The 100 most-cited articles in Proceedings of the National Academy of Sciences, 2022

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to…

As the global urban population is poised to grow by 2.5 billion over the next 30 y, urban land conversions are expected to be an increasingly prominent driver of habitat and biodiversity loss. Mitigating these impacts urgently requires an improved understanding of where and how these biodiversity losses might occur. Here, we use a recently developed suite of land-use projections to provide an assessment of projected habitat that will be lost to urban land expansion for 30,393 species of terrestrial vertebrates from 2015 to 2050 across three shared socioeconomic pathway (SSP) scenarios. We find that urban land expansion is a contributing driver of habitat loss (≥5% of total loss) for around one-third (26 to 39%) of the species assessed. For up to 855 species (2 to 3% of those assessed), urban land is a direct driver of species imperilment, driving at least one-quarter of a net habitat loss of 10% or more. Urban clusters with the greatest threats to species due to projected expansion are predominantly located in the developing tropical regions of sub-Saharan Africa, South America,…

Prudent risk management requires consideration of bad-to-worst-case scenarios. Yet, for climate change, such potential futures are poorly understood. Could anthropogenic climate change result in worldwide societal collapse or even eventual human extinction? At present, this is a dangerously underexplored topic. Yet there are ample reasons to suspect that climate change could result in a global catastrophe. Analyzing the mechanisms for these extreme consequences could help galvanize action, improve resilience, and inform policy, including emergency responses. We outline current knowledge about the likelihood of extreme climate change, discuss why understanding bad-to-worst cases is vital, articulate reasons for concern about catastrophic outcomes, define key terms, and put forward a research agenda. The proposed agenda covers four main questions: 1) What is the potential for climate change to drive mass extinction events? 2) What are the mechanisms that could result in human mass mortality and morbidity? 3) What are human societies' vulnerabilities to climate-triggered risk cascades,…

Relapse to anti-HER2 monoclonal antibody (mAb) therapies, such as trastuzumab in HER2 + breast cancer (BC), is associated with residual disease progression due to resistance to therapy. Here, we identify interferon-γ inducible protein 16 (IFI16)-dependent STING signaling as a significant determinant of trastuzumab responses in HER2 + BC. We show that down-regulation of immune-regulated genes (IRG) is specifically associated with poor survival of HER2 + , but not other BC subtypes. Among IRG, IFI16 is identified as a direct target of EZH2, the underexpression of which leads to deficient STING activation and downstream CXCL10/11 expression in response to trastuzumab treatment. Dual inhibition of EZH2 and histone deacetylase (HDAC) significantly activates IFI16-dependent immune responses to trastuzumab. Notably, a combination of a novel histone methylation inhibitor with an HDAC inhibitor induces complete tumor eradication and long-term T cell memory in a HER2 + BC mouse model. Our findings demonstrate an epigenetic regulatory mechanism suppressing the expression of the IFI16-CXCL10/11…

The goals of the Earth Biogenome Project-to sequence the genomes of all eukaryotic life on earth-are as daunting as they are ambitious. The Darwin Tree of Life Project was founded to demonstrate the credibility of these goals and to deliver at-scale genome sequences of unprecedented quality for a biogeographic region: the archipelago of islands that constitute Britain and Ireland. The Darwin Tree of Life Project is a collaboration between biodiversity organizations (museums, botanical gardens, and biodiversity institutes) and genomics institutes. Together, we have built a workflow that collects specimens from the field, robustly identifies them, performs sequencing, generates high-quality, curated assemblies, and releases these openly for the global community to use to build future science and conservation efforts.

Significance The current application of messenger RNA (mRNA)-based technology has largely been confined to liver diseases because of the lack of a specific and efficient extrahepatic in vivo systemic mRNA delivery system. Here, we have developed a library of N-series lipid nanoparticles (LNPs) that could specifically regulate the protein composition of protein corona on the surface of LNPs, which allows specific delivery of mRNA to the lung. We further demonstrated that our lung-targeting LNP could effectively deliver mouse tuberous sclerosis complex 2 ( Tsc2 ) mRNA into TSC2-null cells and restore its function, resulting in enhanced control of tumor burden in a preclinical model of lymphangioleiomyomatosis, a destructive lung disease caused by loss-of-function mutations in the Tsc2 gene.

Land use is central to addressing sustainability issues, including biodiversity conservation, climate change, food security, poverty alleviation, and sustainable energy. In this paper, we synthesize knowledge accumulated in land system science, the integrated study of terrestrial social-ecological systems, into 10 hard truths that have strong, general, empirical support. These facts help to explain the challenges of achieving sustainability in land use and thus also point toward solutions. The 10 facts are as follows: 1) Meanings and values of land are socially constructed and contested; 2) land systems exhibit complex behaviors with abrupt, hard-to-predict changes; 3) irreversible changes and path dependence are common features of land systems; 4) some land uses have a small footprint but very large impacts; 5) drivers and impacts of land-use change are globally interconnected and spill over to distant locations; 6) humanity lives on a used planet where all land provides benefits to societies; 7) land-use change usually entails trade-offs between different benefits-"win-wins" are…

Significance The Fenton-like process based on peroxymonosulfate (PMS) has been widely investigated and recognized as a promising alternative in recent years for the degradation of persistent organic pollutants. However, the sluggish kinetics of PMS activation results in prohibitive costs and substantial chemical inputs, impeding its practical applications in water purification. This work demonstrates that tuning the electronic structure of single-atom sites at the atomic level is a powerful approach to achieve superior PMS activation kinetics. The Cu-based catalyst with the optimized electronic structure exhibits superior performance over most of the state-of-the-art heterogeneous Fenton-like catalysts, while homogeneous Cu(II) shows very poor activity. This work provides insights into the electronic structure regulation of metal centers and structure–activity relationship at the atomic level.

The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific expression in the LN compared with LNP formulated with ALC-0315, a synthetic lipid used in the COVID-19 vaccine Comirnaty. The targeted delivery of mRNA to the LN increased the CD8 + T cell response to the encoded full-length ovalbumin (OVA) model antigen. As a result, the protective and therapeutic effect of the OVA-encoding mRNA vaccine on the OVA-antigen–bearing B16F10 melanoma model was also improved. Moreover, 113-O12B encapsulated with TRP-2 peptide (TRP2 180–188 )–encoding mRNA also exhibited excellent tumor inhibition, with the complete response of 40% in the regular B16F10 tumor model…

Artificial intelligence (AI)-synthesized text, audio, image, and video are being weaponized for the purposes of nonconsensual intimate imagery, financial fraud, and disinformation campaigns. Our evaluation of the photorealism of AI-synthesized faces indicates that synthesis engines have passed through the uncanny valley and are capable of creating faces that are indistinguishable-and more trustworthy-than real faces.

To meet the 1.5 °C target, methane (CH4) from ruminants must be reduced by 11 to 30% by 2030 and 24 to 47% by 2050 compared to 2010 levels. A meta-analysis identified strategies to decrease product-based (PB; CH4 per unit meat or milk) and absolute (ABS) enteric CH4 emissions while maintaining or increasing animal productivity (AP; weight gain or milk yield). Next, the potential of different adoption rates of one PB or one ABS strategy to contribute to the 1.5 °C target was estimated. The database included findings from 430 peer-reviewed studies, which reported 98 mitigation strategies that can be classified into three categories: animal and feed management, diet formulation, and rumen manipulation. A random-effects meta-analysis weighted by inverse variance was carried out. Three PB strategies—namely, increasing feeding level, decreasing grass maturity, and decreasing dietary forage-to-concentrate ratio—decreased CH4 per unit meat or milk by on average 12% and increased AP by a median of 17%. Five ABS strategies—namely CH4 inhibitors, tanniferous forages, electron sinks, oils and…

Nonradical Fenton-like catalysis offers opportunities to overcome the low efficiency and secondary pollution limitations of existing advanced oxidation decontamination technologies, but realizing this on transition metal spinel oxide catalysts remains challenging due to insufficient understanding of their catalytic mechanisms. Here, we explore the origins of catalytic selectivity of Fe–Mn spinel oxide and identify electron delocalization of the surface metal active site as the key driver of its nonradical catalysis. Through fine-tuning the crystal geometry to trigger Fe–Mn superexchange interaction at the spinel octahedra, ZnFeMnO 4 with high-degree electron delocalization of the Mn–O unit was created to enable near 100% nonradical activation of peroxymonosulfate (PMS) at unprecedented utilization efficiency. The resulting surface-bound PMS* complex can efficiently oxidize electron-rich pollutants with extraordinary degradation activity, selectivity, and good environmental robustness to favor water decontamination applications. Our work provides a molecule-level understanding of the…

Science's changing demographics raise new questions about research team diversity and research outcomes. We study mixed-gender research teams, examining 6.6 million papers published across the medical sciences since 2000 and establishing several core findings. First, the fraction of publications by mixed-gender teams has grown rapidly, yet mixed-gender teams continue to be underrepresented compared to the expectations of a null model. Second, despite their underrepresentation, the publications of mixed-gender teams are substantially more novel and impactful than the publications of same-gender teams of equivalent size. Third, the greater the gender balance on a team, the better the team scores on these performance measures. Fourth, these patterns generalize across medical subfields. Finally, the novelty and impact advantages seen with mixed-gender teams persist when considering numerous controls and potential related features, including fixed effects for the individual researchers, team structures, and network positioning, suggesting that a team's gender balance is an…

Optical sensors, with great potential to convert invisible bioanalytical response into readable information, have been envisioned as a powerful platform for biological analysis and early diagnosis of diseases. However, the current extraction of sensing data is basically processed via a series of complicated and time-consuming calibrations between samples and reference, which inevitably introduce extra measurement errors and potentially annihilate small intrinsic responses. Here, we have proposed and experimentally demonstrated a calibration-free sensor for achieving high-precision biosensing detection, based on an optically controlled terahertz (THz) ultrafast metasurface. Photoexcitation of the silicon bridge enables the resonant frequency shifting from 1.385 to 0.825 THz and reaches the maximal phase variation up to 50° at 1.11 THz. The typical environmental measurement errors are completely eliminated in theory by normalizing the Fourier-transformed transmission spectra between ultrashort time delays of 37 ps, resulting in an extremely robust sensing device for monitoring the…

Understanding spoken language requires transforming ambiguous acoustic streams into a hierarchy of representations, from phonemes to meaning. It has been suggested that the brain uses prediction to guide the interpretation of incoming input. However, the role of prediction in language processing remains disputed, with disagreement about both the ubiquity and representational nature of predictions. Here, we address both issues by analyzing brain recordings of participants listening to audiobooks, and using a deep neural network (GPT-2) to precisely quantify contextual predictions. First, we establish that brain responses to words are modulated by ubiquitous predictions. Next, we disentangle model-based predictions into distinct dimensions, revealing dissociable neural signatures of predictions about syntactic category (parts of speech), phonemes, and semantics. Finally, we show that high-level (word) predictions inform low-level (phoneme) predictions, supporting hierarchical predictive processing. Together, these results underscore the ubiquity of prediction in language processing,…

SignificanceAgricultural systems are already major forces of ammonia pollution and environmental degradation. How agricultural ammonia emissions affect the spatio-temporal patterns of nitrogen deposition and where to target future mitigation efforts, remains poorly understood. We develop a substantially complete and coherent agricultural ammonia emissions dataset in nearly recent four decades, and evaluate the relative role of reduced nitrogen in total nitrogen deposition in a spatially explicit way. Global reduced nitrogen deposition has grown rapidly, and will occupy a greater dominant position in total nitrogen deposition without future ammonia regulations. Recognition of agricultural ammonia emissions on nitrogen deposition is critical to formulate effective policies to address ammonia related environmental challenges and protect ecosystems from excessive nitrogen inputs.

Understanding and communicating the environmental impacts of food products is key to enabling transitions to environmentally sustainable food systems [El Bilali and Allahyari, Inf. Process. Agric. 5, 456–464 (2018)]. While previous analyses compared the impacts of food commodities such as fruits, wheat, and beef [Poore and Nemecek, Science 360, 987–992 (2018)], most food products contain numerous ingredients. However, because the amount of each ingredient in a product is often known only by the manufacturer, it has been difficult to assess their environmental impacts. Here, we develop an approach to overcome this limitation. It uses prior knowledge from ingredient lists to infer the composition of each ingredient, and then pairs this with environmental databases [Poore and Nemecek Science 360, 987–992 (2018); Gephart et al., Nature 597, 360–365 (2021)] to derive estimates of a food product’s environmental impact across four indicators: greenhouse gas emissions, land use, water stress, and eutrophication potential. Using the approach on 57,000 products in the United Kingdom and…

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2…

Forest ecosystems are strongly impacted by continuing climate change and increasing disturbance activity, but how forest dynamics will respond remains highly uncertain. Here, we argue that a short time window after disturbance (i.e., a discrete event that disrupts prevailing ecosystem structure and composition and releases resources) is pivotal for future forest development. Trees that establish during this reorganization phase can shape forest structure and composition for centuries, providing operational early indications of forest change. While forest change has been fruitfully studied through a lens of resilience, profound ecological changes can be masked by a resilience versus regime shift dichotomy. We present a framework for characterizing the full spectrum of change after disturbance, analyzing forest reorganization along dimensions of forest structure (number, size, and spatial arrangement of trees) and composition (identity and diversity of tree species). We propose four major pathways through which forest cover can persist but reorganize following disturbance: resilience…

The US scientific workforce is primarily composed of White men. Studies have demonstrated the systemic barriers preventing women and other minoritized populations from gaining entry to science; few, however, have taken an intersectional perspective and examined the consequences of these inequalities on scientific knowledge. We provide a large-scale bibliometric analysis of the relationship between intersectional identities, topics, and scientific impact. We find homophily between identities and topic, suggesting a relationship between diversity in the scientific workforce and expansion of the knowledge base. However, topic selection comes at a cost to minoritized individuals for whom we observe both between- and within-topic citation disadvantages. To enhance the robustness of science, research organizations should provide adequate resources to historically underfunded research areas while simultaneously providing access for minoritized individuals into high-prestige networks and topics.

SignificanceOur work shows a fascinating application of finite-momentum superconductivity, the supercurrent diode effect, which is being reported in a growing number of experiments. We show that, under external magnetic field, Cooper pairs can acquire finite momentum so that critical currents in the direction parallel and antiparallel to the Cooper pair momentum become unequal.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high…

= 435). We hypothesized that infants in the high-cash gift group would have greater EEG power in the mid- to high-frequency bands and reduced power in a low-frequency band compared with infants in the low-cash gift group. Indeed, infants in the high-cash gift group showed more power in high-frequency bands. Effect sizes were similar in magnitude to many scalable education interventions, although the significance of estimates varied with the analytic specification. In sum, using a rigorous randomized design, we provide evidence that giving monthly unconditional cash transfers to mothers experiencing poverty in the first year of their children's lives may change infant brain activity. Such changes reflect neuroplasticity and environmental adaptation and display a pattern that has been associated with the development of subsequent cognitive skills.

Knowledge on the distribution and abundance of organisms is fundamental to understanding their roles within ecosystems and their ecological importance for other taxa. Such knowledge is currently lacking for insects, which have long been regarded as the “little things that run the world”. Even for ubiquitous insects, such as ants, which are of tremendous ecological significance, there is currently neither a reliable estimate of their total number on Earth nor of their abundance in particular biomes or habitats. We compile data on ground-dwelling and arboreal ants to obtain an empirical estimate of global ant abundance. Our analysis is based on 489 studies, spanning all continents, major biomes, and habitats. We conservatively estimate total abundance of ground-dwelling ants at over 3 × 10 15 and estimate the number of all ants on Earth to be almost 20 × 10 15 individuals. The latter corresponds to a biomass of ∼12 megatons of dry carbon. This exceeds the combined biomass of wild birds and mammals and is equivalent to ∼20% of human biomass. Abundances of ground-dwelling ants are…

CRISPR diagnostics based on nucleic acid amplification faces barriers to its commercial use, such as contamination risks and insufficient sensitivity. Here, we propose a robust solution involving optochemical control of CRISPR RNA (crRNA) activation in CRISPR detection. Based on this strategy, recombinase polymerase amplification (RPA) and CRISPR-Cas12a detection systems can be integrated into a completely closed test tube. crRNA can be designed to be temporarily inactivated so that RPA is not affected by Cas12a cleavage. After the RPA reaction is completed, the CRISPR-Cas12a detection system is activated under rapid light irradiation. This photocontrolled, fully closed CRISPR diagnostic system avoids contamination risks and exhibits a more than two orders of magnitude improvement in sensitivity compared with the conventional one-pot assay. This photocontrolled CRISPR method was applied to the clinical detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, achieving detection sensitivity and specificity comparable to those of PCR. Furthermore, a compact and…

Managing agricultural landscapes to support biodiversity conservation requires profound structural changes worldwide. Often, discussions are centered on management at the field level. However, a wide and growing body of evidence calls for zooming out and targeting agricultural policies, research, and interventions at the landscape level to halt and reverse the decline in biodiversity, increase biodiversity-mediated ecosystem services in agricultural landscapes, and improve the resilience and adaptability of these ecosystems. We conducted the most comprehensive assessment to date on landscape complexity effects on nondomesticated terrestrial biodiversity through a meta-analysis of 1,134 effect sizes from 157 peer-reviewed articles. Increasing landscape complexity through changes in composition, configuration, or heterogeneity significatively and positively affects biodiversity. More complex landscapes host more biodiversity (richness, abundance, and evenness) with potential benefits to sustainable agricultural production and conservation, and effects are likely underestimated. The…

Significance Stream/river carbon dioxide (CO 2 ) emission has significant spatial and seasonal variations critical for understanding its macroecosystem controls and plumbing of the terrestrial carbon budget. We relied on direct fluvial CO 2 partial pressure measurements and seasonally varying gas transfer velocity and river network surface area estimates to resolve reach-level seasonal variations of the flux at the global scale. The percentage of terrestrial primary production (GPP) shunted into rivers that ultimately contributes to CO 2 evasion increases with discharge across regions, due to a stronger response in fluvial CO 2 evasion to discharge than GPP. This highlights the importance of hydrology, in particular water throughput, in terrestrial–fluvial carbon transfers and the need to account for this effect in plumbing the terrestrial carbon budget.

No evidence for nudging after adjusting for publication bias

Politics has in recent decades entered an era of intense polarization. Explanations have implicated digital media, with the so-called echo chamber remaining a dominant causal hypothesis despite growing challenge by empirical evidence. This paper suggests that this mounting evidence provides not only reason to reject the echo chamber hypothesis but also the foundation for an alternative causal mechanism. To propose such a mechanism, the paper draws on the literatures on affective polarization, digital media, and opinion dynamics. From the affective polarization literature, we follow the move from seeing polarization as diverging issue positions to rooted in sorting: an alignment of differences which is effectively dividing the electorate into two increasingly homogeneous megaparties. To explain the rise in sorting, the paper draws on opinion dynamics and digital media research to present a model which essentially turns the echo chamber on its head: it is not isolation from opposing views that drives polarization but precisely the fact that digital media bring us to interact outside…

Abstract Macromolecular phase separation is thought to be one of the processes that drives the formation of membraneless biomolecular condensates in cells. The dynamics of phase separation, especially at low endogenous concentrations found in cells, are thought to follow the tenets of classical nucleation theory describing a sharp transition between a dense phase and a dilute phase characterized by dispersed monomers. Here, we used in vitro biophysical studies to study subsaturated solutions of phase separating RNA binding proteins with intrinsically disordered prion like domains (PLDs) and RNA binding domains (RBDs). Surprisingly, we find that subsaturated solutions are characterized by heterogeneous distributions of clusters comprising tens to hundreds of molecules. These clusters also include low abundance mesoscale species that are several hundreds of nanometers in diameter. Our results show that cluster formation in subsaturated solutions and phase separation in supersaturated solutions are strongly coupled via sequence-encoded interactions. Interestingly, however, cluster…

Many critical policy decisions, from strategic investments to the allocation of humanitarian aid, rely on data about the geographic distribution of wealth and poverty. Yet many poverty maps are out of date or exist only at very coarse levels of granularity. Here we develop microestimates of the relative wealth and poverty of the populated surface of all 135 low- and middle-income countries (LMICs) at 2.4 km resolution. The estimates are built by applying machine-learning algorithms to vast and heterogeneous data from satellites, mobile phone networks, and topographic maps, as well as aggregated and deidentified connectivity data from Facebook. We train and calibrate the estimates using nationally representative household survey data from 56 LMICs and then validate their accuracy using four independent sources of household survey data from 18 countries. We also provide confidence intervals for each microestimate to facilitate responsible downstream use. These estimates are provided free for public use in the hope that they enable targeted policy response to the COVID-19 pandemic,…

The Renewable Fuel Standard (RFS) specifies the use of biofuels in the United States and thereby guides nearly half of all global biofuel production, yet outcomes of this keystone climate and environmental regulation remain unclear. Here we combine econometric analyses, land use observations, and biophysical models to estimate the realized effects of the RFS in aggregate and down to the scale of individual agricultural fields across the United States. We find that the RFS increased corn prices by 30% and the prices of other crops by 20%, which, in turn, expanded US corn cultivation by 2.8 Mha (8.7%) and total cropland by 2.1 Mha (2.4%) in the years following policy enactment (2008 to 2016). These changes increased annual nationwide fertilizer use by 3 to 8%, increased water quality degradants by 3 to 5%, and caused enough domestic land use change emissions such that the carbon intensity of corn ethanol produced under the RFS is no less than gasoline and likely at least 24% higher. These tradeoffs must be weighed alongside the benefits of biofuels as decision-makers consider the…

Heterogeneous peroxymonosulfate (PMS)–based advanced oxidation processes (AOPs) have shown a great potential for pollutant degradation, but their feasibility for large-scale water treatment application has not been demonstrated. Herein, we develop a facile coprecipitation method for the scalable production (∼10 kg) of the Cu-Fe-Mn spinel oxide (CuFeMnO). Such a catalyst has rich oxygen vacancies and symmetry-breaking sites, which endorse it with a superior PMS-catalytic capacity. We find that the working reactive species and their contributions are highly dependent on the properties of target organic pollutants. For the organics with electron-donating group (e.g., -OH), high-valent metal species are mainly responsible for the pollutant degradation, whereas for the organics with electron-withdrawing group (e.g., -COOH and -NO 2 ), hydroxyl radical (•OH) as the secondary oxidant also plays an important role. We demonstrate that the CuFeMnO–PMS system is able to achieve efficient and stable removal of the pollutants in the secondary effluent from a municipal wastewater plant at both…

Significance The results provide strong evidence of extensive SARS-CoV-2 infection of white-tailed deer, a free-living wild animal species with widespread distribution across North, Central, and South America. The analysis shows infection of deer resulted from multiple spillovers from humans, followed by efficient deer-to-deer transmission. The discovery of widespread infection of white-tailed deer indicates their establishment as potential reservoir hosts for SARS-CoV-2, a finding with important implications for the ecology, long-term persistence, and evolution of the virus, including the potential for spillback to humans.

In idiopathic Parkinson’s disease (PD), pathologic αSyn aggregates drive oxidative and nitrative stress that may cause genomic and mitochondrial DNA damage. These events are associated with activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) immune pathway, but it is not known whether STING is activated in or contributes to α-synucleinopathies. Herein, we used primary cell cultures and the intrastriatal αSyn preformed fibril (αSyn-PFF) mouse model of PD to demonstrate that αSyn pathology causes STING-dependent neuroinflammation and dopaminergic neurodegeneration. In microglia-astrocyte cultures, αSyn-PFFs induced DNA double-strand break (DSB) damage response signaling (γH2A.X), as well as TBK1 activation that was blocked by STING inhibition. In the αSyn-PFF mouse model, we similarly observed TBK1 activation and increased γH2A.X within striatal microglia prior to the onset of dopaminergic neurodegeneration. Using STING-deficient (Stinggt) mice, we demonstrated that striatal interferon activation in the α-Syn PFF model is STING-dependent.…

Constraining the climate crisis requires urgent action to reduce anthropogenic emissions while simultaneously removing carbon dioxide from the atmosphere. Improved information about the maximum magnitude and spatial distribution of opportunities for additional land-based removals of CO2 is needed to guide on-the-ground decision-making about where to implement climate change mitigation strategies. Here, we present a globally consistent spatial dataset (approximately 500-m resolution) of current, potential, and unrealized potential carbon storage in woody plant biomass and soil organic matter. We also provide a framework for prioritizing actions related to the restoration, management, and maintenance of woody carbon stocks and associated soils. By comparing current to potential carbon storage, while excluding areas critical to food production and human habitation, we find 287 petagrams (PgC) of unrealized potential storage opportunity, of which 78% (224 PgC) is in biomass and 22% (63 PgC) is in soil. Improved management of existing forests may offer nearly three-fourths (206 PgC) of…

Soft robots that can harvest energy from environmental resources for autonomous locomotion is highly desired; however, few are capable of adaptive navigation without human interventions. Here, we report twisting soft robots with embodied physical intelligence for adaptive, intelligent autonomous locomotion in various unstructured environments, without on-board or external controls and human interventions. The soft robots are constructed of twisted thermal-responsive liquid crystal elastomer ribbons with a straight centerline. They can harvest thermal energy from environments to roll on outdoor hard surfaces and challenging granular substrates without slip, including ascending loose sandy slopes, crossing sand ripples, escaping from burying sand, and crossing rocks with additional camouflaging features. The twisting body provides anchoring functionality by burrowing into loose sand. When encountering obstacles, they can either self-turn or self-snap for obstacle negotiation and avoidance. Theoretical models and finite element simulation reveal that such physical intelligence is…

SignificanceThis study uses large-scale news media and social media data to show that nationwide Black Lives Matter (BLM) protests occur concurrently with sharp increases in public attention to components of the BLM agenda. We also show that attention to BLM and related concepts is not limited to these brief periods of protest but is sustained after protest has ceased. This suggests that protest events incited a change in public awareness of BLM's vision of social change and the dissemination of antiracist ideas into popular discourse.

Breast cancer is the most frequent malignancy in women worldwide, and triple-negative breast cancer (TNBC) patients have the worst prognosis and highest risk of recurrence. The therapeutic strategies for TNBC are limited. It is urgent to develop new methods to enhance the efficacy of TNBC treatment. Previous studies demonstrated that D-mannose, a hexose, can enhance chemotherapy in cancer and suppress the immunopathology of autoimmune diseases. Here, we show that D-mannose can significantly facilitate TNBC treatment via degradation of PD-L1. Specifically, D-mannose can activate AMP-activated protein kinase (AMPK) to phosphorylate PD-L1 at S195, which leads to abnormal glycosylation and proteasomal degradation of PD-L1. D-mannose-mediated PD-L1 degradation promotes T cell activation and T cell killing of tumor cells. The combination of D-mannose and PD-1 blockade therapy dramatically inhibits TNBC growth and extends the lifespan of tumor-bearing mice. Moreover, D-mannose-induced PD-L1 degradation also results in messenger RNA destabilization of DNA damage repair-related genes,…

One of the most fundamental questions in ecology is how many species inhabit the Earth. However, due to massive logistical and financial challenges and taxonomic difficulties connected to the species concept definition, the global numbers of species, including those of important and well-studied life forms such as trees, still remain largely unknown. Here, based on global ground-sourced data, we estimate the total tree species richness at global, continental, and biome levels. Our results indicate that there are ∼73,000 tree species globally, among which ∼9,000 tree species are yet to be discovered. Roughly 40% of undiscovered tree species are in South America. Moreover, almost one-third of all tree species to be discovered may be rare, with very low populations and limited spatial distribution (likely in remote tropical lowlands and mountains). These findings highlight the vulnerability of global forest biodiversity to anthropogenic changes in land use and climate, which disproportionately threaten rare species and thus, global tree richness.

Significance Electrochemical reduction of nitrate pollution in water into value-added ammonium is essential for modern agriculture and industry and represents a potentially sustainable strategy to replace the traditional Haber–Bosch process. However, the nitrate reduction reaction (NO 3 − RR) process under ambient conditions often suffers from low selectivity. Here, we developed a strategy of tuning an electronic structure for preparing cobalt-doped Fe@Fe 2 O 3 electrocatalysts. Cobalt doping tunes the Fe d-band center, thereby modulating the adsorption energies of intermediates and suppressing hydrogen production. Therefore, the electrocatalysts exhibit superior NO 3 − RR activity with a high nitrate removal capacity (100.8 mg N g cat −1 h −1 ), NH 3 selectivity (99.0 ± 0.1%), and faradaic efficiency (85.2 ± 0.6%). This strategy provides an approach to design advanced materials for NO 3 − RR.

Contact electrification between water and a solid surface is crucial for physicochemical processes at water–solid interfaces. However, the nature of the involved processes remains poorly understood, especially in the initial stage of the interface formation. Here we report that H 2 O 2 is spontaneously produced from the hydroxyl groups on the solid surface when contact occurred. The density of hydroxyl groups affects the H 2 O 2 yield. The participation of hydroxyl groups in H 2 O 2 generation is confirmed by mass spectrometric detection of 18 O in the product of the reaction between 4-carboxyphenylboronic acid and 18 O–labeled H 2 O 2 resulting from 18 O 2 plasma treatment of the surface. We propose a model for H 2 O 2 generation based on recombination of the hydroxyl radicals produced from the surface hydroxyl groups in the water–solid contact process. Our observations show that the spontaneous generation of H 2 O 2 is universal on the surfaces of soil and atmospheric fine particles in a humid environment.

Although they are staple foods in cuisines globally, many commercial fruit varieties have become progressively less flavorful over time. Due to the cost and difficulty associated with flavor phenotyping, breeding programs have long been challenged in selecting for this complex trait. To address this issue, we leveraged targeted metabolomics of diverse tomato and blueberry accessions and their corresponding consumer panel ratings to create statistical and machine learning models that can predict sensory perceptions of fruit flavor. Using these models, a breeding program can assess flavor ratings for a large number of genotypes, previously limited by the low throughput of consumer sensory panels. The ability to predict consumer ratings of liking, sweet, sour, umami, and flavor intensity was evaluated by a 10-fold cross-validation, and the accuracies of 18 different models were assessed. The prediction accuracies were high for most attributes and ranged from 0.87 for sourness intensity in blueberry using XGBoost to 0.46 for overall liking in tomato using linear regression. Further, the…

This study explores how researchers' analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers' expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each team's workflow. This reveals a universe of uncertainty that remains hidden when…

Political scientists, pundits, and citizens worry that America is entering a new period of violent partisan conflict. Provocative survey data show that a large share of Americans (between 8% and 40%) support politically motivated violence. Yet, despite media attention, political violence is rare, amounting to a little more than 1% of violent hate crimes in the United States. We reconcile these seemingly conflicting facts with four large survey experiments ( n = 4,904), demonstrating that self-reported attitudes on political violence are biased upward because of respondent disengagement and survey questions that allow multiple interpretations of political violence. Addressing question wording and respondent disengagement, we find that the median of existing estimates of support for partisan violence is nearly 6 times larger than the median of our estimates (18.5% versus 2.9%). Critically, we show the prior estimates overstate support for political violence because of random responding by disengaged respondents. Respondent disengagement also inflates the relationship between support…

Mean annual temperature and mean annual precipitation drive much of the variation in productivity across Earth's terrestrial ecosystems but do not explain variation in gross primary productivity (GPP) or ecosystem respiration (ER) in flowing waters. We document substantial variation in the magnitude and seasonality of GPP and ER across 222 US rivers. In contrast to their terrestrial counterparts, most river ecosystems respire far more carbon than they fix and have less pronounced and consistent seasonality in their metabolic rates. We find that variation in annual solar energy inputs and stability of flows are the primary drivers of GPP and ER across rivers. A classification schema based on these drivers advances river science and informs management.

As a midsized gene family conserved more by lineage than function, the typical plant terpene synthases (TPSs) could be a valuable tool to examine plant evolution. TPSs are pivotal in biosynthesis of gibberellins and related phytohormones as well as in formation of the extensive arsenal of specialized plant metabolites mediating ecological interactions whose production is often lineage specific. Yet the origin and early evolution of the TPS family is not well understood. Systematic analysis of an array of transcriptomes and sequenced genomes indicated that the TPS family originated after the divergence of land plants from charophytic algae. Phylogenetic and biochemical analyses support the hypothesis that the ancestral TPS gene encoded a bifunctional class I and II diterpene synthase producing the ent-kaurene required for phytohormone production in all extant lineages of land plants. Moreover, the ancestral TPS gene likely underwent duplication at least twice early in land plant evolution. Together these two gave rise to three TPS lineages leading to the extant TPS-c, TPS-e/f, and…

Urbanization can challenge sustainable development if it produces unequal outcomes. Infrastructure is an important urbanization dimension, providing services to support diverse urban activities. However, it can lock in unequal outcomes due to its durable nature. This paper studies inequalities in infrastructure distributions to derive insights into the structure and characteristics of unequal outcomes associated with urbanization. We analyzed infrastructure inequalities in two emerging economies in the Global South: India and South Africa. We developed and applied an inequality measure to understand the structure of inequality in infrastructure provisioning (based on census data) and infrastructure availability (based on satellite nighttime lights [NTLs] data). Consistent with differences in economic inequality, results show greater inequalities in South Africa than in India and greater urban inequalities than rural inequalities. Nevertheless, inequalities in urban infrastructure provisioning and infrastructure availability increase from finer to coarser spatial scales. NTL-based…

effector Tconvs, including tumor antigen-specific ones, that were more activated and less exhausted than those induced by PD-1 immune checkpoint blockade. Anti-CCR8 mAb treatment also evoked strong secondary immune responses against the same tumor cell line inoculated several months after tumor eradication, indicating that elimination of tumor-reactive multiclonal Tregs was sufficient to induce memory-type tumor-specific effector Tconvs. Despite induction of such potent tumor immunity, anti-CCR8 mAb treatment elicited minimal autoimmunity in mice, contrasting with systemic Treg depletion, which eradicated tumors but induced severe autoimmune disease. Thus, specific removal of clonally expanding Tregs in tumor tissues for a limited period by cell-depleting anti-CCR8 mAb treatment can generate potent tumor immunity with long-lasting memory and without deleterious autoimmunity.

Hard carbon is regarded as the most promising anode material for sodium-ion (Na-ion) batteries, owing to its advantages of high abundance, low cost, and low operating potential. However, the rate capability and cycle life span of hard carbon anodes are far from satisfactory, severely hindering its industrial applications. Here, we demonstrate that the desolvation process defines the Na-ion diffusion kinetics and the formation of a solid electrolyte interface (SEI). The 3A zeolite molecular sieve film on the hard carbon is proposed to develop a step-by-step desolvation pathway that effectively reduces the high activation energy of the direct desolvation process. Moreover, step-by-step desolvation yields a thin and inorganic-dominated SEI with a lower activation energy for Na + transport. As a result, it contributes to greatly improved power density and cycling stability for both ester and ether electrolytes. When the above insights are applied, the hard carbon anode achieves the longest life span and minimum capacity fading rate at all evaluated current densities. Moreover, with the…

The Omicron SARS-CoV-2 virus contains extensive sequence changes relative to the earlier arising B.1, B.1.1 and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing vaccines. Using SARS-CoV-2 virus-like particles (SC2-VLPs), we examined mutations in all four structural proteins and found that Omicron showed increased infectivity relative to B.1, B.1.1 and similar to Delta, a property conferred by S and N protein mutations. Thirty-eight antisera samples from individuals vaccinated with tozinameran (Pfizer/BioNTech), elasomeran (Moderna), Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had moderately to dramatically reduced efficacy to prevent cell transduction by VLPs containing the Omicron mutations. The Pfizer/BioNTech and Moderna vaccine antisera showed strong neutralizing activity against VLPs possessing the ancestral spike protein (B.1, B.1.1), with 3-fold reduced efficacy against Delta and 15-fold lower neutralization against Omicron VLPs. Johnson & Johnson antisera showed minimal neutralization…

Recent events have pushed RNA research into the spotlight. Continued discoveries of RNA with unexpected diverse functions in healthy and diseased cells, such as the role of RNA as both the source and countermeasure to a severe acute respiratory syndrome coronavirus 2 infection, are igniting a new passion for understanding this functionally and structurally versatile molecule. Although RNA structure is key to function, many foundational characteristics of RNA structure are misunderstood, and the default state of RNA is often thought of and depicted as a single floppy strand. The purpose of this perspective is to help adjust mental models, equipping the community to better use the fundamental aspects of RNA structural information in new mechanistic models, enhance experimental design to test these models, and refine data interpretation. We discuss six core observations focused on the inherent nature of RNA structure and how to incorporate these characteristics to better understand RNA structure. We also offer some ideas for future efforts to make validated RNA structural information…

Quantitative understanding of factors driving yield increases of major food crops is essential for effective prioritization of research and development. Yet previous estimates had limitations in distinguishing among contributing factors such as changing climate and new agronomic and genetic technologies. Here, we distinguished the separate contribution of these factors to yield advance using an extensive database collected from the largest irrigated maize-production domain in the world located in Nebraska (United States) during the 2005-to-2018 period. We found that 48% of the yield gain was associated with a decadal climate trend, 39% with agronomic improvements, and, by difference, only 13% with improvement in genetic yield potential. The fact that these findings were so different from most previous studies, which gave much-greater weight to genetic yield potential improvement, gives urgency to the need to reevaluate contributions to yield advances for all major food crops to help guide future investments in research and development to achieve sustainable global food security. If…

The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models. The STING ADC further synergized with an anti-PD-L1 antibody to achieve superior antitumor efficacy. The STING ADC promoted multiple aspects of innate and adaptive antitumor immune responses, including activation of dendritic cells, T cells, natural killer cells and natural killer T cells, as well as promotion of M2 to M1 polarization of tumor-associated macrophages. These results provided the proof of concept for clinical development of the STING ADCs.

Significance In recent years, lithium-ion batteries (LIBs) have been widely applied in electric vehicles as energy storage devices. However, it is a great challenge to deal with the large number of spent LIBs. In this work, we employ a rapid thermal radiation method to convert the spent LIBs into highly efficient bifunctional NiMnCo-activated carbon (NiMnCo-AC) catalysts for zinc-air batteries (ZABs). The obtained NiMnCo-AC catalyst shows excellent electrochemical performance in ZABs due to the unique core-shell structure, with face-centered cubic Ni in the core and spinel NiMnCoO 4 in the shell. This work provides an economical and environment-friendly approach to recycling the spent LIBs and converting them into novel energy storage devices.

Trends in surface air temperature (SAT) are a common metric for global warming. Using observations and observationally driven models, we show that a more comprehensive metric for global warming and weather extremes is the trend in surface equivalent potential temperature (Thetae_sfc) since it also accounts for the increase in atmospheric humidity and latent energy. From 1980 to 2019, while SAT increased by 0.79[Formula: see text], Thetae_sfc increased by 1.48[Formula: see text] globally and as much as 4[Formula: see text] in the tropics. The increase in water vapor is responsible for the factor of 2 difference between SAT and Thetae_sfc trends. Thetae_sfc increased more uniformly (than SAT) between the midlatitudes of the southern hemisphere and the northern hemisphere, revealing the global nature of the heating added by greenhouse gases (GHGs). Trends in heat extremes and extreme precipitation are correlated strongly with the global/tropical trends in Thetae_sfc. The tropical amplification of Thetae_sfc is as large as the arctic amplification of SAT, accounting for the observed…

The constant provision of plant productivity is integral to supporting the liability of ecosystems and human wellbeing in global drylands. Drylands are paradigmatic examples of systems prone to experiencing abrupt changes in their functioning. Indeed, space-for-time substitution approaches suggest that abrupt changes in plant productivity are widespread, but this evidence is less clear using observational time series or experimental data at a large scale. Studying the prevalence and, most importantly, the unknown drivers of abrupt (rather than gradual) dynamical patterns in drylands may help to unveil hotspots of current and future dynamical instabilities in drylands. Using a 20-y global satellite-derived temporal assessment of dryland Normalized Difference Vegetation Index (NDVI), we show that 50% of all dryland ecosystems exhibiting gains or losses of NDVI are characterized by abrupt positive/negative temporal dynamics. We further show that abrupt changes are more common among negative than positive NDVI trends and can be found in global regions suffering recent droughts,…

There are still significant knowledge gaps in understanding the intrusion and retention of exogeneous particles into the central nervous system (CNS). Here, we uncovered various exogeneous fine particles in human cerebrospinal fluids (CSFs) and identified the ambient environmental or occupational exposure sources of these particles, including commonly found particles (e.g., Fe- and Ca-containing ones) and other compositions that have not been reported previously (such as malayaite and anatase TiO 2 ), by mapping their chemical and structural fingerprints. Furthermore, using mouse and in vitro models, we unveiled a possible translocation pathway of various inhaled fine particles from the lung to the brain through blood circulation (via dedicated biodistribution and mechanistic studies). Importantly, with the aid of isotope labeling, we obtained the retention kinetics of inhaled fine particles in mice, indicating a much slower clearance rate of localized exogenous particles from the brain than from other main metabolic organs. Collectively, our results provide a piece of evidence on…

People of Middle Eastern and North African (MENA) descent are categorized as non-White in many Western countries but counted as White on the US Census. Yet, it is not clear that MENA people see themselves or are seen by others as White. We examine both sides of this ethnoracial boundary in two experiments. First, we examined how non-MENA White and MENA individuals perceive the racial status of MENA traits (external categorization), and then, how MENA individuals identify themselves (self-identification). We found non-MENA Whites and MENAs consider MENA-related traits-including ancestry, names, and religion-to be MENA rather than White. Furthermore, when given the option, most MENA individuals self-identify as MENA or as MENA and White, particularly second-generation individuals and those who identify as Muslim. In addition, MENAs who perceive more anti-MENA discrimination are more likely to embrace a MENA identity, which suggests that perceived racial hostility may be activating a stronger group identity. Our findings provide evidence about the suitability of adding a separate MENA…

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from…

Encouraging vaccination is a pressing policy problem. To assess whether text-based reminders can encourage pharmacy vaccination and what kinds of messages work best, we conducted a megastudy. We randomly assigned 689,693 Walmart pharmacy patients to receive one of 22 different text reminders using a variety of different behavioral science principles to nudge flu vaccination or to a business-as-usual control condition that received no messages. We found that the reminder texts that we tested increased pharmacy vaccination rates by an average of 2.0 percentage points, or 6.8%, over a 3-mo follow-up period. The most-effective messages reminded patients that a flu shot was waiting for them and delivered reminders on multiple days. The top-performing intervention included two texts delivered 3 d apart and communicated to patients that a vaccine was "waiting for you." Neither experts nor lay people anticipated that this would be the best-performing treatment, underscoring the value of simultaneously testing many different nudges in a highly powered megastudy.

α-Synuclein (α-syn) phosphorylation at serine 129 (pS129–α-syn) is substantially increased in Lewy body disease, such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, the pathogenic relevance of pS129–α-syn remains controversial, so we sought to identify when pS129 modification occurs during α-syn aggregation and its role in initiation, progression and cellular toxicity of disease. Using diverse aggregation assays, including real-time quaking-induced conversion (RT-QuIC) on brain homogenates from PD and DLB cases, we demonstrated that pS129–α-syn inhibits α-syn fibril formation and seeded aggregation. We also identified lower seeding propensity of pS129–α-syn in cultured cells and correspondingly attenuated cellular toxicity. To build upon these findings, we developed a monoclonal antibody (4B1) specifically recognizing nonphosphorylated S129–α-syn (WT–α-syn) and noted that S129 residue is more efficiently phosphorylated when the protein is aggregated. Using this antibody, we characterized the time-course of α-syn phosphorylation in organotypic mouse…

We demonstrate that a neural network pretrained on text and fine-tuned on code solves mathematics course problems, explains solutions, and generates questions at a human level. We automatically synthesize programs using few-shot learning and OpenAI's Codex transformer and execute them to solve course problems at 81% automatic accuracy. We curate a dataset of questions from Massachusetts Institute of Technology (MIT)'s largest mathematics courses (Single Variable and Multivariable Calculus, Differential Equations, Introduction to Probability and Statistics, Linear Algebra, and Mathematics for Computer Science) and Columbia University's Computational Linear Algebra. We solve questions from a MATH dataset (on Prealgebra, Algebra, Counting and Probability, Intermediate Algebra, Number Theory, and Precalculus), the latest benchmark of advanced mathematics problems designed to assess mathematical reasoning. We randomly sample questions and generate solutions with multiple modalities, including numbers, equations, and plots. The latest GPT-3 language model pretrained on text automatically…

Overall seawater electrolysis is an important direction for the development of hydrogen energy conversion. The key issues include how to achieve high selectivity, activity, and stability in seawater electrolysis reactions. In this report, the heterostructures of graphdiyne-RhO x -graphdiyne (GDY/RhO x /GDY) were constructed by in situ-controlled growth of GDY on RhO x nanocrystals. A double layer interface of sp -hybridized carbon-oxide-Rhodium ( sp -C∼O-Rh) was formed in this system. The microstructures at the interface are composed of active sites of sp -C∼O-Rh. The obvious electron-withdrawing surface enhances the catalytic activity with orders of magnitude, while the GDY outer of the metal oxides guarantees the stability. The electron-donating and withdrawing sp -C∼O-Rh structures enhance the catalytic activity, achieving high-performance overall seawater electrolysis with very small cell voltages of 1.42 and 1.52 V at large current densities of 10 and 500 mA cm −2 at room temperatures and ambient pressures, respectively. The compositional and structural superiority of the…

Significance The magnitude of the CO 2 fertilization effect on terrestrial photosynthesis is uncertain because it is not directly observed and is subject to confounding effects of climatic variability. We apply three well-established eco-evolutionary optimality theories of gas exchange and photosynthesis, constraining the main processes of CO 2 fertilization using measurable variables. Using this framework, we provide robust observationally inferred evidence that a strong CO 2 fertilization effect is detectable in globally distributed eddy covariance networks. Applying our method to upscale photosynthesis globally, we find that the magnitude of the CO 2 fertilization effect is comparable to its in situ counterpart but highlight the potential for substantial underestimation of this effect in tropical forests for many reflectance-based satellite photosynthesis products.

Significance Networks are fundamental units for studying complex systems, but reconstructing networks from large-scale experimental data is very challenging in systems biology and microbial ecology, primarily due to the difficulty in unraveling direct and indirect interactions. By tackling several mathematical challenges, this study provides a conceptual framework for disentangling direct and indirect relationships in association networks. The application of iDIRECT (Inference of Direct and Indirect Relationships with Effective Copula-based Transitivity) to synthetic, gene expression, and microbial community data demonstrates that it is a powerful, robust, and reliable tool for network inference. The framework developed here will greatly enhance our capability to discern network interactions in various complex systems and allow scientists to address research questions that could not be approached previously.

Abstract Understanding the factors that influence the airborne survival of viruses such as SARS-CoV-2 in aerosols is important for identifying routes of transmission and the value of various mitigation strategies for preventing transmission. We present measurements of the stability of SARS-CoV-2 in aerosol droplets (∼5-10µm equilibrated radius) over timescales spanning from 5 seconds to 20 minutes using a novel instrument to probe survival in a small population of droplets (typically 5-10) containing ∼1 virus/droplet. Measurements of airborne infectivity change are coupled with a detailed physicochemical analysis of the airborne droplets containing the virus. A decrease in infectivity to ∼10 % of the starting value was observable for SARS-CoV-2 over 20 minutes, with a large proportion of the loss occurring within the first 5 minutes after aerosolisation. The initial rate of infectivity loss was found to correlate with physical transformation of the equilibrating droplet; salts within the droplets crystallise at RHs below 50% leading to a near instant loss of infectivity in 50–60% of…

Abstract Immunotherapy has had a tremendous impact on cancer treatment in the past decade, with hitherto unseen responses at advanced and metastatic stages of the disease. However, the aggressive brain tumor glioblastoma (GBM) is highly immunosuppressive and remains largely refractory to current immunotherapeutic approaches. The cGAS-STING cytoplasmic double stranded DNA (dsDNA) sensing pathway has emerged as a next-generation immunotherapy target with potent local immune stimulatory properties. Here, we investigated the status of the STING pathway in GBM and the modulation of the brain tumor microenvironment (TME) with the STING agonist ADU-S100. Our data reveal the presence of STING in human GBM specimens, where it stains strongly in the tumor vasculature. We show that human GBM explants can respond to STING agonist treatment by secretion of inflammatory cytokines. In murine GBM models, we show a profound shift in the tumor immune landscape after STING agonist treatment, with massive infiltration of the tumor-bearing hemisphere with innate immune cells including inflammatory…

High-fidelity replication of the large RNA genome of coronaviruses (CoVs) is mediated by a 3'-to-5' exoribonuclease (ExoN) in non-structural protein 14 (nsp14), which excises nucleotides including antiviral drugs mis-incorporated by the low-fidelity viral RNA-dependent RNA polymerase (RdRp) and has also been implicated in viral RNA recombination and resistance to innate immunity. Here we determined a 1.6-Å resolution crystal structure of SARS-CoV-2 ExoN in complex with its essential co-factor, nsp10. The structure shows a highly basic and concave surface flanking the active site, comprising several Lys residues of nsp14 and the N-terminal amino group of nsp10. Modeling suggests that this basic patch binds to the template strand of double-stranded RNA substrates to position the 3' end of the nascent strand in the ExoN active site, which is corroborated by mutational and computational analyses. Molecular dynamics simulations further show remarkable flexibility of multi-domain nsp14 and suggest that nsp10 stabilizes ExoN for substrate RNA-binding to support its exoribonuclease…

Thin endometrium has been widely recognized as a critical cause of infertility, recurrent pregnancy loss, and placental abnormalities; however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of thin endometrium. Here, we profiled the transcriptomes of human endometrial cells at single-cell resolution to characterize cell types, their communications, and the underlying mechanism of endometrial growth in normal and thin endometrium during the proliferative phase. Stromal cells were the most abundant cell type in the endometrium, with a subpopulation of proliferating stromal cells whose cell cycle signaling pathways were compromised in thin endometrium. Both single-cell RNA sequencing and experimental verification revealed cellular senescence in the stroma and epithelium accompanied by collagen overdeposition around blood vessels. Moreover, decreased numbers of macrophages and natural killer cells further exacerbated endometrial thinness. In addition, our results uncovered aberrant SEMA3, EGF, PTN, and TWEAK signaling…

The sun (∼6,000 K) and outer space (∼3 K) are two significant renewable thermodynamic resources for human beings on Earth. The solar thermal conversion by photothermal (PT) and harvesting the coldness of outer space by radiative cooling (RC) have already attracted tremendous interest. However, most of the PT and RC approaches are static and monofunctional, which can only provide heating or cooling respectively under sunlight or darkness. Herein, a spectrally self-adaptive absorber/emitter (SSA/E) with strong solar absorption and switchable emissivity within the atmospheric window (i.e., 8 to 13 μm) was developed for the dynamic combination of PT and RC, corresponding to continuously efficient energy harvesting from the sun and rejecting energy to the universe. The as-fabricated SSA/E not only can be heated to ∼170 °C above ambient temperature under sunshine but also be cooled to 20 °C below ambient temperature, and thermal modeling captures the high energy harvesting efficiency of the SSA/E, enabling new technological capabilities.

< 0.01) for an average of 6 water years postfire, compared to the range of results expected from climate alone. Significance is assessed by comparing prefire and postfire streamflow responses to climate and also to streamflow among 107 control basins that experienced little to no wildfire during the study period. The streamflow response scales with fire extent: among the 29 basins where >20% of forest area burned in a year, streamflow over the first 6 water years postfire increased by a multibasin average of 0.38 SDs, or 30%. Postfire streamflow increases were significant in all four seasons. Historical fire-climate relationships combined with climate model projections suggest that 2021 to 2050 will see repeated years when climate is more fire-conducive than in 2020, the year currently holding the modern record for WUS forest area burned. These findings center on relatively small, minimally managed basins, but our results suggest that burned areas will grow enough over the next 3 decades to enhance streamflow at regional scales. Wildfire is an emerging driver of runoff change that…

Intensive crop production on grassland-derived Mollisols has liberated massive amounts of carbon (C) to the atmosphere. Whether minimizing soil disturbance, diversifying crop rotations, or re-establishing perennial grasslands and integrating livestock can slow or reverse this trend remains highly uncertain. We investigated how these management practices affected soil organic carbon (SOC) accrual and distribution between particulate (POM) and mineral-associated (MAOM) organic matter in a 29-y-old field experiment in the North Central United States and assessed how soil microbial traits were related to these changes. Compared to conventional continuous maize monocropping with annual tillage, systems with reduced tillage, diversified crop rotations with cover crops and legumes, or manure addition did not increase total SOC storage or MAOM-C, whereas perennial pastures managed with rotational grazing accumulated more SOC and MAOM-C (18 to 29% higher) than all annual cropping systems after 29 y of management. These results align with a meta-analysis of data from published studies…

Methanol-based biorefinery is a promising strategy to achieve carbon neutrality goals by linking CO 2 capture and solar energy storage. As a typical methylotroph, Pichia pastoris shows great potential in methanol biotransformation. However, challenges still remain in engineering methanol metabolism for chemical overproduction. Here, we present the global rewiring of the central metabolism for efficient production of free fatty acids (FFAs; 23.4 g/L) from methanol, with an enhanced supply of precursors and cofactors, as well as decreased accumulation of formaldehyde. Finally, metabolic transforming of the fatty acid cell factory enabled overproduction of fatty alcohols (2.0 g/L) from methanol. This study demonstrated that global metabolic rewiring released the great potential of P. pastoris for methanol biotransformation toward chemical overproduction.

RNA modifications regulate a variety of cellular processes including DNA repair.The RNA methyltransferase TRDMT1 generates methyl-5-cytosine (m5C) on messen-ger RNA (mRNA) at DNA double-strand breaks (DSBs) in transcribed regions, pro-moting transcription-coupled homologous recombination (HR). Here, we identifiedthat Fragile X mental retardation protein (FMRP) promotes transcription-coupled HRvia its interaction with both the m5C writer TRDMT1 and the m5C eraser ten-eleventranslocation protein 1 (TET1). TRDMT1, FMRP, and TET1 function in a temporalorder at the transcriptionally active sites of DSBs. FMRP displays a higher affinity forDNA:RNA hybrids containing m5C-modified RNA than for hybrids without modifica-tion and facilitates demethylation of m5C by TET1 in vitro. Loss of either the chroma-tin- or RNA-binding domain of FMRP compromises demethylation of damage-inducedm5C in cells. Importantly, FMRP is required for R-loop resolving in cells. Due to unre-solved R-loop and m5C preventing completion of DSB repair, FMRP depletion or lowexpression leads to delayed repair of DSBs at…

Various physical tweezers for manipulating liquid droplets based on optical, electrical, magnetic, acoustic, or other external fields have emerged and revolutionized research and application in medical, biological, and environmental fields. Despite notable progress, the existing modalities for droplet control and manipulation are still limited by the extra responsive additives and relatively poor controllability in terms of droplet motion behaviors, such as distance, velocity, and direction. Herein, we report a versatile droplet electrostatic tweezer (DEST) for remotely and programmatically trapping or guiding the liquid droplets under diverse conditions, such as in open and closed spaces and on flat and tilted surfaces as well as in oil medium. DEST, leveraging on the coulomb attraction force resulting from its electrostatic induction to a droplet, could manipulate droplets of various compositions, volumes, and arrays on various substrates, offering a potential platform for a series of applications, such as high-throughput surface-enhanced Raman spectroscopy detection with single…

Growing demand for minerals continues to drive deforestation worldwide. Tropical forests are particularly vulnerable to the environmental impacts of mining and mineral processing. Many local- to regional-scale studies document extensive, long-lasting impacts of mining on biodiversity and ecosystem services. However, the full scope of deforestation induced by industrial mining across the tropics is yet unknown. Here, we present a biome-wide assessment to show where industrial mine expansion has caused the most deforestation from 2000 to 2019. We find that 3,264 km2 of forest was directly lost due to industrial mining, with 80% occurring in only four countries: Indonesia, Brazil, Ghana, and Suriname. Additionally, controlling for other nonmining determinants of deforestation, we find that mining caused indirect forest loss in two-thirds of the investigated countries. Our results illustrate significant yet unevenly distributed and often unmanaged impacts on these biodiverse ecosystems. Impact assessments and mitigation plans of industrial mining activities must address direct and…

COVID-19 is the latest zoonotic RNA virus epidemic of concern. Learning how it began and spread will help to determine how to reduce the risk of future events. We review major RNA virus outbreaks since 1967 to identify common features and opportunities to prevent emergence, including ancestral viral origins in birds, bats, and other mammals; animal reservoirs and intermediate hosts; and pathways for zoonotic spillover and community spread, leading to local, regional, or international outbreaks. The increasing scientific evidence concerning the origins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is most consistent with a zoonotic origin and a spillover pathway from wildlife to people via wildlife farming and the wildlife trade. We apply what we know about these outbreaks to identify relevant, feasible, and implementable interventions. We identify three primary targets for pandemic prevention and preparedness: first, smart surveillance coupled with epidemiological risk assessment across wildlife-livestock-human (One Health) spillover interfaces; second, research to…

With teams growing in all areas of scientific and scholarly research, we explore the relationship between team structure and the character of knowledge they produce. Drawing on 89,575 self-reports of team member research activity underlying scientific publications, we show how individual activities cohere into broad roles of 1) leadership through the direction and presentation of research and 2) support through data collection, analysis, and discussion. The hidden hierarchy of a scientific team is characterized by its lead (or L) ratio of members playing leadership roles to total team size. The L ratio is validated through correlation with imputed contributions to the specific paper and to science as a whole, which we use to effectively extrapolate the L ratio for 16,397,750 papers where roles are not explicit. We find that, relative to flat, egalitarian teams, tall, hierarchical teams produce less novelty and more often develop existing ideas, increase productivity for those on top and decrease it for those beneath, and increase short-term citations but decrease long-term…

Abstract A century-long debate on bodily states and emotions persists. While the involvement of bodily activity in emotion physiology is widely recognized, the specificity and causal role of such activity related to brain dynamics has not yet been demonstrated. We hypothesize that the peripheral neural monitoring and control of cardiovascular activity prompts and sustains brain dynamics during an emotional experience, so these afferent inputs are processed by the brain by triggering a concurrent efferent information transfer to the body. To this end, we investigated the functional brain-heart interplay under emotion elicitation in publicly available data from 62 healthy participants using a computational model based on synthetic data generation of EEG and ECG signals. Our findings show that sympathovagal activity plays a leading and causal role in initiating the emotional response, in which ascending modulations from vagal activity precede neural dynamics and correlate to the reported level of arousal. The subsequent dynamic interplay observed between the central and autonomic…

In response to inflammatory activation by pathogens, macrophages accumulate triglycerides in intracellular lipid droplets. The mechanisms underlying triglyceride accumulation and its exact role in the inflammatory response of macrophages are not fully understood. Here, we aim to further elucidate the mechanism and function of triglyceride accumulation in the inflammatory response of activated macrophages. Lipopolysaccharide (LPS)-mediated activation markedly increased triglyceride accumulation in macrophages. This increase could be attributed to up-regulation of the hypoxia-inducible lipid droplet–associated (HILPDA) protein, which down-regulated adipose triglyceride lipase (ATGL) protein levels, in turn leading to decreased ATGL-mediated triglyceride hydrolysis. The reduction in ATGL-mediated lipolysis attenuated the inflammatory response in macrophages after ex vivo and in vitro activation, and was accompanied by decreased production of prostaglandin-E2 (PGE2) and interleukin-6 (IL-6). Overall, we provide evidence that LPS-mediated activation of macrophages suppresses lipolysis…

Information on urban built-up infrastructure is essential to understand the role of cities in shaping environmental, economic, and social outcomes. The lack of data on built-up heights over large areas has limited our ability to characterize urban infrastructure and its spatial variations across the world. Here, we developed a global atlas of urban built-up heights circa 2015 at 500-m resolution from the Sentinel-1 Ground Range Detected satellite data. Results show extreme gaps in per capita urban built-up infrastructure in the Global South compared with the global average, and even larger gaps compared with the average levels in the Global North. Per capita urban built-up infrastructures in some countries in the Global North are more than 30 times higher than those in the Global South. The results also show that the built-up infrastructure in 45 countries in the Global North combined, with ∼16% of the global population, is roughly equivalent to that of 114 countries in the Global South, with ∼74% of the global population. The inequality in urban built-up infrastructure, as measured…

ABSTRACT The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some, including glaucoma and cataract, are among the most prevalent causes of blindness in the world. To characterize the cell types that comprise these tissues, we generated an anterior segment cell atlas of the human eye using high throughput single-nucleus RNA sequencing (snRNAseq). We profiled 191,992 nuclei from non-diseased anterior segment tissues from 6 human donors, identifying >60 cell types. Many of these cell types were discrete, whereas others, especially in lens and cornea, formed continua corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment revealing that some cell types are unique to single structure whereas others are shared across tissues. The integrated cell…

The emergence of SARS-CoV-2 triggering the COVID-19 pandemic ranks as arguably the greatest medical emergency of the last century. COVID-19 has highlighted health disparities both within and between countries and will leave a lasting impact on global society. Nonetheless, substantial investment in life sciences over recent decades has facilitated a rapid scientific response with innovations in viral characterization, testing, and sequencing. Perhaps most remarkably, this permitted the development of highly effective vaccines, which are being distributed globally at unprecedented speed. In contrast, drug treatments for the established disease have delivered limited benefits so far. Innovative and rapid approaches in the design and execution of large-scale clinical trials and repurposing of existing drugs have saved many lives; however, many more remain at risk. In this review we describe challenges and unmet needs, discuss existing therapeutics, and address future opportunities. Consideration is given to factors that have hindered drug development in order to support planning for the…

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized stem-cell-derived cortical organoids as well as primary human cortical tissue, both from developmental and adult stages. We find significant and predominant infection in cortical astrocytes in both primary tissue and organoid cultures, with minimal infection of other cortical populations. Infected and bystander astrocytes have a corresponding increase in inflammatory gene expression, reactivity characteristics, increased cytokine and growth factor signaling, and cellular stress. Although human cortical cells, particularly astrocytes, have no observable ACE2 expression, we find high levels of coronavirus coreceptors in infected…

Lead is a developmental neurotoxicant in wide industrial use that was once broadly distributed in the environment. The extent of the US population exposed in early life to high levels of lead is unknown, as are the consequences for population IQ. Serial, cross-sectional blood–lead level (BLL) data from National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of US children aged 1 to 5 ( n = 11,616) from 1976 to 1980 to 2015 to 2016 was combined with population estimates from the US Census, the Human Mortality Database, and the United Nations. NHANES and leaded gasoline consumption data were used to estimate BLLs from 1940 to 1975. We estimated the number and proportion of people that fall within seven BLL categories (<4.99; 5 to 0.9.99; 10 to 14.9: 15 to 19.9; 20.24.9; 25 to 29.9; and ≥30 µg/dL), by year and birth cohort, and calculated IQ points lost because of lead exposure. In 2015, over 170 million people (>53%) had BLLs above 5 µg/dL in early life (±2.84 million [80% CI]), over 54 million (>17%) above 15 µg/dL, and over 4.5 million (>1%)…

SARS-CoV-2 is a highly pathogenic virus that evades antiviral immunity by interfering with host protein synthesis, mRNA stability, and protein trafficking. The SARS-CoV-2 nonstructural protein 1 (Nsp1) uses its C-terminal domain to block the messenger RNA (mRNA) entry channel of the 40S ribosome to inhibit host protein synthesis. However, how SARS-CoV-2 circumvents Nsp1-mediated suppression for viral protein synthesis and if the mechanism can be targeted therapeutically remain unclear. Here, we show that N- and C-terminal domains of Nsp1 coordinate to drive a tuned ratio of viral to host translation, likely to maintain a certain level of host fitness while maximizing replication. We reveal that the stem-loop 1 (SL1) region of the SARS-CoV-2 5' untranslated region (5' UTR) is necessary and sufficient to evade Nsp1-mediated translational suppression. Targeting SL1 with locked nucleic acid antisense oligonucleotides inhibits viral translation and makes SARS-CoV-2 5' UTR vulnerable to Nsp1 suppression, hindering viral replication in vitro at a nanomolar concentration, as well as…

Understanding, prioritizing, and mitigating methane (CH 4 ) emissions requires quantifying CH 4 budgets from facility scales to regional scales with the ability to differentiate between source sectors. We deployed a tiered observing system for multiple basins in the United States (San Joaquin Valley, Uinta, Denver-Julesburg, Permian, Marcellus). We quantify strong point source emissions (>10 kg CH 4 h −1 ) using airborne imaging spectrometers, attribute them to sectors, and assess their intermittency with multiple revisits. We compare these point source emissions to total basin CH 4 fluxes derived from inversion of Sentinel-5p satellite CH 4 observations. Across basins, point sources make up on average 40% of the regional flux. We sampled some basins several times across multiple months and years and find a distinct bimodal structure to emission timescales: the total point source budget is split nearly in half by short-lasting and long-lasting emission events. With the increasing airborne and satellite observing capabilities planned for the near future, tiered observing systems will…

Leaf photosynthesis, coral mineralization, and trabecular bone growth depend on triply periodic minimal surfaces (TPMSs) with hyperboloidal structure on every surface point with varying Gaussian curvatures. However, translation of this structure into tissue-engineered bone grafts is challenging. This article reports the design and fabrication of high-resolution three-dimensional TPMS scaffolds embodying biomimicking hyperboloidal topography with different Gaussian curvatures, composed of body inherent β-tricalcium phosphate, by stereolithography-based three-dimensional printing and sintering. The TPMS bone scaffolds show high porosity and interconnectivity. Notably, compared with conventional scaffolds, they can reduce stress concentration, leading to increased mechanical strength. They are also found to support the attachment, proliferation, osteogenic differentiation, and angiogenic paracrine function of human mesenchymal stem cells (hMSCs). Through transcriptomic analysis, we theorize that the hyperboloid structure induces cytoskeleton reorganization of hMSCs, expressing…

ABSTRACT Diet selection is a fundamental aspect of animal behavior with numerous ecological and evolutionary implications. While the underlying mechanisms are complex, the availability of essential dietary nutrients can strongly influence diet selection behavior. The gut microbiome has been shown to metabolize many of these same nutrients, leading to the untested hypothesis that intestinal microbiota may influence diet selection. Here we show that germ-free mice colonized by gut microbiota from three rodent species with distinct foraging strategies differentially selected diets that varied in macronutrient composition. Specifically, we found that herbivore-conventionalized mice voluntarily selected a higher protein:carbohydrate ratio diet, while omnivore- and carnivore-conventionalized mice selected a lower P:C ratio diet. In support of the long-standing hypothesis that tryptophan – the essential amino acid precursor of serotonin – serves as a peripheral signal regulating diet selection, bacterial genes involved in tryptophan metabolism and plasma tryptophan availability prior to…

SignificanceTwenty-first century trends in hydroclimate are so large that future average conditions will, in most cases, fall into the range of what we would today consider extreme drought or pluvial states. Using large climate model ensembles, we remove the background trend and find that the risk of droughts and pluvials relative to that (changing) baseline is fairly similar to the 20th century risk. By continually adapting to long-term background changes, these risks could therefore perhaps be minimized. However, increases in the frequency of extremely wet and dry years are still present even after removing the trend, indicating that sustainably managing hydroclimate-driven risks in a warmer world will face increasingly difficult challenges.

SignificanceSARS-CoV-2 continues to evolve through emerging variants, more frequently observed with higher transmissibility. Despite the wide application of vaccines and antibodies, the selection pressure on the Spike protein may lead to further evolution of variants that include mutations that can evade immune response. To catch up with the virus's evolution, we introduced a deep learning approach to redesign the complementarity-determining regions (CDRs) to target multiple virus variants and obtained an antibody that broadly neutralizes SARS-CoV-2 variants.

With rapid urbanization and increasing climate risks, enhancing the resilience of urban systems has never been more important. Despite the availability of massive datasets of human behavior (e.g., mobile phone data, satellite imagery), studies on disaster resilience have been limited to using static measures as proxies for resilience. However, static metrics have significant drawbacks such as their inability to capture the effects of compounding and accumulating disaster shocks; dynamic interdependencies of social, economic, and infrastructure systems; and critical transitions and regime shifts, which are essential components of the complex disaster resilience process. In this article, we argue that the disaster resilience literature needs to take the opportunities of big data and move toward a different research direction, which is to develop data-driven, dynamical complex systems models of disaster resilience. Data-driven complex systems modeling approaches could overcome the drawbacks of static measures and allow us to quantitatively model the dynamic recovery trajectories and…

Significance This study provides proof-of-principle evidence for intravesical delivery of messenger RNA (mRNA) via a mucoadhesive nanoparticle (NP) strategy and reveals the therapeutic potential of KDM6A in treating bladder cancer metastasis, which remains difficult due to the physiological bladder barriers. The mucoadhesive NPs could protect loaded mRNA, prolong exposure of mRNA in disease sites, and benefit the penetration and effective expression, which all represent challenging hurdles for intravesical delivery of mRNA therapeutics. mRNA local delivery can also avoid potential toxicity issues via systemic delivery and unwanted protein expression throughout the body. We expect this mucoadhesive mRNA nanotechnology can be useful for the effective up-regulation of targeted proteins in bladder tissues in situ for both mechanistic understanding and translational study of bladder-related diseases.

Capturing mitochondria's intricate and dynamic structure poses a daunting challenge for optical nanoscopy. Different labeling strategies have been demonstrated for live-cell stimulated emission depletion (STED) microscopy of mitochondria, but orthogonal strategies are yet to be established, and image acquisition has suffered either from photodamage to the organelles or from rapid photobleaching. Therefore, live-cell nanoscopy of mitochondria has been largely restricted to two-dimensional (2D) single-color recordings of cancer cells. Here, by conjugation of cyclooctatetraene (COT) to a benzo-fused cyanine dye, we report a mitochondrial inner membrane (IM) fluorescent marker, PK Mito Orange (PKMO), featuring efficient STED at 775 nm, strong photostability, and markedly reduced phototoxicity. PKMO enables super-resolution (SR) recordings of IM dynamics for extended periods in immortalized mammalian cell lines, primary cells, and organoids. Photostability and reduced phototoxicity of PKMO open the door to live-cell three-dimensional (3D) STED nanoscopy of mitochondria for 3D analysis of…

Ruthenium (Ru) complexes are developed as latent emissive photosensitizers for cancer and pathogen photodiagnosis and therapy. Nevertheless, most existing Ru complexes are limited as photosensitizers in terms of short excitation and emission wavelengths. Herein, we present an emissive Ru(II) metallacycle (herein referred to as 1) that is excited by 808-nm laser and emits at a wavelength of ∼1,000 nm via coordination-driven self-assembly. Metallacycle 1 exhibits good optical penetration (∼7 mm) and satisfactory reactive oxygen species production properties. Furthermore, 1 shows broad-spectrum antibacterial activity (including against drug-resistant Escherichia coli ) as well as low cytotoxicity to normal mammalian cells. In vivo studies reveal that 1 is employed in precise, second near-infrared biomedical window fluorescent imaging–guided, photo-triggered treatments in Staphylococcus aureus –infected mice models, with negligible side effects. This work thus broads the applications of supramolecular photosensitizers through the strategy of lengthening their wavelengths.

The nature of the representational code underlying conceptual knowledge remains a major unsolved problem in cognitive neuroscience. We assessed the extent to which different representational systems contribute to the instantiation of lexical concepts in high-level, heteromodal cortical areas previously associated with semantic cognition. We found that lexical semantic information can be reliably decoded from a wide range of heteromodal cortical areas in the frontal, parietal, and temporal cortex. In most of these areas, we found a striking advantage for experience-based representational structures (i.e., encoding information about sensory-motor, affective, and other features of phenomenal experience), with little evidence for independent taxonomic or distributional organization. These results were found independently for object and event concepts. Our findings indicate that concept representations in the heteromodal cortex are based, at least in part, on experiential information. They also reveal that, in most heteromodal areas, event concepts have more heterogeneous representations…

Green plants play a fundamental role in ecosystems, human health, and agriculture. As de novo genomes are being generated for all known eukaryotic species as advocated by the Earth BioGenome Project, increasing genomic information on green land plants is essential. However, setting standards for the generation and storage of the complex set of genomes that characterize the green lineage of life is a major challenge for plant scientists. Such standards will need to accommodate the immense variation in green plant genome size, transposable element content, and structural complexity while enabling research into the molecular and evolutionary processes that have resulted in this enormous genomic variation. Here we provide an overview and assessment of the current state of knowledge of green plant genomes. To date fewer than 300 complete chromosome-scale genome assemblies representing fewer than 900 species have been generated across the estimated 450,000 to 500,000 species in the green plant clade. These genomes range in size from 12 Mb to 27.6 Gb and are biased toward agricultural…

Abstract The blood-brain barrier represents a significant challenge for the treatment of high-grade gliomas, and our understanding of drug transport across this critical biointerface remains limited. To advance preclinical therapeutic development for gliomas, there is an urgent need for predictive in vitro models with realistic blood-brain barrier vasculature. Here, we report a vascularized human glioblastoma (GBM) model in a microfluidic device that accurately recapitulates brain tumor vasculature with self-assembled endothelial cells, astrocytes, and pericytes to investigate the transport of targeted nanotherapeutics across the blood-brain barrier and into GBM cells. Using modular layer-by-layer assembly, we functionalized the surface of nanoparticles with GBM-targeting motifs to improve trafficking to tumors. We directly compared nanoparticle transport in our in vitro platform with transport across mouse brain capillaries using intravital imaging, validating the ability of the platform to model in vivo blood-brain barrier transport. We investigated the therapeutic potential of…