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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.
Thermodynamically Driven Multi‐Site Photoswitching in Tetraoxindole Cavitands Controlled by Hydrogen Bonding and Mechanochemistry
ABSTRACT Integration of multiple photoswitches into a single multi‐responsive system is a promising strategy toward achieving high information density, complex logic operations, and large‐amplitude motion. However, such systems typically suffer from poor efficiency. In this study, we present a strategy for efficient multi‐site photoswitching that is based on realizing forward and reverse transformations along thermodynamically favorable pathways. We show that tetra‐ E ‐oxindole‐resorcinarene undergoes effective multi‐site photoswitching to form a tetra‐ Z ‐isomer, which is more stable due to the intramolecular hydrogen‐bonding network. To achieve a reverse transformation, modulation of the relative stability of the isomers is required. Here, deprotonation under mechanochemical conditions effectively swaps stability, enabling effective back transformation to the tetra‐ E ‐isomer. Mechanochemistry is indispensable for this transformation, as swapping the stability of isomers is ineffective in solutions. By DFT calculations, we demonstrate that a network of hydrogen bonds is crucial for the modulation of isomers’ stability and multiplication of energetic effects. Finally, gas‐phase ion mobility mass spectrometry provided a complementary picture, confirming the all‐ E ↔ all‐ Z interconversions and their charge‐dependent direction.
Designing Novel Solar‐Blind Ultraviolet Nonlinear Optical Crystals Based on Local Proton Distribution Complementary Effect
ABSTRACT Dipolar π‐conjugated groups with large polarizability anisotropy and hyperpolarizability are generally regarded as important nonlinear optical (NLO) active building units. However, their strong dipole‐dipole interactions remain a key challenge in designing non‐centrosymmetric structures. To overcome this, we proposed a novel non‐centrosymmetric structure design strategy based on the local proton distribution complementary effect. Importantly, it could induce the groups to form a zigzag ordered arrangement along the direction perpendicular to the π‐conjugated plane, thereby significantly increasing the probability of forming non‐centrosymmetric structures. Based on this strategy, we successfully designed and synthesized two novel solar‐blind ultraviolet non‐centrosymmetric crystals, (C 3 N 2 H 5 )Na 3 (S 2 O 3 ) 2 ·2H 2 O and (C 3 N 2 H 5 )ClO 4 ·(C 3 N 2 H 4 ), with imidazolium/imidazole groups. Both crystals exhibit excellent optical performances, with a large birefringence of 0.158 @ 546 nm in (C 3 N 2 H 5 )ClO 4 ·(C 3 N 2 H 4 ) and a strong NLO effect approximately 2.6 times that of KH 2 PO 4 in (C 3 N 2 H 5 )Na 3 (S 2 O 3 ) 2 ·2H 2 O, which mainly result from the intrinsic characteristics of imidazolium/imidazole groups and their ordered arrangement. Consequently, this work not only develops two promising solar‐blind UV NLO crystals but also offers a novel structure design strategy that is expected to promote the development of NLO materials.
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.
Interface engineering with an rGO electron extraction layer for high-efficiency and stable Cu2ZnSnS4-based photocathode
The practical application of Cu2ZnSnS4 (CZTS)-based photocathodes is hindered by severe charge recombination and insufficient charge transport capability. Herein, we demonstrate a high-performance Pt/reduced graphene oxide (rGO)/CdS/CZTS photocathode for solar hydrogen production by incorporating rGO nanosheets as an electron transport layer. The optimized photocathode achieves a photocurrent density of −21.73 mA/cm2 at 0 VRHE and an applied bias photon-to-current efficiency reaches 3.43%, representing 153% and 149% improvements over the control device without rGO, respectively. Furthermore, the incorporation of rGO boosts the charge separation efficiency from 94.89% to 99.07%, and the stability is significantly enhanced, maintaining performance over 10 h. Density functional theory calculations reveal the underlying electronic mechanism: the rGO interlayer facilitates efficient electron extraction from CdS and promotes charge exchange with Pt, thereby suppressing bulk recombination and enhancing interfacial charge transfer. This work provides useful insights into interface engineering of photocathodes for high-efficiency photoelectrochemical systems.
Transmission diffuse EUV scattering by nanoscale Lamb waves in thin membranes
We report time-resolved diffuse extreme ultraviolet (EUV) scattering measurements of optically excited acoustic waves in thin Ti/SiN bilayers in transmission geometry. Following femtosecond optical excitation, the EUV diffuse scattering signal yields circular fringe patterns evolving as a function of the time delay between the optical pump and EUV probe pulses. We demonstrate that these patterns originate from multiple guided acoustic modes (Lamb waves) with wavelengths in the range 60–400 nm. By comparing the experimental frequency–wavevector maps with calculated dispersion curves, we show that diffuse scattering signal from Lamb waves is enhanced at discrete frequencies corresponding to longitudinal thickness resonances of the membrane. This observation indicates that Lamb waves with high in-plane wavevectors originate from the scattering of longitudinal thickness resonances by surface roughness. Our findings establish time-resolved diffuse EUV scattering as an efficient tool for probing nanoscale Lamb waves, applicable to the characterization of elastic properties of thin membranes.
Optimized Nb-doped SnO2 buffer layer for enhanced carrier extraction and Sb2S3 photovoltaic responses
Crystal vertical orientation, deep-level traps, interface charge non-radiative recombination, etc., for Sb2S3 solar cells are the main factors that constrain its optoelectronic performance. Suitable electron transport layers (ETLs) can improve Sb2S3 film deposition and enhance crystallization quality. Here, niobium-doped SnO2 (Nb-SnO2) as the ETLs was prepared to increase the carrier concentration and film conductivity. The optimized Nb-SnO2 film can promote efficient charge separation and transport. The high crystallinity of Nb-SnO2 can also improve fusions between nanocrystals and reduce grain boundaries. The incorporated Nb5+/Nb3+ ions may form the Nb2S5 (Nb2S3) with the S2− ions at the interfaces to induce Sb2S3 film deposition, increase grain sizes, enhance crystal orientation, and reduce deep-level traps. The Nb-doped SnO2 film together with the high-quality Sb2S3 layer and Nb-SnO2/Sb2S3 heterojunction can promote charge separation and extraction and alleviate carrier non-radiative recombination. The best device performance with a high photoelectric conversion efficiency (7.25%, a VOC of 0.703 V, a JSC of 16.87 mAcm−2, and an FF of 0.611) is achieved. The whole dynamic process of charge separation, extraction, and recombination is determined via detailed characterizations. Our simple doping strategy also provides useful guidelines for Sb2S3 solar cells to enhance SnO2 film conductivity, reduce deep-level traps in the Sb2S3 layer, optimize Nb-SnO2/Sb2S3 band alignment, etc.
Exceptionally high thermoelectric power factors at low temperatures in heavily doped p- and n-type Ge-rich Ge1−xSnx films
Low-temperature thermoelectric thin films compatible with semiconductor technology are of increasing interest for cryogenic energy harvesting and thermal management of advanced Si-based electronics. Here, we show that heavily doped p- and n-type Ge1−xSnx epitaxial films exhibit exceptionally high thermoelectric power factors (PF) at low temperatures owing to a pronounced phonon-drag effect. Hall-effect and Seebeck-effect analyses over a wide temperature range of 6–300 K reveal that this phonon-drag contribution, manifested as a strong enhancement of the Seebeck coefficient at low temperatures, persists even at high carrier concentrations approaching 1020 cm−3. Along with the simultaneous increase in electrical conductivity upon cooling, the PFs rise dramatically, reaching 1.4 × 102 and 4.7 × 103 μWcm−1 K−2 around 20 K for the p- and n-type films, respectively. These remarkably high PFs enhanced by phonon-drag effect demonstrate that heavily doped Ge1−xSnx provides a promising platform for low-temperature group-IV thin-film thermoelectrics.
Unlocking room-temperature magnetoelectricity in Ba1.5Sr1.5-based Z-type hexaferrites via magnetic anisotropy modulation
Current research on room-temperature magnetoelectric (ME) Z-type hexaferrites has predominantly centered on modifications based on Sr3Co2Fe24O41, which severely restricts the compositional freedom for regulating the Ba/Sr ratio. In particular, compositions with high Ba content, exemplified by the balanced Ba1.5Sr1.5Co2Fe24O41 (Ba1.5Sr1.5-based), are traditionally regarded as incapable of hosting room-temperature ME coupling, attributed to its distinct Co2+ site preference compared to Sr-rich counterparts. In this work, we realized magnetoelectric coupling above room temperature in the Ba1.5Sr1.5-based system through Al and Cu co-substitution, altering this conventional wisdom. This doping strategy effectively modulates the magnetic anisotropy to stabilize the magnetoelectric phase up to approximately 360 K while significantly enhancing the electric polarization. Furthermore, we demonstrate that the magnetoelectric states exhibit enhanced stability against external fields. Room-temperature magnetization modulation driven by an electric field is also observed. Our findings unlock the potential of the Ba-rich Z-type system and provide a broader compositional space for designing high-performance room-temperature multiferroics.
Chirality-induced spin-regulated synaptic dynamics in 2D perovskite memristors for polarimetric neuromorphic computing
Conventional von Neumann architectures face fundamental energy-efficiency bottlenecks, while current optoelectronic neuromorphic devices remain confined to simple optoelectronic responses, unable to leverage continuous physical degrees of freedom such as light polarization for continuous, analog synaptic modulation. We report a continuously polarization-tunable photonic memristor based on chiral 2D (R/S-MBA)2PbI4 perovskites, which integrates polarimetric sensing with neuromorphic computing. By incorporating molecular chirality into the inorganic framework, we leverage the chirality-induced spin selectivity effect to regulate synaptic relaxation dynamics via spin-dependent carrier transport. This mechanism enables continuous, polarization-tunable synaptic weight updates, significantly extending the functional dimensionality of neuromorphic hardware. We validate this architecture through noise-resilient modified national institute of standards and technology (MNIST) database classification—where chiroptical filtering improves accuracy from 76% to 88%—and high-precision semantic segmentation, achieving a polarization phase resolution of 5° and a Sørensen–Dice coefficient exceeding 0.9. These results establish a physical foundation for integrating spin-dependent degrees of freedom into optoelectronic neuromorphic systems, offering a robust pathway for next-generation intelligent processing.
Rebound dynamics of polymer drops impacting on soft solids at low Weber numbers
The impact of polymer drops on soft solid substrates occurs frequently in engineering applications such as inkjet printing and pesticide spraying. Here, we investigate how substrate elasticity and polymer concentration affect drop rebound at low Weber numbers. Four representative rebound metrics, including the contact time, maximum contact diameter, maximum equatorial diameter, and restitution coefficient, are analyzed. Experiments show that the rebound metrics depend only weakly on substrate elasticity, except for a modest increase in the maximum contact diameter on the ultrasoft gel. With increasing polymer concentration, the contact time increases and the maximum contact diameter decreases, whereas the maximum equatorial diameter and restitution coefficient remain nearly unchanged. Further direct numerical simulations suggest that such an increase in contact time is presumably associated with the increased solution viscosity rather than polymer elasticity. These findings advance our understanding of how substrate elasticity and drop viscoelasticity influence complex drops impacting onto compliant substrates at a low velocity.
Coherent control of solid-state defect spins via patterned boron-doped diamond circuit
We demonstrate the coherent control of nitrogen-vacancy (NV) spins using an electronic circuit integrated within diamond: a patterned, conductive boron-doped diamond (BDD) microwave waveguide. First, we validate the high-frequency performance of the circuit by characterizing its impedance up to the microwave range, confirming microwave transmission sufficient for optically detected magnetic resonance (ODMR) and coherent Rabi control. Under ambient conditions, we perform ODMR and observe Rabi oscillations driven by the heavily doped BDD circuit. We verify that microwave-induced frequency shifts remain limited under the present operating conditions at room temperature. In addition, separate high-pressure and low-temperature continuous-wave ODMR measurements demonstrate that the BDD antenna remains operational as a microwave delivery element in a high-pressure and low-temperature environment. These results indicate the potential of BDD circuits for on-chip microwave delivery in NV-based quantum devices, particularly for ODMR operation under extreme conditions.
Allocation of Peltier heating–cooling through the anomalous Hall effect
We report the observation of a spatial allocation of Peltier-effect-induced temperature modulation through the anomalous Hall effect (AHE) in a hybrid system comprising a magnetic metal and a thermoelectric semiconductor. AHE in the magnetic metal generates a transverse electric field perpendicular to the applied bias voltage, inducing charge injection into the thermoelectric layer via the closed circuit and resultant heating and cooling generation in a transverse geometry. Using an active thermal imaging technique, lock-in thermography, we visually extract the AHE-originating thermal contribution from other magneto-thermoelectric effects. Such heat allocation enables flexible design of transverse thermoelectric conversion, providing a pathway toward on-chip thermal management and selective temperature control at designated regions.
Generation of ultraviolet optical vortex beams with independently controlled topological charge and central wavelength
The development of ultraviolet (UV) optical vortex beams is critical for advancing nanoscale photonic applications; however, it has long been hindered by fundamental limitations in high-performance UV optical components. In this study, we demonstrate a compact, two-stage nonlinear frequency upconversion architecture for generating UV optical vortex beams. The scheme integrates a synchronized dual-quasi-phase-matching process, where second-harmonic generation and sum-frequency generation processes occur concurrently, followed by a cascaded UV upconversion stage. This design enables independent control of the topological charge (TC) of the UV vortex beam and discrete, broadband wavelength selection across the deep- to near-UV spectral range. Experimentally, 269 nm femtosecond UV optical vortex pulses with a TC controllably tuned from ℓ = 1 to ℓ = 4 were generated. Moreover, by selecting distinct cascaded upconversion pathways enabled by the spatiotemporally synchronized multi-vortex output from the preceding SHG–SFG stage, discrete wavelength tuning from 241 to 407 nm was achieved. Collectively, this compact, two-stage nonlinear upconversion platform provides a robust and versatile route to structured light generation at short UV wavelengths.
Domain switching-induced large rigid shift of the bulk photovoltaic effect in (111)-oriented BiFeO3 epitaxial films
The bulk photovoltaic effect (BPVE) in ferroelectric materials exhibits intrinsic sensitivity to light polarization, offering opportunities for self-powered polarization photodetection. However, the impact of ferroelectric domain switching on BPVE and its underlying mechanism remain insufficiently understood. Herein, we report the first experimental demonstration of electric-field modulation of BPVE in (111)-oriented BiFeO3 (BFO) epitaxial films. The (111)-oriented devices exhibit a continuous and rigid vertical shift (i.e., photocurrent offset) of the BPVE curves under external electric field, while preserving their amplitude and phase, in contrast to the (001) counterparts. Notably, the photocurrent modulation range along the in-plane electrode direction is four times larger than that of (001)-oriented devices. Piezoresponse force microscopy and crystal structure analysis reveal multidirectional domain switching in the (111)-oriented BFO films, which continuously modulates the interfacial Schottky barriers, thus accounts for the observed rigid shift. These findings elucidate the orientation dependent electric-field tuning mechanism of BPVE and highlight the advantage of (111)-oriented BFO for polarization-sensitive photodetector applications.