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Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.

All-optical diffractive neural networks, as analog artificial intelligence accelerators, leverage parallelism and analog computation for complex data processing. However, their low space transmission efficiency or large spatial dimensions hinder miniaturization and broader application. Here, we propose a terahertz spoof plasmonic neural network on a planar diffractive platform for direct multi-target recognition. Our approach employs a spoof surface plasmon polariton coupler array to construct a diffractive network layer, resulting in a compact, efficient, and easily integrable architecture. We designed three schemes: basis vector classification, multi-user recognition, and MNIST handwritten digit classification. Experimental results reveal that the terahertz spoof plasmonic neural network successfully classifies basis vectors, recognizes multi-user orientation information, and directly processes handwritten digits using a designed input framework comprising a metal grating array, transmitters, and receivers. This work broadens the application of terahertz plasmonic metamaterials, paving the way for terahertz on-chip integration, intelligent communication, and advanced computing systems., (© 2024. The Author(s).)

Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases., (© 2024. The Author(s).)

As the most abundant organic substances in nature, carbohydrates are essential for life. Understanding how carbohydrates regulate proteins in the physiological and pathological processes presents opportunities to address crucial biological problems and develop new therapeutics. However, the diversity and complexity of carbohydrates pose a challenge in experimentally identifying the sites where carbohydrates bind to and act on proteins. Here, we introduce a deep learning model, DeepGlycanSite, capable of accurately predicting carbohydrate-binding sites on a given protein structure. Incorporating geometric and evolutionary features of proteins into a deep equivariant graph neural network with the transformer architecture, DeepGlycanSite remarkably outperforms previous state-of-the-art methods and effectively predicts binding sites for diverse carbohydrates. Integrating with a mutagenesis study, DeepGlycanSite reveals the guanosine-5'-diphosphate-sugar-recognition site of an important G-protein coupled receptor. These findings demonstrate DeepGlycanSite is invaluable for carbohydrate-binding site prediction and could provide insights into molecular mechanisms underlying carbohydrate-regulation of therapeutically important proteins., (© 2024. The Author(s).)

The viral polymerase complex, comprising the large protein (L) and phosphoprotein (P), is crucial for both genome replication and transcription in non-segmented negative-strand RNA viruses (nsNSVs), while structures corresponding to these activities remain obscure. Here, we resolved two L-P complex conformations from the mumps virus (MuV), a typical member of nsNSVs, via cryogenic-electron microscopy. One conformation presents all five domains of L forming a continuous RNA tunnel to the methyltransferase domain (MTase), preferably as a transcription state. The other conformation has the appendage averaged out, which is inaccessible to MTase. In both conformations, parallel P tetramers are revealed around MuV L, which, together with structures of other nsNSVs, demonstrates the diverse origins of the L-binding X domain of P. Our study links varying structures of nsNSV polymerase complexes with genome replication and transcription and points to a sliding model for polymerase complexes to advance along the RNA templates., (© 2024. The Author(s).)

The electrochemical synthesis of propylene oxide is far from practical application due to the limited performance (including activity, stability, and selectivity). In this work, we spatially decouple the bromide-mediated process to avoid direct contact between the anode and propylene, where bromine is generated at the anode and then transferred into an independent reactor to react with propylene. This strategy effectively prevents the side reactions and eliminates the interference to stability caused by massive alkene input and vigorously stirred electrolytes. As expected, the selectivity for propylene oxide reaches above 99.9% with a remarkable Faradaic efficiency of 91% and stability of 750-h (>30 days). When the electrode area is scaled up to 25 cm 2 , 262 g of pure propylene oxide is obtained after 50-h continuous electrolysis at 6.25 A. These findings demonstrate that the electrochemical bromohydrin route represents a viable alternative for the manufacture of epoxides., (© 2024. The Author(s).)

The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction. A pod-shaped vest-pocket analysis device achieves the whole process for reaction execution, signal acquisition, and result interpretation. SCOPE can detect as low as 0.5 copies/µL (2.5 copies/reaction) of MPXV within 15 min from the sample input to the answer. We validate the developed assay on 102 clinical samples from male patients / volunteers, and the testing results are 100% concordant with the real-time PCR. SCOPE achieves a single-molecular level sensitivity in minutes with a simplified procedure performed on a miniaturized wireless device, which is expected to spur substantial progress to enable the practice application of CRISPR-based diagnostics techniques in a point-of-care setting., (© 2024. The Author(s).)

Class I KNOTTED-like homeobox (KNOXI) genes are parts of the regulatory network that control the evolutionary diversification of leaf morphology. Their specific spatiotemporal expression patterns in developing leaves correlate with the degrees of leaf complexity between simple-leafed and compound-leafed species. However, KNOXI genes are not involved in compound leaf formation in several legume species. Here, we identify a pathway for dual repression of MtKNOXI function in Medicago truncatula. PINNATE-LIKE PENTAFOLIATA1 (PINNA1) represses the expression of MtKNOXI, while PINNA1 interacts with MtKNOXI and sequesters it to the cytoplasm. Further investigations reveal that UNUSUAL FLORAL ORGANS (MtUFO) is the direct target of MtKNOXI, and mediates the transition from trifoliate to pinnate-like pentafoliate leaves. These data suggest a new layer of regulation for morphological diversity in compound-leafed species, in which the conserved regulators of floral development, MtUFO, and leaf development, MtKNOXI, are involved in variation of pinnate-like compound leaves in M. truncatula., (© 2024. The Author(s).)

RORγt + group 3 innate lymphoid cells (ILC3s) are essential for intestinal homeostasis. Dysregulation of ILC3s has been found in the gut of patients with inflammatory bowel disease and colorectal cancer, yet the specific mechanisms still require more investigation. Here we observe increased β-catenin in intestinal ILC3s from inflammatory bowel disease and colon cancer patients compared with healthy donors. In contrast to promoting RORγt expression in T cells, activation of Wnt/β-catenin signaling in ILC3s suppresses RORγt expression, inhibits its proliferation and function, and leads to a deficiency of ILC3s and subsequent intestinal inflammation in mice. Activated β-catenin and its interacting transcription factor, TCF-1, cannot directly suppress RORγt expression, but rather alters global chromatin accessibility and inhibits JunB expression, which is essential for RORγt expression in ILC3s. Together, our findings suggest that dysregulated Wnt/β-catenin signaling impairs intestinal ILC3s through TCF-1/JunB/RORγt regulation, further disrupting intestinal homeostasis, and promoting inflammation and cancer., (© 2024. The Author(s).)

Plasma membrane lysis is an effective anticancer strategy, which mostly relying on soluble molecular membranolytic agents. However, nanomaterial-based membranolytic agents has been largely unexplored. Herein, we introduce a mesoporous membranolytic nanoperforators (MLNPs) via a nano- and molecular-scale multi-patterning strategy, featuring a spiky surface topography (nanoscale patterning) and molecular-level periodicity in the spikes with a benzene-bridged organosilica composition (molecular-scale patterning), which cooperatively endow an intrinsic membranolytic activity. Computational modelling reveals a nanospike-mediated multivalent perforation behaviour, i.e., multiple spikes induce nonlinearly enlarged membrane pores compared to a single spike, and that benzene groups aligned parallelly to a phospholipid molecule show considerably higher binding energy than other alignments, underpinning the importance of molecular ordering in phospholipid extraction for membranolysis. Finally, the antitumour activity of MLNPs is demonstrated in female Balb/c mouse models. This work demonstrates assembly of organosilica based bioactive nanostructures, enabling new understandings on nano-/molecular patterns co-governed nano-bio interaction., (© 2024. The Author(s).)

Plant lateral organs are often elaborated through repetitive formation of developmental units, which progress robustly in predetermined patterns along their axes. Leaflets in compound leaves provide an example of such units that are generated sequentially along the longitudinal axis, in species-specific patterns. In this context, we explored the molecular mechanisms underlying an acropetal mode of leaflet initiation in chickpea pinnate compound leaf patterning. By analyzing naturally occurring mutants multi-pinnate leaf1 (mpl1) that develop higher-ordered pinnate leaves with more than forty leaflets, we show that MPL1 encoding a C2H2-zinc finger protein sculpts a morphogenetic gradient along the proximodistal axis of the early leaf primordium, thereby conferring the acropetal leaflet formation. This is achieved by defining the spatiotemporal expression pattern of CaLEAFY, a key regulator of leaflet initiation, and also perhaps by modulating the auxin signaling pathway. Our work provides novel molecular insights into the sequential progression of leaflet formation., (© 2023. The Author(s).)

Nanorobotic motion on solid substrates is greatly hindered by strong nanofriction, and powerful nanomotors‒the core components for nanorobotic motion‒are still lacking. Optical actuation addresses power and motion control issues simultaneously, while conventional technologies with small thrust usually apply to fluid environments. Here, we demonstrate micronewton-thrust nanomotors that enable the autonomous nanorobots working like conventional robots with precise motion control on dry surfaces by a photothermal-shock technique. We build a pulsed laser-based actuation and trapping platform, termed photothermal-shock tweezers, for general motion control of metallic nanomaterials and assembled nanorobots with nanoscale precision. The thrust-to-weight ratios up to 10 7 enable nanomotors output forces to interact with external micro/nano-objects. Leveraging machine vision and deep learning technologies, we assemble the nanomotors into autonomous nanorobots with complex structures, and demonstrate multi-degree-of-freedom motion and sophisticated functions. Our photothermal shock-actuation concept fundamentally addresses the nanotribology challenges and expands the nanorobotic horizon from fluids to dry solid surfaces., (© 2023. The Author(s).)

Current techniques for visualizing and quantifying cellular forces have limitations in live cell imaging, throughput, and multi-scale analysis, which impede progress in cell force research and its practical applications. We developed a photonic crystal cellular force microscopy (PCCFM) to image vertical cell forces over a wide field of view (1.3 mm ⨯ 1.0 mm, a 10 ⨯ objective image) at high speed (about 20 frames per second) without references. The photonic crystal hydrogel substrate (PCS) converts micro-nano deformations into perceivable color changes, enabling in situ visualization and quantification of tiny vertical cell forces with high throughput. It enabled long-term, cross-scale monitoring from subcellular focal adhesions to tissue-level cell sheets and aggregates., (© 2023. The Author(s).)

Immune checkpoints play key roles in maintaining self-tolerance. Targeted potentiation of the checkpoint molecule PD-L1 through in situ manipulation offers clinical promise for patients with autoimmune diseases. However, the therapeutic effects of these approaches are often compromised by limited specificity and inadequate expression. Here, we report a two-step dual-anchor coupling strategy for enhanced immobilization of PD-L1 on target endogenous cells by integrating bioorthogonal chemistry and physical insertion of the cell membrane. In both type 1 diabetes and rheumatoid arthritis mouse models, we demonstrate that this approach leads to elevated and sustained conjugation of PD-L1 on target cells, resulting in significant suppression of autoreactive immune cell activation, recruitment of regulatory T cells, and systematic reshaping of the immune environment. Furthermore, it restores glucose homeostasis in type 1 diabetic mice for over 100 days. This specific in situ bioengineering approach potentiates the functions of PD-L1 and represents its translational potential., (© 2023. The Author(s).)

Electrocatalytic oxidation offers opportunities for sustainable environmental remediation, but it is often hampered by the slow mass transfer and short lives of electro-generated radicals. Here, we achieve a four times higher kinetic constant (18.9 min -1 ) for the oxidation of 4-chlorophenol on the reactive electrochemical membrane by reducing the pore size from 105 to 7 μm, with the predominate mechanism shifting from hydroxyl radical oxidation to direct electron transfer. More interestingly, such an enhancement effect is largely dependent on the molecular structure and its sensitivity to the direct electron transfer process. The spatial distributions of reactant and hydroxyl radicals are visualized via multiphysics simulation, revealing the compressed diffusion layer and restricted hydroxyl radical generation in the microchannels. This study demonstrates that both the reaction kinetics and the electron transfer pathway can be effectively regulated by the spatial confinement effect, which sheds light on the design of cost-effective electrochemical platforms for water purification and chemical synthesis., (© 2023. Springer Nature Limited.)

Hydrogen spillover is the migration of activated hydrogen atoms from a metal particle onto the surface of catalyst support, which has made significant progress in heterogeneous catalysis. The phenomenon has been well researched on oxide supports, yet its occurrence, detection method and mechanism on non-oxide supports such as metal-organic frameworks (MOFs) remain controversial. Herein, we develop a facile strategy for efficiency enhancement of hydrogen spillover on various MOFs with the aid of water molecules. By encapsulating platinum (Pt) nanoparticles in MOF-801 for activating hydrogen and hydrogenation of C=C in the MOF ligand as activated hydrogen detector, a research platform is built with Pt@MOF-801 to measure the hydrogenation region for quantifying the efficiency and spatial extent of hydrogen spillover. A water-assisted hydrogen spillover path is found with lower migration energy barrier than the traditional spillover path via ligand. The synergy of the two paths explains a significant boost of hydrogen spillover in MOF-801 from imperceptible existence to spanning at least 100-nm-diameter region. Moreover, such strategy shows universality in different MOF and covalent organic framework materials for efficiency promotion of hydrogen spillover and improvement of catalytic activity and antitoxicity, opening up new horizons for catalyst design in porous crystalline materials., (© 2023. Springer Nature Limited.)

Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors., (© 2023. Springer Nature Limited.)

Chemotherapy remains as the first-choice treatment option for triple-negative breast cancer (TNBC). However, the limited tumor penetration and low cellular internalization efficiency of current nanocarrier-based systems impede the access of anticancer drugs to TNBC with dense stroma and thereby greatly restricts clinical therapeutic efficacy, especially for TNBC bone metastasis. In this work, biomimetic head/hollow tail nanorobots were designed through a site-selective superassembly strategy. We show that nanorobots enable efficient remodeling of the dense tumor stromal microenvironments (TSM) for deep tumor penetration. Furthermore, the self-movement ability and spiky head markedly promote interfacial cellular uptake efficacy, transvascular extravasation, and intratumoral penetration. These nanorobots, which integrate deep tumor penetration, active cellular internalization, near-infrared (NIR) light-responsive release, and photothermal therapy capacities into a single nanodevice efficiently suppress tumor growth in a bone metastasis female mouse model of TNBC and also demonstrate potent antitumor efficacy in three different subcutaneous tumor models., (© 2023. The Author(s).)

To enable the development of all-solid-state batteries, an inorganic solid-state electrolyte should demonstrate high ionic conductivity (i.e., > 1 mS cm -1 at 25 °C), compressibility (e.g., > 90% density under 250-350 MPa), and cost-effectiveness (e.g., < $50/kg). Here we report the development and preparation of Li 1.75 ZrCl 4.75 O 0.5 oxychloride solid-state electrolyte that demonstrates an ionic conductivity of 2.42 mS cm -1 at 25 °C, a compressibility enabling 94.2% density under 300 MPa and an estimated raw materials cost of $11.60/kg. As proof of concept, the Li 1.75 ZrCl 4.75 O 0.5 is tested in combination with a LiNi 0.8 Mn 0.1 Co 0.1 O 2 -based positive electrode and a Li 6 PS 5 Cl-coated Li-In negative electrode in lab-scale cell configuration. This all-solid-state cell delivers a discharge capacity retention of 70.34% (final discharge capacity of 70.2 mAh g -1 ) after 2082 cycles at 1 A g -1 , 25 °C and 1.5 tons of stacking pressure., (© 2023. The Author(s).)

Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Herein, a core-shell structured microneedle array patch with programmed functions (PF-MNs) is designed to dynamically modulate the wound immune microenvironment according to the varied healing phases. Specifically, PF-MNs combat multidrug-resistant bacterial biofilm at the early stage via generating reactive oxygen species (ROS) under laser irradiation. Subsequently, the ROS-sensitive MN shell gradually degrades to expose the MN core component, which neutralizes various inflammatory factors and promotes the phase transition from inflammation to proliferation. In addition, the released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. Our experiments demonstrate that PF-MNs promote scarless wound repair in mouse models of both acute and chronic wounds, and inhibit the formation of hypertrophic scar in rabbit ear models., (© 2023. The Author(s).)

Boron neutron capture therapy (BNCT) was clinically approved in 2020 and exhibits remarkable tumour rejection in preclinical and clinical studies. It is binary radiotherapy that may selectively deposit two deadly high-energy particles ( 4 He and 7 Li) within a cancer cell. As a radiotherapy induced by localized nuclear reaction, few studies have reported its abscopal anti-tumour effect, which has limited its further clinical applications. Here, we engineer a neutron-activated boron capsule that synergizes BNCT and controlled immune adjuvants release to provoke a potent anti-tumour immune response. This study demonstrates that boron neutron capture nuclear reaction forms considerable defects in boron capsule that augments the drug release. The following single-cell sequencing unveils the fact and mechanism that BNCT heats anti-tumour immunity. In female mice tumour models, BNCT and the controlled drug release triggered by localized nuclear reaction causes nearly complete regression of both primary and distant tumour grafts., (© 2023. The Author(s).)

Space-charge layers are frequently believed responsible for the large resistance of different interfaces in all-solid-state Li batteries. However, such propositions are based on the presumed existence of a Li-deficient space-charge layer with insufficient charge carriers, instead of a comprehensive investigation on the atomic configuration and its ion transport behavior. Consequently, the real influence of space-charge layers remains elusive. Here, we clarify the role of space-charge layers in Li 0.33 La 0.56 TiO 3 , a prototype solid electrolyte with large grain-boundary resistance, through a combined experimental and computational study at the atomic scale. In contrast to previous speculations, we do not observe the Li-deficient space-charge layers commonly believed to result in large resistance. Instead, the actual space-charge layers are Li-excess; accommodating the additional Li + at the 3c interstitials, such space-charge layers allow for rather efficient ion transport. With the space-charge layers excluded from the potential bottlenecks, we identify the Li-depleted grain-boundary cores as the major cause for the large grain-boundary resistance in Li 0.33 La 0.56 TiO 3 ., (© 2023. The Author(s).)

The development of energy-dense all-solid-state Li-based batteries requires positive electrode active materials that are ionic conductive and compressible at room temperature. Indeed, these material properties could contribute to a sensible reduction of the amount of the solid-state electrolyte in the composite electrode, thus, enabling higher mass loading of active materials. Here, we propose the synthesis and use of lithium titanium chloride (Li 3 TiCl 6 ) as room-temperature ionic conductive (i.e., 1.04 mS cm -1 at 25 °C) and compressible active materials for all-solid-state Li-based batteries. When a composite positive electrode comprising 95 wt.% of Li 3 TiCl 6 is tested in combination with a Li-In alloy negative electrode and Li 6 PS 5 Cl/Li 2 ZrCl 6 solid-state electrolytes, an initial discharge capacity of about 90 mAh g -1 and an average cell discharge voltage of about 2.53 V are obtained. Furthermore, a capacity retention of more than 62% is attainable after 2500 cycles at 92.5 mA g -1 and 25 °C with an applied external pressure of 1.5 tons. We also report the assembly and testing of a "single Li 3 TiCl 6 " cell where this chloride material is used as the solid electrolyte, negative electrode and positive electrode., (© 2023. The Author(s).)

Base editors, including dual base editors, are innovative techniques for efficient base conversions in genomic DNA. However, the low efficiency of A-to-G base conversion at positions proximal to the protospacer adjacent motif (PAM) and the A/C simultaneous conversion of the dual base editor hinder their broad applications. In this study, through fusion of ABE8e with Rad51 DNA-binding domain, we generate a hyperactive ABE (hyABE) which offers improved A-to-G editing efficiency at the region (A 10 -A 15 ) proximal to the PAM, with 1.2- to 7-fold improvement compared to ABE8e. Similarly, we develop optimized dual base editors (eA&C-BEmax and hyA&C-BEmax) with markedly improved simultaneous A/C conversion efficiency (1.2-fold and 1.5-fold improvement, respectively) compared to A&C-BEmax in human cells. Moreover, these optimized base editors catalyze efficiently nucleotide conversions in zebrafish embryos to mirror human syndrome or in human cells to potentially treat genetic diseases, indicating their great potential in broad applications for disease modeling and gene therapy., (© 2023. The Author(s).)

The discovery of non-Hermitian skin effect (NHSE) has opened an exciting direction for unveiling unusual physics and phenomena in non-Hermitian system. Despite notable theoretical breakthroughs, actual observation of NHSE's whole evolvement, however, relies mainly on gain medium to provide amplified mode. It typically impedes the development of simple, robust system. Here, we show that a passive system is fully capable of supporting the observation of the complete evolution picture of NHSE, without the need of any gain medium. With a simple lattice model and acoustic ring resonators, we use complex-frequency excitation to create virtual gain effect, and experimentally demonstrate that exact NHSE can persist in a totally passive system during a quasi-stationary stage. This results in the transient NHSE: passive construction of NHSE in a short time window. Despite the general energy decay, the localization character of skin modes can still be clearly witnessed and successfully exploited. Our findings unveil the importance of excitation in realizing NHSE and paves the way towards studying the peculiar features of non-Hermitian physics with diverse passive platforms., (© 2022. The Author(s).)

The Qinghai-Tibet Plateau (QTP), possesses a climate as cold as that of the Arctic, and also presents uniquely low oxygen concentrations and intense ultraviolet (UV) radiation. QTP animals have adapted to these extreme conditions, but whether they obtained genetic variations from the Arctic during cold adaptation, and how genomic mutations in non-coding regions regulate gene expression under hypoxia and intense UV environment, remain largely unknown. Here, we assemble a high-quality saker falcon genome and resequence populations across Eurasia. We identify female-biased hybridization with Arctic gyrfalcons in the last glacial maximum, that endowed eastern sakers with alleles conveying larger body size and changes in fat metabolism, predisposing their QTP cold adaptation. We discover that QTP hypoxia and UV adaptations mainly involve independent changes in non-coding genomic variants. Our study highlights key roles of gene flow from Arctic relatives during QTP hypothermia adaptation, and cis-regulatory elements during hypoxic response and UV protection., (© 2022. The Author(s).)

Nontrivial band topologies have been discovered in classical systems and hold great potential for device applications. Unlike photons, sound has fundamentally different dynamics and symmetries in fluids and solids, represented as scalar and vector fields, respectively. So far, searches for topological phononic materials have only concerned sound in either fluids or solids alone, overlooking their intricate interactions in "mixtures". Here, we report an approach for topological phononics employing such unique interplay, and demonstrate the realization of type-II nodal rings, elusive in phononics, in a simple three-dimensional phononic crystal. Type-II nodal rings, as line degeneracies in momentum space with exotic properties from strong tilting, are directly observed through ultrasonic near-field scanning. Strongly tilted drumhead surface states, the hallmark phenomena, are also experimentally demonstrated. This phononic approach opens a door to explore topological physics in classical systems, which is easy to implement that can be used for designing high-performance acoustic devices., (© 2022. The Author(s).)

Recent realizations of ultrathin freestanding perovskite oxides offer a unique platform to probe novel properties in two-dimensional oxides. Here, we observe a giant flexoelectric response in freestanding BiFeO 3 and SrTiO 3 in their bent state arising from strain gradients up to 3.5 × 10 7  m -1 , suggesting a promising approach for realizing ultra-large polarizations. Additionally, a substantial change in membrane thickness is discovered in bent freestanding BiFeO 3 , which implies an unusual bending-expansion/shrinkage effect in the ferroelectric membrane that has never been seen before in crystalline materials. Our theoretical model reveals that this unprecedented flexural deformation within the membrane is attributable to a flexoelectricity-piezoelectricity interplay. The finding unveils intriguing nanoscale electromechanical properties and provides guidance for their practical applications in flexible nanoelectromechanical systems., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The orderly arrangement of nanomaterials' tiny units at the nanometer-scale accounts for a substantial part of their remarkable properties. Maintaining this orderness and meanwhile endowing the nanomaterials with highly precise and free-designed 3D micro architectures will open an exciting prospect for various novel applications. In this paper, we developed a sacrificial-scaffold-mediated two-photon lithography (TPL) strategy that enables the fabrication of complex 3D colloidal crystal microstructures with orderly-arranged nanoparticles inside. We show that, with the help of a degradable hydrogel scaffold, the disturbance effect of the femtosecond laser to the nanoparticle self-assembling could be overcome. Therefore, hydrogel-state and solid-state colloidal crystal microstructures with diverse compositions, free-designed geometries and variable structural colors could be easily fabricated. This enables the possibility to create novel colloidal crystal microsensing systems that have not been achieved before., (© 2022. The Author(s).)

Ferroelectric domain wall memories have been proposed as a promising candidate for nonvolatile memories, given their intriguing advantages including low energy consumption and high-density integration. Perovskite oxides possess superior ferroelectric prosperities but perovskite-based domain wall memory integrated on silicon has rarely been reported due to the technical challenges in the sample preparation. Here, we demonstrate a domain wall memory prototype utilizing freestanding BaTiO 3 membranes transferred onto silicon. While as-grown BaTiO 3 films on (001) SrTiO 3 substrate are purely c-axis polarized, we find they exhibit distinct in-plane multidomain structures after released from the substrate and integrated onto silicon due to the collective effects from depolarizing field and strain relaxation. Based on the strong in-plane ferroelectricity, conductive domain walls with reading currents up to nanoampere are observed and can be both created and erased artificially, highlighting the great potential of the integration of perovskite oxides with silicon for ferroelectric domain wall memories., (© 2022. The Author(s).)

Mitochondria are essential for brain development. While previous studies linked dysfunctional mitochondria with autism spectrum disorder (ASD), the role of the mitochondrial genome (mtDNA) in ASD risk is largely unexplored. This study investigates the association of mtDNA heteroplasmies (co-existence of mutated and unmutated mtDNA) and content with ASD, as well as its inter-generational transmission and sex differences among two independent samples: a family-based study (n = 1,938 families with parents, probands and sibling controls) and a prospective birth cohort (n = 997 mother-child pairs). In both samples, predicted pathogenic (PP) heteroplasmies in children are associated with ASD risk (Meta-OR = 1.56, P = 0.00068). Inter-generational transmission of mtDNA reveals attenuated effects of purifying selection on maternal heteroplasmies in children with ASD relative to controls, particularly among males. Among children with ASD and PP heteroplasmies, increased mtDNA content shows benefits for cognition, communication, and behaviors (P ≤ 0.02). These results underscore the value of exploring maternal and newborn mtDNA in ASD., (© 2022. The Author(s).)

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations., (© 2022. The Author(s).)

Interleukin-7 receptor α (encoded by IL7R) is essential for lymphoid development. Whether acute lymphoblastic leukemia (ALL)-related IL7R gain-of-function mutations can trigger leukemogenesis remains unclear. Here, we demonstrate that lymphoid-restricted mutant IL7R, expressed at physiological levels in conditional knock-in mice, establishes a pre-leukemic stage in which B-cell precursors display self-renewal ability, initiating leukemia resembling PAX5 P80R or Ph-like human B-ALL. Full transformation associates with transcriptional upregulation of oncogenes such as Myc or Bcl2, downregulation of tumor suppressors such as Ikzf1 or Arid2, and major IL-7R signaling upregulation (involving JAK/STAT5 and PI3K/mTOR), required for leukemia cell viability. Accordingly, maximal signaling drives full penetrance and early leukemia onset in homozygous IL7R mutant animals. Notably, we identify 2 transcriptional subgroups in mouse and human Ph-like ALL, and show that dactolisib and sphingosine-kinase inhibitors are potential treatment avenues for IL-7R-related cases. Our model, a resource to explore the pathophysiology and therapeutic vulnerabilities of B-ALL, demonstrates that IL7R can initiate this malignancy., (© 2021. The Author(s).)

Cancers develop from the accumulation of somatic mutations, yet it remains unclear how oncogenic lesions cooperate to drive cancer progression. Using a mouse model harboring NRas G12D and EZH2 mutations that recapitulates leukemic progression, we employ single-cell transcriptomic profiling to map cellular composition and gene expression alterations in healthy or diseased bone marrows during leukemogenesis. At cellular level, NRas G12D induces myeloid lineage-biased differentiation and EZH2-deficiency impairs myeloid cell maturation, whereas they cooperate to promote myeloid neoplasms with dysregulated transcriptional programs. At gene level, NRas G12D and EZH2-deficiency independently and synergistically deregulate gene expression. We integrate results from histopathology, leukemia repopulation, and leukemia-initiating cell assays to validate transcriptome-based cellular profiles. We use this resource to relate developmental hierarchies to leukemia phenotypes, evaluate oncogenic cooperation at single-cell and single-gene levels, and identify GEM as a regulator of leukemia-initiating cells. Our studies establish an integrative approach to deconvolute cancer evolution at single-cell resolution in vivo., (© 2021. The Author(s).)

Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3'UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats. Importantly, increased fibronectin expression on sEVs surface contributes to targeting of osteoprogenitors in bone by TBI sEVs, thereby implying that modification of the sEVs surface fibronectin could be used in bone-targeted drug delivery. Together, our work unveils a role of central regulation in bone formation and a clear link between injured neurons and osteogenitors, both in animals and clinical settings., (© 2021. The Author(s).)

In vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication., (© 2021. The Author(s).)

White matter structural connections are likely to support flow of functional activation or functional connectivity. While the relationship between structural and functional connectivity profiles, here called SC-FC coupling, has been studied on a whole-brain, global level, few studies have investigated this relationship at a regional scale. Here we quantify regional SC-FC coupling in healthy young adults using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project and study how SC-FC coupling may be heritable and varies between individuals. We show that regional SC-FC coupling strength varies widely across brain regions, but was strongest in highly structurally connected visual and subcortical areas. We also show interindividual regional differences based on age, sex and composite cognitive scores, and that SC-FC coupling was highly heritable within certain networks. These results suggest regional structure-function coupling is an idiosyncratic feature of brain organisation that may be influenced by genetic factors., (© 2021. The Author(s).)

Li-ion-conducting chloride solid electrolytes receive considerable attention due to their physicochemical characteristics such as high ionic conductivity, deformability and oxidative stability. However, the raw materials are expensive, and large-scale use of this class of inorganic superionic conductors seems unlikely. Here, a cost-effective chloride solid electrolyte, Li 2 ZrCl 6 , is reported. Its raw materials are several orders of magnitude cheaper than those for the state-of-the-art chloride solid electrolytes, but high ionic conductivity (0.81 mS cm -1 at room temperature), deformability, and compatibility with 4V-class cathodes are still simultaneously achieved in Li 2 ZrCl 6 . Moreover, Li 2 ZrCl 6 demonstrates a humidity tolerance with no sign of moisture uptake or conductivity degradation after exposure to an atmosphere with 5% relative humidity. By combining Li 2 ZrCl 6 with the Li-In anode and the single-crystal LiNi 0.8 Mn 0.1 Co 0.1 O 2 cathode, we report a room-temperature all-solid-state cell with a stable specific capacity of about 150 mAh g -1 for 200 cycles at 200 mA g -1 ., (© 2021. The Author(s).)

Trivalent rare earth elements (REEs) are widely used in agriculture. Aerially applied REEs enter leaf epidermal cells by endocytosis and act systemically to improve the growth of the whole plant. The mechanistic basis of their systemic activity is unclear. Here, we show that treatment of Arabidopsis leaves with trivalent lanthanum [La(III)], a representative of REEs, triggers systemic endocytosis from leaves to roots. La(III)-induced systemic endocytosis requires AtrbohD-mediated reactive oxygen species production and jasmonic acid. Systemic endocytosis impacts the accumulation of mineral elements and the development of roots consistent with the growth promoting effects induced by aerially applied REEs. These findings provide insights into the mechanistic basis of REE activity in plants., (© 2021. The Author(s).)

Although therapies of cancer are advancing, it remains challenging for therapeutics to reach the sites of metastasis, which accounts for majority of cancer associated death. In this study, we have developed a strategy that guides an anti-programmed cell death-ligand 1 (aPDL1) antibody to accumulate in metastatic lesions to promote anti-tumour immune responses. Briefly, we have developed a combination in which Vadimezan disrupts tumour blood vessels of tumour metastases and facilitates the recruitment and activation of adoptively transferred aPDL1-conjugated platelets. In situ activated platelets generate aPDL1-decorated platelet-derived microparticles (PMP) that diffuse within the tumour and elicit immune responses. The proposed combination increases 10-fold aPDL1 antibody accumulation in lung metastases as compared to the intravenous administration of the antibody and enhances the magnitude of immune responses leading to improved antitumour effects.

Topological phases of matter are classified based on their Hermitian Hamiltonians, whose real-valued dispersions together with orthogonal eigenstates form nontrivial topology. In the recently discovered higher-order topological insulators (TIs), the bulk topology can even exhibit hierarchical features, leading to topological corner states, as demonstrated in many photonic and acoustic artificial materials. Naturally, the intrinsic loss in these artificial materials has been omitted in the topology definition, due to its non-Hermitian nature; in practice, the presence of loss is generally considered harmful to the topological corner states. Here, we report the experimental realization of a higher-order TI in an acoustic crystal, whose nontrivial topology is induced by deliberately introduced losses. With local acoustic measurements, we identify a topological bulk bandgap that is populated with gapped edge states and in-gap corner states, as the hallmark signatures of hierarchical higher-order topology. Our work establishes the non-Hermitian route to higher-order topology, and paves the way to exploring various exotic non-Hermiticity-induced topological phases.

Double-stranded RNA (dsRNA) is a virus-encoded signature capable of triggering intracellular Rig-like receptors (RLR) to activate antiviral signaling, but whether intercellular dsRNA structural reshaping mediated by the N 6 -methyladenosine (m 6 A) modification modulates this process remains largely unknown. Here, we show that, in response to infection by the RNA virus Vesicular Stomatitis Virus (VSV), the m 6 A methyltransferase METTL3 translocates into the cytoplasm to increase m 6 A modification on virus-derived transcripts and decrease viral dsRNA formation, thereby reducing virus-sensing efficacy by RLRs such as RIG-I and MDA5 and dampening antiviral immune signaling. Meanwhile, the genetic ablation of METTL3 in monocyte or hepatocyte causes enhanced type I IFN expression and accelerates VSV clearance. Our findings thus implicate METTL3-mediated m 6 A RNA modification on viral RNAs as a negative regulator for innate sensing pathways of dsRNA, and also hint METTL3 as a potential therapeutic target for the modulation of anti-viral immunity.

DNA nanostructures have been demonstrated as promising carriers for gene delivery. In the carrier design, spatiotemporally programmable assembly of DNA under nanoconfinement is important but has proven highly challenging due to the complexity-scalability-error of DNA. Herein, a DNA nanotechnology-based strategy via the cascade hybridization chain reaction (HCR) of DNA hairpins in polymeric nanoframework has been developed to achieve spatiotemporally programmable assembly of DNA under nanoconfinement for precise siRNA delivery. The nanoframework is prepared via precipitation polymerization with Acrydite-DNA as cross-linker. The potential energy stored in the loops of DNA hairpins can overcome the steric effect in the nanoframework, which can help initiate cascade HCR of DNA hairpins and achieve efficient siRNA loading. The designer tethering sequence between DNA and RNA guarantees a triphosadenine triggered siRNA release specifically in cellular cytoplasm. Nanoframework provides stability and ease of functionalization, which helps address the complexity-scalability-error of DNA. It is exemplified that the phenylboronate installation on nanoframework enhanced cellular uptake and smoothed the lysosomal escape. Cellular results show that the siRNA loaded nanoframework down-regulated the levels of relevant mRNA and protein. In vivo experiments show significant therapeutic efficacy of using siPLK1 loaded nanoframework to suppress tumor growth.

Chemically synthesized metal nanowires are promising building blocks for next-generation photonic integrated circuits, but technological implementation in monolithic integration will be severely hampered by the lack of controllable and precise manipulation approaches, due to the strong adhesion of nanowires to substrates in non-liquid environments. Here, we demonstrate this obstacle can be removed by our proposed earthworm-like peristaltic crawling motion mechanism, based on the synergistic expansion, friction, and contraction in plasmon-driven metal nanowires in non-liquid environments. The evanescently excited surface plasmon greatly enhances the heating effect in metal nanowires, thereby generating surface acoustic waves to drive the nanowires crawling along silica microfibres. Advantages include sub-nanometer positioning accuracy, low actuation power, and self-parallel parking. We further demonstrate on-chip manipulations including transporting, positioning, orientation, and sorting, with on-situ operation, high selectivity, and great versatility. Our work paves the way to realize full co-integration of various functionalized photonic components on single chips.

Glioblastoma frequently exhibits therapy-associated subtype transitions to mesenchymal phenotypes with adverse prognosis. Here, we perform multi-omic profiling of 60 glioblastoma primary tumours and use orthogonal analysis of chromatin and RNA-derived gene regulatory networks to identify 38 subtype master regulators, whose cell population-specific activities we further map in published single-cell RNA sequencing data. These analyses identify the oligodendrocyte precursor marker and chromatin modifier SOX10 as a master regulator in RTK I-subtype tumours. In vitro functional studies demonstrate that SOX10 loss causes a subtype switch analogous to the proneural-mesenchymal transition observed in patients at the transcriptomic, epigenetic and phenotypic levels. SOX10 repression in an in vivo syngeneic graft glioblastoma mouse model results in increased tumour invasion, immune cell infiltration and significantly reduced survival, reminiscent of progressive human glioblastoma. These results identify SOX10 as a bona fide master regulator of the RTK I subtype, with both tumour cell-intrinsic and microenvironmental effects.

Conventional atomic force microscopy (AFM) tips have remained largely unchanged in nanomachining processes, constituent materials, and microstructural constructions for decades, which limits the measurement performance based on force-sensing feedbacks. In order to save the scanning images from distortions due to excessive mechanical interactions in the intermittent shear-mode contact between scanning tips and sample, we propose the application of controlled microstructural architectured material to construct AFM tips by exploiting material-related energy-absorbing behavior in response to the tip-sample impact, leading to visual promotions of imaging quality. Evidenced by numerical analysis of compressive responses and practical scanning tests on various samples, the essential scanning functionality and the unique contribution of the cellular buffer layer to imaging optimization are strongly proved. This approach opens new avenues towards the specific applications of cellular solids in the energy-absorption field and sheds light on novel AFM studies based on 3D-printed tips possessing exotic properties.

Defects from grain interiors and boundaries of perovskite films cause significant nonradiative recombination energy loss, and thus perovskite films with controlled crystallinity and large grains is critical for improvement of both photovoltaic performance and stability for perovskite-based solar cells. Here, a methylamine (MA 0 ) gas-assisted crystallization method is developed for fabrication of methylammonium lead iodide (MAPbI 3 ) perovskite films. In the process, the perovskite film is formed via controlled release of MA0 gas molecules from a liquid intermediate phase MAPbI 3 ·xMA 0 . The resulting perovskite film comprises millimeter-sized grains with (110)-uniaxial crystallographic orientation, exhibiting much low trap density, long carrier lifetime, and excellent environmental stability. The corresponding perovskite solar cell exhibits a power conversion efficiency (PCE) of ~ 21.36%, which is among the highest reported for MAPbI 3 -based devices. This method provides important progress towards the fabrication of high-quality perovskite thin films for low-cost, highly efficient and stable perovskite solar cells.

Atropisomers are important organic frameworks in bioactive natural products, drugs as well as chiral catalysts. Meanwhile, silanols display unique properties compared to their alcohol analogs, however, the catalytic synthesis of atropisomers bearing silanol groups is challenging. Here, we show a rhodium-catalyzed torsional strain-promoted asymmetric ring-opening reaction for the synthesis of α-silyl biaryl atropisomers. The reaction features a dynamic kinetic resolution of C(Ar)-Si bond cleavage, whose stereochemistry was controlled by a phosphoramidite ligand derived from (S)-3-methyl-1-((2,4,6-triisopropylphenyl)sulfonyl)piperazine. This work is a demonstration of an aryl-Narasaka acylation, where the C(Ar)-Si bond cleavage is promoted by the torsional strain of α, α'-disubstituted silafluorene.