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Physical/TechAugust 11, 2026

Nature's antivenom: Combinations of conserved rattlesnake serum metalloproteinase inhibitors block the lethal action of viper venoms.

Snakebite maims or kills several hundred thousand people each year. For more than a century, treatment has relied on antivenoms derived from animals immunized with whole venoms, but their efficacy, safety, and availability are highly variable, and it is often not well understood which specific venom components must be inhibited to prevent mortality and major morbidities. New therapeutic approaches are needed. Here, we take an evolutionary approach to antivenom design inspired by the longstanding

Society & CultureAugust 4, 2026

Christopher A. Sims (1942-2026): Paradigm-shifting macroeconomist and econometrician.

Christopher A. Sims, who died on March 14, 2026, left behind an indelible mark on macroeconomics and econometrics. His Nobel Prize winning research reshaped the paradigm for empirical macroeconomics, creating a rigorous and flexible framework for inferring the effects of macroeconomic policies. He also made important contributions to time series forecasting, Bayesian econometrics, factor modeling, approximation theory, and models of monetary and fiscal policy. Few academics have had as direct an

EnvironmentAugust 4, 2026

Reversing vegetable biodiversity loss to diversify diets.

Vegetables are a critical component of diets, with inadequate intake of this essential food group leading to poor dietary quality and malnutrition. Food system assessments identify insufficient production, comparatively high prices, and sociocultural barriers as key constraints to vegetable consumption. We argue that vegetable biodiversity, spanning vegetable species and their varieties, as well as their wild relative species, is a central yet underutilized lever for enhancing vegetable consumpt

Artificial IntelligenceAugust 4, 2026

PLK1-mediated phosphorylation of PHGDH reprograms serine metabolism in advanced prostate cancer.

Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet their increased biosynthetic and energetic demands. Although cells possess the capacity for de novo serine biosynthesis, most transformed cancer cells preferentially rely on exogenous serine uptake to sustain their growth, yet the regulatory mechanisms driving this metabolic dependency remain poorly understood. Here, we uncover a mechanism by which Polo-like kinase 1 (PLK1), frequently overexpressed in prostate cancer,

Artificial IntelligenceAugust 4, 2026

When coordination is avoidable: A monotonicity analysis of organizational tasks.

Organizations devote substantial resources to coordination, yet which tasks actually require it for correctness remains unclear. The problem is acute in multiagent AI systems, where coordination cost is directly measurable and can exceed the cost of the work itself. Distributed systems theory provides a precise criterion: Coordination is required when a task specification is nonmonotonic, meaning that as histories grow, new information can invalidate prior conclusions. Here we show that Thompson

Physical/TechAugust 4, 2026

Abrupt transition to irreversible damage in the overdrafted Sacramento Valley aquifer system.

Groundwater extraction decreases water pressure in aquifer systems, causing reversible or irreversible deformation of the water-bearing layers that manifests as recoverable or permanent displacements of the land surface, respectively. Detecting and forecasting when and where an aquifer system transitions from a reversible, poroelastic regime, to an irreversible, inelastic regime remains a crucial challenge given the complex, heterogeneous nature of aquifer systems. Here we leverage high-resoluti

Health & MedicineAugust 4, 2026

Cryoelectron tomography reveals an age-related decline in mitoribosomes that contributes to T cell dysfunction in older individuals.

Mitochondrial dysfunction drives T cell aging in mice. Yet, due to fundamental differences in T cell aging mechanisms between species, whether human T cells exhibit similar mitochondrial alterations remains unclear, with existing evidence often conflicting. Using cryoelectron tomography, we resolved the structure and spatial organization of mitochondrial ribosomes in primary human CD8 + T cells under physiological conditions. Comparative analysis with human aging models revealed an age-related r

Health & MedicineAugust 4, 2026

RelB NF-κB tunes Notch2 signaling to promote IL-23-secreting solitary isolated lymphoid tissue-resident DCs critical for gut immunity.

While preserving tolerance toward commensals, dendritic cells (DCs) also orchestrate response against pathogens. The noncanonical RelB NF-κB pathway in DCs curbs tolerogenic Tregs in the intestine. Whether RelB-dependent DC regulations also impact intestinal immunity remains less clear. Here, we show that genetic ablation of RelB in DCs compromises IL-23-dependent immune response in the intestine, imparting vulnerability in Relb ΔCD11c mice to infection with Citrobacter rodentium , a

EnvironmentAugust 4, 2026

Sediment accumulation rate predicts the temporal resolution of marine fossil assemblages.

Time averaging (TA), the mixing of noncontemporaneous organisms in fossil assemblages, governs the resolution of paleontological data and determines which biological and environmental processes are recorded in the geological record. To assess variation in TA and its dependence on external drivers, we used amino acid and radiocarbon methods to individually date 7,593 specimens across 384 samples from late Quaternary marine assemblages of calcifying organisms. Bivalve mollusks dominated the data,

Health & MedicineAugust 4, 2026

X-linked SYTL4 missense variant disrupts RAB27A-dependent vesicle trafficking and synaptic transmission in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive behaviors, with genetic studies implicating widespread synaptic dysfunction. However, the contribution of presynaptic vesicle trafficking mechanisms to ASD pathogenesis remains incompletely understood. Here, we identify synaptotagmin-like protein 4 (SYTL4), a RAB27A effector previously characterized in secretory cells, as a regulator of presynaptic function in the mammal

Health & MedicineAugust 4, 2026

Folic acid prevention of neural tube defects requires retinoic acid produced by ALDH1L1.

Folic acid (FA) supplementation during pregnancy is the commonly accepted treatment to prevent neural tube defects. The mechanism by which FA prevents neural tube defects (NTDs) remains unclear. FA also prevents other developmental malformations, including alcohol-induced malformations in Fetal Alcohol Syndrome models. We show that FA acts through a metabolic link to retinoic acid (RA) signaling. Using a pax3 -knockdown Xenopus model of FA-rescuable NTDs, we show that RA or its precursors equall

Health & MedicineAugust 4, 2026

Dynamic principles of concentration buffering through liquid-liquid phase separation.

Living systems must maintain robust biochemical function despite fluctuations that span a wide range of timescales. Biomolecular condensates formed by liquid-liquid phase separation (LLPS) have been shown to buffer concentration fluctuations, but the principles governing their dynamic regulation remain unclear. We address this by probing the response of LLPS to oscillatory perturbations that mimic fluctuations across different timescales, establishing the first systematic frequency-domain analys

Health & MedicineJuly 31, 2026

Initial HIV Therapy for Adults and Treatment-Associated Weight Gain: The Opti-DOR Randomized Clinical Trial.

Antiretroviral therapy (ART), particularly regimens containing tenofovir alafenamide with dolutegravir or bictegravir, is associated with substantial weight gain, potentially exacerbating cardiometabolic risk in people with HIV. To determine whether a regimen with doravirine, lamivudine, and tenofovir disoproxil fumarate results in less weight gain than a regimen with dolutegravir, emtricitabine, and tenofovir alafenamide while maintaining noninferior viral suppression. Open-label, noninferiorit

Artificial IntelligenceJuly 30, 2026

Dapagliflozin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Two percent to 50% of patients undergoing elective cardiac surgery experience acute kidney injury (AKI) postoperatively. Medications to prevent AKI after elective cardiac surgery have not been identified. In patients undergoing elective cardiac surgery, to evaluate whether initiating dapagliflozin 1 day prior to surgery reduces the incidence of AKI at 7 days after cardiac surgery, compared with placebo. Multicenter, double-blind, placebo-controlled randomized clinical trial conducted at 2 academ

Health & MedicineJuly 30, 2026

Nicotine E-Cigarettes for Cigarette Smoking Cessation: Recommendations to US-Based Clinicians.

Cigarette smoking, maintained predominantly by nicotine dependence, is a long-term and relapsing behavior that continues to be a leading cause of preventable death and disease worldwide. E-cigarettes with nicotine are less harmful than cigarettes and have been shown to be more effective for smoking cessation than US Food and Drug Administration-approved nicotine replacement therapies. However, misperceptions of the harms of e-cigarettes are common, even among clinicians. This Special Communicati

Health & MedicineJuly 30, 2026

Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-cont

Zenagamtide (formerly amycretin) is a unimolecular agonist of GLP-1, amylin, and calcitonin receptors. We aimed to investigate the dose-response relationship with respect to the efficacy and safety of once-weekly subcutaneous zenagamtide compared with placebo in adults with type 2 diabetes. This 36-week, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was conducted at 83 hospital and clinic sites across 11 countries. The trial consisted of a 3-week screening p

Health & MedicineJuly 30, 2026

Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-c

Zenagamtide (formerly amycretin) is a unimolecular peptide agonist of GLP-1, amylin, and calcitonin receptors. We aimed to investigate the dose-response relationship with respect to the efficacy and safety of once-daily oral zenagamtide compared with placebo in adults with type 2 diabetes. This 36-week, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was conducted at 83 hospital and clinic sites across 11 countries. The trial consisted of a 3-week screening pe

Health & MedicineJuly 30, 2026

Dietary arginine drives codon-dependent MHC class I translation and improves immunity in colon tumorigenesis and respiratory viral infection.

Amino acid levels fluctuate across diverse pathological conditions. Whether such amino acid modulations directly shape pathophysiology by regulating host gene expression remains unknown. We found that extracellular arginine restriction, observed in cancer and infection, represses specific arginine tRNAs-directly suppressing translation of major histocompatibility complex I (MHC class I) and antigen presentation. Arginine regulation of MHC class I was codon-usage dependent, as synonymous codon mu

Health & MedicineJuly 30, 2026

Basement membrane turnover controls cell shape.

The regulation of 3D cell shape is a fundamental problem of life. In multicellular tissues, cell shape emerges through the balance of forces inside and outside the cell. In epithelia, the basement membrane (BM) is the first extracellular barrier that cells sense biochemically and mechanically. Despite this, little is known about how BM mechanical properties are regulated and how they impact cell shape. Through mathematical modeling, we show that the stress relaxation time of the BM can regulate

Health & MedicineJuly 29, 2026

Global Burden of Elevated LDL-C: Findings From the Global Burden of Disease Study 2023.

Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C-related burden is critical for guiding prevention and treatment strategies. To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-dele

Health & MedicineJuly 29, 2026

Gasdermin E couples viral pyroptosis to lethal hepatic lipid accumulation.

Tick-borne orthonairoviruses, including the emerging wetland virus (WELV), pose a growing public health concern as cases increase, yet their pathogenesis remains unclear. Here, we show that WELV infection causes fatal liver dysfunction in patients, characterized by elevated hepatic enzymes, triacylglycerol accumulation, and hyperinflammation. WELV induces gasdermin E (GSDME)-dependent pyroptosis in hepatocytes through mitochondrial and Fas-mediated apoptotic pathways. Viral RNA activates RIG-I/C

Health & MedicineJuly 29, 2026

CRISPR screens identify targets to rescue age-related T cell dysfunction in cancer.

Immune aging impairs T cell-mediated tumor control as well as cancer immunotherapy outcomes. The most important drivers of T cell dysfunction in aged tumors remain unknown. We performed single-cell CRISPR screens to identify Dusp5 and Zfp219 as key regulators of CD8 + T cell persistence and effector differentiation within aged tumors. Loss of Dusp5 increased extracellular signal-regulated kinase (ERK) phosphorylation and globally enhanced T cell proliferation. Conversely, Zfp219 deletion induced

EnvironmentJuly 28, 2026

Geometry controls momentum flux in the sprinkler problem.

Hydro- and aero-mechanical devices convert fluid flows into useful motions, force, and power. The operating principles can involve subtle and poorly understood physics, as epitomized by open questions about systems that aspirate flows through curving tubular arms. Since its introduction by Mach and popularization by Feynman, the so-called reverse sprinkler problem has evoked many competing theories and fluid mechanical effects that have not to date been distinguished by experiments. Here we cond

EnvironmentJuly 28, 2026

Guanidine fuels rapid resurrection of desert cyanobacteria.

In desert ecosystems, microbial activity is driven by brief hydration pulses but is severely limited by persistent nutrient scarcity. Cyanobacteria serve as essential pioneer photoautotrophs, maintaining biogeochemical cycles and ecosystem stability in these arid landscapes. However, their ability to quickly reactivate after rehydration is critically restricted by nitrogen availability. Although the nitrogen demand can be met later by biological nitrogen fixation, it is ineffective and irrelevan

Health & MedicineJuly 28, 2026

Ligand regulation and function of preformed EGFR dimers.

Receptor tyrosine kinases (RTKs) are key therapeutic targets in cancer, diabetes, and other diseases. With only one transmembrane α-helix-compared with seven in G-protein-coupled receptors-RTKs are thought to be activated by ligand-induced dimerization. Complicating this view, however, one of the best-studied RTKs, the insulin receptor (IR), forms allosterically regulated covalent dimers. Moreover, noncovalent "preformed" dimers have frequently been reported for the sequence-related epider

EnvironmentJuly 28, 2026

The unique Efg1 fungal virulence regulon in the catheterized bladder environment.

Urinary catheterization, a frequent procedure in hospitals, nursing homes, and other healthcare facilities, is a primary driver of nosocomial infections. The most common of these are catheter-associated urinary tract infections (CAUTIs), which often progress to severe complication, sepsis, and ultimately death. The fungus Candida albicans is a primary causative agent of CAUTIs; yet, its tissue-specific pathogenesis remains poorly understood, which complicates development of efficient treatments.

Physical/TechJuly 28, 2026

Synergistic action of different molecular mechanisms causes striking levels of insecticide resistance in the malaria vector Anopheles gambiae .

Intensifying insecticide resistance in the malaria vector Anopheles gambiae poses a serious threat to the progress achieved the last decades in reducing malaria deaths in Africa. The genetic basis of insecticide resistance is often complex, involving multiple genes and mutations. However, we still lack a clear understanding of how each mechanism contributes to overall resistance and how highly resistant phenotypes arise. In this study, we generated a suite of transgenic An. gambiae strains carry

Physical/TechJuly 28, 2026

There is no free benchmark: An institutional view of legal AI benchmarking.

Despite substantial excitement around the use of AI in law, little information exists on the performance and associated risks of the domain's widely marketed tools. Recent work, for instance, has demonstrated the significant potential for "hallucinations"-wherein models make up facts, law, and precedent-leading Chief Justice Roberts to spotlight this risk in his annual report on the judiciary. We argue that there is a need for public AI benchmarking in law. First, relative to other AI applicatio

Physical/TechJuly 28, 2026

A phosphorylation cascade involving ZmSnRK2.10-ZmRIPK2-ZmWRKY38 attenuates drought response by derepressing ZmSUS2 in maize.

Drought stress severely limits crop productivity, with transcription factors (TFs) playing pivotal roles in plant adaptation. Here, we identify the maize TF ZmWRKY38 as a positive regulator of drought tolerance. CRISPR/Cas9-mediated knockout of ZmWRKY38 increased plant sensitivity to drought compared with the wild type. We demonstrate that ZmWRKY38 binds to the promoter of the sucrose synthase gene ZmSUS2 and represses its transcription. Conversely, ZmSUS2 functions as a negative regulator of dr

Health & MedicineJuly 28, 2026

FGFR2 is an oncogenic driver critical for successful human gammaherpesvirus latent infection and oncogenesis.

Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) drive multiple aggressive lymphomas, yet effective targeted therapies for these virus-associated malignancies remain limited. Using an unbiased kinome-wide screen combined with analysis of virus-positive patient tumors, we identified fibroblast growth factor receptor 2 (FGFR2) as a selectively activated host kinase in EBV- and KSHV-associated lymphomas. Importantly, FGFR2 is required for efficient establishment of EBV la

Physical/TechJuly 28, 2026

The quantum ensemble variational optimization algorithm: Applications to molecular inverse design.

Designing molecules with optimized properties remains a fundamental challenge due to the intricate relationship between molecular structure and properties. Traditional computational approaches that address the combinatorial number of possible molecular designs become unfeasible as the molecular size increases, suffering from the so-called "curse of dimensionality" problem. Recent advances in quantum computing hardware present new opportunities to address this problem. Here, we introduce the quan

Health & MedicineJuly 28, 2026

VAMP7-dependent mitochondria-lysosome contacts contribute to glial mitochondrial dynamics and dopaminergic neuron survival.

Although disrupted mitochondrial dynamics in neurons are closely linked to neurodegenerative diseases, far less is known about how mitochondrial dynamics are regulated in glia or whether glial mitochondrial dysfunction contributes to neurodegeneration. Here, we show that the R-SNARE protein VAMP7 regulates the untethering of mitochondria-lysosome contacts (MLCs) in adult fly glia. Glial-specific knockdown of VAMP7 leads to prolonged MLCs and mitochondrial elongation associated with altered fissi

Physical/TechJuly 28, 2026

Mechanostereochemical modulation of polymer mechanical properties.

Stereochemistry profoundly affects the physical and mechanical properties of polymers, illustrated by the contrast between elastic natural rubber ( cis -polyisoprene) and the stiffer, less extensible gutta-percha ( trans -isomer). Traditional stereochemistry such as tacticity and cis / trans isomerism primarily governs polymer properties based on fixed structural or conformational factors. Herein, by incorporating the mechanostereochemistry concept into polymers, we demonstrate a stereochemistry

Society & CultureJuly 28, 2026

The social-class gap in negotiation: Lower-class individuals negotiate less and face more backlash.

Economic inequality has widened considerably in the United States and globally, raising pressing questions about the mechanisms that reproduce social stratification. One prominent manifestation of this inequality is the "class ceiling" in organizations: individuals from lower social classes earn less and advance more slowly than their higher-class counterparts, even with comparable credentials. We identify a crucial behavioral pathway contributing to this class ceiling: a social-class gap in the

EnvironmentJuly 28, 2026

A unified machine-learning framework for ab initio multiscale modeling of liquids.

Understanding and predicting the behavior of liquid matter across length scales-using only the microscopic interactions encoded in the Schrödinger equation-remains a central challenge in the physical sciences. Achieving this goal requires not only an accurate and efficient description of intermolecular forces but also a consistent framework that bridges the micro-, meso-, and macroscales. Here, by combining machine-learned interatomic potentials (MLIPs) with neural classical density functio

Physical/TechJuly 28, 2026

Resolving weak moments in canted antiferromagnets via time-domain terahertz emission spectroscopy.

Canted antiferromagnets host weak net magnetization arising from spin canting while preserving the ultrafast response of antiferromagnetic order. Probing such minute moments-especially in thin films-remains challenging, as conventional magneto-optical and electrical techniques lack sufficient sensitivity. Here, we employ time-domain terahertz emission spectroscopy as a contact-free probe of such weak magnetism. Using epitaxial TmFeO 3 /Pt heterostructures as a model system, the emitted THz signa

Health & MedicineJuly 28, 2026

Antimalarial cytoskeletal targeting with broad apicomplexan activity.

Malaria is a devastating disease that resulted in an estimated 610,000 deaths in 2024, the majority being children under the age of five. Here, we use KNX-115 to illustrate multistage antiparasitic activity upon targeting the cytoskeletal enzyme Plasmodium falciparum myosin A (PfMyoA). KNX-115 inhibits purified actin-activated ATPase with a potency in the low nanomolar range and >50-fold selectivity against cardiac, skeletal, and smooth muscle myosins. KNX-115 traps PfMyoA in a state that bin

Artificial IntelligenceJuly 28, 2026

Context-aware multimodal AI navigates hidden pathways in five centuries of art evolution.

The rise of multimodal generative AI transforms the intersection of technology and art, offering richer insights into large-scale artworks. While significant research has focused on their creative potential, their ability to represent artworks in latent spaces remains underexamined. We use generative AI, specifically Stable Diffusion, to analyze 500 y of Western paintings by extracting two types of latent information with the model: formal aspects (e.g., colors) and contextual aspects (e.g., sub

Health & MedicineJuly 28, 2026

Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES): a randomised, double-blind, placebo-controlled phase 3 study.

Pulmonary arterial hypertension (PAH) is a rare, progressive disease characterised by elevated pulmonary vascular resistance that can lead to right ventricular failure and premature death. Ralinepag is an oral, once-daily, selective prostacyclin IP receptor agonist developed to treat PAH. We aimed to evaluate the efficacy and safety of ralinepag in patients with PAH. ADVANCE OUTCOMES was a randomised, double-blind, placebo-controlled, event-driven, phase 3 trial of ralinepag in patients with PAH

Health & MedicineJuly 28, 2026

Integrated care pathway in individuals with Long COVID: STIMULATE-ICP, a cluster-randomized, phase 3 trial.

Combining multidisciplinary care plans into integrated care pathways (ICPs) is scalable, generalizable and effective for several long-term conditions, but not evaluated in Long COVID (LC). Our phase 3, cluster-randomized, multicenter clinical trial investigated the effectiveness of ICP interventions for LC. Recruitment of adults ≥18 years with LC was conducted in 6 National Health Service LC clinics in England with specialist ICPs. The intervention arms were (i) multi-organ magnetic reson