Groundwater salinization in coastal reclamation areas severely threatens regional water security. To address the limitation that machine learning models tend to overlook hydrogeochemical processes in black-box predictions, a PMF-weighted SHAP framework was proposed, which directly embeds source-apportionment information into feature selection. Qualitative evidence first indicated that trapped seawater in reclamation sediments, rather than active modern seawater intrusion, was the primary source of salinization. The PMF-derived contributions of trapped seawater were then integrated into SHAP as sample-specific physical weights, allowing samples with stronger trapped-seawater signatures to exert greater influence on feature ranking. Finally, following model benchmarking, XGBoost was selected as the base learner to predict the Groundwater Quality Index (GQI) using 407 groundwater samples, and three feature-input strategies were compared. The results show that compared to the conventional SHAP model, the PMF-weighted framework raised the importance ranking of land use and suppressed the spuriously high importance of tidal level, thereby aligning feature selection with the trapped-seawater-dominated salinization mechanism and increasing the test-set R2 from 0.755 to 0.887. Stratified SHAP importance was further found to be highly consistent with the physical zonation revealed by PMF: irrigation predominantly affects the shallow zone (0-200 cm) in the paddy field, whereas trapped seawater dominates the deeper layer (300-400 cm) in both dryland and paddy field. This study demonstrates that embedding physical mechanisms into feature selection is an effective approach for constructing highly reliable predictive models in hydrology.
Antiphospholipid syndrome (APS) is an autoimmune thrombotic disorder characterized by the presence of antiphospholipid antibodies, including anti-phosphatidylserine/prothrombin antibodies (aPS/PT). While neutrophil extracellular traps (NETs) are implicated in the pathogenesis of APS, the role of aPS/PT in NET induction and its contribution to thrombosis remain unclear. This study aimed to clarify the effects of NETs induced by a monoclonal aPS/PT antibody on platelet activation and their potential contribution to thrombo-inflammatory responses. NETs were induced by stimulating peripheral blood neutrophils from healthy donors with aPS/PT. Their morphology and platelet-activating capacity were compared with NETs induced by anti-neutrophil cytoplasmic antibodies (ANCAs). Proteomic analyses were conducted to comprehensively compare protein compositions of these NETs, and candidate proteins associated with platelet activation in aPS/PT-induced NETs were identified. Functional inhibition assays were then conducted to assess whether blocking these candidates would suppress aPS/PT-induced NET-mediated platelet activation. We found that binding of aPS/PT to neutrophils induced NET formation, with a larger and more fibrous morphology compared to ANCA-induced NETs. Platelets trapped in aPS/PT-induced NETs showed significantly higher activation compared to those trapped in ANCA-induced NETs. Proteomic analyses identified histone H3 as a potential mediator of platelet activation in aPS/PT-induced NETs. Correspondingly, plasma concentrations of H3.1 nucleosome were significantly higher in patients with APS than in healthy controls. Blockade of histone H3 using a neutralizing antibody significantly suppressed platelet activation mediated by aPS/PT-induced NETs. These findings suggest that aPS/PT-induced NETs contribute to platelet activation and may promote thrombo-inflammatory responses in APS. Targeting histone H3 within aPS/PT-induced NETs may provide a potential therapeutic strategy for thrombo-inflammatory processes in APS.
Temporal reflection in nonlinear optical fibers provides a powerful framework for manipulating light. In this work, we theoretically and experimentally demonstrate a novel, to the best of our knowledge, mechanism for wave trapping induced by the dynamical evolution of a single high-order soliton pulse. Experimental measurements performed in a 5-km-long nonlinear dispersion-shifted fiber confirm the coexistence of reflected, transmitted, and trapped components, in excellent agreement with theoretical predictions. These results establish a simple and versatile route toward dynamic temporal waveguiding using a single optical pulse, opening new opportunities for all-optical control and manipulation of ultrafast signals.
Gyrokinetic simulations of a turbulence-reduced Wendelstein 7-X discharge-characterized by a steep density gradient, moderate temperature gradients, and low plasma beta-show that microtearing mode (MTM) turbulence dominates transport. The simulated heat and particle fluxes agree with experimental measurements, leaving MTMs as the only mode consistent with the data. These conditions, the quasi-isodynamic and nearly max-J magnetic configuration of the Wendelstein 7-X stabilize ion temperature gradient modes and density-gradient-driven trapped-electron modes, while moderate collisionality and low magnetic shear further enable MTM growth. Further nonlinear scans of the density gradient reveal a significant reduction in turbulent transport at the experimentally observed threshold, which we identify as an ion temperature gradient to MTM-dominated turbulence transition. These findings provide a robust explanation for the turbulence suppression and deepen our understanding of low turbulent transport regimes in optimized stellarators.
We introduce the pushy random walk, where a walker can push multiple obstacles, thereby penetrating large distances in environments with finite obstacle density. This process provides a minimal model for experimentally observed interactions of active particles with dense, deformable media. Using scaling arguments and numerical simulations, we show that in one dimension the walker carves out an obstacle-free cavity whose length grows subdiffusively with time. In two dimensions, increasing obstacle density drives a transition from free diffusion to localized behavior, where the walker is trapped within a cavity whose radius again grows subdiffusively with time. These results show how tracer-induced rearrangements qualitatively reshape transport in crowded media.
Photocarrier surface recombination is a critical process in optoelectronics. Here, we report that when photocarriers traverse generic semiconductor surfaces or certain carrier-transport layers, slower carriers-arising from weaker electric-field-driven drift-are more likely to be trapped by defect states and subsequently recombine. This process can be engineered to unlock emergent optoelectronic functionalities. Proof-of-concept experiments are proposed in which a wide space-charge region (tens of µm in width) is created in a semiconductor, and photocarriers are generated at locations with distinct electric potentials to observe their surface collection rates. The transport of photocarriers is intentionally impeded to distinguish their dynamics. We examine a variety of interfaces, including direct electrical contacts, surfaces with intentionally introduced defects, and defective organic contacts. It is observed that carriers generated in regions of low electric potential preferentially recombine, offering the possibility for tailored spectral response in semiconductor heterointerfaces. By manipulating slow-carrier recombination, a silicon (Si) narrowband photodetector with ∼100 nm full width at half maximum (FWHM) is demonstrated. Semiconductor surfaces/interfaces are natural filters that capture weak-drift slow carriers.
Herein, we report a photocatalyzed decarboxylative Giese reaction for the late-stage functionalization of 5'-COOH oligonucleotides. Under mild visible-light conditions, C4' radicals are generated and trapped by diverse Michael acceptors, including simple alkenes, Dha-containing peptides, and alkene-bearing drug molecules. This method enables the rapid synthesis of peptide- and drug-oligonucleotide conjugates and is applicable to dinucleotides as well as 3-4 nt oligonucleotides on a microscale (10-100 nmol).
We report high-precision frequency ratio measurements between optical atomic clocks based on ^{27}Al^{+}, ^{171}Yb, and ^{87}Sr. With total fractional uncertainties at or below 3.2×10^{-18}, these measurements meet an important milestone criterion for redefinition of the second in the International System of Units. Discrepancies in ^{87}Sr ratios at approximately 1×10^{-16} and the Al^{+}/Yb ratio at 1.6×10^{-17} in fractional units compared to our previous measurements underscore the importance of repeated, high-precision comparisons by different laboratories. A key upgrade from our previous work is the use of a common ultrastable reference delivered to all clocks via a 3.6-km phase-stabilized fiber link between two institutions, enabling better accuracy and stability in frequency transfer. Derived from a cryogenic single-crystal silicon cavity, this reference improves comparison stability by a factor of 2-3 over previous systems, with an optical lattice clock ratio achieving a fractional instability of 1.3×10^{-16} at 1 s. Identifying individual clock stabilities with a three-corner-hat measurement, we demonstrate the most stable optical lattice and trapped-ion clocks used in a multispecies comparison. By enabling faster comparisons, this stability will improve sensitivity to nonwhite noise processes and other underlying limits of state-of-the-art optical frequency standards.
Hydrogenation of N2 to NH3 by the enzyme nitrogenase necessarily involves intermediates with H-N bonds. I propose a tactic for trapping these intermediates, through formation of stabilising hydrogen bonds using contiguous hydrogen bond acceptors in the reaction space. Wild type protein contains an aprotic reaction space, significantly bounded by α-70Val. The carboxylate sidechain of aspartate substituted at this position is capable of forming very good O⋯H-N hydrogen bonds with intermediates in proposed mechanisms. Alternatively, serine at this position can form O-H⋯N hydrogen bonds with N lone pairs on some intermediates. These expectations are elaborated with density functional optimisations of nine proposed intermediates and one transition state in the substituted proteins 70Asp, 70Ser and 70Glu. Possible outcomes are discussed, with the expectation that experiments in which these three substituted proteins undergo turnover with N2 could yield trapped intermediates on a time scale that permits their structural characterisation by crystal diffraction or cryoEM.
The presence of naturally occurring radionuclides in coastal groundwater constitutes a significant public health risk, especially in areas susceptible to hydrological variability. This research applies multivariate statistical methods, including principal component analysis and hierarchical cluster analysis, alongside the PHREEQC thermodynamic model to elucidate the mechanisms governing the mobility of naturally occurring radioactive materials (NORM), specifically gross alpha and beta activity, in a tropical coastal aquifer. Examination of 44 groundwater samples collected over two seasons indicated that more than half exceeded the national guideline for gross alpha activity (0.1 Bq/L). The results indicate that mildly acidic and reducing (anaerobic) conditions facilitate the reductive dissolution of iron and manganese hydroxides. The reductive dissolution of Fe/Mn oxides destabilizes the mineral structures that previously acted as sorptive barriers, thereby releasing trapped radionuclides directly into the groundwater. Additionally, this mobilization is synergistically influenced by competitive ion exchange mechanisms. PHREEQC modeling further identifies a potential iron "lock/release" mechanism: at mildly acidic conditions (mean pH 5.36-5.39), ferrihydrite precipitation is inhibited, maintaining elevated radionuclide mobility. Conversely, as pH increases (up to 7.32), the system approaches supersaturation (saturation index, SI > 0), promoting co-precipitation and resulting in a more than 31-fold decrease in alpha activity during the rainy season (from 0.405 to 0.013 Bq/L). In contrast, beta-emitting radionuclides are less affected by iron-related processes and are predominantly influenced by dilution, with a reduction of approximately threefold (from 0.358 to 0.109 Bq/L). These findings establish a scientific basis for developing cost-effective water treatment approaches, such as aeration combined with pH adjustment, to simultaneously remove heavy metals and alpha radioactivity from tropical coastal aquifer systems.
Antioxidant activity is commonly discussed in fields like chemistry, biology, nutrition, and medicine, but it is often viewed in functional terms rather than as a process controlled by basic radical kinetics. In many cases, antioxidant efficiency is described within a simple scavenging model, where antioxidants mainly intercept reactive radicals stoichiometrically and are then irreversibly consumed. While this model highlights an important aspect of antioxidant behavior, it does not fully capture the complexity of oxidative processes.In this review, antioxidant chemistry is examined as a competitive reaction network where chemical repair and regeneration pathways play a key mechanistic role. These pathways allow for the restoration of radical intermediates before damage terminates and enable the recycling of oxidized antioxidant species, thus extending antioxidant activity beyond just radical trapping. In this context, the identity of radicals, branching ratios, oxygen-dependent competition, and radical lifetimes are crucial factors that determine whether oxidative processes lead to propagation, termination, or repair.Special focus is given to phenolic antioxidants and to reaction networks involving the hydroperoxyl/superoxide couple (HO2•/O2•-). Although superoxide is often described as a weak oxidant or a precursor to more reactive species, its reactivity depends heavily on conditions. Under the right kinetic conditions, superoxide can participate in reductive pathways that contribute to antioxidant regeneration and radical repair.By combining insights from radiation chemistry, electrochemistry, and computational kinetics, this review highlights chemical repair as an important mechanistic component of antioxidant activity and offers a unified framework for understanding antioxidant function in various chemical and biological settings.
Leptospirosis (caused by Leptospira, a bacterium) and hantavirus disease (caused by hantavirus, a virus) are important zoonoses with rodents as main reservoirs. In this study, we investigated the prevalence and genetic diversity of Leptospira and hantavirus in rodents from rural Lanxi City, Zhejiang Province. Rodents showed a higher Leptospira carriage rate than the national average. All hantavirus isolates were Seoul virus (SEOV) and displayed high genetic divergence from vaccine strains. Notably, a unique local phylogenetic cluster of Leptospira borgpetersenii was identified, indicating potential vaccine mismatch and local evolutionary divergence. Samples were collected from April 2023 to August 2025, with intensive trapping from April to August annually in 2023-2024 and additional sampling in April 2025. Liver and kidney tissues were collected via aseptic dissection. Real-time fluorescent PCR was used to detect pathogen nucleic acids, and gene sequencing and phylogenetic analysis were performed on positive samples. A total of 350 rodents were captured, with Rattus norvegicus (brown rat) as the dominant species (80.00%). The overall Leptospira carriage rate was 7.14% (25/350), with the highest rate in R. norvegicus (7.86%). The overall hantavirus carriage rate was 1.43% (5/350), distributed mainly in R. norvegicus and Rattus flavipectus (yellow-breasted rat). No coinfection with both pathogens was detected. Genetic analysis identified 12 Leptospira strains as Leptospira interrogans and 2 as L. borgpetersenii; the latter showed genetic differences from domestic and foreign strains, suggesting a potential evolutionary trend. The two hantavirus strains were both SEOV, closely related to domestic SEOV strains from 2021 but with only 86.08-86.81% nucleotide homology to vaccine strains (e.g., 80-39, Z37), indicating natural variation. Rodents in rural Lanxi have a relatively high Leptospira carriage rate, and hantavirus is dominated by the SEOV type. R. norvegicus is the main host of both pathogens. Targeted monitoring and prevention/control measures should be strengthened. Natural genetic variation suggests potential antigenic drift and reduced vaccine matching, which requires further serological validation. Attention should be paid to the impact of pathogen genetic variation on control efforts.
Nanopore-based single-molecule sensing has emerged as a powerful tool for analyzing proteins, peptides, and nucleic acids. However, label-free control of analyte transport has predominantly relied on electrophoretic and electro-osmotic forces, whereas the deliberate engineering of hydrophobic interactions to modulate translocation kinetics remains underexplored. Here, we introduce aromatic residues at strategically distinct positions (T83F and S116F) within the Mycobacterium smegmatis Porin A (M2-MspA) constriction region to spatially segregate hydrophobic trapping from electrostatic steering, thereby establishing a position-dependent 'molecular brake' mechanism. These mutations were strategically introduced to modulate hydrophobic interactions and electrostatic forces within the pore. S116F elongates dwell times by ∼2.5-fold and deepens current blockades by 8-11% for negatively charged analytes, consistent with cooperative hydrophobic-electrostatic trapping near the R118 vestibule. Conversely, for positively-charged lysozyme, T83F prolongs dwell times by ∼3.2-fold while sharpening blockade distributions (ΔI/I0 = 63.97 ± 1.00%), whereas S116F introduces electrostatic repulsion that partially offsets hydrophobic attraction, thereby reducing residence time and revealing charge-dependent modulation of analyte-pore interactions. Notably, the combination of T83F and S116F enables the differentiation of complex mixtures, such as single-stranded DNA (ssDNA) and lysozyme, under symmetric salt conditions and neutral pH. Our work highlights the importance of precise spatial positioning of aromatic residues and shaping of charge distributions in nanopore engineering, offering a foundation for designing multifunctional nanopores. These position-dependent hydrophobic 'molecular brakes' enable label-free differentiation of oppositely-charged analytes under symmetric, neutral-pH conditions, advancing M2-MspA toward peptide profiling and protein fingerprinting.
Neutrophil extracellular traps (NETs) are web-like structures of DNA released by neutrophils during a specialized form of cell death called NETosis. Originally described as a mechanism of pathogen neutralization, NETs have since been implicated in a growing number of pathological conditions, including inflammatory diseases, autoimmunity, cancer, and neurodegeneration. The complexity and rapid dynamics of neutrophils and NET formation pose significant challenges for conventional approaches, highlighting a need for tools that can report molecular events with high spatial and temporal precision. Fluorescent probes have proven invaluable in this regard, offering both the sensitivity and selectivity required to study this process. This review provides a comprehensive overview of recent progress on the development of fluorescent probes for imaging NETosis, focusing on their design principles, biological applications, and key limitations. We discuss how these tools have advanced our understanding of the stimulus-dependent and spatiotemporally distinct activation dynamics of enzymes central to NETosis. We further highlight remaining challenges and outline design strategies that we believe will guide the development of next-generation tools to investigate neutrophil biology in health and disease.
Drug-target occupancy time-the cumulative duration a target remains bound-critically influences therapeutic efficacy. While Copeland's widely-used residence time ([Formula: see text]) emphasizes dissociation kinetics, it neglects association rates, rebinding events, and drug elimination that affect in vivo outcomes. Returning to Paul Ehrlich's 1913 principle that drugs act only when bound ("Corpora non agunt nisi fixata"), we develop a mathematically rigorous framework defining Ehrlich occupancy time, EOT, as the integral of fractional target occupancy over time. Our approach explicitly incorporates association ([Formula: see text]) and dissociation ([Formula: see text]) kinetics, accounts for rebinding, and extends to systems with drug removal. For drug-receptor closed systems at equilibrium, we prove that relative EOT equals the equilibrium occupancy fraction; under ligand-excess conditions this reduces to [Formula: see text], where [Formula: see text] is the dissociation constant and [Formula: see text] the drug concentration. For induced-fit mechanisms, conformational changes reduce the effective dissociation constant to [Formula: see text] (where [Formula: see text] and [Formula: see text] are forward and reverse isomerization rates), prolonging occupancy through kinetic trapping. Critically, for drug-receptor systems with first-order drug elimination at rate [Formula: see text], we derive rigorous bounds: [Formula: see text], where [Formula: see text] is the total cumulative occupancy time as [Formula: see text], revealing that both binding affinity and elimination rate jointly determine occupancy. This explains why high-affinity drugs can fail clinically if eliminated rapidly, and identifies pharmacokinetic optimization opportunities. We prove Copeland's definition is a special case of Ehrlich occupancy time when rebinding is absent. Our framework provides quantitative tools for optimizing drug design beyond binding affinity and enables improved prediction of in vivo efficacy where pharmacokinetics dominate.
Birds contribute to seed dispersal through endozoochory, often creating spatially aggregated patterns of seed deposition around perching sites. While this process has been extensively studied in open habitats, the role of deadwood in structuring bird-mediated seed rain within forest ecosystems remains poorly understood. This study investigated whether decaying logs function as important perching sites which influence the distribution of bird droppings and associated seed rain in a temperate deciduous forest. Bird droppings were collected during three seasons in 2021-2023 in an oak-hornbeam forest, using seed traps placed either beneath decaying logs or at randomly selected forest-floor locations. A total of 524 droppings were recorded. The abundance of droppings was significantly higher beneath logs than in random plots throughout the study period, with 73.7% of all droppings found in log-associated plots. This created a strongly aggregated pattern of seed deposition, as 80.6% of all recovered seeds occurred beneath logs. Overall seed dispersal by birds was low. Only 4.6% of droppings contained seeds, and mean seed rain reached 0.39 seeds × m-2 × season-1. These findings suggest that although bird-mediated seed input is limited, its distribution is strongly shaped by deadwood availability. Decaying logs therefore represent an overlooked structural component linking birds and fleshy-fruited plants.
Revealing the hidden interactions that bind electronic and lattice components of cooperative quantum order is central to sculpting new states of matter. This challenge is epitomized by the charge density wave material 1T-TiSe2, where photoexcitation disrupts its presumed hybrid exciton-phonon order: the electronic component collapses within femtoseconds, while the periodic lattice distortion persists, challenging the definition of hybrid order. Here we resolve this paradox by uncovering a low-frequency mode (~0.13 THz) that emerges only in the ordered state and signals exciton-phonon coupling. This mode is consistent with a locked phason, a collective excitation arising when excitonic and lattice degrees of freedom share a coupled potential landscape. At a critical photoexcitation threshold, the collapse of the excitonic order flattens this potential, causing the locked phason to disappear, the charge density wave phonon to selectively overheat, and the surviving lattice distortion to become a trapped non-thermal remnant.
The gut microbiota functions as a metabolically active microbial ecosystem that engages in bidirectional communication with the host nervous and immune systems, thereby contributing to homeostasis and disease pathogenesis. Eosinophil extracellular traps (EETs)-web-like structures composed of DNA and granule proteins released by activated eosinophils-exert context-dependent roles in host defence and immune regulation, with both pro-inflammatory and anti-inflammatory effects. Their function in tumour immunity, however, remains controversial. This review summarizes recent advances in understanding how the gut microbiota regulates eosinophil function and EET formation through the neuroimmune axis, encompassing the vagus nerve, neurotransmitters, and neuropeptides. We focus on the role of this regulatory network within the tumour microenvironment and discuss its potential influence on the efficacy of immune checkpoint inhibitors and the development of immune-related adverse events. By integrating evidence across microbial metabolism, neural signalling, and eosinophil biology, we aim to delineate the molecular mechanisms underlying this multilevel network and to provide a theoretical framework for anti-tumour strategies that co-target the gut microbiota and the neuroimmune axis, with the goal of improving immunotherapy outcomes while limiting treatment-related toxicity.
Neutrophil extracellular traps (NETs) have emerged as important mediators at the interface of innate immunity, thrombosis, and vascular remodeling. Aortic aneurysms and cerebrovascular diseases are now recognized as prototypical NET-driven conditions in which dysregulated immunothrombosis accelerates wall degeneration, promotes thrombus formation, and exacerbates tissue damage. This narrative review synthesizes current evidence on NET biology in the context of abdominal and thoracic aortic aneurysms, acute aortic syndromes, ischemic stroke, and intracerebral hemorrhage. First, we summarize the molecular mechanisms of NET formation, regulation, and clearance, outlining how NETs shape the immunothrombotic niche in aneurysm thrombi and the cerebral vasculature. Following this, experimental and clinical data on circulating and tissue NET markers are examined in relation to disease presence, lesion instability, hematoma expansion, and functional outcome, thereby highlighting their potential as diagnostic and prognostic biomarkers. Thereafter, pharmacological strategies that either inhibit NET formation or enhance NET degradation are discussed. We then examine how multilayered flow modulators, biodegradable scaffolds, and bioinspired stent coatings can modulate NET responses at the blood-device interface. Finally, we explore the emerging roles of multi-omics profiling, molecular imaging, artificial intelligence (AI)-based analyses in integrating NET-related signals into personalized risk prediction, device selection, and treatment monitoring. Collectively, these findings position NETs as central targets for biomarker development, immunomodulatory therapy, and immunobioengineered vascular devices. NET-informed precision management of aortic and cerebrovascular diseases is therefore a key area for further research.
Despite the biological significance of stereodefined phenolic O-glycosides, their efficient synthesis remains challenging. Here, we report the stereoselective O-furanosylation of phenols toward bench-stable glycosyl fluorides by cooperative activation of a Lewis acid and transition-metal complex, proceeding in high yields at room temperature. The novel glycosylation strategy is demonstrated to be effective for a wide substrate scope of acceptors, including small molecules, natural products, and commercial drugs. Mechanistic studies, supported by TEMPO-trapping and DFT simulations, established a radical-mediated pathway for this glycosylation. To demonstrate the utility of this strategy for bioactive molecule diversification, we focused on phenolic compounds with known anti-inflammatory properties (e.g., sesamol). Their ribofuranose conjugates were synthesized and evaluated, leading to the discovery that glycosylation could potentiate the parent compounds' ability to inhibit IL-6 production in LPS-stimulated macrophages, thereby demonstrating the potential of this glycosylation strategy to improve the pharmacological profiles of bioactive phenols.