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Tailoring structural and optical properties of ZnS nanoparticles via strontium doping

Nanomedicine for neuroinflammation modulation: Next-generation nano-immunotherapies for neurodegenerative disorders

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 observation that vipers have evolved serum-borne toxin inhibitors that confer resistance to their own venoms. We have investigated the abilities of a family of four rattlesnake metalloproteinase (MP) inhibitors derived from the ancestral serum glycoprotein Fetuin-A (FETUAs) to neutralize the enzymatic, hemorrhagic, and lethal activities of viper venoms. We find that while certain individual FETUA proteins are able to inhibit enzymatic or hemorrhagic activity, they are unable or only partially able to inhibit venom lethality. However, we show that specific combinations of FETUA proteins complement one another’s activities and are sufficient to fully neutralize rattlesnake venom lethality with approximately 10 times greater potency than commercial antivenom. Moreover, we demonstrate that FETUA proteins are well conserved among viper subfamilies and that rattlesnake FETUAs are able to inhibit the MPs and neutralize the lethality of several evolutionarily distant pit viper or true viper venoms. Our results highlight the critical importance of inhibiting MPs in hemorrhagic venoms and the potential general utility of combinations of naturally evolved, recombinant MP inhibitors in the treatment of viper snakebite.

Accelerating <i>Campylobacter</i> zoonosis in the Anthropocene

Intensive poultry farming has transformed global bird populations, concentrating billions of chickens into dense industrial systems that fundamentally reshape ecological space. As birds are important pathogen reservoirs, these changes can have important consequences for the spread of zoonoses including Campylobacter jejuni —the leading cause of bacterial gastroenteritis. Analyzing 2,747 genomes from chickens and wild birds, we show that poultry intensification has eroded historic host–strain associations and created a new and expanding ecological niche. Phylogenetic reconstructions reveal an estimated 100-fold increase in chicken-to-wild-bird host transitions since 1900 compared to predomestication levels, alongside dramatic post-1960 expansions of chicken-associated lineages and rising pathogen effective population sizes. Model simulations further indicate that expanding, high-density chicken populations could act as ecological “pathogen sponges,” absorbing and amplifying diverse strains while sustaining high prevalence and coinfection rates. Genome-wide association analyses show that strains adapted to the chicken niche frequently acquire genes linked to oxidative stress, metal homeostasis, motility, and antimicrobial resistance. Together, these findings demonstrate that intensive poultry farming is reshaping pathogen ecology and accelerating the evolution and spread of a major zoonotic bacterium, with direct implications for human health.

Global threat exposure of islands in a changing world

Islands are at the forefront of global environmental change. Biological invasions, land-use change, and climate change are driving population declines and causing irreversible losses in island ecosystems. Although global threat exposure maps have been developed in recent years, they are mostly designed for coarse-grained, continental-extent analyses, often overlooking islands. Here, we assessed the cumulative exposure to biological invasion, land-use change, and climate change by 2050, for more than 16,000 islands worldwide using multiple threat markers. Climate change emerged as a ubiquitous threat, being the dominant threat for 65% of all islands, followed by land-use change (22%) and biological invasions (13%). Islands with the highest cumulative exposure were more likely to be isolated, without historical connection with the mainland. Small and low-elevation islands at low latitudes exhibited greater exposure to climate change, whereas larger, high-elevation islands tended to be more exposed to land-use change. Certain countries and subdivisions, such as Seychelles, Bangladesh, China, French Polynesia, and Micronesia, harbored statistically disproportionate numbers of highly exposed islands, highlighting geographic hotspots of cumulative exposure where conservation efforts might be particularly urgent. Our study indicates that by 2050, most islands will be simultaneously exposed to a triple threat arising from the combined impacts of land-use change, climate change, and biological invasions. This study provides robust quantification of island cumulative exposure to three key drivers of biodiversity loss, making a crucial step toward assessing global biodiversity vulnerability.

A wearable patch for continuous levodopa monitoring in sweat: Towards exertion and power-free pharmacodynamic assessment in Parkinson’s disease

Precision management of Parkinson’s disease (PD) requires frequent levodopa (L-dopa) dose adjustments, yet current monitoring relies on subjective symptom reporting and infrequent blood testing. Here, we present a soft, fingertip-mounted wearable platform for continuous, noninvasive L-dopa monitoring. By combining osmotically harvested passive sweat with soft hydrogels, a potentiometric sensing strategy, and individualized calibration, the platform estimates blood L-dopa information from sweat without external power or iontophoresis. Strong correlations between sweat and high-performance liquid chromatography (HPLC)-measured blood L-dopa concentrations were observed in healthy ( P r = 0.85 ) and PD subjects ( P r = 0.88 ) following a single immediate-release L-dopa/carbidopa dose. Low motor symptom scores aligned with peak L-dopa levels, confirming pharmacodynamic relevance. L-dopa cleared faster in PD patients despite similar bioavailability to healthy subjects, while recorded hemodynamic responses showed short hypotensive trends for both groups. Machine learning identified sweat and blood pressure as key contributors toward accurate estimation of blood L-dopa levels (mean absolute error = 2.02 µM vs. ground truth). Overall, our easy-to-use, energy-efficient wearable supports real-time, stimulation-free monitoring, potentially enabling at-home dosage adjustments and paving the way for future autonomous closed-loop L-dopa therapeutic system development.

Energy prioritization and neurometabolic scaling in a social insect brain

Brains are metabolically costly and due to their high energetic demands may receive priority under conditions of reduced energy availability. Such preferential energy allocation to the brain has been described for humans and other mammals, but previous studies have not directly quantified brain metabolic rate or simultaneously considered whole-body metabolism. We recorded brain metabolic rate ex vivo, brain mass, body mass, and whole-body metabolic rate in workers of the ant Tetramorium immigrans and found the proportion of whole-body energy allocated to the brain nearly doubled to 45% when nutritionally stressed. Body metabolic rate was significantly reduced without a comparable decrease in brain metabolic rate. The ability of nutritionally compromised workers to recognize and aggressively respond to a sympatric competitor was not affected, indicating that sensory perception and neural processing necessary for this critical behavior are maintained during energy limitation. Our finding that similar patterns of brain energy prioritization occur across remotely related clades with exceptionally different body sizes, respiratory systems, and brain allometries suggests conservation of ancient neurohormonal mechanisms or functional convergence of processes to protect the brain. Furthermore, although the worker brain was 5% of body mass, brain metabolic rate was 24 to 30% of body metabolic rate under unstressed conditions, remarkably similar to the pattern of humans and other mammals. Brain metabolic rate of T. immigrans was predictable from the scaling of brain metabolic rate in mammals, suggesting ecological, physiological, and evolutionary effects of body size on brain metabolic rate are common.

Rapid acceleration of ice-cover loss from Northern Hemisphere lakes above critical air temperature thresholds

Widespread declines in lake-ice cover are a hallmark of climate warming, yet the dynamic sensitivity of ice cover to thermal forcing remains poorly understood across broad climatic gradients. By analyzing an extensive dataset from 724 Northern Hemisphere lakes between 2000 and 2022, we quantify the responsiveness of lake-ice phenology to changes in air temperature and project their future trajectories. Our hemispheric analysis reveals a pronounced asymmetrical sensitivity where ice-decay processes are significantly more responsive to warming than ice-formation events. We identify critical thermal threshold of mean winter air temperature (AT) ranging from −13.7 to −6.8 °C, beyond which phenological sensitivity accelerates nonlinearly. Once these winter temperature breakpoints are surpassed, the sensitivity of ice loss increases by up to 22-fold, signaling a threshold-dependent collapse of the seasonal ice cycle. These threshold-dependent responses are primarily driven by broad-scale thermal and radiative regimes, particularly winter AT and surface albedo, rather than localized lake morphology. Future projections indicate that under high-emission scenarios, ice-cover duration will contract by approximately 40 d, and the proportion of lakes crossing critical thermal thresholds and entering a state of accelerated phenological sensitivity is expected to rise from 23 to 70% by the end of the century. These findings suggest that many temperate and southern boreal lakes are nearing a state of heightened vulnerability where marginal warming will trigger abrupt and potentially irreversible ecological shifts.

Digestion-resistant proteins support the healthy metabolite profiles associated with plant-based diets

Plant-based diets are associated with both positive health outcomes and a diverse gut microbiome. Such diets alter the microbiome’s metabolic outputs, including increasing phenylalanine-derived phenols associated with beneficial health outcomes (hippuric acid and 3-phenylpropionate), while decreasing tyrosine-derived phenols considered uremic toxins (phenol sulfate and p-cresol sulfate). The mechanisms linking plant eating to these phenol metabolites are not known. Plant-based foods are fiber and phytochemical rich. They also contain proteins that are resistant to host digestion and thus reach the gut microbiome. Here, we show that fiber and digestion-resistant protein work in concert to shift the phenol profile by altering gut microbiome nutrient supply. Through isotope-tracing studies, we reveal that host secreted proteins are a source for phenol sulfate and p-cresol sulfate, while digestion-resistant dietary protein is the source for hippuric acid and 3-phenylpropionate. Fiber decreases bacterial digestion of host secreted proteins (e.g., mucins) and thus suppresses tyrosine-derived phenol sulfate and p-cresol sulfate, whose levels correlate with the mucin-digesting bacterial family Oscillospiraceae. Digestion-resistant dietary protein increases bacterial access to phenylalanine and thereby boosts phenylalanine-derived hippuric acid and 3-phenylpropionate. Thus, digestion-resistant plant protein modulates microbiome metabolism and, together with fiber, supports healthy metabolite profiles associated with plant-based diets.

Source limitation drives slow compositional recovery in tropical secondary forests

Tropical forests can recover diversity, structure, and function rapidly after disturbance. However, plant compositional recovery remains incomplete even after many decades, and the reasons for this lag are poorly understood. We investigated the roles of source, dispersal, and establishment limitation in affecting compositional recovery in Costa Rican forests using long-term data on species composition of trees, seeds, seedlings, and saplings, along with measurements of herbivory and leaf pathogen damage in seedlings and saplings from old-growth (OG) and second-growth (SG) forest plots. We classified tree species into successional groups, including: generalist (similar relative abundance in OG and SG), old-growth specialist (higher relative abundance in OG), old-growth exclusive (detected only in OG), and too rare to classify conclusively. Infrequent species drove community dissimilarity between old-growth and second-growth plots, and 40% of species in old-growth plots were absent as trees in second-growth forests up to 55 y old. Old-growth exclusive species (as trees and seedlings and saplings in OG plots and as seeds in seed traps in OG and SG) have extremely low abundance (11 trees/ha; 1 seedling or sapling/ha; 8 seeds/ha), indicating strong source limitation. Old-growth exclusive species shared seed dispersal traits with old-growth specialists established in SG, providing no evidence of dispersal limitation. Old-growth specialist seedlings and saplings had higher survival in SG than in OG, providing no evidence of establishment limitation. These findings suggest source limitation as the primary driver of delayed compositional recovery in mid-to-late stages of forest succession and underscore the potential for targeted enrichment plantings to accelerate full compositional recovery.

Dietary DNA in municipal wastewater reveals signatures of wealth, immigration, and coastal proximity

Public health nutrition lacks scalable, objective tools for real-time dietary surveillance. We developed FoodSeq-FLOW (Food Landscape Observation in Wastewater), a genomic platform that sequences chloroplast trnL and mitochondrial 12SV5 DNA in municipal wastewater. Across 183 samples from 21 North Carolina wastewater treatment plants serving 2.1 million people, we detected 184 plant and 116 animal food taxa at a cost of &lt;US $0.01 per person. Wastewater-derived dietary profiles correlated with paired individual stool dietary data (Spearman ρ = 0.64), and 98% of animal-derived sequences mapped to known food taxa. Temporal sampling revealed seasonal shifts in food taxa consistent with regional food availability patterns. Spatial analysis revealed community-level dietary signatures associated with per capita income and education, beer ingredient abundance with discretionary income, tropical fruits and pulses with foreign-born population size, and local seafood with coastal geography. FoodSeq-FLOW extends wastewater-based epidemiology from pathogens to diet, providing a scalable platform that existing global wastewater surveillance networks can deploy to inform nutrition policy and market analytics.

Correction for Newman et al., The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity

A generative model for bipartite gene-sharing networks

Gene-sharing networks provide a powerful framework to study the evolution of viruses and mobile genetic elements. These bipartite networks, which link genes to the genomes that contain them, exhibit characteristic degree distributions: a scale-free distribution for genes and an exponential-like decay for genomes. Here, we propose a mechanistic model that explains these patterns through fundamental evolutionary processes including horizontal gene transfer, capture of new genes, emergence of new genomes, and gene loss. Using a mean-field approximation, we derive analytical expressions for the asymptotic gene and genome degree distributions, recapitulating a power-law distribution for genes and an exponential distribution for genomes. Numerical simulations validate these predictions and yield parameter values that closely fit empirical data from dsDNA viruses, RNA viruses, and prokaryotic pangenomes. This simple model with only two parameters provides a generative framework for bipartite gene-sharing networks, offering qualitative and quantitative insights into the main evolutionary forces driving genome plasticity. Setting the gene loss rate to zero, the gene and genome degree distributions of the model closely fit the empirically observed distributions. Thus, evolution of viruses appears to be dominated by gene gain, in agreement with the results of independent reconstructions of viral evolution.

Spatiotemporal control of Atg2 association with the ER during autophagosome formation

Autophagy degrades various intracellular components by sequestering them within membrane vesicles called autophagosomes and delivering them to lysosomes or vacuoles. Previous studies have revealed that the conserved, bridge-like lipid transfer protein Atg2 tethers autophagosome precursors to the endoplasmic reticulum (ER) and mediates lipid supply from the ER to drive their expansion into autophagosomes. However, how Atg2 docks onto the ER has remained unclear. Here, we show in Saccharomyces cerevisiae that Atg2 interacts with the ER-resident VAP family protein Scs2. This interaction is mediated by a phospho-FFAT motif in Atg2 and the major sperm protein domain of Scs2 and enhanced by phosphorylation of the motif by the autophagy-initiating kinase Atg1, which is activated at the autophagosome formation site upon autophagy induction. This interaction cooperates with the N-terminal region of Atg2, which contains a weakly amphipathic helix, to mediate Atg2 association with the ER. Thus, the Atg2–Scs2 interaction functions as a spatiotemporal switch that controls Atg2–ER association. We also show that mammalian ATG2 interacts with the VAP-like proteins MOSPD1 and MOSPD3 to promote autophagosome formation. Collectively, this study reveals a conserved mechanism that initiates lipid transfer during autophagosome formation.

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 reduction in mitoribosome abundance and in higher-order mitoribosome organization, which is necessary for cooperative translation. Defective mitochondrial translation suppressed cytosolic ribosomal protein expression, thereby limiting mitochondrial biogenesis. The consequent reduction in mitochondrial mass induced an aged T cell phenotype characterized by compromised memory phenotypes and proliferative capacity. Enhancing mitochondrial translation via overexpression of the mitoribosomal component Mrps5 reversed aged T cell phenotypes in a mouse model of viral infection or tumor. Together, our findings provide nanoscale-resolution views of internal mitochondrial structures in situ, revealing an age-related loss of mitoribosomes. This loss contributes to mitochondrial dysfunction and the subsequent decline in T cell function observed in older individuals. Restoring mitochondrial translation may therefore represent a strategy for mitigating T cell dysfunction in the aging population.

A fungal effector inhibits plant MAPK signaling by acting as a decoy substrate of MKK5

Plant immune responses rely on mitogen-activated protein kinase (MAPK) cascade that integrates pattern-triggered immunity and effector-triggered immunity. How fungal pathogens suppress this central signaling hub remains poorly understood. Here, we identify a secreted effector from phytopathogenic fungus Verticillium dahliae , VdHCE1, that is required for full virulence and directly targets host MAPK signaling. VdHCE1 interacts with the MAPK kinase MKK5 and is phosphorylated at threonine 166 in planta. Biochemical analyses demonstrated that VdHCE1 competes with MPK3 and MPK6 as a substrate of MKK5, thereby attenuating downstream MAPK activation. Consistently, VdHCE1 suppresses elicitor- and NLR-triggered immune responses, while deletion of VdHCE1 compromises fungal virulence in Arabidopsis and cotton. Genetic disruption of MKK5 restores the virulence of VdHCE1-deficient strains, establishing MKK5 as the functional target of VdHCE1. These findings reveal a strategy by which a filamentous fungal pathogen suppresses plant immunity by acting as a decoy substrate within the MAPK cascade and provide a molecular framework for engineering resistance to vascular wilt disease.

Effective mass of a migrating interface

Interfaces are ubiquitous in materials and play a central role in microstructural evolution and material properties. Although interface migration has been studied for more than a century and remains an active field, several foundational assumptions of interface kinetics remain largely untested. In particular, interfaces are commonly treated as massless objects governed by overdamped dynamics. In this study, we show that grain boundaries exhibit measurable inertial behavior under high-frequency oscillatory driving. We introduce a quantitative method to extract an effective interface mass from the phase lag between the applied force and the interface velocity and find that this mass scales with the atoms participating in boundary migration. Using this framework, we identify regimes in which inertial effects significantly modify interfacial kinetics, especially at frequencies relevant to thermal fluctuations. These results challenge the conventional overdamped description and establish effective interface mass as a key ingredient in a physically complete theory of interface migration.

A posttranslational modification of fimbriae drives pathogenicity in <i> <i>Klebsiella pneumoniae</i> </i>

Antimicrobial resistance is a severe public health burden. Especially concerning are multidrug resistant (MDR) infections, which restrict treatment options and significantly increase mortality risk. A major cause of MDR infections worldwide is carbapenem-resistant Klebsiella pneumoniae (CR Kp ). The predominant CR Kp sequence type worldwide is ST258. However, the factors underlying ST258’s epidemic success are not well defined. Genomic analyses of clinical isolates of CR Kp have found that the two-component regulatory system CrrAB is a genomic feature of ST258, suggesting that it may contribute to its global dominance. Despite this, the molecular details underpinning CrrAB’s contribution to ST258 Kp biology and pathogenicity are poorly understood. We used RNA-sequencing to identify the regulon of CrrA and found that CrrAB induces the expression of a gene, encoding Crr-regulated fimbriae modifying protein (CfmP), that is essential for pathogenesis driven by this two-component system. We performed mass spectrometry analyses of fimbriae purified from Kp expressing or lacking cfmP and found that CfmP induces a novel oxidation to a histidine residue in the major pilin subunit of fimbriae, FimA. We demonstrate that this oxidation significantly increases host cell adhesion and high bacterial loads within the host. CrrAB also drives high antibiotic resistance in CR Kp . Thus, our results place CrrAB at the intersection of pathogenicity and antibiotic resistance supporting its function as an important regulatory system driving the global dominance of ST258.

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, but 65 samples represented other taxa. Estimates of TA, measured by dispersion of specimen ages within samples, ranged from decades to millennia and scaled proportionally ( r 2 = 0.77) with sediment accumulation time (SAT), an inverse of sediment accumulation rate (SAR) that accounts for the stratigraphic span of samples. In agreement with numerical modeling, the observed TA estimates were an order-of-magnitude higher than SAT and modulated by SAT-dependent effects of vertical mixing and skeletal disintegration. When SAT is short, effective disintegration rates are too slow to suppress the amplifying role of mixing but increase in importance when SAT is long. The strong dependency of TA on SAT points to the overriding role of SAR in controlling the temporal resolution of fossil assemblages, notwithstanding other interacting drivers known to influence TA. These results demonstrate a long-suspected paleontological rule: The temporal resolution of fossil assemblages scales predictably with SAR. This straightforward relationship provides a quantitative guideline for determining the temporal adequacy of sedimentary records as archives of Earth system processes.

AI will reorganize science. Will research remain a human enterprise?