-OSTβ; hereafter referred to as OSTα/β) is a BA transporter that has a key role in the secretion and distribution of BAs3-6. Pathogenic mutations in OSTα/β have been associated with cholestasis7,8. Despite the functional importance of OSTα/β in BA homeostasis, the stoichiometry and assembly of the complex and the molecular mechanism that underlies BA transport by OSTα/β remain unknown. Here we present cryo-electron microscopy structures of human OSTα/β in complex with cholesterols and an endogenous substrate, elucidating the structural basis for the function of OSTα/β. OSTα/β is assembled in a novel dimer-of-heterodimers manner: two OSTα units form the homodimeric core, with two OSTβ units bound to the periphery. OSTα adopts the G-protein-coupled-receptor (GPCR) fold and contains a unique cysteine-rich loop with seven palmitoylation sites; these cooperate with transmembrane helices 5 and 6, constituting a BA recognition site. A positive cavity in OSTα connects the BA site and facilitates the transmembrane translocation of BAs through OSTα/β. Together, this study reveals the architecture and transport mechanism of OSTα/β and provides insights into the structure-function relationships of this crucial transporter in BA homeostasis.