Bioaccessibility and health risk assessment of hydrophobic organic pollutants in soils from four typical industrial contaminated sites in China.

There have been reports of potential health risks for people from hydrophobic organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), and organophosphate flame retardants (OPFRs). When a contaminated site is used for residential housing or public utility and recreation areas, the soil-bound organic pollutants might pose a threat to human health. In this study, we investigated the contamination profiles and potential risks to human health of 15 PAHs, 6 PCHs, and 12 OPFRs in soils from four contaminated sites in China. We used an in vitro method to determine the oral bioaccessibility of soil pollutants. Total PAHs were found at concentrations ranging from 26.4 ng/g to 987 ng/g. PCHs (0.27‒14.3 ng/g) and OPFRs (6.30‒310 ng/g) were detected, but at low levels compared to earlier reports. The levels of PAHs, PCHs, and OPFRs released from contaminated soils into simulated gastrointestinal fluids ranged from 1.74% to 91.0%, 2.51% to 39.6%, and 1.37% to 96.9%, respectively. Based on both spiked and unspiked samples, we found that the oral bioaccessibility of pollutants was correlated with their logKow and molecular weight, and the total organic carbon content and pH of soils. PAHs in 13 out of 38 contaminated soil samples posed potential high risks to children. When considering oral bioaccessibility, nine soils still posed potential risks, while the risks in the remaining soils became negligible. The contribution of this paper is that it corrects the health risk of soil-bound organic pollutants by detecting bioaccessibility in actual soils from different contaminated sites.

Study on the Hydrophobic Modification Mechanism of Stearic Acid on the Surface of Coal Gasification Fly Ash.

In this study, the hydrophobic modification of coal gasification fly ash (FA) was investigated given the adverse effects of surface hydrophilic structures on the material field. The surface of FA was modified using stearic acid (SA), which successfully altered its hydrophilic structure. When the contact angle of S-FA increased from 23.4° to 127.2°, the activation index increased from 0 to 0.98, the oil absorption decreased from 0.564 g/g to 0.510 g/g, and the BET-specific surface area decreased from 13.973 m2/g to 3.218 m2/g. The failure temperature of SA on the surface of S-FA was 210 °C. The adsorption mechanism of FA was analyzed using density functional theory (DFT) and molecular dynamics (MD). The adsorption of water molecules by FA involved both chemical and physical adsorption, with active adsorption sites for Al, Fe, and Si. The adsorbed water molecules on the surface of FA formed hydrogen bonds with a bond length of 1.5-2.5 Å, leading to agglomeration. In addition, the long alkyl chain in SA mainly relied on the central carbon atom in the (-CH3) structure to obtain electrons in different directions from the H atoms in space, increasing the Coulomb repulsion with the O atoms in the water molecule and thereby achieving the hydrophobic effect. In the temperature range of 298 K to 358 K, the combination of FA and SA became stronger as the temperature increased.

Partitioning / self-assembly of artificial water channels - toward controlled permselectivity through bilayer membrane.

Artificial water channels (AWCs) have been extensively explored to mimic natural proteins, which enables to effectively transport water while blocking ions. As one of the first AWCs, self-assembled I-quartets (HCx) have showcased high water-permselectivity that can be enhanced by improving their distribution and stability within membrane. The use of long alkyl chains (n>8) is constrained by their low solubility and aggregation. Herein, we considered cycloalkyl moieties, explored for the increase of the solubility favoring enhanced partition and/ for their self-assembly behaviors resulting the formation of effective stable water-channels with increased water permeability in bilayer membranes. This class of cycloalkyl-ureido-ethyl-imidazole amphiphilic (CxUH) channel could serve as a new reference for the effective design of self-assembled artificial water channels, it may give rise to the applications in desalination or in water treatment.

Elucidation of d-allulose recognition mechanism in ketose 3-epimerase.

d-Allulose is a low-calorie sweetener with multiple nutritional functions that can be produced through d-fructose isomerization by ketose 3-epimerase (KEase). l-Ribulose 3-epimerase from Arthrobacterglobiformis (AgLRE) is one of the most important enzymes that produce d-allulose; however, its substrate recognition mechanism is unknown. In this study, the crystal structures of AgLRE and its complex with d-allulose and d-fructose were determined. Upon substrate binding, the hydrophobic residues around the active-site entrance move toward the bound substrate. A comparison of AgLRE and other KEase structures revealed that the substrate-binding residues are not the main factors responsible for its marked specificity for d-allulose and d-fructose, but the hydrophobicity of the active site pocket influences substrate recognition. Particularly, the two hydrophobic regions at the active site entrance are the regulatory elements that modulate substrate recognition by AgLRE. This study provides useful information for designing AgLRE to increase its affinity for d-allulose and d-fructose.

Dual cross-linked network of the active starch film by incorporating palmitic acid and geraniol: A comprehensive evaluation of the hydrophobic mechanism and antimicrobial activity.

In this study, (3-Aminopropyl) triethoxysilane (APTES) was employed as a bridging agent to enhance the compatibility between the hydrophilic starch/pectin film and the hydrophobic palmitic acid (PA) coating through hydrogen bonding and chemical reactions. To address the insufficient antibacterial activity of starch films, geraniol was also incorporated. The intermolecular interactions among APTES, PA, and starch were confirmed using x-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and hydrogen nuclear magnetic resonance spectroscopy (1H NMR). Notably, the inclusion of APTES and PA significantly increased the film's hydrophobicity, resulting in a water contact angle (WCA) of 95.12°, a water vapor permeability (WVP) of 2.08 × 10-10 g/(mm·s·Pa), and an oxygen permeability (OP) of 2.61 × 10-9 g·mm·mm-2·s-1. Molecular dynamics (MD) simulations revealed strong non-covalent interactions and exceptional compatibility between starch and PA. Furthermore, the integration of pectin and geraniol improved the mechanical strength and antimicrobial properties of the modified films compared to unmodified starch films. These environmentally friendly and biodegradable hydrophobic starch-based films present a promising option for sustainable packaging materials in food preservation.

Combustion and mechanical properties enhancement strategy based on stearic acid surface activated boron powders.

Boric acid and other impurities on the surface of boron (B) particles can interact with hydroxyl-terminated polybutadiene (HTPB), weakening the mechanical properties and energy release efficiency of boron-based solid rocket propellants. SA@B composite particles were created by coating stearic acid (SA) on the surface of B particles through solvent evaporation-induced self-assembly. The study investigated the impact of SA coating on the combustion performance of B particles and the mechanical properties of HTPB matrix composites. The results showed that the SA coating enhanced the oxidation efficiency of B particles in air. The combustion heat of SA@B composite particles is 30.29 MJ/g, about 50% higher than that of B particles. During the combustion of SA@B composite particles, fewer molten solid particles surround the flame, which enhances the stability of the combustion process of the B particles. Furthermore, the SA coating effectively enhanced the dispersion of B particles in HTPB. At a stretching speed of 100 mm/min, the tensile strength of the SA@B/HTPB composite materials is higher than that of the B/HTPB composite materials. Moreover, when the mass loading of the SA@B composite particles reaches 50 wt%, the tensile strength of SA@B/HTPB composite materials is 2.46 MPa. Activating the surface of boron particles with SA can significantly improve their compatibility with HTPB, which is crucial for the stable storage of boron-based solid rocket propellants.

A Paper-Based Wearable Moist-Electric Generator for Sustained High-Efficiency Power Output and Enhanced Moisture Capture.

Disposable wearable electronics are valuable for diagnostic and healthcare purposes, reducing maintenance needs and enabling broad accessibility. However, integrating a reliable power supply is crucial for their advancement, but conventional power sources present significant challenges. To address that issue, a novel paper-based moist-electric generator is developed that harnesses ambient moisture for power generation. The device features gradients for functional groups and moisture adsorption and architecture of nanostructures within a disposable paper substrate. The nanoporous, gradient-formed spore-based biofilm and asymmetric electrode deposition enable sustained high-efficiency power output. A Janus hydrophobic-hydrophilic paper layer enhances moisture harvesting, ensuring effective operation even in low-humidity environments. This research reveals that the water adsorption gradient is crucial for performance under high humidity, whereas the functional group gradient is dominant under low humidity. The device delivers consistent performance across diverse conditions and flexibly conforms to various surfaces, making it ideal for wearable applications. Its eco-friendly, cost-effective, and disposable nature makes it a viable solution for widespread use with minimal environmental effects. This innovative approach overcomes the limitations of traditional power sources for wearable electronics, offering a sustainable solution for future disposable wearables. It significantly enhances personalized medicine through improved health monitoring and diagnostics.

Novel rebreathing adaptation extends dive time in a semi-aquatic lizard.

Bubble use evolved in many small invertebrates to enable underwater respiration, but, until recently, there has been no evidence that vertebrate animals use bubbles in a similar manner. Only one group of vertebrates, semi-aquatic Anolis lizards, may be an exception: these lizards dive underwater when threatened and, while underwater, rebreathe a bubble of air over their nostrils. Although it seems that rebreathing should be adaptive, possibly functioning to extend the time that lizards remain in underwater refugia, this has not been empirically tested. Here, I demonstrate that rebreathing serves to extend dive time in a semi-aquatic anole, Anolis aquaticus. I prevented the formation of normal rebreathing bubbles by applying a commercial emollient on the skin surface where bubbles form to assess the impact of bubbles on rebreathing cycles, gular pumps, and dive times. Lizards that were allowed to rebreathe normally remained underwater an average of 32% longer than those with impaired rebreathing, suggesting a functional role of rebreathing in underwater respiration. Unlike rebreathing, gular pumping was unaffected by treatment and may warrant further research regarding its role in supplementing underwater respiration. This study provides evidence that vertebrates can use bubbles to respire underwater and raises questions about adaptive mechanisms and potential bio-inspired applications.

Pathological C-terminal phosphomimetic substitutions alter the mechanism of liquid-liquid phase separation of TDP-43 low complexity domain.

C-terminally phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) marks the proteinaceous inclusions that characterize a number of age-related neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal lobar degeneration and Alzheimer's disease. TDP-43 phosphorylation at S403/S404 and (especially) at S409/S410 is, in fact, accepted as a biomarker of proteinopathy. These residues are located within the low complexity domain (LCD), which also drives the protein's liquid-liquid phase separation (LLPS). The impact of phosphorylation at these LCD sites on phase separation of the protein is a topic of great interest, as these post-translational modifications and LLPS are both implicated in proteinopathies. Here, we employed a combination of experimental and simulation-based approaches to explore this question on a phosphomimetic model of the TDP-43 LCD. Our turbidity and fluorescence microscopy data show that phosphomimetic Ser-to-Asp substitutions at residues S403, S404, S409 and S410 alter the LLPS behavior of TDP-43 LCD. In particular, unlike the LLPS of unmodified protein, LLPS of the phosphomimetic variants displays a biphasic dependence on salt concentration. Through coarse-grained modeling, we find that this biphasic salt dependence is derived from an altered mechanism of phase separation, in which LLPS-driving short-range intermolecular hydrophobic interactions are modulated by long-range attractive electrostatic interactions. Overall, this in vitro and in silico study provides a physiochemical foundation for understanding the impact of pathologically relevant C-terminal phosphorylation on the LLPS of TDP-43 in a more complex cellular environment.

Capability lignin from Acacia crassicarpa black liquor as an environmentally benign antibacterial agent to produce antibacterial and hydrophobic textiles.

Recently, the growing health awareness of society on the utilization of fabrics has led to an increasing demand for natural-based antibacterial textiles. Lignin, a generous polyphenol compound in nature, is capable of preventing bacterial growth; in particular, it dwells bacteria closely together on human skin, such as Staphylococcus epidermidis, Bacillus subtilis, Propionibacterium acnes, and Staphylococcus aureus. However, the antibacterial properties of lignin are limited by factors such as the lignin concentration, source, and type of bacteria. This study aimed to evaluate the potency of lignin as an antibacterial agent for textiles. Moreover, the thermal properties and wettability of the textile after lignin coating were also investigated. This study showed that lignin isolation methods significantly contributed to the inhibition of bacterial growth in the clear zone diameter. In addition, the lignin structure, lignin concentration, and type of bacteria had notably different antibacterial effects. SEM images showed that lignin was successfully coated on the fiber, and the antibacterial textile was successfully fabricated with clear zones in the range of 0.1-0.5 cm against four different bacteria. Lignin did not significantly improve the thermal stability of the textile, as proven by the TGA results. After the HDTMS coating by dispersion method, the wettability of the lignin-textile improved to that of the hydrophobic material, with a contact angle greater than 119.05° with excellent antibacterial properties (clear zone of 0.1-0.43 cm).

Effects of transient flow conditions on colloid-facilitated release of decabromodiphenyl ether: Implications for contaminant mobility at e-waste recycling sites.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous contaminants, especially in the soil and groundwater of contaminated sites and landfills. Notably, 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209), one of the most frequently and abundantly detected PBDE congeners in the environment, has recently been designated as a new pollutant subject to rigorous control in China. Colloid-facilitated transport is a key mechanism for the release of PBDEs from surface soils and their migration in the aquifer, but the effects of hydrodynamic conditions, particularly transient flow, on colloid-facilitated release of PBDEs are not well understood. Herein, we examined the effects of typical transient flow conditions on the release characteristics of colloids and BDE-209 from surface soil collected from an e-waste recycling site by undisturbed soil core leaching tests involving multiple dry-wet cycles (with different drying durations) and freeze-thaw cycles. We observed significant positive correlations between BDE-209 and colloid concentrations in the leachate in both the dry-wet and freeze-thaw leaching experiments, highlighting the critical role of colloids in facilitating BDE-209 release. However, colloids mobilized during the dry-wet cycles contained higher contents of BDE-209 than those in the freeze-thaw cycle tests, and the difference was primarily due to the more intensive disintegration of soil aggregates and elution of newly formed inorganic colloidal particles (mainly primary silicate minerals such as quartz and albite) with low BDE-209 content during the freeze-thaw process. These findings underscore the necessity of considering transient flow conditions when assessing the fate and risks of PBDEs at contaminated sites.

Impact of hydrophobically modified cellulose nanofiber on the stability of Pickering emulsion containing insect protein.

BACKGROUND: Cellulose nanofiber (CNF) is an ideal Pickering emulsion stabilizer because of its high aspect ratio and flexibility. CNF was hydrophobically modified by dodecenyl succinic anhydride and used to stabilize the simulated food emulsion system containing insect protein. The prepared dodecenyl succinate nanofiber (D-CNFs) was characterized by contact angle and laser particle size analyzer. The stability of the emulsion system under different conditions was characterized by zeta potential and appearance observation. Lastly, in vitro digestion simulation experiments were carried out to investigate whether the addition of D-CNFs had an effect on the digestion and absorption of oil. RESULTS: The modification process for dodecenyl succinic anhydride to CNFs was that the system temperature was 40 °C, the system pH value was 8.5 and the reaction time was 6 h. The water contact angle of the modified CNFs increased to 83.2 ± 0.9°. D-CNFs were introduced into the simulated food emulsion system containing insect protein. The increase in the concentration of D-CNFs in the aqueous phase promoted the stability of the simulated emulsion system. Increasing the ratio of insect protein was not conducive to the stability of the emulsion. The final fat digestibility of the emulsion with D-CNFs was lower than that of the emulsion without D-CNFs. CONCLUSION: Overall, the analysis and characterization results show the potential of the modified CNF as a food simulant emulsion stabilizer containing insect protein, which can be used for the development of specific functional foods. © 2024 Society of Chemical Industry.

Electrodeposition of Ce-Zr myristate superhydrophobic coating on copper substrate.

Copper and its alloys due to favorable properties such as ductility, high electrical and thermal conductivity are very important in various industries. The coating of rare earth elements and intermediate elements is a suitable method to form a super-hydrophobic coating on copper substrate. The aim of this research is to fabricate a controlled super-hydrophobic coating of cerium-zirconium myristate on the copper base using the electrochemical deposition process and to prevent the corrosive solution penetration and reaching to the copper substrate due to removing the corrosive solution from the surface of the coating. The variables parameters in this process are the change of deposition time, the different concentrations of cerium chloride, and zirconium chloride salts and is necessary to investigate their effect of them on the structural morphology, wettability and corrosion properties. According to the results of Field Emission Scanning Electron Microscope (FE-SEM), the surface morphology of the coatings is consisted of lotus-like nano and micro leaves. Furthermore, the wettability of the prepared coatings was analyzed and observed by measuring the contact angle of the coating with water droplet that the fabricated coating from the electrolyte containing 0.056 M of cerium chloride, 0.014 M of zirconium chloride, 0.1 M of myristic acid, 10 ml of hydrochloric acid and ethanol solvent has super-hydrophobic properties and the contact angle with water droplet is measured at 161°. The FT-IR and EDS analysis showed that the chemical composition of lotus-like leaves is cerium myristate and zirconium myristate. As a result, it can be inferred that the type of morphology and surface roughness play an important role in inducing the super-hydrophobic properties and has the most effect on the corrosion resistance of the coating due to the formation air pockets and then to prevents the corrosive solution penetration through the cross section of the coating and reaches to the copper substrate.

Hydrophobic interaction chromatography in continuous flow-through mode for product-related variant removal.

Product-related impurities are challenging to remove during monoclonal antibody (mAb) purification process due to molecular similarity. Frontal chromatography on hydrophobic interaction resins has demonstrated its capability to effectively remove such impurities. However, process improvements geared towards purity level comes as a trade-off with the yield loss. In this work, we present a hydrophobic interaction chromatography process using multicolumn continuous chromatography (MCC) concept and frontal analysis to remove a high prevalence product related impurity. This design uses a two-column continuous system where the two columns are directly connected during product chase step to capture product wash loss without any in-process adjustment. This polish MCC operation resulted in a 10 % increase in yield while maintaining 99 % purity, despite the presence of 20 % product-related impurities in the feed material. One challenge associated with polish MCC design is that the accumulation of the impurities renders a non-steady state recycling. To surmount this issue and ensure a robust process, a mechanistic model was developed and validated to predict multicomponent breakthrough. This model was capable to predict multiple cycle behavior and accounts for increased impurity concentration. Assisted by the model, the optimized operation parameters and conditions can be determined to account for variation in product load quality. The simulated results demonstrate an effective doubling of productivity compared to conventional batch chromatography.

Systematic Study on Swelling/Delamination of Layered Metal Oxides with Quaternary Ammonium Ions: Production of Well-Shaped/Oversized Unilamellar Nanosheets.

Enormous swelling of layered host compounds in an aqueous solution of various amines has been investigated as an important step in the synthesis of molecularly thin 2D nanosheets. However, a complete understanding of the reaction process has not been attained, which is the barrier for producing high-quality unilamellar nanosheets. Here, the swelling and delamination behaviors of platelet single crystals of protonated layered metal oxides are systematically examined with a series of tetraalkylammonium (TAA) hydroxide solutions. Upon contact with the solutions, the crystals immediately underwent massive expansion by several tens to hundreds of times. The swollen crystals can be delaminated into elementary layers by the application of external shear force. The exfoliation behavior is dependent on TAA ions, especially in terms of yield and lateral size/shape of the delaminated nanosheets. The swollen crystals with TAA ions with longer alkyl chains are delaminated almost completely, but irregular and fractured small sheets are yielded. Such long alkyl chains become entangled on the oxide layer and resulting hydrophobic interactions may be responsible for the lateral fragmentation. It is found that replacement of aqueous solutions with organic solvents to suppress the hydrophobic interactions is effective to produce oversized nanosheets in rectangular shape with sharp edges.

Patterned Hybrid Surfaces for Efficient Dew Harvesting.

Dew harvesting, minimally influenced by climate and geographical locations, is an ideal method for addressing water shortage problems. Superhydrophilic surfaces, characterized by their highest affinity for water, are particularly attractive for this purpose as they can attract more water molecules via condensation. However, a significant challenge arises from the high surface capillary force that impedes water from sliding down and being effectively collected. The resulting water film on the superhydrophilic surface tends to stay around the edge of the water collection surface, leading to evaporation loss and reduced collection efficacy. To overcome this problem, triangular patterns with low surface adhesion to water were introduced at the edge of superhydrophilic surfaces. This modification, achieved through a wet chemical method and masked oxygen plasma treatment, has significantly improved the efficiency of water collection. Results indicate that the hybrid surface reduced the time for the first water droplet to slide down by half and increased water collection efficiency by 78% compared to uniform superhydrophilic surfaces and by 536% compared to uniform superhydrophobic surfaces under a relative humidity of 55% with a temperature difference of 15 °C. The underlying principles were elucidated through computational simulations, and the mechanisms driving the enhancement in collection efficiency were explained.

Development of natural product-based targeted protein degraders as anticancer agents.

Targeted protein degradation (TPD) has emerged as a powerful approach for eliminating cancer-causing proteins through an "event-driven" pharmacological mode. Proteolysis-targeting chimeras (PROTACs), molecular glues (MGs), and hydrophobic tagging (HyTing) have evolved into three major classes of TPD technologies. Natural products (NPs) are a primary source of anticancer drugs and have played important roles in the development of TPD technology. NPs potentially expand the toolbox of TPD by providing a variety of E3 ligase ligands, protein of interest (POI) warheads, and hydrophobic tags (HyTs). As a promising direction in the TPD field, NP-based degraders have shown great potential for anticancer therapy. In this review, we summarize recent advances in the development of NP-based degraders (PROTACs, MGs and HyTing) with anticancer applications. Moreover, we put forward the challenges while presenting potential opportunities for the advancement of future targeted protein degraders derived from NPs.

Development of a Janus tissue adhesive hemostatic patch based on hydrophobically-modified Alaska pollock gelatin.

Uncontrollable hemorrhage from trauma and open surgery leads to a high percentage of death. Even though some patch-type hemostatic materials have been used in the clinic, sufficient tissue adhesion property and the management of tissue adhesion and anti-adhesion have been the challenges. In this report, we designed Janus tissue adhesive hemostatic patch, consisting of Alaska pollock gelatin (Org-ApGltn) as a support layer and decanoyl group-modified ApGltn (C10-ApGltn) with pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-PEG) as an adhesive layer, named as the C10-ApGltn patch. The C10-ApGltn patch adhered onto blood vessel surface by the activation 4S-PEG and hydrophobic groups in C10-ApGltn through the covalent bond formation and physical interaction. The burst strength of the C10-ApGltn patch was optimized in terms of the degree of substitution, the molecular weight of 4S-PEG, the concentration of C10-ApGltn, and the NHS/NH2 ratio. The optimized C10-ApGltn patch showed significantly higher burst strength with commercially available TachoSil®. The C10-ApGltn patch showed enzymatic degradability in a buffer solution with collagenase. In a rat liver hemorrhage model, the C10-ApGltn patch acted as a sealant on the hemorrhage site and exhibited competitive hemostatic property to TachoSil®.

Starch/ionic liquid/hydrophobic association hydrogel with high stretchability, fatigue resistance, self-recovery and conductivity for sensitive wireless wearable sensors.

Conductive hydrogels have been widely used in wearable electronics due to their flexible, conductive and adjustable properties. With ever-growing demand for sustainable and biocompatible sensing materials, biopolymer-based hydrogels have drawn significant attention. Among them, starch-based hydrogels have a great potential for wearable electronics. However, it remains challenging to develop multifunctional starch-based hydrogels with high stretchability, good conductivity, excellent durability and high sensitivity. Herein, amylopectin and ionic liquid were introduced into a hydrophobic association hydrogel to endow it with versatility. Benefiting from the synergistic effect of amylopectin and ionic liquid, the hydrogel exhibited excellent mechanical properties (the elongation of 2540 % with a Young's modulus of 12.0 kPa and a toughness of 1.3 MJ·m-3), self-recovery, good electrical properties (a conductivity of 1.8 S·m-1 and electrical self-healing), high sensitivity (gauge factor up to 26.85) and excellent durability (5850 cycles). The above properties of the hydrogel were closely correlated to its internal structure from hydrophobic association, H-bonding and electrostatic interaction, and can be regulated by changing the component contents. A wireless wearable sensor based on the hydrogel realized accurate and stable monitoring of joint motions and expression changes. This work demonstrates a kind of promising biopolymer-based materials as candidates for high-performance flexible wearable sensors.

Tanomastat exerts multi-targeted inhibitory effects on viral capsid dissociation and RNA replication in human enteroviruses.

BACKGROUND: Global cyclical outbreaks of human enterovirus infections has positioned human enterovirus A71 (EV-A71) as a neurotropic virus of clinical importance. However, there remains a scarcity of internationally approved antivirals and vaccines. METHODS: In pursuit of repurposing drugs for combating human enteroviruses, we employed a comprehensive pharmacophore- and molecular docking-based virtual screen targeting EV-A71 capsid protein VP1-4, 3C protease, and 3D polymerase proteins. Among 15 shortlisted ligand candidates, we dissected the inhibitory mechanism of Tanomastat in cell-based studies and evaluated its in vivo efficacy in an EV-A71-infected murine model. FINDINGS: We demonstrated that Tanomastat exerts dose-dependent inhibition on EV-A71 replication, with comparable efficacy profiles in enterovirus species A, B, C, and D in vitro. Time-course studies suggested that Tanomastat predominantly disrupts early process(es) of the EV-A71 replication cycle. Mechanistically, live virus particle tracking and docking predictions revealed that Tanomastat specifically impedes viral capsid dissociation, potentially via VP1 hydrophobic pocket binding. Bypassing its inhibition on entry stages, we utilized EV-A71 replication-competent, 3Dpol replication-defective, and bicistronic IRES reporter replicons to show that Tanomastat also inhibits viral RNA replication, but not viral IRES translation. We further showed that orally administered Tanomastat achieved 85% protective therapeutic effect and alleviated clinical symptoms in EV-A71-infected neonatal mice. INTERPRETATION: Our study establishes Tanomastat as a broad-spectrum anti-enterovirus candidate with promising pre-clinical efficacy, warranting further testing for potential therapeutic application. FUNDING: MOE Tier 2 grants (MOE-T2EP30221-0005, R571-000-068-592, R571-000-076-515, R571-000-074-733) and A∗STARBiomedical Research Council (BMRC).