The spin supersolid-a magnetic analogue of the supersolid that simultaneously exhibits solid and superfluid orders-has emerged as a promising sub-Kelvin refrigerant with strong low-energy fluctuations and associated entropic effects1. However, the stringent prerequisites have so far confined its presence to certain magnetic insulators. Here we report the discovery of a metallic spin supersolid in a rare-earth compound EuCo2Al9 (ECA), which is a good metal with excellent electrical and thermal conductivity. The high-spin Eu2+ ions form a three-dimensional lattice with stacked triangular layers, in which the spin-supersolid state is stabilized through a mechanism involving both Ruderman-Kittel-Kasuya-Yosida (RKKY) and dipolar couplings. Neutron diffraction shows microscopic evidence of spin supersolidity, demonstrating the coexistence of out-of-plane and in-plane spin orders in this alloy. Our RKKY-dipolar model successfully captures the metallic spin-supersolid Y and V phases in ECA, along with the 1/3 magnetization plateau. The observed nonclassical magnetization behaviours within these phases point to significant quantum fluctuations, probably enhanced by the conduction electrons. The resistivity measurements provide a transport probe for the spin-supersolid transitions, because of scattering of conduction electrons from local moments. Through the adiabatic demagnetization process, ECA achieves ultralow cooling to 106 mK, exhibiting a giant magnetocaloric effect that manifests sharp anomalies in the magnetic Grüneisen ratio. ECA emerges as one of the first metallic spin supersolids, combining low cooling temperature, large magnetic entropy and ultrahigh thermal conductivity for high-performance sub-Kelvin refrigeration.

Volumetric additive manufacturing has emerged as a promising technique for the flexible production of complex structures, with diverse applications in engineering, photonics and biology1,2. However, present methods still face a trade-off between resolution and volumetric build rate, restricting efficient and flexible production of high-resolution 3D structures. Here we propose a method, called digital incoherent synthesis of holographic light fields (DISH), to generate high-resolution 3D light distributions through continuous multi-angle projections with a high-speed rotating periscope without the requirement of sample rotation. The iterative optimization of the holograms for different angles in DISH maintains 19-μm printing resolution across the 1-cm range that is far beyond the depth of field of the objective and enables high-resolution in situ 3D printing of millimetre-scale objects within only 0.6 s. Acrylate materials in a range of viscosities are used to demonstrate the general compatibility of DISH. Integrating DISH with a fluid channel, we achieved mass production of complex and diverse 3D structures within low-viscosity materials, demonstrating its potential for broad applications in diverse fields.

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission throughout the brain1. As obligate heterotetramers, their activation requires the binding of both glycine and glutamate2. Although recent structural studies have provided insights into endogenous receptors from select brain regions3, most previous work has relied on recombinant receptors and engineered constructs, which limits our understanding of native NMDARs across the whole brain. Here we identify and resolve ten distinct native NMDAR assemblies from the whole-brain tissue of female C57BL/6 mice using immunoaffinity purification, single-molecule total internal reflection fluorescence microscopy and cryo-electron microscopy. Analyses of the GluN1-GluN2A(S1), GluN1-GluN2A(S2), GluN1-GluN2A(S3), GluN1-GluN2B, GluN1-GluN2A-GluN2B(S1), GluN1-GluN2A-GluN2B(S2), GluN1-GluN2A-GluNX(S1), GluN1-GluN2A-GluNX(S2), GluN1-GluN2B-GluNX and GluN1-GluNX structures reveal that GluN2A is the most prevalent subunit across assemblies. Moreover, the substantial conformational flexibility observed in the GluN2A amino-terminal domain may explain its fast kinetics and dominant role in gating. Dynamic movements of S-ketamine were also captured at the channel vestibule, as was pore dilation in both the GluN1 and GluN2B subunits of a native GluN1-GluN2B receptor. The latter observation represents a previously unknown fully open state of NMDAR. Our large collection of heterogeneous NMDAR structures from whole brain reveals previously unrecognized properties of conformational diversity and channel dilation.

Ancient DNA studies revealed that, in Europe from 6500 to 4000 BCE, descendants of western Anatolian farmers mixed with local hunter-gatherers resulting in 70-100% ancestry turnover1, then steppe ancestry spread with the Corded Ware complex 3000-2500 BCE2. Here we document an exception in the wetland, riverine and coastal areas of the Netherlands, Belgium and western Germany, using genome-wide data from 112 people 8500-1700 BCE. A distinctive population with high (approximately 50%) hunter-gatherer ancestry persisted 3,000 years later than in most European regions, reflecting incorporation of female individuals of Early European Farmer ancestry into local communities. In the western Netherlands, the arrival of the Corded Ware complex was also exceptional: lowland individuals from settlements adopting Corded Ware pottery had hardly any steppe ancestry, despite a Y-chromosome characteristic of people associated with the early Corded Ware complex. These distinctive patterns may reflect the specific ecology that they inhabited, which was not amenable to full adoption of the early Neolithic type of farming introduced with Linearbandkeramik3, and resulted in distinct communities where transfer of ideas was accompanied by little gene flow. This changed with the formation of Lower Rhine-Meuse Bell Beaker users by fusion of local people (13-18%) and Corded Ware associated migrants of both sexes. Their subsequent expansion then had a disruptive impact across a much wider part of northwestern Europe, especially in Great Britain where they were the main source of a 90-100% replacement of local Neolithic ancestry.

The exceptionally low-energy isomeric transition in 229Th at around 148.4 nm (refs. 1-6) offers a unique opportunity for coherent nuclear control and the realization of a nuclear clock7,8. Recent advances, most notably the incorporation of large ensembles of 229Th nuclei in transparent crystals6,9-11 and the development of pulsed vacuum ultraviolet (VUV) lasers12-14, have enabled initial laser spectroscopy of this transition15-17. However, the lack of an intense, narrow-linewidth VUV laser has precluded coherent nuclear manipulation8,18. Here we introduce and report a continuous-wave (CW) laser at 148.4 nm, generated by means of four-wave mixing (FWM)19 in cadmium vapour. The source delivers more than 100 nW of power with a projected linewidth well below 100 Hz and supports broad wavelength tunability. This represents a five-orders-of-magnitude improvement in linewidth over all previous single-frequency lasers below 190 nm (refs. 12-14,20). We develop a spatially resolved homodyne technique that places a stringent upper bound on FWM-induced phase noise, thereby supporting the feasibility of sub-hertz VUV linewidths. Our work addresses the central challenge towards a 229Th-based nuclear clock and establishes a widely tunable, ultranarrow-linewidth laser platform for potential applications across quantum information science21-24, condensed-matter physics25 and high-resolution VUV spectroscopy26.

Brain systems mediating responses to previously encountered threats provide critical survival functions. Fear memory and extinction are underpinned by neural representations in the basolateral amygdala (BLA)1-7, but the contribution of non-neuronal cells, including astrocytes, to these processes remains unresolved. Here, using in vivo calcium (Ca2+) imaging and causal astrocyte manipulations, we find that BLA astrocytes dynamically track fear state and support fear memory retrieval and extinction. By combining astrocyte manipulations with in vivo BLA neuronal Ca2+ imaging and electrophysiological recordings, we show that astrocyte Ca2+ signalling enables neuronal encoding of fear memory retrieval and extinction, and readout through a BLA-prefrontal circuit. Our findings reveal a key role for astrocytes in the generation and adaptation of fear-state-related neural representations, revising neurocentric models of critical amygdala-mediated adaptive functions.

Inhibitory receptors like PD-1 and CTLA-4 contribute to T cell dysfunction in cancer1-3. Monoclonal antibodies (mAbs) blocking the interactions in trans of these receptors with their ligands on cancer cells or in the tumour microenvironment lead to clinical responses in some but not all types of cancer. Signalling lymphocytic activation molecule 6 (SLAMF6, also known as Ly108) is a homotypic receptor preferentially expressed on progenitor or stem-like exhausted T (Tpex) cells, but not on terminally exhausted T (Tex) cells, as demonstrated in mouse models4-9. In contrast to Tex cells, Tpex cells retain the capacity for functional restoration after immune checkpoint blockade10-12. The role of SLAMF6 in T cells remains ambiguous, as it has both activating and inhibitory effects, complicating its evaluation as a therapeutic target. Here we find that SLAMF6 was triggered in cis by homotypic interactions at the T cell surface. These interactions elicited inhibitory effects that suppressed activation of T cells and limited anti-tumour immunity, independently of SLAMF6 expression on tumour cells. mAbs against human SLAMF6 with a robust ability to disrupt the cis interactions strongly augmented T cell activation, reduced the proportions of exhausted T cells and inhibited tumour growth in vivo. Collectively, these findings show that SLAMF6 functions exclusively as a T cell inhibitory receptor, which is triggered by cis homotypic interactions. They also position SLAMF6 as a promising target for therapies aimed at enhancing anti-tumour immunity, regardless of SLAMF6 expression on tumour cells.

Sleep is viewed typically through a brain-centric lens, with little known about the role of the periphery1,2. Here we identify a sleep function for peripheral macrophage-like cells (haemocytes) in the Drosophila circulation, showing that haemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in haemocytes, we discovered that knockdown of eater-a member of the Nimrod receptor family-reduces sleep. Loss of eater also disrupts haemocyte localization to the brain and lipid uptake, which results in increased brain levels of acetyl-CoA and acetylated proteins, including mitochondrial proteins PGC1α and DRP1. Dysregulation of mitochondria, reflected in high oxidation and reduced NAD+, is accompanied by impaired memory and lifespan. Thus, peripheral blood cells, which we suggest are precursors of mammalian microglia, perform a daily function of sleep to maintain brain function and fitness.

Spatial orientation enables animals to navigate their environment by rapidly mapping the external world and remembering key locations1. In mammals, the head-direction (HD) system is an essential component of the navigation system of the brain2. Although the tuning of neurons in other areas of this system is unstable-evidenced, for example, by the change in the spatial tuning of hippocampal place cells3 across days4-11-the stability of the neuronal code that underlies the sense of direction remains unclear. Here, by longitudinally tracking the activity of the same HD cells in the post-subiculum of freely moving mice, we show stability and plasticity at two levels. Although the population structure remained highly conserved across environments and over time, subtle shifts in population coherence encoded environment identity. In addition, the HD system established a distinct, environment-specific alignment between its internal representation and external landmarks, which persisted for weeks, even after a single exposure. These findings suggest that the HD system forms long-lasting orientation memories that are anchored to specific environments.

Goal-directed navigation requires animals to continuously evaluate their current direction and speed of travel relative to landmarks to discern whether they are approaching or deviating from their goal. Striatal dopamine release signals the reward-predictive value of cues1,2, probably contributing to motivation3,4, but it is unclear how dopamine incorporates an animal's ongoing trajectory for effective behavioural guidance. Here we demonstrate that cue-evoked striatal dopamine release in mice encodes bidirectional trajectory errors reflecting the relationship between the speed and direction of ongoing movement relative to optimal goal trajectories. Trajectory error signals could be computed from locomotion or visual flow, and were independent from simultaneous dopamine increases reflecting learned cue value. Joint trajectory error and cue-value encoding were reproduced by the reward prediction error term in a standard reinforcement learning algorithm with mixed sensorimotor inputs. However, these two signals had distinct state space requirements, suggesting that they could arise from a common reinforcement learning algorithm with distinct neural inputs. Striatum-wide multifibre array measurements resolved overlapping, yet temporally and anatomically separable, representations of trajectory error and cue value, indicating how functionally distinct dopamine signals for motivation and guidance are multiplexed across striatal regions to facilitate goal-directed behaviour.

Lymphoedema is a chronic debilitating disease caused by impaired lymphatic drainage and is characterized by tissue swelling, fat expansion, inflammation and fibrosis1,2. However, the exact mechanisms that drive lymphoedema are poorly understood. Although lymphatic vessels are known to transport cholesterol from peripheral tissues back to the systemic circulation3, the importance of impaired lymphatic drainage for cholesterol clearance in humans and its relevance to lymphoedema remain unknown. Here we show that lymphatic drainage insufficiency in human lymphoedema leads to excessive cholesterol accumulation in the lymphoedematous dermal tissue and around lymphatic vessels. Cholesterol deposition resulted in dermal adipose tissue remodelling, characterized by adipocyte hypertrophy and dysfunction, progressing to death and dermal fibrosis. Surgical intervention improved lymphatic drainage and reduced cholesterol deposition. Using two mouse models that reproduce features of human lymphoedema, we demonstrated that tissue swelling and dermal adipose tissue remodelling were ameliorated by the cholesterol-depleting agent cyclodextrin. Mechanistically, we demonstrated that cyclodextrin restored lymphatic drainage by promoting the regeneration of lymphatic vessels. This study unravels the role of impaired cholesterol clearance in driving lymphoedema and identifies tissue cholesterol as a promising therapeutic target for this currently incurable disease.

Mpox, caused by the monkeypox virus (MPXV; Orthopoxvirus monkeypox), is on the rise in West and Central Africa1-3. African rodents, especially squirrels, are suspected to be involved in MPXV emergence, but no evidence of a direct transmission to humans or non-human primates has been established4-9. Here we describe an outbreak of MPXV in a group of wild sooty mangabeys (Cercocebus atys) in Taï National Park (Côte d'Ivoire). The outbreak affected one-third of the group, killing four infants. To track its origin, we analysed rodents and wildlife carcasses from the region. We identified a MPXV-infected fire-footed rope squirrel (Funisciurus pyrropus), found dead 3 km from the mangabey territory 12 weeks before the outbreak. MPXV genomes from the squirrel and the mangabey were nearly identical. A video record from 2014 showed a mangabey from this group eating the same squirrel species and diet metabarcoding of faecal samples collected from mangabeys before the outbreak identified two samples containing fire-footed rope squirrel DNA. One of these samples was also the first positive for MPXV. This represents a rare case of direct detection of interspecies transmission. Our findings indicate that rope squirrels were the source of the MPXV outbreak in mangabeys. Because squirrels and non-human primates are hunted, traded and consumed by humans in West and Central Africa10,11, exposure to these animals probably represents risk for zoonotic transmission of MPXV.