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The rich set of mechanoreceptors found in human skin 1,2 offers a versatile engineering interface for transmitting information and eliciting perceptions 3,4 , potentially serving a broad range of applications in patient care 5 and other important industries 6,7 . Targeted multisensory engagement of these afferent units, however, faces persistent challenges, especially for wearable, programmable systems that need to operate adaptively across the body 8-11 . Here we present a miniaturized electromechanical structure that, when combined with skin as an elastic, energy-storing element, supports bistable, self-sensing modes of deformation. Targeting specific classes of mechanoreceptors as the basis for distinct, programmed sensory responses, this haptic unit can deliver both dynamic and static stimuli, directed as either normal or shear forces. Systematic experimental and theoretical studies establish foundational principles and practical criteria for low-energy operation across natural anatomical variations in the mechanical properties of human skin. A wireless, skin-conformable haptic interface, integrating an array of these bistable transducers, serves as a high-density channel capable of rendering input from smartphone-based 3D scanning and inertial sensors. Demonstrations of this system include sensory substitution designed to improve the quality of life for patients with visual and proprioceptive impairments., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Allergic diseases, affecting over a quarter of individuals in industrialized countries, have become significant public health concerns 1,2 . The high-affinity Fc receptor for IgE (FcεRI), mainly present on mast cells and basophils, plays a crucial role in allergic diseases 3-5 . Monomeric IgE binding to FcεRI regulates mast cell survival, differentiation, and maturation 6-8 . However, the underlying molecular mechanism remains unclear. Here we demonstrate that, prior to IgE binding, FcεRI mostly exists as a homo-dimer on human mast cell membrane. The structure of human FcεRI confirms the dimeric organization, with each promoter comprising one α subunit, one β subunit, and two γ subunits. The transmembrane helices of the α subunits form a layered arrangement with those of the γ and β subunits. The dimeric interface is mediated by a four-helix bundle of the α and γ subunits at the intracellular juxtamembrane region. Cholesterol-like molecules embedded within the transmembrane domain may stabilize the dimeric assembly. Upon IgE binding, the dimeric FcεRI dissociates into two protomers, each binding to an IgE molecule. Importantly, this process elicits transcriptional activation of Egr1/3 and Ccl2 in rat basophils, which can be attenuated by inhibiting the FcεRI dimer-to-monomer transition. Collectively, our study unveils the mechanism of antigen-independent, IgE-mediated FcεRI activation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Obtaining micron-thick perovskite films of high quality is key to realizing efficient and stable positive (p)-intrinsic (i)-negative (n) perovskite solar cells 1,2 , but it remains a critical challenge. Here, we report an effective method for producing high-quality, micron-thick formamidinium-based perovskite films by forming coherent grain boundaries, where high-Miller-index-oriented grains grow on the low-Miller-index-oriented grains in a stabilized atmosphere. The resulting micron-thick perovskite films, with enhanced grain boundaries and grains, showed stable material properties and outstanding optoelectronic performances. The small-area solar cells achieved efficiencies of 26.1%. The 1-square-centimeter devices and 5 cm × 5 cm minimodules delivered efficiencies of 24.3% and 21.4%, respectively. The devices processed in a stabilized atmosphere presented a high reproducibility across all four seasons. The encapsulated devices exhibited superior long-term stability under both light and thermal stressors in ambient air., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Superconductivity in a highly correlated kagome system has been theoretically proposed for years (refs.  1-5 ), yet the experimental realization is hard to achieve 6,7 . The recently discovered vanadium-based kagome materials 8 , which exhibit both superconductivity 9-11 and charge-density-wave orders 12-14 , are nonmagnetic 8,9 and weakly correlated 15,16 . Thus these materials are unlikely to host the exotic superconductivity theoretically proposed. Here we report the discovery of a chromium-based kagome metal, CsCr 3 Sb 5 , which is contrastingly featured with strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. Under ambient pressure, this kagome metal undergoes a concurrent structural and magnetic phase transition at 55 K, with a stripe-like 4a 0 structural modulation. At high pressure, the phase transition evolves into two transitions, possibly associated with charge-density-wave and antiferromagnetic spin-density-wave orderings. These density-wave-like orders are gradually suppressed with pressure and, remarkably, a superconducting dome emerges at 3.65-8.0 GPa. The maximum of the superconducting transition temperature, T c max . Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems.17,18 . Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Molecule-based selective contacts have become a crucial component to ensure high-efficiency inverted perovskite solar cells 1-5 . These molecules always consist of a conjugated core with heteroatom substitution to render the desirable carrier-transport capability 6-9 . So far, the design of successful conjugation cores has been limited to two N-substituted π-conjugated structures, carbazole and triphenylamine, with molecular optimization evolving around their derivatives 2,5,10-12 . However, further improvement of the device longevity has been hampered by the concomitant limitations of the molecular stability induced by such heteroatom-substituted structures 13,14 . A more robust molecular contact without sacrificing the electronic properties is in urgent demand, but remains a challenge. Here we report a peri-fused polyaromatic core structure without heteroatom substitution that yields superior carrier transport and selectivity over conventional heteroatom-substituted core structures. This core structure produced a relatively chemically inert and structurally rigid molecular contact, which considerably improved the performance of perovskite solar cells in terms of both efficiency and durability. The champion device showed an efficiency up to 26.1% with greatly improved longevity under different accelerated-ageing tests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Nucleotide-binding leucine-rich repeat (NLR) proteins play a pivotal role in plant immunity by recognizing pathogen effectors 1,2 . Maintaining a balanced immune response is crucial, as excessive NLR expression can lead to unintended autoimmunity 3,4 . Unlike most NLRs, the plant NLR required for cell death 2 (NRC2) belongs to a small NLR group characterized by constitutively high expression without self-activation 5 . The mechanisms underlying NRC2 autoinhibition and activation are not yet understood. Here we show that Solanum lycopersicum (tomato) NRC2 (SlNRC2) forms dimers and tetramers and higher-order oligomers at elevated concentrations. Cryo-electron microscopy shows an inactive conformation of SlNRC2 in these oligomers. Dimerization and oligomerization not only stabilize the inactive state but also sequester SlNRC2 from assembling into an active form. Mutations at the dimeric or interdimeric interfaces enhance pathogen-induced cell death and immunity in Nicotiana benthamiana. The cryo-electron microscopy structures unexpectedly show inositol hexakisphosphate (IP 6 ) or pentakisphosphate (IP 5 ) bound to the inner surface of the C-terminal leucine-rich repeat domain of SlNRC2, as confirmed by mass spectrometry. Mutations at the inositol phosphate-binding site impair inositol phosphate binding of SlNRC2 and pathogen-induced SlNRC2-mediated cell death in N. benthamiana. Our study indicates a negative regulatory mechanism of NLR activation and suggests inositol phosphates as cofactors of NRCs., (© 2024. The Author(s).)

AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins 1,2 . Here we show that, with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity towards the phosphoryl group of phosphoribose on PR R42 -Ub that is generated by the SidE family of effectors, and deubiquitinases DupA and DupB in an E1- and E2-independent ubiquitination process 3-7 . The product of LnaB is further hydrolysed by an ADP-ribosylhydrolase, MavL, to Ub, thereby preventing the accumulation of PR R42 -Ub and ADPR R42 -Ub and protecting canonical ubiquitination in host cells. LnaB represents a large family of AMPylases that adopt a common structural fold, distinct from those of the previously known AMPylases, and LnaB homologues are found in more than 20 species of bacterial pathogens. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity towards phosphorylated residues and produces unique ADPylation modifications in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family of kinases 8,9 , which dampens downstream phosphorylation signalling in the host. Structural studies reveal the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study identifies, to our knowledge, an unprecedented molecular regulation mechanism in bacterial pathogenesis and protein phosphorylation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The interplay among frustrated lattice geometry, non-trivial band topology and correlation yields rich quantum states of matter in kagome systems 1,2 . A series of recent members in this family, AV 3 Sb 5 (A = K, Rb or Cs), exhibit a cascade of symmetry-breaking transitions 3 , involving the 3Q chiral charge ordering 4-8 , electronic nematicity 9,10 , roton pair density wave 11 and superconductivity 12 . The nature of the superconducting order is yet to be resolved. Here we report an indication of dynamic superconducting domains with boundary supercurrents in intrinsic CsV 3 Sb 5 flakes. The magnetic field-free superconducting diode effect is observed with polarity modulated by thermal histories, suggesting that there are dynamic superconducting order domains in a spontaneous time-reversal symmetry-breaking background. Strikingly, the critical current exhibits double-slit superconductivity interference patterns when subjected to an external magnetic field. The characteristics of the patterns are modulated by thermal cycling. These phenomena are proposed as a consequence of periodically modulated supercurrents flowing along certain domain boundaries constrained by fluxoid quantization. Our results imply a time-reversal symmetry-breaking superconducting order, opening a potential for exploring exotic physics, for example, Majorana zero modes, in this intriguing topological kagome system., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology 1-3 . The γδ T cell receptor (TCR), which is generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex 2 . The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy 4 . Here we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes 5,6 , revealing two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ-TCRδ extracellular domain and connecting peptides. The length of the connecting peptides regulates the ligand association and T cell activation. A cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signalling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, whereby two protomers nestle back to back through the Vγ5 domains of the TCR extracellular domains. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the unique properties of γδ TCR and facilitating immunotherapeutic interventions., (© 2024. The Author(s).)

Fentanyl is a powerful painkiller that elicits euphoria and positive reinforcement 1 . Fentanyl also leads to dependence, defined by the aversive withdrawal syndrome, which fuels negative reinforcement 2,3 (that is, individuals retake the drug to avoid withdrawal). Positive and negative reinforcement maintain opioid consumption, which leads to addiction in one-fourth of users, the largest fraction for all addictive drugs 4 . Among the opioid receptors, µ-opioid receptors have a key role 5 , yet the induction loci of circuit adaptations that eventually lead to addiction remain unknown. Here we injected mice with fentanyl to acutely inhibit γ-aminobutyric acid-expressing neurons in the ventral tegmental area (VTA), causing disinhibition of dopamine neurons, which eventually increased dopamine in the nucleus accumbens. Knockdown of µ-opioid receptors in VTA abolished dopamine transients and positive reinforcement, but withdrawal remained unchanged. We identified neurons expressing µ-opioid receptors in the central amygdala (CeA) whose activity was enhanced during withdrawal. Knockdown of µ-opioid receptors in CeA eliminated aversive symptoms, suggesting that they mediate negative reinforcement. Thus, optogenetic stimulation caused place aversion, and mice readily learned to press a lever to pause optogenetic stimulation of CeA neurons that express µ-opioid receptors. Our study parses the neuronal populations that trigger positive and negative reinforcement in VTA and CeA, respectively. We lay out the circuit organization to develop interventions for reducing fentanyl addiction and facilitating rehabilitation., (© 2024. The Author(s).)

Ice surfaces are closely relevant to many physical and chemical properties, such as melting, freezing, friction, gas uptake and atmospheric reaction 1-8 . Despite extensive experimental and theoretical investigations 9-17 , the exact atomic structures of ice interfaces remain elusive owing to the vulnerable hydrogen-bonding network and the complicated premelting process. Here we realize atomic-resolution imaging of the basal (0001) surface structure of hexagonal water ice (ice Ih) by using qPlus-based cryogenic atomic force microscopy with a carbon monoxide-functionalized tip. We find that the crystalline ice-Ih surface consists of mixed Ih- and cubic (Ic)-stacking nanodomains, forming 19 × 19 periodic superstructures. Density functional theory reveals that this reconstructed surface is stabilized over the ideal ice surface mainly by minimizing the electrostatic repulsion between dangling OH bonds. Moreover, we observe that the ice surface gradually becomes disordered with increasing temperature (above 120 Kelvin), indicating the onset of the premelting process. The surface premelting occurs from the defective boundaries between the Ih and Ic domains and can be promoted by the formation of a planar local structure. These results put an end to the longstanding debate on ice surface structures and shed light on the molecular origin of ice premelting, which may lead to a paradigm shift in the understanding of ice physics and chemistry., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

From AD 567-568, at the onset of the Avar period, populations from the Eurasian Steppe settled in the Carpathian Basin for approximately 250 years 1 . Extensive sampling for archaeogenomics (424 individuals) and isotopes, combined with archaeological, anthropological and historical contextualization of four Avar-period cemeteries, allowed for a detailed description of the genomic structure of these communities and their kinship and social practices. We present a set of large pedigrees, reconstructed using ancient DNA, spanning nine generations and comprising around 300 individuals. We uncover a strict patrilineal kinship system, in which patrilocality and female exogamy were the norm and multiple reproductive partnering and levirate unions were common. The absence of consanguinity indicates that this society maintained a detailed memory of ancestry over generations. These kinship practices correspond with previous evidence from historical sources and anthropological research on Eurasian Steppe societies 2 . Network analyses of identity-by-descent DNA connections suggest that social cohesion between communities was maintained via female exogamy. Finally, despite the absence of major ancestry shifts, the level of resolution of our analyses allowed us to detect genetic discontinuity caused by the replacement of a community at one of the sites. This was paralleled with changes in the archaeological record and was probably a result of local political realignment., (© 2024. The Author(s).)

Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens 1-7 . However, a molecular and cellular profile of sex differences and their modulation by androgens is still lacking. Here we constructed a high-dimensional single-cell transcriptomic atlas comprising over 2.3 million cells from 17 tissues in Mus musculus and explored the effects of sex and androgens on the molecular programs and cellular populations. In particular, we found that sex-biased immune gene expression and immune cell populations, such as group 2 innate lymphoid cells, were modulated by androgens. Integration with the UK Biobank dataset revealed potential cellular targets and risk gene enrichment in antigen presentation for sex-biased diseases. This study lays the groundwork for understanding the sex differences orchestrated by androgens and provides important evidence for targeting the androgen pathway as a broad therapeutic strategy for sex-biased diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Within the family of two-dimensional dielectrics, rhombohedral boron nitride (rBN) is considerably promising owing to having not only the superior properties of hexagonal boron nitride 1-4 -including low permittivity and dissipation, strong electrical insulation, good chemical stability, high thermal conductivity and atomic flatness without dangling bonds-but also useful optical nonlinearity and interfacial ferroelectricity originating from the broken in-plane and out-of-plane centrosymmetry 5-23 . However, the preparation of large-sized single-crystal rBN layers remains a challenge 24-26 , owing to the requisite unprecedented growth controls to coordinate the lattice orientation of each layer and the sliding vector of every interface. Here we report a facile methodology using bevel-edge epitaxy to prepare centimetre-sized single-crystal rBN layers with exact interlayer ABC stacking on a vicinal nickel surface. We realized successful accurate fabrication over a single-crystal nickel substrate with bunched step edges of the terrace facet (100) at the bevel facet (110), which simultaneously guided the consistent boron-nitrogen bond orientation in each BN layer and the rhombohedral stacking of BN layers via nucleation near each bevel facet. The pure rhombohedral phase of the as-grown BN layers was verified, and consequently showed robust, homogeneous and switchable ferroelectricity with a high Curie temperature. Our work provides an effective route for accurate stacking-controlled growth of single-crystal two-dimensional layers and presents a foundation for applicable multifunctional devices based on stacked two-dimensional materials., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions 1-3 . Here we address these issues by analysing the genomes of 363 bird species 4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous-Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Insects have a pivotal role in ecosystem function, thus the decline of more than 75% in insect biomass in protected areas over recent decades in Central Europe 1 and elsewhere 2,3 has alarmed the public, pushed decision-makers 4 and stimulated research on insect population trends. However, the drivers of this decline are still not well understood. Here, we reanalysed 27 years of insect biomass data from Hallmann et al. 1 , using sample-specific information on weather conditions during sampling and weather anomalies during the insect life cycle. This model explained variation in temporal decline in insect biomass, including an observed increase in biomass in recent years, solely on the basis of these weather variables. Our finding that terrestrial insect biomass is largely driven by complex weather conditions challenges previous assumptions that climate change is more critical in the tropics 5,6 or that negative consequences in the temperate zone might only occur in the future 7 . Despite the recent observed increase in biomass, new combinations of unfavourable multi-annual weather conditions might be expected to further threaten insect populations under continuing climate change. Our findings also highlight the need for more climate change research on physiological mechanisms affected by annual weather conditions and anomalies., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain mediate recognition of strain-specific pathogen effectors, typically via their C-terminal ligand-sensing domains 1 . Effector binding enables TIR-encoded enzymatic activities that are required for TIR-NLR (TNL)-mediated immunity 2,3 . Many truncated TNL proteins lack effector-sensing domains but retain similar enzymatic and immune activities 4,5 . The mechanism underlying the activation of these TIR domain proteins remain unclear. Here we show that binding of the TIR substrates NAD + and ATP induces phase separation of TIR domain proteins in vitro. A similar condensation occurs with a TIR domain protein expressed via its native promoter in response to pathogen inoculation in planta. The formation of TIR condensates is mediated by conserved self-association interfaces and a predicted intrinsically disordered loop region of TIRs. Mutations that disrupt TIR condensates impair the cell death activity of TIR domain proteins. Our data reveal phase separation as a mechanism for the activation of TIR domain proteins and provide insight into substrate-induced autonomous activation of TIR signalling to confer plant immunity., (© 2024. The Author(s).)

White dwarfs are stellar remnants devoid of a nuclear energy source, gradually cooling over billions of years 1,2 and eventually freezing into a solid state from the inside out 3,4 . Recently, it was discovered that a population of freezing white dwarfs maintains a constant luminosity for a duration comparable with the age of the universe 5 , signalling the presence of a powerful, yet unknown, energy source that inhibits the cooling. For certain core compositions, the freezing process is predicted to trigger a solid-liquid distillation mechanism, owing to the solid phase being depleted in heavy impurities 6-8 . The crystals thus formed are buoyant and float up, thereby displacing heavier liquid downward and releasing gravitational energy. Here we show that distillation interrupts the cooling for billions of years and explains all the observational properties of the unusual delayed population. With a steady luminosity surpassing that of some main-sequence stars, these white dwarfs defy their conventional portrayal as dead stars. Our results highlight the existence of peculiar merger remnants 9,10 and have profound implications for the use of white dwarfs in dating stellar populations 11,12 ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The glymphatic movement of fluid through the brain removes metabolic waste 1-4 . Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease 5-8 . Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid., (© 2024. The Author(s).)

Trace amine-associated receptor 1 (TAAR1), the founding member of a nine-member family of trace amine receptors, is responsible for recognizing a range of biogenic amines in the brain, including the endogenous β-phenylethylamine (β-PEA) 1 as well as methamphetamine 2 , an abused substance that has posed a severe threat to human health and society 3 . Given its unique physiological role in the brain, TAAR1 is also an emerging target for a range of neurological disorders including schizophrenia, depression and drug addiction 2,4,5 . Here we report structures of human TAAR1-G-protein complexes bound to methamphetamine and β-PEA as well as complexes bound to RO5256390, a TAAR1-selective agonist, and SEP-363856, a clinical-stage dual agonist for TAAR1 and serotonin receptor 5-HT 1A R (refs. 6,7 ). Together with systematic mutagenesis and functional studies, the structures reveal the molecular basis of methamphetamine recognition and underlying mechanisms of ligand selectivity and polypharmacology between TAAR1 and other monoamine receptors. We identify a lid-like extracellular loop 2 helix/loop structure and a hydrogen-bonding network in the ligand-binding pockets, which may contribute to the ligand recognition in TAAR1. These findings shed light on the ligand recognition mode and activation mechanism for TAAR1 and should guide the development of next-generation therapeutics for drug addiction and various neurological disorders., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The capability to reach ultracold atomic temperatures in compact instruments has recently been extended into space 1,2 . Ultracold temperatures amplify quantum effects, whereas free fall allows further cooling and longer interactions time with gravity-the final force without a quantum description. On Earth, these devices have produced macroscopic quantum phenomena such as Bose-Einstein condensates (BECs), superfluidity, and strongly interacting quantum gases 3 . Terrestrial quantum sensors interfering the superposition of two ultracold atomic isotopes have tested the universality of free fall (UFF), a core tenet of Einstein's classical gravitational theory, at the 10 -12 level 4 . In space, cooling the elements needed to explore the rich physics of strong interactions or perform quantum tests of the UFF has remained elusive. Here, using upgraded hardware of the multiuser Cold Atom Lab (CAL) instrument aboard the International Space Station (ISS), we report, to our knowledge, the first simultaneous production of a dual-species BEC in space (formed from 87 Rb and 41 K), observation of interspecies interactions, as well as the production of 39 K ultracold gases. Operating a single laser at a 'magic wavelength' at which Rabi rates of simultaneously applied Bragg pulses are equal, we have further achieved the first spaceborne demonstration of simultaneous atom interferometry with two atomic species ( 87 Rb and 41 K). These results are an important step towards quantum tests of UFF in space and will allow scientists to investigate aspects of few-body physics, quantum chemistry and fundamental physics in new regimes without the perturbing asymmetry of gravity., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy 1,2 . Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance 2-4 . Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo CRISPR-Cas9 screen in a tumour mouse model and identified CD300ld as a top candidate of tumour-favouring receptors. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumour-bearing. CD300ld knockout inhibits the development of multiple tumour types in a PMN-MDSC-dependent manner. CD300ld is required for the recruitment of PMN-MDSCs into tumours and their function to suppress T cell activation. CD300ld acts via the STAT3-S100A8/A9 axis, and knockout of Cd300ld reverses the tumour immune-suppressive microenvironment. CD300ld is upregulated in human cancers and shows an unfavourable correlation with patient survival. Blocking CD300ld activity inhibits tumour development and has synergistic effects with anti-PD1. Our study identifies CD300ld as a critical immune suppressor present on PMN-MDSCs, being required for tumour immune resistance and providing a potential target for cancer immunotherapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Arrestins have pivotal roles in regulating G protein-coupled receptor (GPCR) signalling by desensitizing G protein activation and mediating receptor internalization 1,2 . It has been proposed that the arrestin binds to the receptor in two different conformations, 'tail' and 'core', which were suggested to govern distinct processes of receptor signalling and trafficking 3,4 . However, little structural information is available for the tail engagement of the arrestins. Here we report two structures of the glucagon receptor (GCGR) bound to β-arrestin 1 (βarr1) in glucagon-bound and ligand-free states. These structures reveal a receptor tail-engaged binding mode of βarr1 with many unique features, to our knowledge, not previously observed. Helix VIII, instead of the receptor core, has a major role in accommodating βarr1 by forming extensive interactions with the central crest of βarr1. The tail-binding pose is further defined by a close proximity between the βarr1 C-edge and the receptor helical bundle, and stabilized by a phosphoinositide derivative that bridges βarr1 with helices I and VIII of GCGR. Lacking any contact with the arrestin, the receptor core is in an inactive state and loosely binds to glucagon. Further functional studies suggest that the tail conformation of GCGR-βarr governs βarr recruitment at the plasma membrane and endocytosis of GCGR, and provides a molecular basis for the receptor forming a super-complex simultaneously with G protein and βarr to promote sustained signalling within endosomes. These findings extend our knowledge about the arrestin-mediated modulation of GPCR functionalities., (© 2023. The Author(s).)

Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function 1-8 . These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory., (© 2023. The Author(s).)

The black phase of formamidinium lead iodide (FAPbI 3 ) perovskite shows huge promise as an efficient photovoltaic, but it is not favoured energetically at room temperature, meaning that the undesirable yellow phases are always present alongside it during crystallization 1-4 . This problem has made it difficult to formulate the fast crystallization process of perovskite and develop guidelines governing the formation of black-phase FAPbI 3 (refs. 5,6 ). Here we use in situ monitoring of the perovskite crystallization process to report an oriented nucleation mechanism that can help to avoid the presence of undesirable phases and improve the performance of photovoltaic devices in different film-processing scenarios. The resulting device has a demonstrated power-conversion efficiency of 25.4% (certified 25.0%) and the module, which has an area of 27.83 cm 2 , has achieved an impressive certified aperture efficiency of 21.4%., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The outer membrane structure is common in Gram-negative bacteria, mitochondria and chloroplasts, and contains outer membrane β-barrel proteins (OMPs) that are essential interchange portals of materials 1-3 . All known OMPs share the antiparallel β-strand topology 4 , implicating a common evolutionary origin and conserved folding mechanism. Models have been proposed for bacterial β-barrel assembly machinery (BAM) to initiate OMP folding 5,6 ; however, mechanisms by which BAM proceeds to complete OMP assembly remain unclear. Here we report intermediate structures of BAM assembling an OMP substrate, EspP, demonstrating sequential conformational dynamics of BAM during the late stages of OMP assembly, which is further supported by molecular dynamics simulations. Mutagenic in vitro and in vivo assembly assays reveal functional residues of BamA and EspP for barrel hybridization, closure and release. Our work provides novel insights into the common mechanism of OMP assembly., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Galaxy mergers produce pairs of supermassive black holes (SMBHs), which may be witnessed as dual quasars if both SMBHs are rapidly accreting. The kiloparsec (kpc)-scale separation represents a physical regime sufficiently close for merger-induced effects to be important 1 yet wide enough to be directly resolvable with the facilities currently available. Whereas many kpc-scale, dual active galactic nuclei-the low-luminosity counterparts of quasars-have been observed in low-redshift mergers 2 , no unambiguous dual quasar is known at cosmic noon (z ≈ 2), the peak of global star formation and quasar activity 3,4 . Here we report multiwavelength observations of Sloan Digital Sky Survey (SDSS) J0749 + 2255 as a kpc-scale, dual-quasar system hosted by a galaxy merger at cosmic noon (z = 2.17). We discover extended host galaxies associated with the much brighter compact quasar nuclei (separated by 0.46″ or 3.8 kpc) and low-surface-brightness tidal features as evidence for galactic interactions. Unlike its low-redshift and low-luminosity counterparts, SDSS J0749 + 2255 is hosted by massive compact disk-dominated galaxies. The apparent lack of stellar bulges and the fact that SDSS J0749 + 2255 already follows the local SMBH mass-host stellar mass relation, suggest that at least some SMBHs may have formed before their host stellar bulges. While still at kpc-scale separations where the host-galaxy gravitational potential dominates, the two SMBHs may evolve into a gravitationally bound binary system in around 0.22 Gyr., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Repression of gene expression by protein complexes of the Polycomb group is a fundamental mechanism that governs embryonic development and cell-type specification 1-3 . The Polycomb repressive deubiquitinase (PR-DUB) complex removes the ubiquitin moiety from monoubiquitinated histone H2A K119 (H2AK119ub1) on the nucleosome 4 , counteracting the ubiquitin E3 ligase activity of Polycomb repressive complex 1 (PRC1) 5 to facilitate the correct silencing of genes by Polycomb proteins and safeguard active genes from inadvertent silencing by PRC1 (refs. 6-9 ). The intricate biological function of PR-DUB requires accurate targeting of H2AK119ub1, but PR-DUB can deubiquitinate monoubiquitinated free histones and peptide substrates indiscriminately; the basis for its exquisite nucleosome-dependent substrate specificity therefore remains unclear. Here we report the cryo-electron microscopy structure of human PR-DUB, composed of BAP1 and ASXL1, in complex with the chromatosome. We find that ASXL1 directs the binding of the positively charged C-terminal extension of BAP1 to nucleosomal DNA and histones H3-H4 near the dyad, an addition to its role in forming the ubiquitin-binding cleft. Furthermore, a conserved loop segment of the catalytic domain of BAP1 is situated near the H2A-H2B acidic patch. This distinct nucleosome-binding mode displaces the C-terminal tail of H2A from the nucleosome surface, and endows PR-DUB with the specificity for H2AK119ub1., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The newly discovered nickelate superconductors so far only exist in epitaxial thin films synthesized by a topotactic reaction with metal hydrides 1 . This method changes the nickelates from the perovskite to an infinite-layer structure by deintercalation of apical oxygens 1-3 . Such a chemical reaction may introduce hydrogen (H), influencing the physical properties of the end materials 4-9 . Unfortunately, H is insensitive to most characterization techniques and is difficult to detect because of its light weight. Here, in optimally Sr doped Nd 0.8 Sr 0.2 NiO 2 H epitaxial films, secondary-ion mass spectroscopy shows abundant H existing in the form of Nd 0.8 Sr 0.2 NiO 2 H x (x ≅ 0.2-0.5). Zero resistivity is found within a very narrow H-doping window of 0.22 ≤ x ≤ 0.28, showing unequivocally the critical role of H in superconductivity. Resonant inelastic X-ray scattering demonstrates the existence of itinerant interstitial s (IIS) orbitals originating from apical oxygen deintercalation. Density functional theory calculations show that electronegative H - occupies the apical oxygen sites annihilating IIS orbitals, reducing the IIS-Ni 3d orbital hybridization. This leads the electronic structure of H-doped Nd 0.8 Sr 0.2 NiO 2 H x to be more two-dimensional-like, which might be relevant for the observed superconductivity. We highlight that H is an important ingredient for superconductivity in epitaxial infinite-layer nickelates., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The nucleolus is the most prominent membraneless condensate in the nucleus. It comprises hundreds of proteins with distinct roles in the rapid transcription of ribosomal RNA (rRNA) and efficient processing within units comprising a fibrillar centre and a dense fibrillar component and ribosome assembly in a granular component 1 . The precise localization of most nucleolar proteins and whether their specific localization contributes to the radial flux of pre-rRNA processing have remained unknown owing to insufficient resolution in imaging studies 2-5 . Therefore, how these nucleolar proteins are functionally coordinated with stepwise pre-rRNA processing requires further investigation. Here we screened 200 candidate nucleolar proteins using high-resolution live-cell microscopy and identified 12 proteins that are enriched towards the periphery of the dense fibrillar component (PDFC). Among these proteins, unhealthy ribosome biogenesis 1 (URB1) is a static, nucleolar protein that ensures 3' end pre-rRNA anchoring and folding for U8 small nucleolar RNA recognition and the subsequent removal of the 3' external transcribed spacer (ETS) at the dense fibrillar component-PDFC boundary. URB1 depletion leads to a disrupted PDFC, uncontrolled pre-rRNA movement, altered pre-rRNA conformation and retention of the 3' ETS. These aberrant 3' ETS-attached pre-rRNA intermediates activate exosome-dependent nucleolar surveillance, resulting in decreased 28S rRNA production, head malformations in zebrafish and delayed embryonic development in mice. This study provides insight into functional sub-nucleolar organization and identifies a physiologically essential step in rRNA maturation that requires the static protein URB1 in the phase-separated nucleolus., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Phytoplankton blooms in coastal oceans can be beneficial to coastal fisheries production and ecosystem function, but can also cause major environmental problems 1,2 -yet detailed characterizations of bloom incidence and distribution are not available worldwide. Here we map daily marine coastal algal blooms between 2003 and 2020 using global satellite observations at 1-km spatial resolution. We found that algal blooms occurred in 126 out of the 153 coastal countries examined. Globally, the spatial extent (+13.2%) and frequency (+59.2%) of blooms increased significantly (P < 0.05) over the study period, whereas blooms weakened in tropical and subtropical areas of the Northern Hemisphere. We documented the relationship between the bloom trends and ocean circulation, and identified the stimulatory effects of recent increases in sea surface temperature. Our compilation of daily mapped coastal phytoplankton blooms provides the basis for global assessments of bloom risks and benefits, and for the formulation or evaluation of management or policy actions., (© 2023. The Author(s).)

The discovery of a method to separate isotopologues, molecular entities that differ in only isotopic composition 1 , is fundamentally and technologically essential but remains challenging 2,3 . Water isotopologues, which are very important in biological processes, industry, medical care, etc. are among the most difficult isotopologue pairs to separate because of their very similar physicochemical properties and chemical exchange equilibrium. Herein, we report efficient separation of water isotopologues at room temperature by constructing two porous coordination polymers (PCPs, or metal-organic frameworks) in which flip-flop molecular motions within the frameworks provide diffusion-regulatory functionality. Guest traffic is regulated by the local motions of dynamic gates on contracted pore apertures, thereby amplifying the slight differences in the diffusion rates of water isotopologues. Significant temperature-responsive adsorption occurs on both PCPs: H 2 O vapour is preferentially adsorbed into the PCPs, with substantially increased uptake compared to that of D 2 O vapour, facilitating kinetics-based vapour separation of H 2 O/HDO/D 2 O ternary mixtures with high H 2 O separation factors of around 210 at room temperature., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes 1 . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel 2 ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries., (© 2022. The Author(s).)

Advancing the spontaneous bottom-up construction of artificial cells with high organizational complexity and diverse functionality remains an unresolved issue at the interface between living and non-living matter 1-4 . Here, to address this challenge, we developed a living material assembly process based on the capture and on-site processing of spatially segregated bacterial colonies within individual coacervate microdroplets for the endogenous construction of membrane-bounded, molecularly crowded, and compositionally, structurally and morphologically complex synthetic cells. The bacteriogenic protocells inherit diverse biological components, exhibit multifunctional cytomimetic properties and can be endogenously remodelled to include a spatially partitioned DNA-histone nucleus-like condensate, membranized water vacuoles and a three-dimensional network of F-actin proto-cytoskeletal filaments. The ensemble is biochemically energized by ATP production derived from implanted live Escherichia coli cells to produce a cellular bionic system with amoeba-like external morphology and integrated life-like properties. Our results demonstrate a bacteriogenic strategy for the bottom-up construction of functional protoliving microdevices and provide opportunities for the fabrication of new synthetic cell modules and augmented living/synthetic cell constructs with potential applications in engineered synthetic biology and biotechnology., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Missense driver mutations in cancer are concentrated in a few hotspots 1 . Various mechanisms have been proposed to explain this skew, including biased mutational processes 2 , phenotypic differences 3-6 and immunoediting of neoantigens 7,8 ; however, to our knowledge, no existing model weighs the relative contribution of these features to tumour evolution. We propose a unified theoretical 'free fitness' framework that parsimoniously integrates multimodal genomic, epigenetic, transcriptomic and proteomic data into a biophysical model of the rate-limiting processes underlying the fitness advantage conferred on cancer cells by driver gene mutations. Focusing on TP53, the most mutated gene in cancer 1 , we present an inference of mutant p53 concentration and demonstrate that TP53 hotspot mutations optimally solve an evolutionary trade-off between oncogenic potential and neoantigen immunogenicity. Our model anticipates patient survival in The Cancer Genome Atlas and patients with lung cancer treated with immunotherapy as well as the age of tumour onset in germline carriers of TP53 variants. The predicted differential immunogenicity between hotspot mutations was validated experimentally in patients with cancer and in a unique large dataset of healthy individuals. Our data indicate that immune selective pressure on TP53 mutations has a smaller role in non-cancerous lesions than in tumours, suggesting that targeted immunotherapy may offer an early prophylactic opportunity for the former. Determining the relative contribution of immunogenicity and oncogenic function to the selective advantage of hotspot mutations thus has important implications for both precision immunotherapies and our understanding of tumour evolution., (© 2022. The Author(s).)

Optoelectronic devices consist of heterointerfaces formed between dissimilar semiconducting materials. The relative energy-level alignment between contacting semiconductors determinately affects the heterointerface charge injection and extraction dynamics. For perovskite solar cells (PSCs), the heterointerface between the top perovskite surface and a charge-transporting material is often treated for defect passivation 1-4 to improve the PSC stability and performance. However, such surface treatments can also affect the heterointerface energetics 1 . Here we show that surface treatments may induce a negative work function shift (that is, more n-type), which activates halide migration to aggravate PSC instability. Therefore, despite the beneficial effects of surface passivation, this detrimental side effect limits the maximum stability improvement attainable for PSCs treated in this way. This trade-off between the beneficial and detrimental effects should guide further work on improving PSC stability via surface treatments., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Moiré superlattices have led to observations of exotic emergent electronic properties such as superconductivity and strong correlated states in small-rotation-angle twisted bilayer graphene (tBLG) 1,2 . Recently, these findings have inspired the search for new properties in moiré plasmons. Although plasmon propagation in the tBLG basal plane has been studied by near-field nano-imaging techniques 3-7 , the general electromagnetic character and properties of these plasmons remain elusive. Here we report the direct observation of two new plasmon modes in macroscopic tBLG with a highly ordered moiré superlattice. Using spiral structured nanoribbons of tBLG, we identify signatures of chiral plasmons that arise owing to the uncompensated Berry flux of the electron gas under optical pumping. The salient features of these chiral plasmons are shown through their dependence on optical pumping intensity and electron fillings, in conjunction with distinct resonance splitting and Faraday rotation coinciding with the spectral window of maximal Berry flux. Moreover, we also identify a slow plasmonic mode around 0.4 electronvolts, which stems from the interband transitions between the nested subbands in lattice-relaxed AB-stacked domains. This mode may open up opportunities for strong light-matter interactions within the highly sought after mid-wave infrared spectral window 8 . Our results unveil the new electromagnetic dynamics of small-angle tBLG and exemplify it as a unique quantum optical platform., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis 1-7 . An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs 8,9 , but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk-transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs., (© 2022. The Author(s).)

The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various industrial applications, from actuators and medical devices to high-precision instruments 1,2 . The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys 3 -including gum metals 4,5 and strain glass alloys 6,7 -may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation 3 . Recently, chemically complex alloys, such as 'high-entropy' alloys 8 , have attracted tremendous research interest owing to their promising properties 9-15 . In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10 -4 ) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The methanogenic degradation of oil hydrocarbons can proceed through syntrophic partnerships of hydrocarbon-degrading bacteria and methanogenic archaea 1-3 . However, recent culture-independent studies have suggested that the archaeon 'Candidatus Methanoliparum' alone can combine the degradation of long-chain alkanes with methanogenesis 4,5 . Here we cultured Ca. Methanoliparum from a subsurface oil reservoir. Molecular analyses revealed that Ca. Methanoliparum contains and overexpresses genes encoding alkyl-coenzyme M reductases and methyl-coenzyme M reductases, the marker genes for archaeal multicarbon alkane and methane metabolism. Incubation experiments with different substrates and mass spectrometric detection of coenzyme-M-bound intermediates confirm that Ca. Methanoliparum thrives not only on a variety of long-chain alkanes, but also on n-alkylcyclohexanes and n-alkylbenzenes with long n-alkyl (C ≥13 ) moieties. By contrast, short-chain alkanes (such as ethane to octane) or aromatics with short alkyl chains (C ≤12 ) were not consumed. The wide distribution of Ca. Methanoliparum 4-6 in oil-rich environments indicates that this alkylotrophic methanogen may have a crucial role in the transformation of hydrocarbons into methane., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted 1 . Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture., (© 2021. The Author(s).)

Exotic phenomena can be achieved in quantum materials by confining electronic states into two dimensions. For example, relativistic fermions are realized in a single layer of carbon atoms 1 , the quantized Hall effect can result from two-dimensional (2D) systems 2,3 , and the superconducting transition temperature can be considerably increased in a one-atomic-layer material 4,5 . Ordinarily, a 2D electronic system can be obtained by exfoliating the layered materials, growing monolayer materials on substrates, or establishing interfaces between different materials. Here we use femtosecond infrared laser pulses to invert the periodic lattice distortion sectionally in a three-dimensional (3D) charge density wave material (1T-TiSe 2 ), creating macroscopic domain walls of transient 2D ordered electronic states with unusual properties. The corresponding ultrafast electronic and lattice dynamics are captured by time-resolved and angle-resolved photoemission spectroscopy 6 and ultrafast electron diffraction at energies of the order of megaelectronvolts 7 . Moreover, in the photoinduced 2D domain wall near the surface we identify a phase with enhanced density of states and signatures of potential opening of an energy gap near the Fermi energy. Such optical modulation of atomic motion is an alternative path towards realizing 2D electronic states and will be a useful platform upon which novel phases in quantum materials may be discovered.

The cation channel of sperm (CatSper) is essential for sperm motility and fertility 1,2 . CatSper comprises the pore-forming proteins CATSPER1-4 and multiple auxiliary subunits, including CATSPERβ, γ, δ, ε, ζ, and EFCAB9 1,3-9 . Here we report the cryo-electron microscopy (cryo-EM) structure of the CatSper complex isolated from mouse sperm. In the extracellular view, CATSPER1-4 conform to the conventional domain-swapped voltage-gated ion channel fold 10 , following a counterclockwise arrangement. The auxiliary subunits CATSPERβ, γ, δ and ε-each of which contains a single transmembrane segment and a large extracellular domain-constitute a pavilion-like structure that stabilizes the entire complex through interactions with CATSPER4, 1, 3 and 2, respectively. Our EM map reveals several previously uncharacterized components, exemplified by the organic anion transporter SLCO6C1. We name this channel-transporter ultracomplex the CatSpermasome. The assembly and organization details of the CatSpermasome presented here lay the foundation for the development of CatSpermasome-related treatments for male infertility and non-hormonal contraceptives., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

When the Coulomb repulsion between electrons dominates over their kinetic energy, electrons in two-dimensional systems are predicted to spontaneously break continuous-translation symmetry and form a quantum crystal 1 . Efforts to observe 2-12 this elusive state of matter, termed a Wigner crystal, in two-dimensional extended systems have primarily focused on conductivity measurements on electrons confined to a single Landau level at high magnetic fields. Here we use optical spectroscopy to demonstrate that electrons in a monolayer semiconductor with density lower than 3 × 10 11  per centimetre squared form a Wigner crystal. The combination of a high electron effective mass and reduced dielectric screening enables us to observe electronic charge order even in the absence of a moiré potential or an external magnetic field. The interactions between a resonantly injected exciton and electrons arranged in a periodic lattice modify the exciton bandstructure so that an umklapp resonance arises in the optical reflection spectrum, heralding the presence of charge order 13 . Our findings demonstrate that charge-tunable transition metal dichalcogenide monolayers 14 enable the investigation of previously uncharted territory for many-body physics where interaction energy dominates over kinetic energy.