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To fully exploit van der Waals materials and their vertically stacked heterostructures, new mass-scalable production routes which are low cost but preserve the high electronic and optical quality of the single crystals are required. Here, we demonstrate an approach to realise a variety of functional heterostructures based on van der Waals nanocrystal films produced through the mechanical abrasion of bulk powders. We find significant performance enhancements in abraded heterostructures compared to those fabricated through inkjet printing of nanocrystal dispersions. To highlight the simplicity, applicability and scalability of the device fabrication, we demonstrate a multitude of different functional heterostructures such as resistors, capacitors and photovoltaics. We also demonstrate the creation of energy harvesting devices, such as large area catalytically active coatings for the hydrogen evolution reaction and enhanced triboelectric nanogenerator performance in multilayer films. The ease of device production makes this a promising technological route for up-scalable films and heterostructures.

Landslides modify the natural landscape and cause fatalities and property damage worldwide. Quantifying landslide dynamics is challenging due to the stochastic nature of the environment. With its large area of ~1 km 2 and perennial motions at ~10-20 mm per day, the Slumgullion landslide in Colorado, USA, represents an ideal natural laboratory to better understand landslide behavior. Here, we use hybrid remote sensing data and methods to recover the four-dimensional surface motions during 2011-2018. We refine the boundaries of an area of ~0.35 km 2 below the crest of the prehistoric landslide. We construct a mechanical framework to quantify the rheology, subsurface channel geometry, mass flow rate, and spatiotemporally dependent pore-water pressure feedback through a joint analysis of displacement and hydrometeorological measurements from ground, air and space. Our study demonstrates the importance of remotely characterizing often inaccessible, dangerous slopes to better understand landslides and other quasi-static mass fluxes in natural and industrial environments, which will ultimately help reduce associated hazards.

The design and development of self-charging supercapacitor power cells are rapidly gaining interest due to their ability to convert and store energy in an integrated device. Here, we have demonstrated the fabrication of a self-charging supercapacitor using siloxene sheets as electrodes and siloxene-based polymeric piezofiber separator immobilized with an ionogel electrolyte. The self-charging properties of the fabricated device subjected to various levels of compressive forces showed their ability to self-charge up to a maximum of 207 mV. The mechanism of self-charging process in the fabricated device is discussed via "piezoelectrochemical effect" with the aid of piezoelectrochemical spectroscopy measurements. These studies revealed the direct evidence of the piezoelectrochemical phenomenon involved in the energy conversion and storage process in the fabricated device. This study can provide insight towards understanding the energy conversion process in self-charging supercapacitors, which is of significance considering the state of the art of piezoelectric driven self-charging supercapacitors.

Flexible reduced graphene oxide (rGO) sheets are being considered for applications in portable electrical devices and flexible energy storage systems. However, the poor mechanical properties and electrical conductivities of rGO sheets are limiting factors for the development of such devices. Here we use MXene (M) nanosheets to functionalize graphene oxide platelets through Ti-O-C covalent bonding to obtain MrGO sheets. A MrGO sheet was crosslinked by a conjugated molecule (1-aminopyrene-disuccinimidyl suberate, AD). The incorporation of MXene nanosheets and AD molecules reduces the voids within the graphene sheet and improves the alignment of graphene platelets, resulting in much higher compactness and high toughness. In situ Raman spectroscopy and molecular dynamics simulations reveal the synergistic interfacial interaction mechanisms of Ti-O-C covalent bonding, sliding of MXene nanosheets, and π-π bridging. Furthermore, a supercapacitor based on our super-tough MXene-functionalized graphene sheets provides a combination of energy and power densities that are high for flexible supercapacitors.

In many developing countries, aquaculture is key to ensuring food security for millions of people. It is thus important to measure the full implications of environmental changes on the sustainability of aquaculture. We conduct a double meta-analysis (460 articles) to explore how global warming and antimicrobial resistance (AMR) impact aquaculture. We calculate a Multi-Antibiotic Resistance index (MAR) of aquaculture-related bacteria (11,274 isolates) for 40 countries, of which mostly low- and middle-income countries present high AMR levels. Here we show that aquaculture MAR indices correlate with MAR indices from human clinical bacteria, temperature and countries' climate vulnerability. We also find that infected aquatic animals present higher mortalities at warmer temperatures. Countries most vulnerable to climate change will probably face the highest AMR risks, impacting human health beyond the aquaculture sector, highlighting the need for urgent action. Sustainable solutions to minimise antibiotic use and increase system resilience are therefore needed.

We use a laboratory version of the intergenerational goods game (IGG) to investigate whether peer punishment facilitates the successful provision of multigenerational public goods. In our experiment, groups (generations) decide sequentially about the provision of a multigenerational public good through the voluntary contributions of their members. Successful provision requires that contributions meet a threshold and exclusively benefits members of future generations. Provision costs are borne only by the current generation. We compare a baseline condition without a punishment institution to a treatment condition where peer punishment can be inflicted exclusively on members of the same generation but not on members of past or future generations. We find that without punishment the likelihood of reaching the contribution threshold is low and that making punishment available within a generation is partially successful in sustaining cooperation in a succession of multiple generations.

A content-addressable memory compares an input search word against all rows of stored words in an array in a highly parallel manner. While supplying a very powerful functionality for many applications in pattern matching and search, it suffers from large area, cost and power consumption, limiting its use. Past improvements have been realized by using memristors to replace the static random-access memory cell in conventional designs, but employ similar schemes based only on binary or ternary states for storage and search. We propose a new analog content-addressable memory concept and circuit to overcome these limitations by utilizing the analog conductance tunability of memristors. Our analog content-addressable memory stores data within the programmable conductance and can take as input either analog or digital search values. Experimental demonstrations, scaled simulations and analysis show that our analog content-addressable memory can reduce area and power consumption, which enables the acceleration of existing applications, but also new computing application areas.

Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.

Since its invention in the 1960s, one of the most significant evolutions of metal-oxide-semiconductor field effect transistors (MOS-FETs) would be the three dimensionalized version that makes the semiconducting channel vertically wrapped by conformal gate electrodes, also recognized as FinFET. During the past decades, the width of fin (W[Formula: see text]) in FinFETs has shrunk from about 150 nm to a few nanometers. However, W[Formula: see text] seems to have been levelling off in recent years, owing to the limitation of lithography precision. Here, we show that by adapting a template-growth method, different types of mono-layered two-dimensional crystals are isolated in a vertical manner. Based on this, FinFETs with one atomic layer fin are obtained, with on/off ratios reaching [Formula: see text]. Our findings push the FinFET to the sub 1 nm fin-width limit, and may shed light on the next generation nanoelectronics for higher integration and lower power consumption.

Enzymatic digestion for protein sequencing usually requires much time, and does not always result in high sequence coverage. Here we report the use of aqueous microdroplets to accelerate enzymatic reactions and, in particular, to improve protein sequencing. When a room temperature aqueous solution containing 10 µM myoglobin and 5 µg mL -1 trypsin is electrosonically sprayed (-3 kV) from a homemade setup to produce tiny (∼9 µm) microdroplets, we obtain 100% sequence coverage in less than 1 ms of digestion time, in sharp contrast to 60% coverage achieved by incubating the same solution at 37 °C for 14 h followed by analysis with a commercial electrospray ionization source that produces larger (∼60 µm) droplets. We also confirm the sequence of the therapeutic antibody trastuzumab (∼148 kDa), with a sequence coverage of 100% for light chains and 85% for heavy chains, demonstrating the practical utility of microdroplets in drug development.

Social networks shape perceptions by exposing people to the actions and opinions of their peers. However, the perceived popularity of a trait or an opinion may be very different from its actual popularity. We attribute this perception bias to friendship paradox and identify conditions under which it appears. We validate the findings empirically using Twitter data. Within posts made by users in our sample, we identify topics that appear more often within users' social feeds than they do globally among all posts. We also present a polling algorithm that leverages the friendship paradox to obtain a statistically efficient estimate of a topic's global prevalence from biased individual perceptions. We characterize the polling estimate and validate it through synthetic polling experiments on Twitter data. Our paper elucidates the non-intuitive ways in which the structure of directed networks can distort perceptions and presents approaches to mitigate this bias.

Assembling thermoelectric modules into fabric to harvest energy from body heat could one day power multitudinous wearable electronics. However, the invalid 2D architecture of fabric limits the application in thermoelectrics. Here, we make the valid thermoelectric fabric woven out of thermoelectric fibers producing an unobtrusive working thermoelectric module. Alternately doped carbon nanotube fibers wrapped with acrylic fibers are woven into π-type thermoelectric modules. Utilizing elasticity originating from interlocked thermoelectric modules, stretchable 3D thermoelectric generators without substrate can be made to enable sufficient alignment with the heat flow direction. The textile generator shows a peak power density of 70 mWm -2 for a temperature difference of 44 K and excellent stretchability (~80% strain) with no output degradation. The compatibility between body movement and sustained power supply is further displayed. The generators described here are true textiles, proving active thermoelectrics can be woven into various fabric architectures for sensing, energy harvesting, or thermal management.

Ambitious climate action requires sustained long-term attention from political leaders. To understand how climate change entered the political agenda in a developing country, we examine from an agenda-setting perspective the attention paid by Mexican presidents to this issue from 1994 to 2018. We perform a longitudinal analysis of 968 documents referring to climate change published by four presidencies to describe changes in attention levels over time and to determine how changes in international agreements and public policies (i.e. systemic agenda) and National Development Plans (NDPs)(i.e. governmental agenda) influence them. Our results indicate international agreements and national legislation establish a baseline for inclusion of climate change into governmental actions. Agenda changes driven by international agreements result in reactive changes in attention, while ambitious approaches are aligned with proactive NDPs. Our results also indicate public awareness and electoral periods can open windows of opportunity for reframing agendas and promoting ambitious climate action.

In microbial cell factory, CO 2 release during acetyl-CoA production from pyruvate significantly decreases the carbon atom economy. Here, we construct and optimize a synthetic carbon conserving pathway named as Sedoheptulose-1,7-bisphosphatase Cycle with Trifunctional PhosphoKetolase (SCTPK) in Escherichia coli. This cycle relies on a generalist phosphoketolase Xfspk and converts glucose into the stoichiometric amounts of acetylphosphate (AcP). Furthermore, genetic circuits responding to AcP positively or negatively are created. Together with SCTPK, they constitute a gene-metabolic oscillator that regulates Xfspk and enzymes converting AcP into valuable chemicals in response to intracellular AcP level autonomously, allocating metabolic flux rationally and improving the carbon atom economy of bioconversion process. Using this synthetic machinery, mevalonate is produced with a yield higher than its native theoretical yield, and the highest titer and yield of 3-hydroxypropionate via malonyl-CoA pathway are achieved. This study provides a strategy for improving the carbon yield of microbial cell factories., (© 2023. Springer Nature Limited.)

Tie strengths in social networks are heterogeneous, with strong and weak ties playing different roles at the network and individual levels. Egocentric networks, networks of relationships around an individual, exhibit few strong ties and more weaker ties, as evidenced by electronic communication records. Mobile phone data has also revealed persistent individual differences within this pattern. However, the generality and driving mechanisms of social tie strength heterogeneity remain unclear. Here, we study tie strengths in egocentric networks across multiple datasets of interactions between millions of people during months to years. We find universality in tie strength distributions and their individual-level variation across communication modes, even in channels not reflecting offline social relationships. Via a simple model of egocentric network evolution, we show that the observed universality arises from the competition between cumulative advantage and random choice, two tie reinforcement mechanisms whose balance determines the diversity of tie strengths. Our results provide insight into the driving mechanisms of tie strength heterogeneity in social networks and have implications for the understanding of social network structure and individual behavior., (© 2023. Springer Nature Limited.)

Electrifying sub-Saharan Africa (SSA) requires major investments and policy intervention. Existing analyses focus on the levelized cost of electricity at aggregate levels, leaving the feasibility and affordability of reaching Sustainable Development Goal #7 - access to affordable, reliable, sustainable and modern energy for all - by country unclear. Here, we use the electrification model OnSSET to estimate granular and spatially explicit levelized costs of electricity and costs per person per day (pp/d) for 40 countries in SSA. We find that solar-powered mini-grids and standalone systems drastically lower the cost of electrifying remote and high-cost areas, particularly for lower tiers of electrification. On average, least-cost electrification in SSA at Tier 3 (ca. 365 kWh/household/year), can be provided at 14c USD/kWh or 7c USD pp/d. These results are sensitive to demand assumptions, for example, misguided electrification planning or oversizing due to overestimated demand can lead to substantial cost increases. Our results highlight large variances within countries, which we propose to visualise using electrification cost curves by country. Policymakers should consider such cost curves and use a tailored approach by country and region to reach SDG7 in SSA., (© 2023. Springer Nature Limited.)

Seventy percent of global electricity is generated by steam-cycle power plants. A hydrophobic condenser surface within these plants could boost overall cycle efficiency by 2%. In 2022, this enhancement equates to an additional electrical power generation of 1000 TWh annually, or 83% of the global solar electricity production. Furthermore, this efficiency increase reduces CO 2 emissions by 460 million tons /year with a decreased use of 2 trillion gallons of cooling water per year. However, the main challenge with hydrophobic surfaces is their poor durability. Here, we show that solid microscale-thick fluorinated diamond-like carbon (F-DLC) possesses mechanical and thermal properties that ensure durability in moist, abrasive, and thermally harsh conditions. The F-DLC coating achieves this without relying on atmospheric interactions, infused lubricants, self-healing strategies, or sacrificial surface designs. Through tailored substrate adhesion and multilayer deposition, we develop a pinhole-free F-DLC coating with low surface energy and comparable Young's modulus to metals. In a three-year steam condensation experiment, the F-DLC coating maintains hydrophobicity, resulting in sustained and improved dropwise condensation on multiple metallic substrates. Our findings provide a promising solution to hydrophobic material fragility and can enhance the sustainability of renewable and non-renewable energy sources., (© 2023. Springer Nature Limited.)

The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increases prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R 2 increases of up to 9-fold for attention-deficit/hyperactivity disorder compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks., (© 2023. Springer Nature Limited.)

The optical microscope is customarily an instrument of substantial size and expense but limited performance. Here we report an integrated microscope that achieves optical performance beyond a commercial microscope with a 5×, NA 0.1 objective but only at 0.15 cm 3 and 0.5 g, whose size is five orders of magnitude smaller than that of a conventional microscope. To achieve this, a progressive optimization pipeline is proposed which systematically optimizes both aspherical lenses and diffractive optical elements with over 30 times memory reduction compared to the end-to-end optimization. By designing a simulation-supervision deep neural network for spatially varying deconvolution during optical design, we accomplish over 10 times improvement in the depth-of-field compared to traditional microscopes with great generalization in a wide variety of samples. To show the unique advantages, the integrated microscope is equipped in a cell phone without any accessories for the application of portable diagnostics. We believe our method provides a new framework for the design of miniaturized high-performance imaging systems by integrating aspherical optics, computational optics, and deep learning., (© 2023. The Author(s).)

Intra-tumoral heterogeneity and cell-state plasticity are key drivers for the therapeutic resistance of glioblastoma. Here, we investigate the association between spatial cellular organization and glioblastoma prognosis. Leveraging single-cell RNA-seq and spatial transcriptomics data, we develop a deep learning model to predict transcriptional subtypes of glioblastoma cells from histology images. Employing this model, we phenotypically analyze 40 million tissue spots from 410 patients and identify consistent associations between tumor architecture and prognosis across two independent cohorts. Patients with poor prognosis exhibit higher proportions of tumor cells expressing a hypoxia-induced transcriptional program. Furthermore, a clustering pattern of astrocyte-like tumor cells is associated with worse prognosis, while dispersion and connection of the astrocytes with other transcriptional subtypes correlate with decreased risk. To validate these results, we develop a separate deep learning model that utilizes histology images to predict prognosis. Applying this model to spatial transcriptomics data reveal survival-associated regional gene expression programs. Overall, our study presents a scalable approach to unravel the transcriptional heterogeneity of glioblastoma and establishes a critical connection between spatial cellular architecture and clinical outcomes., (© 2023. The Author(s).)

Three types of DNA methyl modifications have been detected in bacterial genomes, and mechanistic studies have demonstrated roles for DNA methylation in physiological functions ranging from phage defense to transcriptional control of virulence and host-pathogen interactions. Despite the ubiquity of methyltransferases and the immense variety of possible methylation patterns, epigenomic diversity remains unexplored for most bacterial species. Members of the Bacteroides fragilis group (BFG) reside in the human gastrointestinal tract as key players in symbiotic communities but also can establish anaerobic infections that are increasingly multi-drug resistant. In this work, we utilize long-read sequencing technologies to perform pangenomic (n = 383) and panepigenomic (n = 268) analysis of clinical BFG isolates cultured from infections seen at the NIH Clinical Center over four decades. Our analysis reveals that single BFG species harbor hundreds of DNA methylation motifs, with most individual motif combinations occurring uniquely in single isolates, implying immense unsampled methylation diversity within BFG epigenomes. Mining of BFG genomes identified more than 6000 methyltransferase genes, approximately 1000 of which were associated with intact prophages. Network analysis revealed substantial gene flow among disparate phage genomes, implying a role for genetic exchange between BFG phages as one of the ultimate sources driving BFG epigenome diversity., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment., (© 2023. The Author(s).)

Climate-driven changes in precipitation amounts and their seasonal variability are expected in many continental-scale regions during the remainder of the 21st century. However, much less is known about future changes in the predictability of seasonal precipitation, an important earth system property relevant for climate adaptation. Here, on the basis of CMIP6 models that capture the present-day teleconnections between seasonal precipitation and previous-season sea surface temperature (SST), we show that climate change is expected to alter the SST-precipitation relationships and thus our ability to predict seasonal precipitation by 2100. Specifically, in the tropics, seasonal precipitation predictability from SSTs is projected to increase throughout the year, except the northern Amazonia during boreal winter. Concurrently, in the extra-tropics predictability is likely to increase in central Asia during boreal spring and winter. The altered predictability, together with enhanced interannual variability of seasonal precipitation, poses new opportunities and challenges for regional water management., (© 2023. The Author(s).)

Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses., (© 2023. The Author(s).)

Despite the extensive developments of flexible capacitive pressure sensors, it is still elusive to simultaneously achieve excellent linearity over a broad pressure range, high sensitivity, and ultrahigh pressure resolution under large pressure preloads. Here, we present a programmable fabrication method for microstructures to integrate an ultrathin ionic layer. The resulting optimized sensor exhibits a sensitivity of 33.7 kPa -1 over a linear range of 1700 kPa, a detection limit of 0.36 Pa, and a pressure resolution of 0.00725% under the pressure of 2000 kPa. Taken together with rapid response/recovery and excellent repeatability, the sensor is applied to subtle pulse detection, interactive robotic hand, and ultrahigh-resolution smart weight scale/chair. The proposed fabrication approaches and design toolkit from this work can also be leveraged to easily tune the pressure sensor performance for varying target applications and open up opportunities to create other iontronic sensors., (© 2023. The Author(s).)

Mfsd2a is the transporter for docosahexaenoic acid (DHA), an omega-3 fatty acid, across the blood brain barrier (BBB). Defects in Mfsd2a are linked to ailments from behavioral and motor dysfunctions to microcephaly. Mfsd2a transports long-chain unsaturated fatty-acids, including DHA and α-linolenic acid (ALA), that are attached to the zwitterionic lysophosphatidylcholine (LPC) headgroup. Even with the recently determined structures of Mfsd2a, the molecular details of how this transporter performs the energetically unfavorable task of translocating and flipping lysolipids across the lipid bilayer remains unclear. Here, we report five single-particle cryo-EM structures of Danio rerio Mfsd2a (drMfsd2a): in the inward-open conformation in the ligand-free state and displaying lipid-like densities modeled as ALA-LPC at four distinct positions. These Mfsd2a snapshots detail the flipping mechanism for lipid-LPC from outer to inner membrane leaflet and release for membrane integration on the cytoplasmic side. These results also map Mfsd2a mutants that disrupt lipid-LPC transport and are associated with disease., (© 2023. The Author(s).)

Existing annotation paradigms rely on controlled vocabularies, where each data instance is classified into one term from a predefined set of controlled vocabularies. This paradigm restricts the analysis to concepts that are known and well-characterized. Here, we present the novel multilingual translation method BioTranslator to address this problem. BioTranslator takes a user-written textual description of a new concept and then translates this description to a non-text biological data instance. The key idea of BioTranslator is to develop a multilingual translation framework, where multiple modalities of biological data are all translated to text. We demonstrate how BioTranslator enables the identification of novel cell types using only a textual description and how BioTranslator can be further generalized to protein function prediction and drug target identification. Our tool frees scientists from limiting their analyses within predefined controlled vocabularies, enabling them to interact with biological data using free text., (© 2023. The Author(s).)

Covalent organic frameworks have shown considerable application potential and exceptional properties in the construction of stimulus-responsive materials. Here, we designed a sweat-responsive covalent organic framework film for material-based fingerprint liveness detection. When exposed to human sweat, the COF TPDA-TFPy film can transform from yellow to red. The COF TPDA-TFPy film, when touched by living fingers, can produce the naked-eye-identified fingerprint pattern through the sweat-induced color change, while artificial fake fingerprints cannot. This technique, which we named material-based liveness detection, can thus intuitively discern living fingers from fake fingerprints with a 100% accuracy rate. Additionally, the distribution of sweat pores on human skin can also be collected and analyzed by shortening the contact time. By merely washing them with ethanol, all the samples can be utilized again. This work inventively accomplished material-based liveness detection and naked-eye-identified sweat pore analysis and highlighted their potential for use in clinical research and personal identification., (© 2023. The Author(s).)

Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies destabilizing desmosomal adhesion. Current therapies focus on suppression of autoantibody formation and thus treatments directly stabilizing keratinocyte adhesion would fulfill an unmet medical need. We here demonstrate that apremilast, a phosphodiesterase 4 inhibitor used in psoriasis, prevents skin blistering in pemphigus vulgaris. Apremilast abrogates pemphigus autoantibody-induced loss of keratinocyte cohesion in ex-vivo human epidermis, cultured keratinocytes in vitro and in vivo in mice. In parallel, apremilast inhibits keratin retraction as well as desmosome splitting, induces phosphorylation of plakoglobin at serine 665 and desmoplakin assembly into desmosomal plaques. We established a plakoglobin phospho-deficient mouse model that reveals fragile epidermis with altered organization of keratin filaments and desmosomal cadherins. In keratinocytes derived from these mice, intercellular adhesion is impaired and not rescued by apremilast. These data identify an unreported mechanism of desmosome regulation and propose that apremilast stabilizes keratinocyte adhesion and is protective in pemphigus., (© 2023. The Author(s).)

The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Here, we have engineer a series of designer cells which we term autonomous, intelligent, virus-inducible immune-like (ALICE) cells as sense-and-destroy antiviral system. After developing a destabilized STING-based sensor to detect viruses from seven different genera, we have used a synthetic signal transduction system to link viral detection to the expression of multiple antiviral effector molecules, including antiviral cytokines, a CRISPR-Cas9 module for viral degradation and the secretion of a neutralizing antibody. We perform a proof-of-concept study using multiple iterations of our ALICE system in vitro, followed by in vivo functionality testing in mice. We show that dual output ALICE SaCas9+Ab system delivered by an AAV-vector inhibited viral infection in herpetic simplex keratitis (HSK) mouse model. Our work demonstrates that viral detection and antiviral countermeasures can be paired for intelligent sense-and-destroy applications as a flexible and innovative method against virus infection., (© 2022. The Author(s).)

We developed a family of genetically encoded serotonin (5-HT) sensors (sDarken) on the basis of the native 5-HT1A receptor and circularly permuted GFP. sDarken 5-HT sensors are bright in the unbound state and diminish their fluorescence upon binding of 5-HT. Sensor variants with different affinities for serotonin were engineered to increase the versatility in imaging of serotonin dynamics. Experiments in vitro and in vivo showed the feasibility of imaging serotonin dynamics with high temporal and spatial resolution. As demonstrated here, the designed sensors show excellent membrane expression, have high specificity and a superior signal-to-noise ratio, detect the endogenous release of serotonin and are suitable for two-photon in vivo imaging., (© 2022. The Author(s).)

The success of human civilization is rooted in our ability to cooperate by communicating and making joint plans. We study how artificial agents may use communication to better cooperate in Diplomacy, a long-standing AI challenge. We propose negotiation algorithms allowing agents to agree on contracts regarding joint plans, and show they outperform agents lacking this ability. For humans, misleading others about our intentions forms a barrier to cooperation. Diplomacy requires reasoning about our opponents' future plans, enabling us to study broken commitments between agents and the conditions for honest cooperation. We find that artificial agents face a similar problem as humans: communities of communicating agents are susceptible to peers who deviate from agreements. To defend against this, we show that the inclination to sanction peers who break contracts dramatically reduces the advantage of such deviators. Hence, sanctioning helps foster mostly truthful communication, despite conditions that initially favor deviations from agreements., (© 2022. The Author(s).)

The electrochemiluminescence (ECL) is generally emitted via radiative transition of singlet or triplet excited state (S 1 or T 1 ). Herein, an ECL mechanism with the transitions of both S 1 and T 1 of black phosphorus quantum dots (BPQDs) is found, and an arginine (Arg) modification strategy is proposed to passivate the surface oxidation defects of BPQDs, which could modulate the excited states for enhancing the ECL efficiency of BPQDs. The Arg modification leads to greater spatial overlap of highest and lowest occupied molecular orbitals, and spectral shift of radiative transitions, and improves the stability of anion radical of BPQDs. To verify the application of the proposed mechanism, it is used to construct a sensitive method for conveniently evaluating the inhibiting efficiency of cyclo-arginine-glycine-aspartic acid-d-tyrosine-lysine to cell surface integrin by using Arg containing peptide modified BPQDs as signal tag. The dual excited states mediated ECL emitters provide a paradigm for adjustable ECL generation and extend the application of ECL analysis., (© 2022. The Author(s).)

Multi-principal element alloys (MPEA) demonstrate superior synergetic properties compared to single-element predominated traditional alloys. However, the rapid melting and uniform mixing of multi-elements for the fabrication of MPEA structural materials by metallic 3D printing is challenging as it is difficult to achieve both a high temperature and uniform temperature distribution in a sufficient heating source simultaneously. Herein, we report an ultrahigh-temperature melt printing method that can achieve rapid multi-elemental melting and uniform mixing for MPEA fabrication. In a typical fabrication process, multi-elemental metal powders are loaded into a high-temperature column zone that can be heated up to 3000 K via Joule heating, followed by melting on the order of milliseconds and mixing into homogenous alloys, which we attribute to the sufficiently uniform high-temperature heating zone. As proof-of-concept, we successfully fabricated single-phase bulk NiFeCrCo MPEA with uniform grain size. This ultrahigh-temperature rapid melt printing process provides excellent potential toward MPEA 3D printing., (© 2022. The Author(s).)

Using engineered wood for construction has been discussed for climate change mitigation. It remains unclear where and in which way the additional demand for wooden construction material shall be fulfilled. Here we assess the global and regional impacts of increased demand for engineered wood on land use and associated CO 2 emissions until 2100 using an open-source land system model. We show that if 90% of the new urban population would be housed in newly built urban mid-rise buildings with wooden constructions, 106 Gt of additional CO 2 could be saved by 2100. Forest plantations would need to expand by up to 149 Mha by 2100 and harvests from unprotected natural forests would increase. Our results indicate that expansion of timber plantations for wooden buildings is possible without major repercussions on agricultural production. Strong governance and careful planning are required to ensure a sustainable transition to timber cities even if frontier forests and biodiversity hotspots are protected., (© 2022. The Author(s).)

The 2030 Sustainable Development Goals (SDGs) aim at jointly improving economic, social, and environmental outcomes for human prosperity and planetary health. However, designing national economic policies that support advancement across multiple Sustainable Development Goals is hindered by the complexities of multi-sector economies and often conflicting policies. To address this, we introduce a national-scale design framework that can enable policymakers to sift through complex, non-linear, multi-sector policy spaces to identify efficient policy portfolios that balance economic, social, and environmental goals. The framework combines economy-wide sustainability simulation and artificial intelligence-driven multiobjective, multi-SDG policy search and machine learning. The framework can support multi-sector, multi-actor policy deliberation to screen efficient policy portfolios. We demonstrate the utility of the framework for a case study of Egypt by identifying policy portfolios that achieve efficient mixes of poverty and inequality reduction, economic growth, and climate change mitigation. The results show that integrated policy strategies can help achieve sustainable development while balancing adverse economic, social, and political impacts of reforms., (© 2022. The Author(s).)

In this study, we perform a thermal curve analysis with terahertz (THz) metamaterials to develop a label-free identification tool for pathogens such as bacteria and yeasts. The resonant frequency of the metasensor coated with a bacterial layer changes as a function of temperature; this provides a unique fingerprint specific to the individual microbial species without the use of fluorescent dyes and antibodies. Differential thermal curves obtained from the temperature-dependent resonance exhibit the peaks consistent with bacterial phases, such as growth, thermal inactivation, DNA denaturation, and cell wall destruction. In addition, we can distinguish gram-negative bacteria from gram-positive bacteria which show strong peaks in the temperature range of cell wall destruction. Finally, we perform THz melting curve analysis on the mixture of bacterial species in which the pathogenic bacteria are successfully distinguished from each other, which is essential for practical clinical and environmental applications such as in blood culture., (© 2022. The Author(s).)

The first step towards assessing hazards in seismically active regions involves mapping capable faults and estimating their recurrence times. While the mapping of active faults is commonly based on distinct geologic and geomorphic features evident at the surface, mapping blind seismogenic faults is complicated by the absence of on-fault diagnostic features. Here we investigated the Pichilemu Fault in coastal Chile, unknown until it generated a Mw 7.0 earthquake in 2010. The lack of evident surface faulting suggests activity along a partly-hidden blind fault. We used off-fault deformed marine terraces to estimate a fault-slip rate of 0.52 ± 0.04 m/ka, which, when integrated with satellite geodesy suggests a 2.12 ± 0.2 ka recurrence time for Mw~7.0 normal-faulting earthquakes. We propose that extension in the Pichilemu region is associated with stress changes during megathrust earthquakes and accommodated by sporadic slip during upper-plate earthquakes, which has implications for assessing the seismic potential of cryptic faults along convergent margins and elsewhere., (© 2022. The Author(s).)

Laser-based ranging (LiDAR) - already ubiquitously used in industrial monitoring, atmospheric dynamics, or geodesy - is a key sensor technology. Coherent laser ranging, in contrast to time-of-flight approaches, is immune to ambient light, operates continuous-wave allowing higher average powers, and yields simultaneous velocity and distance information. State-of-the-art coherent single laser-detector architectures reach hundreds of kilopixel per second sampling rates, while emerging applications - autonomous driving, robotics, and augmented reality - mandate megapixel per second point sampling to support real-time video-rate imaging. Yet, such rates of coherent LiDAR have not been demonstrated. Recent advances in photonic chip-based microcombs provide a route to higher acquisition speeds via parallelization but require separation of individual channels at the detector side, increasing photonic integration complexity. Here we overcome the challenge and report a hardware-efficient swept dual-soliton microcomb technique that achieves coherent ranging and velocimetry at megapixel per second line scan measurement rates with up to 64 optical channels. Multiheterodyning two synchronously frequency-modulated microcombs yields distance and velocity information of all individual ranging channels on a single receiver alleviating the need for individual separation, detection, and digitization. The reported LiDAR implementation is compatible with photonic integration and demonstrates the significant advantages of acquisition speed afforded by the convergence of optical telecommunication and metrology technologies., (© 2022. The Author(s).)

Self-assembly and fibril formation play important roles in protein behaviour. Amyloid fibril formation is well-studied due to its role in neurodegenerative diseases and characterized by refolding of the protein into predominantly β-sheet form. However, much less is known about the assembly of proteins into other types of supramolecular structures. Using cryo-electron microscopy at a resolution of 1.97 Å, we show that a triple-mutant of the anti-microbial peptide plectasin, PPI42, assembles into helical non-amyloid fibrils. The in vitro anti-microbial activity was determined and shown to be enhanced compared to the wildtype. Plectasin contains a cysteine-stabilised α-helix-β-sheet structure, which remains intact upon fibril formation. Two protofilaments form a right-handed protein fibril. The fibril formation is reversible and follows sigmoidal kinetics with a pH- and concentration dependent equilibrium between soluble monomer and protein fibril. This high-resolution structure reveals that α/β proteins can natively assemble into fibrils., (© 2022. The Author(s).)

Biophotovoltaics (BPV) generates electricity from reducing equivalent(s) produced by photosynthetic organisms by exploiting a phenomenon called extracellular electron transfer (EET), where reducing equivalent(s) is transferred to external electron acceptors. Although cyanobacteria have been extensively studied for BPV because of their high photosynthetic activity and ease of handling, their low EET activity poses a limitation. Here, we show an order-of-magnitude enhancement in photocurrent generation of the cyanobacterium Synechocystis sp. PCC 6803 by deprivation of the outer membrane, where electrons are suggested to stem from pathway(s) downstream of photosystem I. A marked enhancement of EET activity itself is verified by rapid reduction of exogenous electron acceptor, ferricyanide. The extracellular organic substances, including reducing equivalent(s), produced by this cyanobacterium serve as respiratory substrates for other heterotrophic bacteria. These findings demonstrate that the outer membrane is a barrier that limits EET. Therefore, depriving this membrane is an effective approach to exploit the cyanobacterial reducing equivalent(s)., (© 2022. The Author(s).)

Abnormal neddylation activation is frequently observed in human cancers and neddylation inhibition has been proposed as a therapy for cancer. Here, we report that MLN4924, a small-molecule inhibitor of neddylation activating enzyme, increases glutamine uptake in breast cancer cells by causing accumulation of glutamine transporter ASCT2/SLC1A5, via inactivation of CRL3-SPOP E3 ligase. We show the E3 ligase SPOP promotes ASCT2 ubiquitylation, whereas SPOP itself is auto-ubiquitylated upon glutamine deprivation. Thus, SPOP and ASCT2 inversely regulate glutamine uptake and metabolism. SPOP knockdown increases ASCT2 levels to promote growth which is rescued by ASCT2 knockdown. Adding ASCT2 inhibitor V-9302 enhances MLN4924 suppression of tumor growth. In human breast cancer specimens, SPOP and ASCT2 levels are inversely correlated, whereas lower SPOP with higher ASCT2 predicts a worse patient survival. Collectively, our study links neddylation to glutamine metabolism via the SPOP-ASCT2 axis and provides a rational drug combination for enhanced cancer therapy., (© 2022. The Author(s).)

The initial melts erupted by a Hawaiian volcano have a range of alkalic compositions but are rarely observed as they are covered by enormous volumes of shield stage tholeiites. A remarkable record of the early evolution of Hawaiian volcanoes, however, is preserved by a volcanic sandstone dredged from the submarine flank of Kilauea, which contains a suite of petrogenetically related pre-shield basanite to nephelinite glasses. Here we show that the systematic variation in the rare earth element (REE) patterns of these samples requires the fractional crystallisation of garnet. A fractionating assemblage of Ca-rich garnet (32%), omphacitic clinopyroxene (63%), and minor phlogopite can explain the variation in the major and trace element contents of the suite. The results suggest fractional crystallisation of eclogite from a primitive Hawaiian melt near the base of the lithosphere (>90 km) and that a deep magma chamber is the first stage in the development of a Hawaiian volcano., (© 2022. The Author(s).)

Volcanic activity can induce flank failure, sometimes generating large earthquakes and tsunamis. However, the failure structures have never been fully characterized and the failure mechanism is still debated. Magmatic activity is a possible trigger, either through fault slip, which might be induced by dyke intrusions, or through sill intrusions, which might be undergoing coeval normal displacements and slip. At the Piton de la Fournaise volcano, satellite imagery combined with inverse modeling highlights the pathways of 57 magmatic intrusions that took place between 1998 and 2020. We show that a major arcuate dyke intrusion zone is connected at depth to a sill intrusion zone, which becomes a fault zone towards the sea, forming a spoon-shaped structure. Some sills are affected by coeval normal displacement and seaward slip. Overall, the structure is characterized by a continuum of displacement from no slip, to sheared sills and finally pure slip. Repeated intrusions into this spoon-shaped structure could trigger catastrophic collapses., (© 2022. The Author(s).)

We present a machine learning framework to automate knowledge discovery through knowledge graph construction, inconsistency resolution, and iterative link prediction. By incorporating knowledge from 10 publicly available sources, we construct an Escherichia coli antibiotic resistance knowledge graph with 651,758 triples from 23 triple types after resolving 236 sets of inconsistencies. Iteratively applying link prediction to this graph and wet-lab validation of the generated hypotheses reveal 15 antibiotic resistant E. coli genes, with 6 of them never associated with antibiotic resistance for any microbe. Iterative link prediction leads to a performance improvement and more findings. The probability of positive findings highly correlates with experimentally validated findings (R 2  = 0.94). We also identify 5 homologs in Salmonella enterica that are all validated to confer resistance to antibiotics. This work demonstrates how evidence-driven decisions are a step toward automating knowledge discovery with high confidence and accelerated pace, thereby substituting traditional time-consuming and expensive methods., (© 2022. The Author(s).)

Developing non-noble catalysts with superior activity and durability for oxygen evolution reaction (OER) in acidic media is paramount for hydrogen production from water. Still, challenges remain due to the inadequate activity and stability of the OER catalyst. Here, we report a cost-effective and stable manganese oxybromide (Mn 7.5 O 10 Br 3 ) catalyst exhibiting an excellent OER activity in acidic electrolytes, with an overpotential of as low as 295 ± 5 mV at a current density of 10 mA cm -2 . Mn 7.5 O 10 Br 3 maintains good stability under operating conditions for at least 500 h. In situ Raman spectroscopy, X ray absorption near edge spectroscopy, and density functional theory calculations confirm that a self-oxidized surface with enhanced electronic transmission capacity forms on Mn 7.5 O 10 Br 3 and is responsible for both the high catalytic activity and long-term stability during catalysis. The development of Mn 7.5 O 10 Br 3 as an OER catalyst provides crucial insights into the design of non-noble metal electrocatalysts for water oxidation., (© 2022. The Author(s).)

Using high-throughput first-principles calculations to search for layered van der Waals materials with the largest piezoelectric stress coefficients, we discover NbOI 2 to be the one among 2940 monolayers screened. The piezoelectric performance of NbOI 2 is independent of thickness, and its electromechanical coupling factor of near unity is a hallmark of optimal interconversion between electrical and mechanical energy. Laser scanning vibrometer studies on bulk and few-layer NbOI 2 crystals verify their huge piezoelectric responses, which exceed internal references such as In 2 Se 3 and CuInP 2 S 6 . Furthermore, we provide insights into the atomic origins of anti-correlated piezoelectric and ferroelectric responses in NbOX 2 (X = Cl, Br, I), based on bond covalency and structural distortions in these materials. Our discovery that NbOI 2 has the largest piezoelectric stress coefficients among 2D materials calls for the development of NbOI 2 -based flexible nanoscale piezoelectric devices., (© 2022. The Author(s).)

Electrochemical reduction of CO 2 to multi-carbon fuels and chemical feedstocks is an appealing approach to mitigate excessive CO 2 emissions. However, the reported catalysts always show either a low Faradaic efficiency of the C 2+ product or poor long-term stability. Herein, we report a facile and scalable anodic corrosion method to synthesize oxygen-rich ultrathin CuO nanoplate arrays, which form Cu/Cu 2 O heterogeneous interfaces through self-evolution during electrocatalysis. The catalyst exhibits a high C 2 H 4 Faradaic efficiency of 84.5%, stable electrolysis for ~55 h in a flow cell using a neutral KCl electrolyte, and a full-cell ethylene energy efficiency of 27.6% at 200 mA cm -2 in a membrane electrode assembly electrolyzer. Mechanism analyses reveal that the stable nanostructures, stable Cu/Cu 2 O interfaces, and enhanced adsorption of the *OCCOH intermediate preserve selective and prolonged C 2 H 4 production. The robust and scalable produced catalyst coupled with mild electrolytic conditions facilitates the practical application of electrochemical CO 2 reduction., (© 2022. The Author(s).)

Improved analytical tools are urgently required to identify degradation and failure mechanisms in Li-ion batteries. However, understanding and ultimately avoiding these detrimental mechanisms requires continuous tracking of complex electrochemical processes in different battery components. Here, we report an operando spectroscopy method that enables monitoring the chemistry of a carbonate-based liquid electrolyte during electrochemical cycling in Li-ion batteries with a graphite anode and a LiNi 0.8 Mn 0.1 Co 0.1 O 2 cathode. By embedding a hollow-core optical fibre probe inside a lab-scale pouch cell, we demonstrate the effective evolution of the liquid electrolyte species by background-free Raman spectroscopy. The analysis of the spectroscopy measurements reveals changes in the ratio of carbonate solvents and electrolyte additives as a function of the cell voltage and show the potential to track the lithium-ion solvation dynamics. The proposed operando methodology contributes to understanding better the current Li-ion battery limitations and paves the way for studies of the degradation mechanisms in different electrochemical energy storage systems., (© 2022. The Author(s).)