The 100 most-cited articles in Proceedings of the National Academy of Sciences, 2023

Many NLP applications require manual text annotations for a variety of tasks, notably to train classifiers or evaluate the performance of unsupervised models. Depending on the size and degree of complexity, the tasks may be conducted by crowd workers on platforms such as MTurk as well as trained annotators, such as research assistants. Using four samples of tweets and news articles ( n = 6,183), we show that ChatGPT outperforms crowd workers for several annotation tasks, including relevance, stance, topics, and frame detection. Across the four datasets, the zero-shot accuracy of ChatGPT exceeds that of crowd workers by about 25 percentage points on average, while ChatGPT’s intercoder agreement exceeds that of both crowd workers and trained annotators for all tasks. Moreover, the per-annotation cost of ChatGPT is less than $0.003—about thirty times cheaper than MTurk. These results demonstrate the potential of large language models to drastically increase the efficiency of text classification.

We study GPT-3, a recent large language model, using tools from cognitive psychology. More specifically, we assess GPT-3's decision-making, information search, deliberation, and causal reasoning abilities on a battery of canonical experiments from the literature. We find that much of GPT-3's behavior is impressive: It solves vignette-based tasks similarly or better than human subjects, is able to make decent decisions from descriptions, outperforms humans in a multiarmed bandit task, and shows signatures of model-based reinforcement learning. Yet, we also find that small perturbations to vignette-based tasks can lead GPT-3 vastly astray, that it shows no signatures of directed exploration, and that it fails miserably in a causal reasoning task. Taken together, these results enrich our understanding of current large language models and pave the way for future investigations using tools from cognitive psychology to study increasingly capable and opaque artificial agents.

Soil is an immense habitat for diverse organisms across the tree of life, but just how many organisms live in soil is surprisingly unknown. Previous efforts to enumerate soil biodiversity consider only certain types of organisms (e.g., animals) or report values for diverse groups without partitioning species that live in soil versus other habitats. Here, we reviewed the biodiversity literature to show that soil is likely home to 59 ± 15% of the species on Earth. We therefore estimate an approximately two times greater soil biodiversity than previous estimates, and we include representatives from the simplest (microbial) to most complex (mammals) organisms. Enchytraeidae have the greatest percentage of species in soil (98.6%), followed by fungi (90%), Plantae (85.5%), and Isoptera (84.2%). Our results demonstrate that soil is the most biodiverse singular habitat. By using this estimate of soil biodiversity, we can more accurately and quantitatively advocate for soil organismal conservation and restoration as a central goal of the Anthropocene.

Declines in European bird populations are reported for decades but the direct effect of major anthropogenic pressures on such declines remains unquantified. Causal relationships between pressures and bird population responses are difficult to identify as pressures interact at different spatial scales and responses vary among species. Here, we uncover direct relationships between population time-series of 170 common bird species, monitored at more than 20,000 sites in 28 European countries, over 37 y, and four widespread anthropogenic pressures: agricultural intensification, change in forest cover, urbanisation and temperature change over the last decades. We quantify the influence of each pressure on population time-series and its importance relative to other pressures, and we identify traits of most affected species. We find that agricultural intensification, in particular pesticides and fertiliser use, is the main pressure for most bird population declines, especially for invertebrate feeders. Responses to changes in forest cover, urbanisation and temperature are more…

The high-valent cobalt–oxo species (Co(IV)=O) is being increasingly investigated for water purification because of its high redox potential, long half-life, and antiinterference properties. However, generation of Co(IV)=O is inefficient and unsustainable. Here, a cobalt-single-atom catalyst with N/O dual coordination was synthesized by O-doping engineering. The O-doped catalyst (Co-OCN) greatly activated peroxymonosulfate (PMS) and achieved a pollutant degradation kinetic constant of 73.12 min −1 g −2 , which was 4.9 times higher than that of Co-CN (catalyst without O-doping) and higher than those of most reported single-atom catalytic PMS systems. Co-OCN/PMS realized Co(IV)=O dominant oxidation of pollutants by increasing the steady-state concentration of Co(IV)=O (1.03 × 10 −10 M) by 5.9 times compared with Co-CN/PMS. A competitive kinetics calculation showed that the oxidation contribution of Co(IV)=O to micropollutant degradation was 97.5% during the Co-OCN/PMS process. Density functional theory calculations showed that O-doping influenced the charge density (increased the Bader…

The peroxymonosulfate (PMS)-triggered radical and nonradical active species can synergistically guarantee selectively removing micropollutants in complex wastewater; however, realizing this on heterogeneous metal-based catalysts with single active sites remains challenging due to insufficient electron cycle. Herein, we design asymmetric Co–O–Bi triple-atom sites in Co-doped Bi 2 O 2 CO 3 to facilitate PMS oxidation and reduction simultaneously by enhancing the electron transfer between the active sites. We propose that the asymmetric Co–O–Bi sites result in an electron density increase in the Bi sites and decrease in the Co sites, thereby PMS undergoes a reduction reaction to generate SO 4 •- and •OH at the Bi site and an oxidation reaction to generate 1 O 2 at the Co site. We suggest that the synergistic effect of SO 4 •- , •OH, and 1 O 2 enables efficient removal and mineralization of micropollutants without interference from organic and inorganic compounds under the environmental background. As a result, the Co-doped Bi 2 O 2 CO 3 achieves almost 99.3% sulfamethoxazole…

Compound drought and heatwave (CDHW) events have garnered increased attention due to their significant impacts on agriculture, energy, water resources, and ecosystems. We quantify the projected future shifts in CDHW characteristics (such as frequency, duration, and severity) due to continued anthropogenic warming relative to the baseline recent observed period (1982 to 2019). We combine weekly drought and heatwave information for 26 climate divisions across the globe, employing historical and projected model output from eight Coupled Model Intercomparison Project 6 GCMs and three Shared Socioeconomic Pathways. Statistically significant trends are revealed in the CDHW characteristics for both recent observed and model simulated future period (2020 to 2099). East Africa, North Australia, East North America, Central Asia, Central Europe, and Southeastern South America show the greatest increase in frequency through the late 21st century. The Southern Hemisphere displays a greater projected increase in CDHW occurrence, while the Northern Hemisphere displays a greater increase in CDHW…

Human communication is increasingly intermixed with language generated by AI. Across chat, email, and social media, AI systems suggest words, complete sentences, or produce entire conversations. AI-generated language is often not identified as such but presented as language written by humans, raising concerns about novel forms of deception and manipulation. Here, we study how humans discern whether verbal self-presentations, one of the most personal and consequential forms of language, were generated by AI. In six experiments, participants (N = 4,600) were unable to detect self-presentations generated by state-of-the-art AI language models in professional, hospitality, and dating contexts. A computational analysis of language features shows that human judgments of AI-generated language are hindered by intuitive but flawed heuristics such as associating first-person pronouns, use of contractions, or family topics with human-written language. We experimentally demonstrate that these heuristics make human judgment of AI-generated language predictable and manipulable, allowing AI…

We survey a current, heated debate in the artificial intelligence (AI) research community on whether large pretrained language models can be said to understand language-and the physical and social situations language encodes-in any humanlike sense. We describe arguments that have been made for and against such understanding and key questions for the broader sciences of intelligence that have arisen in light of these arguments. We contend that an extended science of intelligence can be developed that will provide insight into distinct modes of understanding, their strengths and limitations, and the challenge of integrating diverse forms of cognition.

The performance optimization of isolated atomically dispersed metal active sites is critical but challenging. Here, TiO 2 @Fe species-N-C catalysts with Fe atomic clusters (ACs) and satellite Fe-N 4 active sites were fabricated to initiate peroxymonosulfate (PMS) oxidation reaction. The AC-induced charge redistribution of single atoms (SAs) was verified, thus strengthening the interaction between SAs and PMS. In detail, the incorporation of ACs optimized the HSO 5 - oxidation and SO 5 ·− desorption steps, accelerating the reaction progress. As a result, the Vis/TiFeAS/PMS system rapidly eliminated 90.81% of 45 mg/L tetracycline (TC) in 10 min. The reaction process characterization suggested that PMS as an electron donor would transfer electron to Fe species in TiFeAS, generating 1 O 2 . Subsequently, the h VB + can induce the generation of electron-deficient Fe species, promoting the reaction circulation. This work provides a strategy to construct catalysts with multiple atom assembly–enabled composite active sites for high-efficiency PMS-based advanced oxidation processes (AOPs).

The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types throughout all tissues in the human body. We conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. We also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Our results indicate that the immune system of a reference 73 kg man consists of 1.8 × 10 12 cells (95% CI 1.5–2.3 × 10 12 ), weighing 1.2 kg (95% CI 0.8–1.9). Lymphocytes constitute 40% of the total number of immune cells and 15% of the mass and are mainly located in the lymph nodes and spleen. Neutrophils account for similar proportions of both the number and total mass of immune cells, with most neutrophils residing in the bone marrow. Macrophages, present in most tissues, account for 10% of immune cells but contribute nearly 50% of the total cellular mass due to their…

Crop diversification has been put forward as a way to reduce the environmental impact of agriculture without penalizing its productivity. In this context, intercropping, the planned combination of two or more crop species in one field, is a promising practice. On an average, intercropping saves land compared with the component sole crops, but it remains unclear whether intercropping produces a higher yield than the most productive single crop per unit area, i.e., whether intercropping achieves transgressive overyielding. Here, we quantified the performance of intercropping for the production of grain, calories, and protein in a global meta-analysis of several production indices. The results show that intercrops outperform sole crops when the objective is to achieve a diversity of crop products on a given land area. However, when intercropping is evaluated for its ability to produce raw products without concern for diversity, intercrops on average generate a small loss in grain or calorie yield compared with the most productive sole crop (-4%) but achieve similar or higher protein…

Abstract RNA therapeutics have the potential to resolve a myriad of diseases caused by gene deficiency. Lipid nanoparticles (LNPs) are one of the most successful RNA delivery systems. However, expanding their application hinges on the discovery of next generation LNPs with high potency, cyto-specific targeting, and low side effects. Overcoming the difficulty of releasing cargo from endocytosed LNPs remains a significant hurdle. The endosomal escape of viral and non-viral nanoparticles relies on the topological transformation of membrane fusion pore formation followed by RNA translocation into the cytosol. In this study we show that LNP-RNA nanostructure modulates the energetic cost of LNP fusion with a target membrane. The inclusion of a new class of structurally-active lipids leads to superior LNP endosomal fusion, fast evasion of endosomal entrapment, and efficacious RNA delivery. Specifically, bicontinuous cubic RNA-LNPs, cuboplexes , have significantly higher endosomal escape rates and deliver more RNA compared to regular lamellar LNPs.

Previous evaluations on the biophysical potential of forest carbon sink have focused on forestation area distribution and the associated carbon stock for equilibrium-state forests after centuries-long growth. These approaches, however, have limited relevance for climate policies because they ignore the near-term and mid-term decadal carbon uptake dynamics and suitable forest species for forestation. This study developed a forestation roadmap to support China’s “carbon neutrality” objective in 2060 by addressing three key questions of forestation: where, with what forest species, and when to afforest. The results yielded a high-confidence potential forestation map for China at a resolution of 1 km with the identified optimal native forest type or species. Our analysis revealed an additional 78 Mha suitable for forestation up to the 2060s, a 43% increase on the current forest area. Selecting forest species for maximal carbon stock in addition to maximizing local environmental suitability enabled almost a doubling in forest carbon sink potential. Progressive forestation of this area…

Abstract The AlphaFold Protein Structure Database contains predicted structures for millions of proteins. For the majority of human proteins that contain intrinsically disordered regions (IDRs), which do not adopt a stable structure, it is generally assumed these regions have low AlphaFold2 confidence scores that reflect low-confidence structural predictions. Here, we show that AlphaFold2 assigns confident structures to nearly 15% of human IDRs. By comparison to experimental NMR data for a subset of IDRs that are known to conditionally fold (i.e., upon binding or under other specific conditions), we find that AlphaFold2 often predicts the structure of the conditionally folded state. Based on databases of IDRs that are known to conditionally fold, we estimate that AlphaFold2 can identify conditionally folding IDRs at a precision as high as 88% at a 10% false positive rate, which is remarkable considering that conditionally folded IDR structures were minimally represented in its training data. We find that human disease mutations are nearly 5-fold enriched in conditionally folded IDRs…

Every year, millions of brain MRI scans are acquired in hospitals, which is a figure considerably larger than the size of any research dataset. Therefore, the ability to analyze such scans could transform neuroimaging research. Yet, their potential remains untapped since no automated algorithm is robust enough to cope with the high variability in clinical acquisitions (MR contrasts, resolutions, orientations, artifacts, and subject populations). Here, we present SynthSeg + , an AI segmentation suite that enables robust analysis of heterogeneous clinical datasets. In addition to whole-brain segmentation, SynthSeg + also performs cortical parcellation, intracranial volume estimation, and automated detection of faulty segmentations (mainly caused by scans of very low quality). We demonstrate SynthSeg + in seven experiments, including an aging study on 14,000 scans, where it accurately replicates atrophy patterns observed on data of much higher quality. SynthSeg + is publicly released as a ready-to-use tool to unlock the potential of quantitative morphometry.

Abstract Cohesin folds mammalian interphase chromosomes by extruding the chromatin fiber into numerous loops. “Loop extrusion” can be impeded by chromatin-bound factors, such as CTCF, which generates characteristic and functional chromatin organization patterns. It has been proposed that transcription relocalizes or interferes with cohesin, and that active promoters are cohesin loading sites. However, the effects of transcription on cohesin have not been reconciled with observations of active extrusion by cohesin. To determine how transcription modulates extrusion, we studied mouse cells in which we could alter cohesin abundance, dynamics, and localization by genetic ‘knockouts’ of the cohesin regulators CTCF and Wapl. Through Hi-C experiments, we discovered intricate, cohesin-dependent contact patterns near active genes. Chromatin organization around active genes exhibited hallmarks of interactions between transcribing RNA polymerases (RNAPs) and extruding cohesins. These observations could be reproduced by polymer simulations in which RNAPs were “moving barriers” to extrusion that…

A precise modulation of heterogeneous catalysts in structural and surface properties promises the development of more sustainable advanced oxidation water purification technologies. However, while catalysts with superior decontamination activity and selectivity are already achievable, maintaining a long-term service life of such materials remains challenging. Here, we propose a crystallinity engineering strategy to break the activity–stability tradeoff of metal oxides in Fenton-like catalysis. The amorphous/crystalline cobalt-manganese spinel oxide (A/C-CoMnO x ) provided highly active, hydroxyl group-rich surface, with moderate peroxymonosulfate (PMS)-binding affinity and charge transfer energy and strong pollutant adsorption, to trigger concerted radical and nonradical reactions for efficient pollutant mineralization, thereby alleviating the catalyst passivation by oxidation intermediate accumulation. Meanwhile, the surface-confined reactions, benefited from the enhanced adsorption of pollutants at A/C interface, rendered the A/C-CoMnO x /PMS system ultrahigh PMS utilization…

Human mpox (monkeypox), a disease with similarities to smallpox, is endemic in Africa where it has persisted as a zoonosis with limited human-to-human spread. Unexpectedly, the disease expanded globally in 2022 driven by human-to-human transmission outside of Africa. It is not yet known whether the latter is due solely to behavioral and environmental factors or whether the mpox virus is adapting to a new host. Genome sequencing has revealed differences between the current outbreak strains, classified as clade IIb, and the prior clade IIa and clade I viruses, but whether these differences contribute to virulence or transmission has not been determined. We demonstrate that the wild-derived inbred castaneous mouse provides an exceptional animal model for investigating clade differences in mpox virus virulence and show that the order is clade I > clade IIa > clade IIb.1. The greatly reduced replication of the clade IIb.1 major outbreak strain in mice and absence of lethality at 100 times the lethal dose of a closely related clade IIa virus, despite similar multiplication in cell…

Single-atom catalysts (SACs) are a promising area in environmental catalysis. We report on a bimetallic Co–Mo SAC that shows excellent performance in activating peroxymonosulfate (PMS) for sustainable degradation of organic pollutants with high ionization potential (IP > 8.5 eV). Density Functional Theory (DFT) calculations and experimental tests demonstrate that the Mo sites in Mo – Co SACs play a critical role in conducting electrons from organic pollutants to Co sites, leading to a 19.4-fold increase in the degradation rate of phenol compared to the CoCl 2 – PMS group. The bimetallic SACs exhibit excellent catalytic performance even under extreme conditions and show long-term activation in 10-d experiments, efficiently degrading 600 mg/L of phenol. Moreover, the catalyst has negligible toxicity toward MDA-MB-231, Hela, and MCF-7 cells, making it an environmentally friendly option for sustainable water treatment. Our findings have important implications for the design of efficient SACs for environmental remediation and other applications in biology and medicine.

Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers. Simultaneous EEG-fMRI was acquired prior to, during, and after a bolus IV administration of 20 mg DMT, and, separately, placebo. At dosages consistent with the present study, DMT, a serotonin 2A receptor (5-HT2AR) agonist, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. GFC × subjective intensity maps correlated with independent positron emission tomography (PET)-derived 5-HT2AR maps, and…

Behavioral change is essential to mitigate climate change. To advance current knowledge, we synthesize research on interventions aiming to promote climate change mitigation behaviors in field settings. In a preregistered second-order meta-analysis, we assess the overall effect of 10 meta-analyses, incorporating a total of 430 primary studies. In addition, we assess subgroup analyses for six types of interventions, five behaviors, and three publication bias adjustments. Results showed that climate change mitigation interventions were generally effective ( d unadjusted = 0.31, 95% CI [0.30, 0.32]). A follow-up analysis using only unique primary studies, adjusted for publication bias, provides a more conservative overall estimate ( d = 0.18, 95% CI [0.13, 0.24]). This translates into a mean treatment effect of 7 percentage points. Furthermore, in a subsample of adequately powered large-scale interventions ( n > 9,000, k = 32), the effect was adjusted downward to approximately 2 percentage points. This discrepancy might be because large-scale interventions often target nonvoluntary…

Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context of known socioeconomic and behavioral associations with aging-related health outcomes in a large, population-based, and diverse sample. This study uses data from a representative, panel study of US older adults to examine the relationship between DNAm-based age acceleration measures in the prediction of cross-sectional and longitudinal health outcomes and mortality. We examine whether recent improvements to these scores, using principal component (PC)-based measures designed to remove some of the technical noise and unreliability in measurement, improve the predictive capability of these measures. We also examine how well DNAm-based measures perform against well-known predictors of health outcomes such as demographics, SES, and health behaviors. In our sample, age acceleration calculated using "second and third generation clocks," PhenoAge, GrimAge, and DunedinPACE, is…

A wide range of macromolecules can undergo phase separation, forming biomolecular condensates in living cells. These membraneless organelles are typically highly dynamic, formed reversibly, and carry out essential functions in biological systems. Crucially, however, a further liquid-to-solid transition of the condensates can lead to irreversible pathological aggregation and cellular dysfunction associated with the onset and development of neurodegenerative diseases. Despite the importance of this liquid-to-solid transition of proteins, the mechanism by which it is initiated in normally functional condensates is unknown. Here we show, by measuring the changes in structure, dynamics, and mechanics in time and space, that single-component FUS condensates do not uniformly convert to a solid gel, but rather that liquid and gel phases coexist simultaneously within the same condensate, resulting in highly inhomogeneous structures. Furthermore, our results show that this transition originates at the interface between the condensate and the dilute continuous phase, and once initiated, the…

Electrochemical nitrate reduction reaction (NO 3 RR) to ammonia has been regarded as a promising strategy to balance the global nitrogen cycle. However, it still suffers from poor Faradaic efficiency (FE) and limited yield rate for ammonia production on heterogeneous electrocatalysts, especially in neutral solutions. Herein, we report one-pot synthesis of ultrathin nanosheet-assembled RuFe nanoflowers with low-coordinated Ru sites to enhance NO 3 RR performances in neutral electrolyte. Significantly, RuFe nanoflowers exhibit outstanding ammonia FE of 92.9% and yield rate of 38.68 mg h −1 mg cat −1 (64.47 mg h −1 mg Ru −1 ) at −0.30 and −0.65 V (vs. reversible hydrogen electrode), respectively. Experimental studies and theoretical calculations reveal that RuFe nanoflowers with low-coordinated Ru sites are highly electroactive with an increased d-band center to guarantee efficient electron transfer, leading to low energy barriers of nitrate reduction. The demonstration of rechargeable zinc-nitrate batteries with large-specific capacity using RuFe nanoflowers indicates their great…

Wild mammals are icons of conservation efforts, yet there is no rigorous estimate available for their overall global biomass. Biomass as a metric allows us to compare species with very different body sizes, and can serve as an indicator of wild mammal presence, trends, and impacts, on a global scale. Here, we compiled estimates of the total abundance (i.e., the number of individuals) of several hundred mammal species from the available data, and used these to build a model that infers the total biomass of terrestrial mammal species for which the global abundance is unknown. We present a detailed assessment, arriving at a total wet biomass of ≈20 million tonnes (Mt) for all terrestrial wild mammals (95% CI 13-38 Mt), i.e., ≈3 kg per person on earth. The primary contributors to the biomass of wild land mammals are large herbivores such as the white-tailed deer, wild boar, and African elephant. We find that even-hoofed mammals (artiodactyls, such as deer and boars) represent about half of the combined mass of terrestrial wild mammals. In addition, we estimated the total biomass of wild…

Singlet oxygen ( 1 O 2 ) plays a pivotal role in numerous catalytic oxidation processes utilized in water purification and chemical synthesis. The spin-trapping method based on electron paramagnetic resonance (EPR) analysis is commonly employed for 1 O 2 detection. However, it is often limited to time-independent acquisition. Recent studies have raised questions about the reliability of the 1 O 2 trapper, 2,2,6,6-tetramethylpiperidine (TEMP), in various systems. In this study, we introduce a comprehensive, kinetic examination to monitor the spin-trapping process in EPR analysis. The EPR intensity of the trapping product was used as a quantitative measurement to evaluate the concentration of 1 O 2 in aqueous systems. This in situ kinetic study was successfully applied to a classical photocatalytic system with exceptional accuracy. Furthermore, we demonstrated the feasibility of our approach in more intricate 1 O 2 -driven catalytic oxidation processes for water decontamination and elucidated the molecular mechanism of direct TEMP oxidation. This method can avoid the false-positive…

Sequence-based prediction of drug–target interactions has the potential to accelerate drug discovery by complementing experimental screens. Such computational prediction needs to be generalizable and scalable while remaining sensitive to subtle variations in the inputs. However, current computational techniques fail to simultaneously meet these goals, often sacrificing performance of one to achieve the others. We develop a deep learning model, ConPLex, successfully leveraging the advances in pretrained protein language models (“PLex”) and employing a protein-anchored contrastive coembedding (“Con”) to outperform state-of-the-art approaches. ConPLex achieves high accuracy, broad adaptivity to unseen data, and specificity against decoy compounds. It makes predictions of binding based on the distance between learned representations, enabling predictions at the scale of massive compound libraries and the human proteome. Experimental testing of 19 kinase-drug interaction predictions validated 12 interactions, including four with subnanomolar affinity, plus a strongly binding EPHB1…

Do larger incomes make people happier? Two authors of the present paper have published contradictory answers. Using dichotomous questions about the preceding day, [Kahneman and Deaton, Proc. Natl. Acad. Sci. U.S.A. 107 , 16489–16493 (2010)] reported a flattening pattern: happiness increased steadily with log(income) up to a threshold and then plateaued. Using experience sampling with a continuous scale, [Killingsworth, Proc. Natl. Acad. Sci. U.S.A. 118 , e2016976118 (2021)] reported a linear-log pattern in which average happiness rose consistently with log(income). We engaged in an adversarial collaboration to search for a coherent interpretation of both studies. A reanalysis of Killingsworth’s experienced sampling data confirmed the flattening pattern only for the least happy people. Happiness increases steadily with log(income) among happier people, and even accelerates in the happiest group. Complementary nonlinearities contribute to the overall linear-log relationship. We then explain why Kahneman and Deaton overstated the flattening pattern and why Killingsworth failed to find…

A longstanding line of research in urban studies explores how cities can be understood through their appearance. However, what remains unclear is to what extent urban dwellers' everyday life can be explained by the visual clues of the urban environment. In this paper, we address this question by applying a computer vision model to 27 million street view images across 80 counties in the United States. Then, we use the spatial distribution of notable urban features identified through the street view images, such as street furniture, sidewalks, building façades, and vegetation, to predict the socioeconomic profiles of their immediate neighborhood. Our results show that these urban features alone can account for up to 83% of the variance in people's travel behavior, 62% in poverty status, 64% in crime, and 68% in health behaviors. The results outperform models based on points of interest (POI), population, and other demographic data alone. Moreover, incorporating urban features captured from street view images can improve the explanatory power of these other methods by 5% to 25%. We…

Cell size and cell count are adaptively regulated and intimately linked to growth and function. Yet, despite their widespread relevance, the relation between cell size and count has never been formally examined over the whole human body. Here, we compile a comprehensive dataset of cell size and count over all major cell types, with data drawn from >1,500 published sources. We consider the body of a representative male (70 kg), which allows further estimates of a female (60 kg) and 10-y-old child (32 kg). We build a hierarchical interface for the cellular organization of the body, giving easy access to data, methods, and sources (https://humancelltreemap.mis.mpg.de/). In total, we estimate total body counts of ≈36 trillion cells in the male, ≈28 trillion in the female, and ≈17 trillion in the child. These data reveal a surprising inverse relation between cell size and count, implying a trade-off between these variables, such that all cells within a given logarithmic size class contribute an equal fraction to the body's total cellular biomass. We also find that the coefficient of…

Improving Coulombic efficiency (CE) is key to the adoption of high energy density lithium metal batteries. Liquid electrolyte engineering has emerged as a promising strategy for improving the CE of lithium metal batteries, but its complexity renders the performance prediction and design of electrolytes challenging. Here, we develop machine learning (ML) models that assist and accelerate the design of high-performance electrolytes. Using the elemental composition of electrolytes as the features of our models, we apply linear regression, random forest, and bagging models to identify the critical features for predicting CE. Our models reveal that a reduction in the solvent oxygen content is critical for superior CE. We use the ML models to design electrolyte formulations with fluorine-free solvents that achieve a high CE of 99.70%. This work highlights the promise of data-driven approaches that can accelerate the design of high-performance electrolytes for lithium metal batteries.

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots. Our findings highlight declining regeneration capacity across the West over the past four decades for the eight dominant conifer species studied. Postfire regeneration is sensitive to high-severity fire, which limits seed availability, and postfire climate, which influences seedling establishment. In the near-term, projected differences in recruitment probability between low- and high-severity fire scenarios were larger than projected climate change impacts for most species, suggesting that reductions in fire severity, and resultant impacts on seed availability, could partially…

The large-scale implementation of renewable energy systems necessitates the development of energy storage solutions to effectively manage imbalances between energy supply and demand. Herein, we investigate such a scalable material solution for energy storage in supercapacitors constructed from readily available material precursors that can be locally sourced from virtually anywhere on the planet, namely cement, water, and carbon black. We characterize our carbon-cement electrodes by combining correlative EDS-Raman spectroscopy with capacitance measurements derived from cyclic voltammetry and galvanostatic charge-discharge experiments using integer and fractional derivatives to correct for rate and current intensity effects. Texture analysis reveals that the hydration reactions of cement in the presence of carbon generate a fractal-like electron-conducting carbon network that permeates the load-bearing cement-based matrix. The energy storage capacity of this space-filling carbon black network of the high specific surface area accessible to charge storage is shown to be an intensive…

Sustainability of agricultural production and mitigation of global warming rely on the regeneration of soil organic carbon (SOC), in particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) forms. We conducted a global systematic meta-analysis of the effects of regenerative management practices on SOC, POC, and MAOC in cropland, finding: 1) no-till (NT) and cropping system intensification increase SOC (11.3% and 12.4%, respectively), MAOC (8.5% and 7.1%, respectively), and POC (19.7% and 33.3%, respectively) in topsoil (0 to 20 cm), but not in subsoil (>20 cm); 2) experimental duration, tillage frequency, the intensification type, and rotation diversity moderate the effects of regenerative management; and 3) NT synergized with integrated crop-livestock (ICL) systems to greatly increase POC (38.1%) and cropping intensification synergized with ICL systems to greatly increase MAOC (33.1 to 53.6%). This analysis shows that regenerative agriculture is a key strategy to reduce the soil C deficit inherent to agriculture to promote both soil health and long-term C…

Circular RNAs (circRNAs) are a class of RNAs commonly found across eukaryotes and viruses, characterized by their resistance to exonuclease-mediated degradation. Their superior stability compared to linear RNAs, combined with previous work showing that engineered circRNAs serve as efficient protein translation templates, make circRNA a promising candidate for RNA medicine. Here, we systematically examine the adjuvant activity, route of administration, and antigen-specific immunity of circRNA vaccination in mice. Potent circRNA adjuvant activity is associated with RNA uptake and activation of myeloid cells in the draining lymph nodes and transient cytokine release. Immunization of mice with engineered circRNA encoding a protein antigen delivered by a charge-altering releasable transporter induced innate activation of dendritic cells, robust antigen-specific CD8 T cell responses in lymph nodes and tissues, and strong antitumor efficacy as a therapeutic cancer vaccine. These results highlight the potential utility of circRNA vaccines for stimulating potent innate and T cell responses…

Leveraging artificial neural networks (ANNs) trained on climate model output, we use the spatial pattern of historical temperature observations to predict the time until critical global warming thresholds are reached. Although no observations are used during the training, validation, or testing, the ANNs accurately predict the timing of historical global warming from maps of historical annual temperature. The central estimate for the 1.5 °C global warming threshold is between 2033 and 2035, including a ±1σ range of 2028 to 2039 in the Intermediate (SSP2-4.5) climate forcing scenario, consistent with previous assessments. However, our data-driven approach also suggests a substantial probability of exceeding the 2 °C threshold even in the Low (SSP1-2.6) climate forcing scenario. While there are limitations to our approach, our results suggest a higher likelihood of reaching 2 °C in the Low scenario than indicated in some previous assessments-though the possibility that 2 °C could be avoided is not ruled out. Explainable AI methods reveal that the ANNs focus on particular geographic…

Transcranial low-intensity ultrasound is a promising neuromodulation modality, with the advantages of noninvasiveness, deep penetration, and high spatiotemporal accuracy. However, the underlying biological mechanism of ultrasonic neuromodulation remains unclear, hindering the development of efficacious treatments. Here, the well-known Piezo1 was studied through a conditional knockout mouse model as a major mediator for ultrasound neuromodulation ex vivo and in vivo. We showed that Piezo1 knockout (P1KO) in the right motor cortex of mice significantly reduced ultrasound-induced neuronal calcium responses, limb movement, and muscle electromyogram (EMG) responses. We also detected higher Piezo1 expression in the central amygdala (CEA), which was found to be more sensitive to ultrasound stimulation than the cortex was. Knocking out the Piezo1 in CEA neurons showed a significant reduction of response under ultrasound stimulation, while knocking out astrocytic Piezo1 showed no-obvious changes in neuronal responses. Additionally, we excluded an auditory confound by monitoring auditory…

Hydroxyl radical (OH) is a key oxidant that triggers atmospheric oxidation chemistry in both gas and aqueous phases. The current understanding of its aqueous sources is mainly based on known bulk (photo)chemical processes, uptake from gaseous OH, or related to interfacial O 3 and NO 3 radical-driven chemistry. Here, we present experimental evidence that OH radicals are spontaneously produced at the air–water interface of aqueous droplets in the dark and the absence of known precursors, possibly due to the strong electric field that forms at such interfaces. The measured OH production rates in atmospherically relevant droplets are comparable to or significantly higher than those from known aqueous bulk sources, especially in the dark. As aqueous droplets are ubiquitous in the troposphere, this interfacial source of OH radicals should significantly impact atmospheric multiphase oxidation chemistry, with substantial implications on air quality, climate, and health.

In online content moderation, two key values may come into conflict: protecting freedom of expression and preventing harm. Robust rules based in part on how citizens think about these moral dilemmas are necessary to deal with this conflict in a principled way, yet little is known about people’s judgments and preferences around content moderation. We examined such moral dilemmas in a conjoint survey experiment where US respondents ( N = 2, 564) indicated whether they would remove problematic social media posts on election denial, antivaccination, Holocaust denial, and climate change denial and whether they would take punitive action against the accounts. Respondents were shown key information about the user and their post as well as the consequences of the misinformation. The majority preferred quashing harmful misinformation over protecting free speech. Respondents were more reluctant to suspend accounts than to remove posts and more likely to do either if the harmful consequences of the misinformation were severe or if sharing it was a repeated offense. Features related to the…

Recent studies have uncovered the therapeutic potential of elesclomol (ES), a copper-ionophore, for copper deficiency disorders. However, we currently do not understand the mechanism by which copper brought into cells as ES–Cu(II) is released and delivered to cuproenzymes present in different subcellular compartments. Here, we have utilized a combination of genetic, biochemical, and cell-biological approaches to demonstrate that intracellular release of copper from ES occurs inside and outside of mitochondria. The mitochondrial matrix reductase, FDX1, catalyzes the reduction of ES–Cu(II) to Cu(I), releasing it into mitochondria where it is bioavailable for the metalation of mitochondrial cuproenzyme— cytochrome c oxidase. Consistently, ES fails to rescue cytochrome c oxidase abundance and activity in copper-deficient cells lacking FDX1. In the absence of FDX1, the ES-dependent increase in cellular copper is attenuated but not abolished. Thus, ES-mediated copper delivery to nonmitochondrial cuproproteins continues even in the absence of FDX1, suggesting alternate mechanism(s) of…

Ionizable lipid nanoparticles (LNPs) pivotal to the success of COVID-19 mRNA (messenger RNA) vaccines hold substantial promise for expanding the landscape of mRNA-based therapies. Nevertheless, the risk of mRNA delivery to off-target tissues highlights the necessity for LNPs with enhanced tissue selectivity. The intricate nature of biological systems and inadequate knowledge of lipid structure-activity relationships emphasize the significance of high-throughput methods to produce chemically diverse lipid libraries for mRNA delivery screening. Here, we introduce a streamlined approach for the rapid design and synthesis of combinatorial libraries of biodegradable ionizable lipids. This led to the identification of iso-A11B5C1, an ionizable lipid uniquely apt for muscle-specific mRNA delivery. It manifested high transfection efficiencies in muscle tissues, while significantly diminishing off-targeting in organs like the liver and spleen. Moreover, iso-A11B5C1 also exhibited reduced mRNA transfection potency in lymph nodes and antigen-presenting cells, prompting investigation into the…

As large language models (LLMs) like GPT become increasingly prevalent, it is essential that we assess their capabilities beyond language processing. This paper examines the economic rationality of GPT by instructing it to make budgetary decisions in four domains: risk, time, social, and food preferences. We measure economic rationality by assessing the consistency of GPT's decisions with utility maximization in classic revealed preference theory. We find that GPT's decisions are largely rational in each domain and demonstrate higher rationality score than those of human subjects in a parallel experiment and in the literature. Moreover, the estimated preference parameters of GPT are slightly different from human subjects and exhibit a lower degree of heterogeneity. We also find that the rationality scores are robust to the degree of randomness and demographic settings such as age and gender but are sensitive to contexts based on the language frames of the choice situations. These results suggest the potential of LLMs to make good decisions and the need to further understand their…

Nanosized zero-valent iron (nZVI) is a promising persulfate (PS) activator, however, its structurally dense oxide shell seriously inhibited electrons transfer for O-O bond cleavage of PS. Herein, we introduced sulfidation and phosphorus-doped biochar for breaking the pristine oxide shell with formation of FeS and FePO 4 -containing mixed shell. In this case, the faster diffusion rate of iron atoms compared to shell components triggered multiple Kirkendall effects, causing inward fluxion of vacancies with further coalescing into radial nanocracks. Exemplified by trichloroethylene (TCE) removal, such a unique “lemon-slice-like” nanocrack structure favored fast outward transfer of electrons and ferrous ions across the mixed shell to PS activation for high-efficient generation and utilization of reactive species, as evidenced by effective dechlorination (90.6%) and mineralization (85.4%) of TCE. O 2 • - contributed most to TCE decomposition, moreover, the SnZVI@PBC gradually became electron-deficient and thus extracted electrons from TCE with achieving nonradical-based degradation.…

(2021)], but a few of them are missing in bird genome assemblies. Here, we present a new chicken reference genome containing all autosomes, a Z and a W chromosome, with all gaps closed except for the W. We identified ten small microchromosomes (termed dot chromosomes) with distinct sequence and epigenetic features, among which six were newly assembled. Those dot chromosomes exhibit extremely high GC content and a high level of DNA methylation and are enriched for housekeeping genes. The pericentromeric heterochromatin of dot chromosomes is disproportionately large and continues to expand with the proliferation of satellite DNA and testis-expressed genes. Our analyses revealed that the 41-bp CNM repeat frequently forms higher-order repeats (HORs) at the centromeres of acrocentric chromosomes. The centromere core regions where the kinetochore attaches often encompass telomeric sequence (TTAGGG)n, and in a one of the dot chromosomes, the centromere core recruits an endogenous retrovirus (ERV). We further demonstrate that the W chromosome shares some common features with dot…

Abstract The expanding catalog of genome-wide association studies (GWAS) provides biological insights across a variety of species, but identifying the causal variants behind these associations remains a significant challenge. Experimental validation is both labor-intensive and costly, highlighting the need for accurate, scalable computational methods to predict the effects of genetic variants across the entire genome. Inspired by recent progress in natural language processing, unsupervised pre-training on large protein sequence databases has proven successful in extracting complex information related to proteins. These models showcase their ability to learn variant effects in coding regions using an unsupervised approach. Expanding on this idea, we here introduce the G enomic P re-trained N etwork ( GPN ), a model designed to learn genome-wide variant effects through unsupervised pre-training on genomic DNA sequences. Our model also successfully learns gene structure and DNA motifs without any supervision. To demonstrate its utility, we train GPN on unaligned reference genomes of…

= 2,476), we show that the structure of online sharing built into social platforms is more important than individual deficits in critical reasoning and partisan bias-commonly cited drivers of misinformation. Due to the reward-based learning systems on social media, users form habits of sharing information that attracts others' attention. Once habits form, information sharing is automatically activated by cues on the platform without users considering response outcomes such as spreading misinformation. As a result of user habits, 30 to 40% of the false news shared in our research was due to the 15% most habitual news sharers. Suggesting that sharing of false news is part of a broader response pattern established by social media platforms, habitual users also shared information that challenged their own political beliefs. Finally, we show that sharing of false news is not an inevitable consequence of user habits: Social media sites could be restructured to build habits to share accurate information.

Efficient H 2 harvesting from wastewater instead of pure water can minimize fresh water consumption, which is expected to solve the problem of water shortage in H 2 production process and contribute to carbon neutrality in the environmental remediation, but the inevitable electron depletion caused by electron-consuming pollutants will result in an exhausted H 2 evolution reaction (HER) performance. In this paper, by coupling piezocatalysis and advanced oxidation processes (AOPs) by a MoS 2 /Fe 0 /peroxymonosulfate (PMS) ternary system, extensive types of wastewater achieved considerable H 2 generation, which exceeded the yield in pure water with synchronous advanced degradation of organic pollutants. In addition, profiting from the crucial bridging role of PMS, the H 2 yield in nitrobenzene wastewater after the introduction of PMS-based AOPs increased 3.37-fold from 267.7 μmol·g −1 ·h −1 to 901.0 μmol·g −1 ·h −1 because the presence of PMS both thermodynamically benefited MoS 2 piezocatalytic H 2 evolution and eliminated the electron depletion caused by organic pollutants. By this…

The selective photocatalytic conversion of CO 2 and H 2 O to high value-added C 2 H 4 remains a great challenge, mainly attributed to the difficulties in C–C coupling of reaction intermediates and desorption of C 2 H 4 * intermediates from the catalyst surface. These two key issues can be simultaneously overcome by alloying Ag with Cu which gives enhanced activity to both reactions. Herein, we developed a facile stepwise photodeposition strategy to load Cu–Ag alloy sub-nanoclusters (ASNCs) on TiO 2 for CO 2 photoreduction to produce C 2 H 4 . The optimized catalyst exhibits a record-high C 2 H 4 formation rate (1110.6 ± 82.5 μmol g −1 h −1 ) with selectivity of 49.1 ± 1.9%, which is an order-of-magnitude enhancement relative to current work for C 2 H 4 photosynthesis. The in situ FT-IR spectra combined with DFT calculations reveal the synergistic effect of Cu and Ag in Cu–Ag ASNCs, which enable an excellent C–C coupling capability like Ag and promoted C 2 H 4 * desorption property like Cu, thus advancing the selective and efficient production of C 2 H 4 . The present work provides a…

Mineral stabilization of soil organic matter is an important regulator of the global carbon (C) cycle. However, the vulnerability of mineral-stabilized organic matter (OM) to climate change is currently unknown. We examined soil profiles from 34 sites across the conterminous USA to investigate how the abundance and persistence of mineral-associated organic C varied with climate at the continental scale. Using a novel combination of radiocarbon and molecular composition measurements, we show that the relationship between the abundance and persistence of mineral-associated organic matter (MAOM) appears to be driven by moisture availability. In wetter climates where precipitation exceeds evapotranspiration, excess moisture leads to deeper and more prolonged periods of wetness, creating conditions which favor greater root abundance and also allow for greater diffusion and interaction of inputs with MAOM. In these humid soils, mineral-associated soil organic C concentration and persistence are strongly linked, whereas this relationship is absent in drier climates. In arid soils, root…

Record-breaking summer forest fires have become a regular occurrence in California. Observations indicate a fivefold increase in summer burned area (BA) in forests in northern and central California during 1996 to 2021 relative to 1971 to 1995. While the higher temperature and increased dryness have been suggested to be the leading causes of increased BA, the extent to which BA changes are due to natural variability or anthropogenic climate change remains unresolved. Here, we develop a climate-driven model of summer BA evolution in California and combine it with natural-only and historical climate simulations to assess the importance of anthropogenic climate change on increased BA. Our results indicate that nearly all the observed increase in BA is due to anthropogenic climate change as historical model simulations accounting for anthropogenic forcing yield 172% (range 84 to 310%) more area burned than simulations with natural forcing only. We detect the signal of combined historical forcing on the observed BA emerging in 2001 with no detectable influence of the natural forcing…

Lipid nanoparticles (LNPs) are advanced core-shell particles for messenger RNA (mRNA) based therapies that are made of polyethylene glycol (PEG) lipid, distearoylphosphatidylcholine (DSPC), cationic ionizable lipid (CIL), cholesterol (chol), and mRNA. Yet the mechanism of pH-dependent response that is believed to cause endosomal release of LNPs is not well understood. Here, we show that eGFP (enhanced green fluorescent protein) protein expression in the mouse liver mediated by the ionizable lipids DLin-MC3-DMA (MC3), DLin-KC2-DMA (KC2), and DLinDMA (DD) ranks MC3 ≥ KC2 > DD despite similar delivery of mRNA per cell in all cell fractions isolated. We hypothesize that the three CIL-LNPs react differently to pH changes and hence study the structure of CIL/chol bulk phases in water. Using synchrotron X-ray scattering a sequence of ordered CIL/chol mesophases with lowering pH values are observed. These phases show isotropic inverse micellar, cubic Fd3m inverse micellar, inverse hexagonal [Formula: see text] and bicontinuous cubic Pn3m symmetry. If polyadenylic acid, as mRNA surrogate, is…

Hepatocellular carcinoma (HCC) remains a global health challenge whose incidence is growing worldwide. Previous evidence strongly supported the notion that the circadian clock controls physiological homeostasis of the liver and plays a key role in hepatocarcinogenesis. Despite the progress, cellular and molecular mechanisms underpinning this HCC-clock crosstalk remain unknown. Addressing this knowledge gap, we show here that although the human HCC cells Hep3B, HepG2, and Huh7 displayed variations in circadian rhythm profiles, all cells relied on the master circadian clock transcription factors, BMAL1 and CLOCK, for sustained cell growth. Down-regulating Bmal1 or Clock in the HCC cells induced apoptosis and arrested cell cycle at the G 2 /M phase. Mechanistically, we found that inhibiting Bmal1 / Clock induced dysregulation of the cell cycle regulators Wee1 and p21 which cooperatively contribute to tumor cell death. Bmal1 / Clock knockdown caused downregulation of Wee1 that led to apoptosis activation and upregulation of p21 which arrested the cell cycle at the G 2 /M phase.…

The gut microbiota plays a role in many human diseases, but high-throughput sequence analysis does not provide a straightforward path for defining healthy microbial communities. Therefore, understanding mechanisms that drive compositional changes during disease (gut dysbiosis) continues to be a central goal in microbiome research. Insights from the microbial pathogenesis field show that an ecological cause for gut dysbiosis is an increased availability of host-derived respiratory electron acceptors, which are dominant drivers of microbial community composition. Similar changes in the host environment also drive gut dysbiosis in several chronic human illnesses, and a better understanding of the underlying mechanisms informs approaches to causatively link compositional changes in the gut microbiota to an exacerbation of symptoms. The emerging picture suggests that homeostasis is maintained by host functions that control the availability of resources governing microbial growth. Defining dysbiosis as a weakening of these host functions directs attention to the underlying cause and…

Clarifying the reaction pathways at the solid–water interface and in bulk water solution is of great significance for the design of heterogeneous catalysts for selective oxidation of organic pollutants. However, achieving this goal is daunting because of the intricate interfacial reactions at the catalyst surface. Herein, we unravel the origin of the organic oxidation reactions with metal oxide catalysts, revealing that the radical-based advanced oxidation processes (AOPs) prevail in bulk water but not on the solid catalyst surfaces. We show that such differing reaction pathways widely exist in various chemical oxidation (e.g., high-valent Mn 3+ and MnO X ) and Fenton and Fenton-like catalytic oxidation (e.g., Fe 2+ and FeOCl catalyzing H 2 O 2 , Co 2+ and Co 3 O 4 catalyzing persulfate) systems. Compared with the radical-based degradation and polymerization pathways of one-electron indirect AOP in homogeneous reactions, the heterogeneous catalysts provide unique surface properties to trigger surface-dependent coupling and polymerization pathways of a two-electron direct oxidative…

The acute decline in global biodiversity includes not only the loss of rare species, but also the rapid collapse of common species across many different taxa. The loss of pollinating insects is of particular concern because of the ecological and economic values these species provide. The western bumble bee ( Bombus occidentalis ) was once common in western North America, but this species has become increasingly rare through much of its range. To understand potential mechanisms driving these declines, we used Bayesian occupancy models to investigate the effects of climate and land cover from 1998 to 2020, pesticide use from 2008 to 2014, and projected expected occupancy under three future scenarios. Using 14,457 surveys across 2.8 million km 2 in the western United States, we found strong negative relationships between increasing temperature and drought on occupancy and identified neonicotinoids as the pesticides of greatest negative influence across our study region. The mean predicted occupancy declined by 57% from 1998 to 2020, ranging from 15 to 83% declines across 16 ecoregions.…

Copper is distinctive in electrocatalyzing reduction of CO 2 into various energy-dense forms, but it often suffers from limited product selectivity including ethanol in competition with ethylene. Here, we describe systematically designed, bimetallic electrocatalysts based on copper/gold heterojunctions with a faradaic efficiency toward ethanol of 60% at currents in excess of 500 mA cm −2 . In the modified catalyst, the ratio of ethanol to ethylene is enhanced by a factor of 200 compared to copper catalysts. Analysis by ATR-IR measurements under operating conditions, and by computational simulations, suggests that reduction of CO 2 at the copper/gold heterojunction is dominated by generation of the intermediate OCCOH*. The latter is a key contributor in the overall, asymmetrical electrohydrogenation of CO 2 giving ethanol rather than ethylene.

Arid and semi-arid regions of the world are particularly vulnerable to greenhouse gas-driven hydroclimate change. Climate models are our primary tool for projecting the future hydroclimate that society in these regions must adapt to, but here, we present a concerning discrepancy between observed and model-based historical hydroclimate trends. Over the arid/semi-arid regions of the world, the predominant signal in all model simulations is an increase in atmospheric water vapor, on average, over the last four decades, in association with the increased water vapor-holding capacity of a warmer atmosphere. In observations, this increase in atmospheric water vapor has not happened, suggesting that the availability of moisture to satisfy the increased atmospheric demand is lower in reality than in models in arid/semi-arid regions. This discrepancy is most clear in locations that are arid/semi-arid year round, but it is also apparent in more humid regions during the most arid months of the year. It indicates a major gap in our understanding and modeling capabilities which could have severe…

Physical laws-such as the laws of motion, gravity, electromagnetism, and thermodynamics-codify the general behavior of varied macroscopic natural systems across space and time. We propose that an additional, hitherto-unarticulated law is required to characterize familiar macroscopic phenomena of our complex, evolving universe. An important feature of the classical laws of physics is the conceptual equivalence of specific characteristics shared by an extensive, seemingly diverse body of natural phenomena. Identifying potential equivalencies among disparate phenomena-for example, falling apples and orbiting moons or hot objects and compressed springs-has been instrumental in advancing the scientific understanding of our world through the articulation of laws of nature. A pervasive wonder of the natural world is the evolution of varied systems, including stars, minerals, atmospheres, and life. These evolving systems appear to be conceptually equivalent in that they display three notable attributes: 1) They form from numerous components that have the potential to adopt combinatorially…

Political discourse is the soul of democracy, but misunderstanding and conflict can fester in divisive conversations. The widespread shift to online discourse exacerbates many of these problems and corrodes the capacity of diverse societies to cooperate in solving social problems. Scholars and civil society groups promote interventions that make conversations less divisive or more productive, but scaling these efforts to online discourse is challenging. We conduct a large-scale experiment that demonstrates how online conversations about divisive topics can be improved with AI tools. Specifically, we employ a large language model to make real-time, evidence-based recommendations intended to improve participants' perception of feeling understood. These interventions improve reported conversation quality, promote democratic reciprocity, and improve the tone, without systematically changing the content of the conversation or moving people's policy attitudes.

Nanoparticle (NP)-based mRNA cancer vaccines hold great promise to realize personalized cancer treatments. To advance this technology requires delivery formulations for efficient intracellular delivery to antigen-presenting cells. We developed a class of bioreducible lipophilic poly(beta-amino ester) nanocarriers with quadpolymer architecture. The platform is agnostic to the mRNA sequence, with one-step self-assembly allowing for delivery of multiple antigen-encoding mRNAs as well as codelivery of nucleic acid-based adjuvants. We examined structure-function relationships for NP-mediated mRNA delivery to dendritic cells (DCs) and identified that a lipid subunit of the polymer structure was critical. Following intravenous administration, the engineered NP design facilitated targeted delivery to the spleen and preferential transfection of DCs without the need for surface functionalization with targeting ligands. Treatment with engineered NPs codelivering antigen-encoding mRNA and toll-like receptor agonist adjuvants led to robust antigen-specific CD8+ T cell responses, resulting in…

Water (H 2 O) microdroplets are sprayed onto a magnetic iron oxide (Fe 3 O 4 ) and Nafion-coated graphite mesh using compressed N 2 or air as the nebulizing gas. The resulting splash of microdroplets enters a mass spectrometer and is found to contain ammonia (NH 3 ). This gas–liquid–solid heterogeneous catalytic system synthesizes ammonia in 0.2 ms. The conversion rate reaches 32.9 ± 1.38 nmol s −1 cm −2 at room temperature without application of an external electric potential and without irradiation. Water microdroplets are the hydrogen source for N 2 in contact with Fe 3 O 4 . Hydrazine (H 2 NNH 2 ) is also observed as a by-product and is suspected to be an intermediate in the formation of ammonia. This one-step nitrogen-fixation strategy to produce ammonia is eco-friendly and low cost, which converts widely available starting materials into a value-added product.

Aqueous zinc-ion batteries are emerging as one of the most promising large-scale energy storage systems due to their low cost and high safety. However, Zn anodes often encounter the problems of Zn dendrite growth, hydrogen evolution reaction, and formation of by-products. Herein, we developed the low ionic association electrolytes (LIAEs) by introducing 2, 2, 2-trifluoroethanol (TFE) into 30 m ZnCl 2 electrolyte. Owing to the electron-withdrawing effect of -CF 3 groups in TFE molecules, in LIAEs, the Zn 2+ solvation structures convert from larger aggregate clusters into smaller parts and TFE will construct H-bonds with H 2 O in Zn 2+ solvation structure simultaneously. Consequently, ionic migration kinetics are significantly enhanced and the ionization of solvated H 2 O is effectively suppressed in LIAEs. As a result, Zn anodes in LIAE display a fast plating/stripping kinetics and high Coulombic efficiency of 99.74%. The corresponding full batteries exhibit an improved comprehensive performance such as high-rate capability and long cycling life.

As the use of large language models (LLMs) grows, it is important to examine whether they exhibit biases in their output. Research in cultural evolution, using transmission chain experiments, demonstrates that humans have biases to attend to, remember, and transmit some types of content over others. Here, in five preregistered experiments using material from previous studies with human participants, we use the same, transmission chain-like methodology, and find that the LLM ChatGPT-3 shows biases analogous to humans for content that is gender-stereotype-consistent, social, negative, threat-related, and biologically counterintuitive, over other content. The presence of these biases in LLM output suggests that such content is widespread in its training data and could have consequential downstream effects, by magnifying preexisting human tendencies for cognitively appealing and not necessarily informative, or valuable, content.

Cancer cells are commonly subjected to endoplasmic reticulum (ER) stress. To gain survival advantage, cancer cells exploit the adaptive aspects of the unfolded protein response such as upregulation of the ER luminal chaperone GRP78. The finding that when overexpressed, GRP78 can escape to other cellular compartments to gain new functions regulating homeostasis and tumorigenesis represents a paradigm shift. Here, toward deciphering the mechanisms whereby GRP78 knockdown suppresses EGFR transcription, we find that nuclear GRP78 is prominent in cancer and stressed cells and uncover a nuclear localization signal critical for its translocation and nuclear activity. Furthermore, nuclear GRP78 can regulate expression of genes and pathways, notably those important for cell migration and invasion, by interacting with and inhibiting the activity of the transcriptional repressor ID2. Our study reveals a mechanism for cancer cells to respond to ER stress via transcriptional regulation mediated by nuclear GRP78 to adopt an invasive phenotype.

Electrochemical synthesis of valuable chemicals and feedstocks through carbon dioxide (CO 2 ) reduction in acidic electrolytes can surmount the considerable CO 2 loss in alkaline and neutral conditions. However, achieving high productivity, while operating steadily in acidic electrolytes, remains a big challenge owing to the severe competing hydrogen evolution reaction. Here, we show that vertically grown bismuth nanosheets on a gas-diffusion layer can create numerous cavities as electrolyte reservoirs, which confine in situ–generated hydroxide and potassium ions and limit inward proton diffusion, producing locally alkaline environments. Based on this design, we achieve formic acid Faradaic efficiency of 96.3% and partial current density of 471 mA cm −2 at pH 2. When operated in a slim continuous-flow electrolyzer, the system exhibits a full-cell formic acid energy efficiency of 40% and a single pass carbon efficiency of 79% and performs steadily over 50 h. We further demonstrate the production of pure formic acid aqueous solution with a concentration of 4.2 weight %.

Lipid nanoparticles (LNPs) are a potent delivery technology that have made it possible for the recent clinical breakthroughs in mRNA therapeutics and vaccines. A key challenge to the broader implementation of mRNA therapeutics and vaccines is the development of technology to produce precisely defined LNP formulations, with throughput that can scale from discovery to commercial manufacturing and meet the stringent manufacturing standards of the pharmaceutical industry. To address these challenges, we have developed a microfluidic chip that incorporates 1×, 10×, or 256× LNP-generating units that achieve scalable production rates of up to 17 L/h of precisely defined LNPs. Using these chips, we demonstrate that LNP physical properties and potency in vivo are unchanged as throughput is scaled. Our chips are fabricated out of silicon and glass substrates, which have excellent solvent compatibility, compatibility with pharmaceutical manufacturing, and can be fully reset and reused. SARS-CoV-2 mRNA-LNP vaccines formulated by our chips triggered potent antibody responses in a preclinical…

Hydrogen peroxide (H 2 O 2 ) is an important green oxidant in the field of sewage treatment, and how to improve its activation efficiency and generate free radicals with stronger oxidation performance is a key issue in current research. Herein, we synthesized a Cu-doped α-Fe 2 O 3 catalyst (7% Cu–Fe 2 O 3 ) for activation of H 2 O 2 under visible light for degradation of organic pollutants. The introduction of a Cu dopant changed the d-band center of Fe closer to the Fermi level, which enhanced the adsorption and activation of the Fe site for H 2 O 2 , and the cleavage pathway of H 2 O 2 changed from heterolytic cleavage to homolytic cleavage, thereby improving the selectivity of •OH generation. In addition, Cu doping also promoted the light absorption ability of α-Fe 2 O 3 and the separation of hole–electron pairs, which enhanced its photocatalytic activities. Benefiting from the high selectivity of •OH, 7% Cu–Fe 2 O 3 exhibited efficient degradation activities against ciprofloxacin, the degradation rate was 3.6 times as much as that of α-Fe 2 O 3 , and it had good degradation…

Exosomes (EXOs) have been proven as biomarkers for disease diagnosis and agents for therapeutics. Great challenge remains in the separation of EXOs with high-purity and low-damage from complex biological media, which is critical for the downstream applications. Herein, we report a DNA-based hydrogel to realize the specific and nondestructive separation of EXOs from complex biological media. The separated EXOs were directly utilized in the detection of human breast cancer in clinical samples, as well as applied in the therapeutics of myocardial infarction in rat models. The materials chemistry basis of this strategy involved the synthesis of ultralong DNA chains via an enzymatic amplification, and the formation of DNA hydrogels through complementary base-pairing. These ultralong DNA chains that contained polyvalent aptamers were able to recognize and bind with the receptors on EXOs, and the specific and efficient binding ensured the selective separation of EXOs from media into the further formed networked DNA hydrogel. Based on this DNA hydrogel, rationally designed optical modules…

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection,…

Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell–dependent immunity against tumors. The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. However, the regulation of cell surface PD-L1 is still poorly understood. Here, we show that lysosomal degradation of PD-L1 is regulated by O -linked N -acetylglucosamine ( O -GlcNAc) during the intracellular trafficking pathway. O -GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. O -GlcNAc inhibition activates T cell–mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. Combination of O -GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1…

Microglial phagocytosis is an energetically demanding process that plays a critical role in the removal of toxic protein aggregates in Alzheimer's disease (AD). Recent evidence indicates that a switch in energy production from mitochondrial respiration to glycolysis disrupts this important protective microglial function and may provide therapeutic targets for AD. Here, we demonstrate that the translocator protein (TSPO) and a member of its mitochondrial complex, hexokinase-2 (HK), play critical roles in microglial respiratory-glycolytic metabolism and phagocytosis. Pharmacological and genetic loss-of-function experiments showed that TSPO is critical for microglial respiratory metabolism and energy supply for phagocytosis, and its expression is enriched in phagocytic microglia of AD mice. Meanwhile, HK controlled glycolytic metabolism and phagocytosis via mitochondrial binding or displacement. In cultured microglia, TSPO deletion impaired mitochondrial respiration and increased mitochondrial recruitment of HK, inducing a switch to glycolysis and reducing phagocytosis. To determine…

Abstract The nonstructural protein 3 (NSP3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a conserved macrodomain enzyme (Mac1) that is critical for pathogenesis and lethality. While small molecule inhibitors of Mac1 have great therapeutic potential, at the outset of the COVID-19 pandemic there were no well-validated inhibitors for this protein nor, indeed, the macrodomain enzyme family, making this target a pharmacological orphan. Here, we report the structure-based discovery and development of several different chemical scaffolds exhibiting low- to sub-micromolar affinity for Mac1 through iterations of computer-aided design, structural characterization by ultra-high resolution protein crystallography, and binding evaluation. Potent scaffolds were designed with in silico fragment linkage and by ultra-large library docking of over 450 million molecules. Both techniques leverage the computational exploration of tangible chemical space and are applicable to other pharmacological orphans. Overall, 160 ligands in 119 different scaffolds were discovered,…

Landscape dynamics are widely thought to govern the tempo and mode of continental radiations, yet the effects of river network rearrangements on dispersal and lineage diversification remain poorly understood. We integrated an unprecedented occurrence dataset of 4,967 species with a newly compiled, time-calibrated phylogeny of South American freshwater fishes-the most species-rich continental vertebrate fauna on Earth-to track the evolutionary processes associated with hydrogeographic events over 100 Ma. Net lineage diversification was heterogeneous through time, across space, and among clades. Five abrupt shifts in net diversification rates occurred during the Paleogene and Miocene (between 30 and 7 Ma) in association with major landscape evolution events. Net diversification accelerated from the Miocene to the Recent (c. 20 to 0 Ma), with Western Amazonia having the highest rates of in situ diversification, which led to it being an important source of species dispersing to other regions. All regional biotic interchanges were associated with documented hydrogeographic events and the…

As heatwaves become more frequent, intense, and longer-lasting due to climate change, the question of breaching thermal limits becomes pressing. A wet-bulb temperature (T w ) of 35 °C has been proposed as a theoretical upper limit on human abilities to biologically thermoregulate. But, recent—empirical—research using human subjects found a significantly lower maximum T w at which thermoregulation is possible even with minimal metabolic activity. Projecting future exposure to this empirical critical environmental limit has not been done. Here, using this more accurate threshold and the latest coupled climate model results, we quantify exposure to dangerous, potentially lethal heat for future climates at various global warming levels. We find that humanity is more vulnerable to moist heat stress than previously proposed because of these lower thermal limits. Still, limiting warming to under 2 °C nearly eliminates exposure and risk of widespread uncompensable moist heatwaves as a sharp rise in exposure occurs at 3 °C of warming. Parts of the Middle East and the Indus River Valley…

Callus is a reprogrammed cell mass involved in plant regeneration and gene transformation in crop engineering. Pluripotent callus cells develop into fertile shoots through shoot regeneration. The molecular basis of the shoot regeneration process in crop callus remains largely elusive. This study pioneers the exploration of the spatial transcriptome of tomato callus during shoot regeneration. The findings reveal the presence of highly heterogeneous cell populations within the callus, including epidermis, vascular tissue, shoot primordia, inner callus, and outgrowth shoots. By characterizing the spatially resolved molecular features of shoot primordia and surrounding cells, specific factors essential for shoot primordia formation are identified. Notably, chlorenchyma cells, enriched in photosynthesis-related processes, play a crucial role in promoting shoot primordia formation and subsequent shoot regeneration. Light is shown to promote shoot regeneration by inducing chlorenchyma cell development and coordinating sugar signaling. These findings significantly advance our understanding…

The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate from their typical trajectories. MRI-derived brain age (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or that lack neuroanatomic interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training on the MRIs of 4,681 cognitively normal (CN) participants and testing on 1,170 CN participants from an independent sample. BA estimation errors are notably lower than those of previous studies. At both individual and cohort levels, the CNN provides detailed anatomic maps of brain aging patterns that reveal sex dimorphisms and neurocognitive trajectories in adults with mild cognitive impairment (MCI, N = 351) and Alzheimer’s disease (AD, N = 359). In individuals with MCI (54% of whom were diagnosed with dementia within 10.9 y from MRI acquisition), BA is significantly better than CA in capturing dementia symptom…

The electrolysis of nitrate reduction to ammonia (NRA) is promising for obtaining value-added chemicals and mitigating environmental concerns. Recently, catalysts with high-performance ammonia synthesis from nitrate has been achieved under alkaline or acidic conditions. However, NRA in neutral solution still suffers from the low yield rate and selectivity of ammonia due to the low binding affinity and nucleophilicity of NO 3 − . Here, we confirmed that the in-situ-generated Fe(II) ions existed as specifically adsorbed cations in the inner Helmholtz plane (IHP) with a low redox potential. Inspired by this, a strategy (Fe-IHP strategy) was proposed to enhance NRA activity by tuning the affinity of the electrode–electrolyte interface. The specifically adsorbed Fe(II) ions [SA-Fe(II)] greatly alleviated the electrostatic repulsion around the interfaceresulting in a 10-fold lower in the adsorption-free energy of NO 3 − when compared to the case without SA-Fe(II). Meanwhile, the modulated interface accelerated the kinetic mass transfer process by 25 folds compared to the control. Under…

Abstract Peptide binding proteins play key roles in biology, and predicting their binding specificity is a long-standing challenge. While considerable protein structural information is available, the most successful current methods use sequence information alone, in part because it has been a challenge to model the subtle structural changes accompanying sequence substitutions. Protein structure prediction networks such as AlphaFold model sequence-structure relationships very accurately, and we reasoned that if it were possible to specifically train such networks on binding data, more generalizable models could be created. We show that placing a classifier on top of the AlphaFold network and fine-tuning the combined network parameters for both classification and structure prediction accuracy leads to a model with strong generalizable performance on a wide range of Class I and Class II peptide-MHC interactions that approaches the overall performance of the state-of-the-art NetMHCpan sequence-based method. The peptide-MHC optimized model shows excellent performance in distinguishing…

Tryptophan and its derivatives perform a variety of biological functions; however, the role and specific mechanism of many tryptophan derivatives in intestinal inflammation remain largely unclear. Here, we identified that an Escherichia coli strain ( Ec- TMU) isolated from the feces of tinidazole-treated individuals, and indole-3-lactic acid (ILA) in its supernatant, decreased the susceptibility of mice to dextran sulfate sodium–induced colitis. Ec- TMU and ILA contribute to the relief of colitis by inhibiting the production of epithelial CCL2/7, thereby reducing the accumulation of inflammatory macrophages in vitro and in vivo. Mechanistically, ILA downregulates glycolysis, NF-κB, and HIF signaling pathways via the aryl hydrocarbon receptor, resulting in decreased CCL2/7 production in epithelial cells. Clinical evidence suggests that the fecal ILA level is negatively correlated with the progression indicator of inflammatory bowel diseases. These results demonstrate that ILA has the potential to regulate intestinal homeostasis by modulating epithelium–macrophage interactions.

Autism spectrum disorder (ASD) has a complex genetic architecture involving contributions from both de novo and inherited variation. Few studies have been designed to address the role of rare inherited variation or its interaction with common polygenic risk in ASD. Here, we performed whole-genome sequencing of the largest cohort of multiplex families to date, consisting of 4,551 individuals in 1,004 families having two or more autistic children. Using this study design, we identify seven previously unrecognized ASD risk genes supported by a majority of rare inherited variants, finding support for a total of 74 genes in our cohort and a total of 152 genes after combined analysis with other studies. Autistic children from multiplex families demonstrate an increased burden of rare inherited protein-truncating variants in known ASD risk genes. We also find that ASD polygenic score (PGS) is overtransmitted from nonautistic parents to autistic children who also harbor rare inherited variants, consistent with combinatorial effects in the offspring, which may explain the reduced penetrance…

Western dietary patterns have been unfavorably linked with mental health. However, the long-term effects of habitual fried food consumption on anxiety and depression and underlying mechanisms remain unclear. Our population-based study with 140,728 people revealed that frequent fried food consumption, especially fried potato consumption, is strongly associated with 12% and 7% higher risk of anxiety and depression, respectively. The associations were more pronounced among male and younger consumers. Consistently, long-term exposure to acrylamide, a representative food processing contaminant in fried products, exacerbates scototaxis and thigmotaxis, and further impairs exploration ability and sociality of adult zebrafish, showing anxiety- and depressive-like behaviors. Moreover, treatment with acrylamide significantly down-regulates the gene expression of tjp2a related to the permeability of blood–brain barrier. Multiomics analysis showed that chronic exposure to acrylamide induces cerebral lipid metabolism disturbance and neuroinflammation. PPAR signaling pathway mediates…

Smart adhesives that can be applied and removed on demand play an important role in modern life and manufacturing. However, current smart adhesives made of elastomers suffer from the long-standing challenges of the adhesion paradox (rapid decrease in adhesion strength on rough surfaces despite adhesive molecular interactions) and the switchability conflict (trade-off between adhesion strength and easy detachment). Here, we report the use of shape-memory polymers (SMPs) to overcome the adhesion paradox and switchability conflict on rough surfaces. Utilizing the rubbery–glassy phase transition in SMPs, we demonstrate, through mechanical testing and mechanics modeling, that the conformal contact in the rubbery state followed by the shape-locking effect in the glassy state results in the so-called rubber-to-glass (R2G) adhesion (defined as making contact in the rubbery state to a certain indentation depth followed by detachment in the glassy state), with extraordinary adhesion strength (>1 MPa) proportional to the true surface area of a rough surface, overcoming the classic adhesion…

Zinc-nitrate batteries can integrate energy supply, ammonia electrosynthesis, and sewage disposal into one electrochemical device. However, current zinc-nitrate batteries still severely suffer from the limited energy density and poor rechargeability. Here, we report the synthesis of tetraphenylporphyrin (tpp)-modified heterophase (amorphous/crystalline) rhodium-copper alloy metallenes (RhCu M-tpp). Using RhCu M-tpp as a bifunctional catalyst for nitrate reduction reaction (NO 3 RR) and ethanol oxidation reaction in neutral solution, a highly rechargeable and low-overpotential zinc-nitrate/ethanol battery is successfully constructed, which exhibits outstanding energy density of 117364.6 Wh kg −1 cat , superior rate capability, excellent cycling stability of ~400 cycles, and potential ammonium acetate production. Ex/in situ experimental studies and theoretical calculations reveal that there is a molecule-metal relay catalysis in NO 3 RR over RhCu M-tpp that significantly facilitates the ammonia selectivity and reaction kinetics via a low energy barrier pathway. This work provides an…

We report in this work several unexpected experimental observations on evaporation from hydrogels under visible light illumination. 1) Partially wetted hydrogels become absorbing in the visible spectral range, where the absorption by both the water and the hydrogel materials is negligible. 2) Illumination of hydrogel under solar or visible-spectrum light-emitting diode leads to evaporation rates exceeding the thermal evaporation limit, even in hydrogels without additional absorbers. 3) The evaporation rates are wavelength dependent, peaking at 520 nm. 4) Temperature of the vapor phase becomes cooler under light illumination and shows a flat region due to breaking-up of the clusters that saturates air. And 5) vapor phase transmission spectra under light show new features and peak shifts. We interpret these observations by introducing the hypothesis that photons in the visible spectrum can cleave water clusters off surfaces due to large electrical field gradients and quadrupole force on molecular clusters. We call the light-induced evaporation process the photomolecular effect. The…

Fast transport of charge carriers in semiconductor photoelectrodes are a major determinant of the solar-to-hydrogen efficiency for photoelectrochemical (PEC) water slitting. While doping metal ions as single atoms/clusters in photoelectrodes has been popularly used to regulate their charge transport, PEC performances are often low due to the limited charge mobility and severe charge recombination. Here, we disperse Ru and P diatomic sites onto hematite (DASs Ru-P:Fe 2 O 3 ) to construct an efficient photoelectrode inspired by the concept of correlated single-atom engineering. The resultant photoanode shows superior photocurrent densities of 4.55 and 6.5 mA cm −2 at 1.23 and 1.50 V RHE , a low-onset potential of 0.58 V RHE , and a high applied bias photon-to-current conversion efficiency of 1.00% under one sun illumination, which are much better than the pristine Fe 2 O 3 . A detailed dynamic analysis reveals that a remarkable synergetic ineraction of the reduced recombination by a low Ru doping concentration with substitution of Fe site as well as the construction of Ru-P bonds in…

Mass extinctions during the past 500 million y rapidly removed branches from the phylogenetic tree of life and required millions of years for evolution to generate functional replacements for the extinct (EX) organisms. Here we show, by examining 5,400 vertebrate genera (excluding fishes) comprising 34,600 species, that 73 genera became EX since 1500 AD. Beyond any doubt, the human-driven sixth mass extinction is more severe than previously assessed and is rapidly accelerating. The current generic extinction rates are 35 times higher than expected background rates prevailing in the last million years under the absence of human impacts. The genera lost in the last five centuries would have taken some 18,000 y to vanish in the absence of human beings. Current generic extinction rates will likely greatly accelerate in the next few decades due to drivers accompanying the growth and consumption of the human enterprise such as habitat destruction, illegal trade, and climate disruption. If all now-endangered genera were to vanish by 2,100, extinction rates would be 354 (average) or 511…

Numerous studies have investigated the impacts of common types of chronic pain (CP) on patients' cognitive function and observed that CP was associated with later dementia. More recently, there is a growing recognition that CP conditions frequently coexist at multiple body sites and may bring more burdens on patients' overall health. However, whether and how multisite CP (MCP) contributes to an increased risk of dementia, compared to single-site CP (SCP) and pain-free (PF), is largely unclear. In the current study, utilizing the UK Biobank cohort, we first investigated dementia risk in individuals (n = 354,943) with different numbers of coexisting CP sites using Cox proportional hazards regression models. We then applied generalized additive models to investigate whether MCP leads to excessive deterioration of participants' (n = 19,116) cognition and brain structure. We found that individuals with MCP were associated with significantly higher dementia risk, broader and faster cognitive impairment, and greater hippocampal atrophy than both PF individuals and those with SCP. Moreover,…

One of the key objectives in geophysics is to characterize the subsurface through the process of analyzing and interpreting geophysical field data that are typically acquired at the surface. Data-driven deep learning methods have enormous potential for accelerating and simplifying the process but also face many challenges, including poor generalizability, weak interpretability, and physical inconsistency. We present three strategies for imposing domain knowledge constraints on deep neural networks (DNNs) to help address these challenges. The first strategy is to integrate constraints into data by generating synthetic training datasets through geological and geophysical forward modeling and properly encoding prior knowledge as part of the input fed into the DNNs. The second strategy is to design nontrainable custom layers of physical operators and preconditioners in the DNN architecture to modify or shape feature maps calculated within the network to make them consistent with the prior knowledge. The final strategy is to implement prior geological information and geophysical laws as…

Neuroinflammation is a common feature of neurodegenerative disorders such as Alzheimer's disease (AD). Neuroinflammation is induced by dysregulated glial activation, and astrocytes, the most abundant glial cells, become reactive upon neuroinflammatory cytokines released from microglia and actively contribute to neuronal loss. Therefore, blocking reactive astrocyte functions is a viable strategy to manage neurodegenerative disorders. However, factors or therapeutics directly regulating astrocyte subtypes remain unexplored. Here, we identified transcription factor NF-E2-related factor 2 (Nrf2) as a therapeutic target in neurotoxic reactive astrocytes upon neuroinflammation. We found that the absence of Nrf2 promoted the activation of reactive astrocytes in the brain tissue samples obtained from AD model 5xFAD mice, whereas enhanced Nrf2 expression blocked the induction of reactive astrocyte gene expression by counteracting NF-κB subunit p65 recruitment. Neuroinflammatory astrocytes robustly up-regulated genes associated with type I interferon and the antigen-presenting pathway, which…

Mechanical instabilities, especially in the form of bistable and multistable mechanisms, have recently garnered a lot of interest as a mode of improving the capabilities and increasing the functionalities of soft robots, structures, and soft mechanical systems in general. Although bistable mechanisms have shown high tunability through the variation of their material and design variables, they lack the option of modifying their attributes dynamically during operation. Here, we propose a facile approach to overcome this limitation by dispersing magnetically active microparticles throughout the structure of bistable elements and using an external magnetic field to tune their responses. We experimentally demonstrate and numerically verify the predictable and deterministic control of the response of different types of bistable elements under varying magnetic fields. Additionally, we show how this approach can be used to induce bistability in intrinsically monostable structures simply by placing them in a controlled magnetic field. Furthermore, we show the application of this strategy in…

Intercalation-type layered oxides have been widely explored as cathode materials for aqueous zinc-ion batteries (ZIBs). Although high-rate capability has been achieved based on the pillar effect of various intercalants for widening interlayer space, an in-depth understanding of atomic orbital variations induced by intercalants is still unknown. Herein, we design an NH 4 + -intercalated vanadium oxide (NH 4 + -V 2 O 5 ) for high-rate ZIBs, together with deeply investigating the role of the intercalant in terms of atomic orbital. Besides extended layer spacing, our X-ray spectroscopies reveal that the insertion of NH 4 + could promote electron transition to 3 d xy state of V t 2 g orbital in V 2 O 5 , which significantly accelerates the electron transfer and Zn-ion migration, further verified by DFT calculations. As results, the NH 4 + -V 2 O 5 electrode delivers a high capacity of 430.0 mA h g −1 at 0.1 A g −1 , especially excellent rate capability (101.0 mA h g −1 at 200 C), enabling fast charging within 18 s. Moreover, the reversible V t 2 g orbital and lattice space variation…

The release of wastewaters containing relatively low levels of nitrate (NO 3 − ) results in sufficient contamination to induce harmful algal blooms and to elevate drinking water NO 3 − concentrations to potentially hazardous levels. In particular, the facile triggering of algal blooms by ultra-low concentrations of NO 3 − necessitates the development of efficient methods for NO 3 − destruction. However, promising electrochemical methods suffer from weak mass transport under low reactant concentrations, resulting in long treatment times (on the order of hours) for complete NO 3 − destruction. In this study, we present flow-through electrofiltration via an electrified membrane incorporating nonprecious metal single-atom catalysts for NO 3 − reduction activity enhancement and selectivity modification, achieving near-complete removal of ultra-low concentration NO 3 − (10 mg-N L −1 ) with a residence time of only a few seconds (10 s). By anchoring Cu single atoms supported on N-doped carbon in a carbon nanotube interwoven framework, we fabricate a free-standing carbonaceous membrane…

We have structurally characterized the liquid crystal (LC) phase that can appear as an intermediate state when a dielectric nematic, having polar disorder of its molecular dipoles, transitions to the almost perfectly polar-ordered ferroelectric nematic. This intermediate phase, which fills a 100-y-old void in the taxonomy of smectic LCs and which we term the “smectic Z A ,” is antiferroelectric, with the nematic director and polarization oriented parallel to smectic layer planes, and the polarization alternating in sign from layer to layer with a 180 Å period. A Landau free energy, originally derived from the Ising model of ferromagnetic ordering of spins in the presence of dipole–dipole interactions, and applied to model incommensurate antiferroelectricity in crystals, describes the key features of the nematic–SmZ A –ferroelectric nematic phase sequence.

Suicide is one of the most devastating aspects of human nature and has puzzled scholars for thousands of years. Most suicide research to date has focused on establishing the prevalence and predictors of the presence or severity of suicidal thoughts/behaviors. Surprisingly little research has documented the fundamental properties of suicidal thoughts/behaviors, such as: when someone has a suicidal thought, how long do such thoughts last? Documenting the basic properties of a phenomenon is necessary to understand, study, and treat it. This study aims to identify the timescale of suicidal thinking, leveraging novel real-time monitoring data and a number of different novel analytic approaches. Participants were 105 adults with past week suicidal thoughts who completed a 42-day real-time monitoring study (total number of observations=20,255). Participants completed two forms of real time assessments: traditional real-time assessments (spaced hours apart each day) and high-frequency assessments (spaced 10 minutes apart over one hour). We found that suicidal thinking changes rapidly. Both…

Aberrantly upregulated choline phospholipid metabolism is a novel emerging hallmark of cancer, and choline kinase α (CHKα), a key enzyme for phosphatidylcholine production, is overexpressed in many types of human cancer through undefined mechanisms. Here, we demonstrate that the expression levels of the glycolytic enzyme enolase-1 (ENO1) are positively correlated with CHKα expression levels in human glioblastoma specimens and that ENO1 tightly governs CHKα expression via posttranslational regulation. Mechanistically, we reveal that both ENO1 and the ubiquitin E3 ligase TRIM25 are associated with CHKα. Highly expressed ENO1 in tumor cells binds to I199/F200 of CHKα, thereby abrogating the interaction between CHKα and TRIM25. This abrogation leads to the inhibition of TRIM25-mediated polyubiquitylation of CHKα at K195, increased stability of CHKα, enhanced choline metabolism in glioblastoma cells, and accelerated brain tumor growth. In addition, the expression levels of both ENO1 and CHKα are associated with poor prognosis in glioblastoma patients. These findings highlight a critical…

Electrocatalytic nitrogen reduction is a challenging process that requires achieving high ammonia yield rate and reasonable faradaic efficiency. To address this issue, this study developed a catalyst by in situ anchoring interfacial intergrown ultrafine MoO 2 nanograins on N-doped carbon fibers. By optimizing the thermal treatment conditions, an abundant number of grain boundaries were generated between MoO 2 nanograins, which led to an increased fraction of oxygen vacancies. This, in turn, improved the transfer of electrons, resulting in the creation of highly active reactive sites and efficient nitrogen trapping. The resulting optimal catalyst, MoO 2 /C 700 , outperformed commercial MoO 2 and state-of-the-art N 2 reduction catalysts, with NH 3 yield and Faradic efficiency of 173.7 μg h −1 mg −1 cat and 27.6%, respectively, under − 0.7 V vs. RHE in 1 M KOH electrolyte. In situ X-ray photoelectron spectroscopy characterization and density functional theory calculation validated the electronic structure effect and advantage of N 2 adsorption over oxygen vacancy, revealing the…

Although tumor-intrinsic fatty acid β-oxidation (FAO) is implicated in multiple aspects of tumorigenesis and progression, the impact of this metabolic pathway on cancer cell susceptibility to immunotherapy remains unknown. Here, we report that cytotoxicity of killer T cells induces activation of FAO and upregulation of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme of FAO in cancer cells. The repression of CPT1A activity or expression renders cancer cells more susceptible to destruction by cytotoxic T lymphocytes. Our mechanistic studies reveal that FAO deficiency abrogates the prosurvival signaling in cancer cells under immune cytolytic stress. Furthermore, we identify T cell-derived IFN-γ as a major factor responsible for induction of CPT1A and FAO in an AMPK-dependent manner, indicating a dynamic interplay between immune effector cells and tumor targets. While cancer growth in the absence of CPT1A remains largely unaffected, established tumors upon FAO inhibition become significantly more responsive to cellular immunotherapies including chimeric antigen…

Four years after the EAT-Lancet landmark report, worldwide movements call for action to reorient food systems to healthy diets that respect planetary boundaries. Since dietary habits are inherently local and personal, any shift toward healthy and sustainable diets going against this identity will have an uphill road. Therefore, research should address the tension between the local and global nature of the biophysical (health, environment) and social dimensions (culture, economy). Advancing the food system transformation to healthy, sustainable diets transcends the personal control of engaging consumers. The challenge for science is to scale-up, to become more interdisciplinary, and to engage with policymakers and food system actors. This will provide the evidential basis to shift from the current narrative of price, convenience, and taste to one of health, sustainability, and equity. The breaches of planetary boundaries and the environmental and health costs of the food system can no longer be considered externalities. However, conflicting interests and traditions frustrate…

Chemical products, such as plastics, solvents, and fertilizers, are essential for supporting modern lifestyles. Yet, producing, using, and disposing of chemicals creates adverse environmental impacts which threaten the industry’s license to operate. This study presents seven planet-compatible pathways toward 2050 employing demand-side and supply-side interventions with cumulative total investment costs of US$1.2–3.7 trillion. Resource efficiency and circularity interventions reduce global chemicals demand by 23 to 33% and are critical for mitigating risks associated with using fossil feedstocks and carbon capture and sequestration, and constraints on available biogenic and recyclate feedstocks. Replacing fossil feedstocks with biogenic/air-capture sources, shifting carbon destinations from the atmosphere to ground, and electrifying/decarbonizing energy supply for production technologies could enable net negative emissions of 0.5 GtCO 2eq y −1 across non-ammonia chemicals, while still delivering essential chemical-based services to society.