All-optical physiology resolves a synaptic basis for behavioral timescale plasticity.

Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals.

Acceleration of radiative recombination for efficient perovskite LEDs.

The increasing demands for more efficient and brighter thin-film light-emitting diodes (LEDs) in flat-panel display and solid-state lighting applications have promoted research into three-dimensional (3D) perovskites. These materials exhibit high charge mobilities and low quantum efficiency droop1-6, making them promising candidates for achieving efficient LEDs with enhanced brightness. To improve the efficiency of LEDs, it is crucial to minimize nonradiative recombination while promoting radiative recombination. Various passivation strategies have been used to reduce defect densities in 3D perovskite films, approaching levels close to those of single crystals3. However, the slow radiative (bimolecular) recombination has limited the photoluminescence quantum efficiencies (PLQEs) of 3D perovskites to less than 80% (refs. 1,3), resulting in external quantum efficiencies (EQEs) of LED devices of less than 25%. Here we present a dual-additive crystallization method that enables the formation of highly efficient 3D perovskites, achieving an exceptional PLQE of 96%. This approach promotes the formation of tetragonal FAPbI3 perovskite, known for its high exciton binding energy, which effectively accelerates the radiative recombination. As a result, we achieve perovskite LEDs with a record peak EQE of 32.0%, with the efficiency remaining greater than 30.0% even at a high current density of 100 mA cm-2. These findings provide valuable insights for advancing the development of high-efficiency and high-brightness perovskite LEDs.

In-plane charged domain walls with memristive behaviour in a ferroelectric film.

Domain-wall nanoelectronics is considered to be a new paradigm for non-volatile memory and logic technologies in which domain walls, rather than domains, serve as an active element. Especially interesting are charged domain walls in ferroelectric structures, which have subnanometre thicknesses and exhibit non-trivial electronic and transport properties that are useful for various nanoelectronics applications1-3. The ability to deterministically create and manipulate charged domain walls is essential to realize their functional properties in electronic devices. Here we report a strategy for the controllable creation and manipulation of in-plane charged domain walls in BiFeO3 ferroelectric films a few nanometres thick. By using an in situ biasing technique within a scanning transmission electron microscope, an unconventional layer-by-layer switching mechanism is detected in which ferroelectric domain growth occurs in the direction parallel to an applied electric field. Based on atomically resolved electron energy-loss spectroscopy, in situ charge mapping by in-line electron holography and theoretical calculations, we show that oxygen vacancies accumulating at the charged domain walls are responsible for the domain-wall stability and motion. Voltage control of the in-plane domain-wall position within a BiFeO3 film gives rise to multiple non-volatile resistance states, thus demonstrating the key functional property of being a memristor a few unit cells thick. These results promote a better understanding of ferroelectric switching behaviour and provide a new strategy for creating unit-cell-scale devices.

Vertical MoS2 transistors with sub-1-nm gate lengths.

Ultra-scaled transistors are of interest in the development of next-generation electronic devices1-3. Although atomically thin molybdenum disulfide (MoS2) transistors have been reported4, the fabrication of devices with gate lengths below 1 nm has been challenging5. Here we demonstrate side-wall MoS2 transistors with an atomically thin channel and a physical gate length of sub-1 nm using the edge of a graphene layer as the gate electrode. The approach uses large-area graphene and MoS2 films grown by chemical vapour deposition for the fabrication of side-wall transistors on a 2-inch wafer. These devices have On/Off ratios up to 1.02 × 105 and subthreshold swing values down to 117 mV dec-1. Simulation results indicate that the MoS2 side-wall effective channel length approaches 0.34 nm in the On state and 4.54 nm in the Off state. This work can promote Moore's law of the scaling down of transistors for next-generation electronics.

Reconstructed covalent organic frameworks.

Covalent organic frameworks (COFs) are distinguished from other organic polymers by their crystallinity1-3, but it remains challenging to obtain robust, highly crystalline COFs because the framework-forming reactions are poorly reversible4,5. More reversible chemistry can improve crystallinity6-9, but this typically yields COFs with poor physicochemical stability and limited application scope5. Here we report a general and scalable protocol to prepare robust, highly crystalline imine COFs, based on an unexpected framework reconstruction. In contrast to standard approaches in which monomers are initially randomly aligned, our method involves the pre-organization of monomers using a reversible and removable covalent tether, followed by confined polymerization. This reconstruction route produces reconstructed COFs with greatly enhanced crystallinity and much higher porosity by means of a simple vacuum-free synthetic procedure. The increased crystallinity in the reconstructed COFs improves charge carrier transport, leading to sacrificial photocatalytic hydrogen evolution rates of up to 27.98 mmol h-1 g-1. This nanoconfinement-assisted reconstruction strategy is a step towards programming function in organic materials through atomistic structural control.

Video-based pooled screening yields improved far-red genetically encoded voltage indicators.

Video-based screening of pooled libraries is a powerful approach for directed evolution of biosensors because it enables selection along multiple dimensions simultaneously from large libraries. Here we develop a screening platform, Photopick, which achieves precise phenotype-activated photoselection over a large field of view (2.3 × 2.3 mm, containing >103 cells, per shot). We used the Photopick platform to evolve archaerhodopsin-derived genetically encoded voltage indicators (GEVIs) with improved signal-to-noise ratio (QuasAr6a) and kinetics (QuasAr6b). These GEVIs gave improved signals in cultured neurons and in live mouse brains. By combining targeted in vivo optogenetic stimulation with high-precision voltage imaging, we characterized inhibitory synaptic coupling between individual cortical NDNF (neuron-derived neurotrophic factor) interneurons, and excitatory electrical synapses between individual hippocampal parvalbumin neurons. The QuasAr6 GEVIs are powerful tools for all-optical electrophysiology and the Photopick approach could be adapted to evolve a broad range of biosensors.

Statistically unbiased prediction enables accurate denoising of voltage imaging data.

Here we report SUPPORT (statistically unbiased prediction utilizing spatiotemporal information in imaging data), a self-supervised learning method for removing Poisson-Gaussian noise in voltage imaging data. SUPPORT is based on the insight that a pixel value in voltage imaging data is highly dependent on its spatiotemporal neighboring pixels, even when its temporally adjacent frames alone do not provide useful information for statistical prediction. Such dependency is captured and used by a convolutional neural network with a spatiotemporal blind spot to accurately denoise voltage imaging data in which the existence of the action potential in a time frame cannot be inferred by the information in other frames. Through simulations and experiments, we show that SUPPORT enables precise denoising of voltage imaging data and other types of microscopy image while preserving the underlying dynamics within the scene.

Gate-Controlled Neuromorphic Functional Transition in an Electrochemical Graphene Transistor.

Neuromorphic devices have attracted significant attention as potential building blocks for the next generation of computing technologies owing to their ability to emulate the functionalities of biological nervous systems. The essential components in artificial neural networks such as synapses and neurons are predominantly implemented by dedicated devices with specific functionalities. In this work, we present a gate-controlled transition of neuromorphic functions between artificial neurons and synapses in monolayer graphene transistors that can be employed as memtransistors or synaptic transistors as required. By harnessing the reliability of reversible electrochemical reactions between carbon atoms and hydrogen ions, we can effectively manipulate the electric conductivity of graphene transistors, resulting in a high on/off resistance ratio, a well-defined set/reset voltage, and a prolonged retention time. Overall, the on-demand switching of neuromorphic functions in a single graphene transistor provides a promising opportunity for developing adaptive neural networks for the upcoming era of artificial intelligence and machine learning.

Real-Time Direct Monitoring of Chirality Fixation and Recognition at the Single-Molecule Level.

Chirality, a fundamental attribute of nature, significantly influences a wide range of phenomena related to physical properties, chemical reactions, biological pharmacology, and so on. As a pivotal aspect of chirality research, chirality recognition contributes to the synthesis of complex chiral products from simple chiral compounds and exhibits intricate interplay between chiral materials. However, macroscopic detection technologies cannot unveil the dynamic process and intrinsic mechanisms of single-molecule chirality recognition. Herein, we present a single-molecule detection platform based on graphene-molecule-graphene single-molecule junctions to measure the chirality recognition involving interactions between amines and chiral alcohols. This approach leads to the realization of in situ and real-time direct observation of chirality recognition at the single-molecule level, demonstrating that chiral alcohols exhibit compelling potential to induce the formation of the corresponding chiral configuration of molecules. The amalgamation of theoretical analyses with experimental findings reveals a synergistic action between electrostatic interactions and steric hindrance effects in the chirality recognition process, thus substantiating the microscopic mechanism governing the chiral structure-activity relationship. These studies open up a pathway for exploring novel chiral phenomena from the fundamental limits of chemistry, such as chiral origin and chiral amplification, and offer important insights into the precise synthesis of chiral materials.

Island-in-Sea Structured Pt3Fe Nanoparticles-in-Fe Single Atoms Loaded in Carbon Materials as Superior Electrocatalysts toward Alkaline HER and Acidic ORR.

In this work, Pt3Fe nanoparticles (Pt3Fe NPs) with the ordered internal structure and Pt-rich shells surrounded by plenty of Fe single atoms (Fe SAs) as active species (Pt3Fe NP-in-Fe SA) loaded in the carbon materials are successfully fabricated, which are abbreviated as island-in-sea structured (IISS) Pt3Fe NP-in-Fe SA catalysts. Moreover, the synergistic effect of O-bridging between Pt3Fe NPs and Fe SAs, and the ordered internal structured Pt3Fe NPs with Pt-rich shells of an optimal thickness contributes to the achievement of the local acidic environments on the surfaces of Pt3Fe NPs in the alkaline hydrogen evolution reaction (HER) and the enhancement of the desorption rate of *OH intermediate in the acidic oxygen reduction reaction (ORR). In addition, the electronic interactions between Pt3Fe NPs and dispersed Fe SAs cannot only provide efficient electrons transfer, but also prevent the aggregation and dissolution of Pt3Fe NPs. Furthermore, the overpotential and the half wave potential of the as-prepared IISS Pt3Fe NP-in-Fe SA catalysts toward the alkaline HER and toward the acidic ORR are 8 mV at a current density of 10 mA cm-2 and 0.933 V, respectively, which is 29 lower and 86 mV higher than those (37 mV and 0.847 V) of commercial Pt/C catalysts.

Discovery of Photoexcited 2-Chloro-3,5-Dinitrobenzoic Acid as a Chemical Deprenylase of i6A RNA.

RNA modifications play crucial roles in regulating gene expression and cellular homeostasis. Modulating RNA modifications, particularly by targeting the enzymes responsible for their catalysis, has emerged as a promising therapeutic strategy. However, limitations, such as the lack of identified modifying enzymes and compensatory mechanisms, hinder targeted interventions. Chemical approaches independent of enzymatic activity offer an alternative strategy for RNA modification modulation. Here, we present the identification of 2-chloro-3,5-dinitrobenzoic acid as a highly effective photochemical deprenylase of i6A RNA. This method demonstrates exceptional selectivity towards i6A, converting its substituent into a "N-doped" ozonide, which upon hydrolysis releases natural adenine. We believe that this chemical approach will pave the way for a better understanding of RNA modification biology and the development of novel therapeutic modalities.

Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury.

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.

Selective Methylation of Nucleosides via an In Situ Generated Methyl Oxonium.

A very mild and efficient procedure has been developed for the preparation of N-methylated uridine, pseudouridine, guanosine and inosine derivatives. This process was compatible with free hydroxyls within the ribose and did not require precautions on the protection or deprotection of other functionalities. The key to this extremely mild methylation without protection relied on the in situ generated methyl oxonium from the Wittig reagent and methanol. A putative mechanism for the selective methylation was also proposed.

Precise Metabolomics Defines Systemic Metabolic Dysregulation Distinct to Acute Myocardial Infarction Associated With Diabetes.

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of death and disability. Diabetes is an important risk factor and a common comorbidity in AMI patients. The higher mortality risk of diabetes-AMI relative to nondiabetes-AMI indicates a need for specific treatment to improve clinical outcome. However, the global metabolic dysregulation of AMI complicated with diabetes is still unclear. We aim to systematically interrogate changes in the metabolic microenvironment immediate to AMI episodes in the absence or presence of diabetes. METHODS: In this work, quantitative metabolomics was used to investigate plasma metabolic differences between diabetes-AMI (n=59) and nondiabetes-AMI (n=59) patients. A diverse array of perturbed metabolic pathways involving carbohydrate metabolism, lipid metabolism, glycolysis, tricarboxylic acid cycle, and amino acid metabolism emerged. RESULTS: In all, our omics-oriented approach defined a metabolic signature of afflicted mitochondrial function aggravated by concurrent diabetes in AMI patients. In particular, our analyses uncovered N-lactoyl-phenylalanine and lysophosphatidylcholines as key functional metabolites that skewed the metabolic picture of diabetes-AMI relative to nondiabetes-AMI. N-lactoyl-phenylalanine was strongly associated with metabolic indicators reflective of mitochondrial overload and negatively correlated with HbA1c (glycosylated hemoglobin, type A1C) specifically in hyperglycemic AMI, suggestive of its central role in glucose utilization and mitochondrial energy production instrumental to the clinical outcome of diabetes-AMI. Reductions in lysophosphatidylcholines, which were negatively correlated with blood glucose and inflammatory markers, might further compromise glucose expenditure and aggravate inflammation leading to poorer prognosis in diabetes-AMI. CONCLUSIONS: As circulating metabolite levels are amenable to therapeutic intervention, such shifts in metabolic signatures provide new clues and potential therapeutic targets specific to the treatment of diabetes-AMI.

Perovskite light-emitting diodes based on spontaneously formed submicrometre-scale structures.

Light-emitting diodes (LEDs), which convert electricity to light, are widely used in modern society-for example, in lighting, flat-panel displays, medical devices and many other situations. Generally, the efficiency of LEDs is limited by nonradiative recombination (whereby charge carriers recombine without releasing photons) and light trapping1-3. In planar LEDs, such as organic LEDs, around 70 to 80 per cent of the light generated from the emitters is trapped in the device4,5, leaving considerable opportunity for improvements in efficiency. Many methods, including the use of diffraction gratings, low-index grids and buckling patterns, have been used to extract the light trapped in LEDs6-9. However, these methods usually involve complicated fabrication processes and can distort the light-output spectrum and directionality6,7. Here we demonstrate efficient and high-brightness electroluminescence from solution-processed perovskites that spontaneously form submicrometre-scale structures, which can efficiently extract light from the device and retain wavelength- and viewing-angle-independent electroluminescence. These perovskites are formed simply by introducing amino-acid additives into the perovskite precursor solutions. Moreover, the additives can effectively passivate perovskite surface defects and reduce nonradiative recombination. Perovskite LEDs with a peak external quantum efficiency of 20.7 per cent (at a current density of 18 milliamperes per square centimetre) and an energy-conversion efficiency of 12 per cent (at a high current density of 100 milliamperes per square centimetre) can be achieved-values that approach those of the best-performing organic LEDs.

Chondroitin sulfate-modified tragacanth gum-gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses,  and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum-gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum-gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1ß, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA.

Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients' poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC.

Dynamic Motion of Polar Skyrmions in Oxide Heterostructures.

Polar skyrmions have been widely investigated in oxide heterostructures due to their exotic properties and intriguing physical insights. However, the field-driven motion of polar skyrmions, akin to that of the magnetic counterpart, remains elusive. Herein, using phase-field simulations, we demonstrate the dynamic motion of polar skyrmions with integrated external thermal, electrical, and mechanical stimuli. External heating reduced the spontaneous polarization, while an applied electric field decreased the skyrmion size and weakened the interactions between the skyrmions. Together, the skyrmion motion barrier is significantly reduced from 40 to 2 eV under 9 V at 500 K. An applied mechanical force transformed the skyrmions into a c-domain region near the indenter center under the electric field, providing the space and driving force needed for the motion of the skyrmions. This study confirms that polar skyrmions can move like particles and provides concrete design principles for polar skyrmion-based electronic devices.

Catalyst-Free Dynamic Covalent C=C/C=N Metathesis Reaction for Associative Covalent Adaptable Networks.

Covalent adaptable networks (CANs), leveraging the dynamic exchange of covalent bonds, emerge as a promising material to address the challenge of irreversible cross-linking in thermosetting polymers. In this work, we explore the introduction of a catalyst-free and associative C=C/C=N metathesis reaction into thermosetting polyurethanes, creating CANs with superior stability, solvent resistance, and thermal/mechanical properties. By incorporating this dynamic exchange reaction, stress-relaxation is significantly accelerated compared to imine-bond-only networks, with the rate adjustable by modifying substituents in the ortho position of the dynamic double bonds. The obtained plasticity enables recycle without altering the chemical structure or mechanical properties, and is also found to be vital for achieving shape memory functions with complex spatial structures. This metathesis reaction as a new dynamic crosslinker of polymer networks has the potential to accelerate the ongoing exploration of malleable and functional thermoset polymers.