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This study evaluates the structural stability of large underground spaces in seismic conditions, represented by the Oya underground stone mining plant. By directly monitoring the seismic response of the underground mining site, significant earthquake activities at the plate boundaries of the Tokyo region and Ibaraki Prefecture offshore area were observed. Additionally, through an in-depth analysis of seismic records from different locations within the underground structure, the dynamic characteristics and motion patterns of the Oya underground stone mining plant were revealed, revealing its movement trajectory during earthquakes. Additionally, this study innovatively applied seismic waves measured at the original site as input parameters and artificially generated seismic waves based on their response spectra. A numerical analysis was performed after ensuring the model's high correlation with the original site was met. The findings demonstrate that the results of both parameter input methods are confirmable and valuable. Under severe seismic conditions, instability was observed in some regions of the underground mining site. The study also discusses the location and damage mechanisms of the mining site's structure under seismic effects, providing valuable insights for the safety assessment of similar large underground spaces and proposing new approaches for selecting input parameters in seismic analysis.

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Lactiplantibacillus plantarum is a widely studied species known for its probiotic properties that can help alleviate serum cholesterol levels. Whole-genome sequencing provides genetic information on probiotic attributes, metabolic activities and safety assessment. This study investigates the probiotic properties of strain CRM56-2, isolated from Thai fermented tea leaves, using Whole-Genome Sequencing (WGS) to evaluate the safety, health-promoting genes and functional analysis. Strain CRM56-2 showed bile salt hydrolase (BSH) activity, assimilated cholesterol at a rate of 75.94%, tolerated acidic and bile environments and attached to Caco-2 cells. Based on ANIb (98.9%), ANIm (99.2%), and digital DNA-DNA hybridisation (98.3%), strain CRM56-2 was identified as L. plantarum. In silico analysis revealed that it was not pathogenic and contained no antibiotic-resistance genes or plasmids. L. plantarum CRM56-2 possessed genes linked to several probiotic properties and beneficial impacts. The genome of strain CRM56-2 suggested that L. plantarum CRM56-2 is non-hazardous, with potential probiotic characteristics and beneficial impacts, which could enhance its probiotic application. Consequently, L. plantarum CRM56-2 demonstrated excellent cholesterol-lowering activity and probiotic properties.

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In response to the growing demand for immune-related products, this study evaluated the safety and immune-modulating potential of three newly discovered Lactiplantibacillus plantarum strains (GKM3, GKK1, and GKD7) through toxicity tests and whole-genome sequencing. Safety evaluations, including the analysis of antimicrobial resistance genes, virulence factors, plasmids, and prophages, classified these strains as safe for human consumption. Acute oral toxicity tests further supported their safety. To evaluate their immune-modulating potential, dendritic cells were exposed to these strains, and the secretion of key cytokines (IFN-ß and IL-12) was measured. Among the strains, GKK1 exhibited the highest enhancement of IFN-ß and IL-12 production, suggesting its potential as an immune-stimulating probiotic. Bioinformatics analysis revealed potential metabolic pathways and secondary metabolites, including predicted bacteriocins, associated with immune modulation. The presence of a nitrate reductase region in the GKK1 strain indicated its ability to produce nitric oxide, a critical molecule involved in immune regulation and host defense. The presence of glucorhamnanrelated gene clusters in GKK1 also suggested immune-enhancing effects. Nitrate reductase expression was confirmed using qPCR, with the highest levels detected in GKK1. Moreover, this study is the first to show an anti-inflammatory effect of plantaricin A, linked to its presence in strain GKM3 and its potential therapeutic applications due to sequence similarity to known antiinflammatory peptides. Overall, these three L. plantarum strains demonstrated a safe profile and GKK1 showed potential as an immunity-enhancing probiotic. However, additional investigation is required to confirm the involvement of specific metabolic pathways, secondary metabolites, and bacteriocins in immune responses.

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Objective: To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness. Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors. Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels >34 g/L, APACHE II scores <13, and treatment duration >10 days correlated with better clinical efficacy. Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application.

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The present study was aimed to assess and validate the safety and functional efficacy of an indigenous probiotic strain Limosilactobacillus fermentum NCDC 400 (hereafter, LFN400) in an immunocompromised murine model. The study included four groups; a normal control (NC) group without immune suppression; an experimental model control (MC) with immune suppression induced via intraperitoneal cyclophosphamide (Cy) administration; and two MC groups orally administered with either low dose (LD) or high dose (HD) of LFN400 at dose 108 and 1010 CFU/mouse/day, respectively, for 15-days. Both control groups received normal saline as placebo control. LFN400 improved specific experimental characteristics including hematological and serum biochemical markers. Compared to MC group, LFN400-fed groups showed markedly (P < 0.05) decreased arrays of detrimental caecal enzymes. We did not observe instances of bacterial translocation of LFN400 from gut to bloodstream or extra-intestinal organs. LFN400 intake significantly (P < 0.05) enhanced spleen cell differentiation, immune and oxidative stress markers, and restored Cy-induced histopathological changes in multiple tissues, including the spleen. There was no genotoxic effect of LFN400 on bone marrow cells. Although not statistically significant, LFN400 feeding moderately increased gut microbiome diversity, supporting the growth of beneficial saccharolytic microorganisms and reducing the presence of pathobionts. The findings demonstrate that the probiotic strain LFN400 possesses in vivo safety and immunomodulatory potency and thus should be considered a potential candidate for future human clinical studies.

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Accumulating studies have highlighted the great potential of postbiotics in alleviating diseases and protecting host health. Compared with traditional functional foods (such as probiotics and prebiotics), postbiotics have the advantages of a single composition, high physiological activity, long shelf life, easy absorption, and high targeting, etc. The development of postbiotics has led to a wide range of potential applications in functional food and drug development. However, the lack of clinical trial data, mechanism analyses, safety evaluations, and effective regulatory frameworks has limited the application of postbiotic products. This review describes the definition, classification, sources, and preparation methods of postbiotics, the progress and mechanism of preclinical and clinical research in improving host diseases, and their application in food. Strengthen understanding of the recognition and development of related products to lay a theoretical foundation.

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BACKGROUND: The highland barley, Hordeum vulgare L., is a staple food crop with superior nutritional functions in Xizang, China. It is often damaged by the black cutworm, Agrotis ipsilon (Hufnagel), which is an underground pest and difficult to effectively manage. To introduce a novel insecticide with unique mode of action, broflanilide (BFL) and its binary mixtures with chlorantraniliprole (CAP), fluxametamide, ß-cypermethrin or imidacloprid were screened out as seed treatment to control black cutworm in highland barley in the present study. RESULTS: In the laboratory bioassays, BFL had outstanding insecticidal activity to black cutworm with a median lethal dose (LD50) of 0.07 mg kg-1. The mixture of BFL × CAP at the concentration ratio of 7:40 exhibited the highest synergistic effect with a co-toxicity coefficient of 280.48. In the greenhouse pot experiments, BFL and BFL × CAP seed treatments at 8 g a.i. kg-1 seed could effectively control black cutworm, with a low percentage of injured seedlings <20% and high control efficacies of 93.33-100% during a period of 3-12 days after seed emergence. Moreover, BFL and BFL × CAP seed treatments could promote the seed germination and seedling growth of highland barley at the tested temperatures of 15, 20 and 25 °C. CONCLUSION: Our results indicated that BFL and BFL × CAP were effective and promising insecticides as seed treatment to control black cutworm in highland barley. © 2024 Society of Chemical Industry.

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ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana officinalis L., commonly known as "valerian", is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear. AIM OF THE STUDY: This study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR). MATERIALS AND METHODS: The genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague-Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague-Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR. RESULTS: AEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight. CONCLUSION: In vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.

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Knee osteoarthritis (OA) poses a significant health care burden globally, necessitating innovative therapeutic approaches. CCoat, a novel poly(2-[methacryloyloxy]ethyl phosphorylcholine) (pMPC)ylated liposome device, protects the cartilage surface of the joint from mechanical wear through an entropy-favored process. Two preclinical studies were performed to explore the safety of CCoat following repeated intra-articular (IA) injections into the knee joint (i.e., femorotibial joint) in Sprague-Dawley rats. The studies involved 2 or 3 IA injections, at an interval of 2 or 3 weeks, and an observation period of 1 or 13 weeks after the last injection. Assessments included clinical, histopathological, and immunofluorescent evaluations. In study 1, no mortality or abnormal clinical signs occurred. At 1 week post last injection, histopathology revealed minimal vacuolated macrophages beneath the synovial membrane, predominantly M2-like, indicating a nonadverse response. Immunofluorescent staining supported M2-like macrophage predominance. Study 2 confirmed these findings with no systemic effects over 13 weeks. Statistical analyses indicated no significant differences in body weight, clinical pathology, or organ weights compared with controls. Results affirming the safety of pMPCylated liposomes following repeated IA injections in rat. This novel lubricant coating approach shows promise in OA therapy, with this safety assessment supporting its potential clinical application.

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Extracellular vesicles (EVs) serve as an intrinsic system for delivering functional molecules within our body, playing significant roles in diverse physiological phenomena and diseases. Both native and engineered EVs are currently the subject of extensive research as promising therapeutics and drug delivery systems, primarily due to their remarkable attributes, such as targeting capabilities, biocompatibility, and low immunogenicity and mutagenicity. Nevertheless, their clinical application is still a long way off owing to multiple limitations. In this context, the Science Board of the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan has conducted a comprehensive assessment to identify the current issues related to the quality and safety of EV-based therapeutic products. Furthermore, we have presented several examples of the state-of-the-art methodologies employed in EV manufacturing, along with guidelines for critical processes, such as production, purification, characterization, quality evaluation and control, safety assessment, and clinical development and evaluation of EV-based therapeutics. These endeavors aim to facilitate the clinical application of EVs and pave the way for their transformative impact in healthcare.

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The effectiveness, tolerance, and safety of pesticides must be established before their scientific or rational. This study evaluates the field control efficacy of broflanilide, tetraniliprole, and chlorantraniliprole in combating Spodoptera frugiperda in maize crops, as well as the resistance of S. frugiperda to these three diamide pesticides after exposure. By assessing field control efficiency, toxicity, effects on development and reproduction, and detoxification enzyme activity of these diamide pesticides on S. frugiperda, highlights broflanilide's significant insecticidal potential. A highly sensitive and efficient method using QuEChERS/HPLCMS/MS was developed to simultaneously detect residues of these three pesticides on maize. Initial concentrations of broflanilide, tetraniliprole, and chlorantraniliprole ranged from 2.13 to 4.02 mg/kg, with their respective half-lives varying between 1.23 and 1.51 days. Following foliar application, by the time of harvest, the terminal residue concentrations of these pesticides were all under 0.01 mg/kg. Chronic dietary intake risk assessments and cumulative chronic dietary exposure for three pesticides indicated that the general population's terminal residue concentration was within acceptable limits. Not only does this research provide valuable insights into field control efficiency, insecticidal effects, resistance, residues, and risk assessment results of broflanilide, tetraniliprole, and chlorantraniliprole on maize, but additionally, it also paves the way for setting suitable Maximum Residue Limits (MRLs) values based on pre-harvest interval values, rational dosage, and application frequency.

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During the operation of fabricated small box girder bridges, which face safety issues such as structural degradation and failure, there is an urgent need to propose a safety evaluation method to cope with the possible risks. This article quantitatively evaluates the safety state of a fabricated small box girder bridge in Wuhan City based on Fuzzy Analytic Hierarchy Process (FAHP) and structural health monitoring (SHM) data. Firstly, the FAHP model is established, and stress, deformation, and temperature are selected as evaluation factors. The safety thresholds of stress and deformation are determined by combining the industry specifications and the historical statistical patterns of the massive SHM data. The temperature field of the bridge is simulated and analyzed by combining ANSYS, HYPERMESH, and TAITHREM, and the most unfavorable temperature gradient is determined as a threshold for the safety evaluation. Finally, the scores of indexes of the bridge are determined based on the measured SHM data, which in turn provides a quantitative description of the safety state. The results show that the thresholds determined by the joint industry specifications and the massive SHM data are reasonable; the temperature field simulation model established in this article is consistent with the measured results, and can accurately determine the temperature gradient of the bridge. The safety evaluation result from the FAHP model is the same as the field test results, which verifies the effectiveness and applicability of the proposed method to actual bridge projects.

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The delivery market in Republic of Korea has experienced significant growth, leading to a surge in motorcycle-related accidents. However, there is a lack of comprehensive data collection systems for motorcycle safety management. This study focused on designing and implementing a foundational data collection system to monitor and evaluate motorcycle driving behavior. To achieve this, eleven risky behaviors were defined, identified using image-based, GIS-based, and inertial-sensor-based methods. A motorcycle-mounted sensing device was installed to assess driving, with drivers reviewing their patterns through an app and all data monitored via a web interface. The system was applied and tested using a testbed. This study is significant as it successfully conducted foundational data collection for motorcycle safety management and designed and implemented a system for monitoring and evaluation.

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This study assesses the nutritional composition and safety of lab-produced snail flour derived from Helix aspersa aspersa, an herbivorous pulmonated gastropod mollusc that occupies various trophic levels in food chains. Our analysis focused on key nutritional aspects, including moisture, ash, protein, and fat contents. Contaminant analysis on the powder showed levels below detectable limits for PAHs, PCBs, PBDEs. The heavy metal concentration was found to be either on par with or lower than values reported in existing literature, indicating the safety of these snail powders for human consumption. Our results revealed a notable presence of polyunsaturated fatty acids and essential amino acids and strongly support the idea that snail powders can serve as sustainable protein sources in both human and animal diets.

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Background: Since RNA sequencing has shown that induced pluripotent stem cells (iPSCs) share a common antigen profile with tumor cells, cancer vaccines that focus on iPSCs have made promising progress in recent years. Previously, we showed that iPSCs derived from leukemic cells of patients with primary T cell acute lymphoblastic leukemia (T-ALL) have a gene expression profile similar to that of T-ALL cell lines. Methods: Mice with T-ALL were treated with dendritic and T (DC-T) cells loaded with intact and complete antigens from T-ALL-derived iPSCs (T-ALL-iPSCs). We evaluated the safety and antitumor efficiency of autologous tumor-derived iPSC antigens by flow cytometry, cytokine release assay, acute toxicity experiments, long-term toxicity experiments, and other methods. Results: Our results indicate that complete tumor antigens from T-ALL-iPSCs could inhibit the growth of inoculated tumors in immunocompromised mice without causing acute and long-term toxicity. Conclusion: T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.

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Ensuring the safety of insecticides to natural enemy insects of pests is crucial for integrating chemical and biological control strategies. Broflanilide, a novel meta-diamide insecticide, exhibits high insecticidal activity against Myzus persicae (Sulzer) (Hemiptera: Aphididae). To integrate chemical and biological control against M. persicae, we assessed the toxicity of broflanilide to Aphidius gifuensis, and evaluated its safety and sublethal effects. The LC10, LC25, and LC50 values of broflanilide against A. gifuensis were 0.733 mg/L, 1.613 mg/L, and 3.852 mg/L, respectively. The selectivity toxicity ratio of broflanilide to A. gifuensis was 1.516, indicating higher toxicity to M. persicae compared to A. gifuensis. The risk quotient of broflanilide to A. gifuensis adults was 6.18. The percent reduction in the emergence of the parasitoid pupae was -1.15, with a risk grade of 1. The sublethal concentration of broflanilide had no significant influence on the intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and mean fecundity (F) of A. gifuensis in the F1 generation. The mean generation time (T) increased by 0.51 days and 0.39 days in the LC10 and LC25 treatments, respectively; the difference between LC10 treatment and the control was significant, while the difference between LC25 treatment and the control was not significant. The results showed that the sublethal concentration of broflanilide did not have a significant inhibitory effect on the population growth of A. gifuensis.

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In recent years, the number of roadway floor rock burst accidents is increasing, which seriously restricts the safe production of the mine. Therefore, safety evaluation method of bottom coal thickness in thick coal seam roadway was studied. The research results shown that the stress concentration area of composite floor is distributed in coal seam or rock stratum with large elastic modulus. With the increase of floor rock strength, the stress of coal-rock composite floor increased gradually, but the displacement and energy decreased gradually. When floor rock strength was equal to bottom coal strength, the increase of floor stress and displacement with the change of bottom coal thickness was the smallest, which was 34.29% and 33.61% respectively. The elastic strain energy decreased from 14.58 to 9.85%. With the increase of bottom coal thickness, the stress and displacement of coal-rock composite floor increased first and then decreased, and the elastic strain energy decreased gradually. It puts forward the safety evaluation method of bottom coal thickness: floor failure depth → reasonable thickness of bottom coal → safety thickness of bottom coal. It can provide reference for design of roadway bottom coal retention and surrounding rock control in thick coal seam face.

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Synthetic preservatives are widely used in the food industry to control spoilage and growth of pathogenic microorganisms, inhibit lipid oxidation processes and extend the shelf life of food. However, synthetic preservatives have some side effects that can lead to poisoning, cancer and other degenerative diseases. With the improvement of living standards, people are developing safer natural preservatives to replace synthetic preservatives, including plant derived preservatives (polyphenols, essential oils, flavonoids), animal derived preservatives (lysozyme, antimicrobial peptide, chitosan) and microorganism derived preservatives (nisin, natamycin, ε-polylysine, phage). These natural preservatives exert antibacterial effects by disrupting microbial cell wall/membrane structures, interfering with DNA/RNA replication and transcription, and affecting protein synthesis and metabolism. This review summarizes the natural bioactive compounds (polyphenols, flavonoids and terpenoids, etc.) in these preservatives, their antioxidant and antibacterial activities, and safety evaluation in various products.

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Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and Clostridium perfringens (C. perfringens). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD50 of 2018.3 mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8 mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated in vivo. Our study found that halicin had a good therapeutic effect on intestinal infection model of C. perfringens. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.

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Antimony (Sb) contamination in certain areas caused by activities such as antimony mining and smelting poses significant risks to human health and ecosystems. In this study, a stable composite material consisting of natural zeolite-supported nanoscale zero-valent iron (Z-ZVI) was successfully prepared. The immobilization effect of Z-ZVI on Sb in contaminated soil was investigated. Experimental results showed that Z-ZVI exhibited superior performance compared to pure nano zero-valent iron (nZVI) in terms of stability, with a lower zeta potential (-25.16 mV) at a pH of 7 and a higher specific surface area (54.54 m2/g). It can be easily applied and dispersed in contaminated soils. Additionally, Z-ZVI demonstrated a more abundant porous structure. After 60 days of treatment with 3% Z-ZVI, the leaching concentration of Sb in the contaminated soil decreased from 1.32 mg/L to 0.31 mg/L (a reduction of 76%), and the concentration of available Sb species decreased from 19.84 mg/kg to 0.71 mg/kg, achieving a fixation efficiency of up to 90%. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis confirmed the effective immobilization of Sb in the soil through reduction of antimonate to antimonite, precipitation, and adsorption processes facilitated by Z-ZVI. Moreover, the addition of Z-ZVI effectively reduced the bioavailability of Sb in the contaminated soil, thereby mitigating its toxicity to earthworms. In conclusion, Z-ZVI can be utilized as a promising material for the safe remediation and antimony and other heavy metal-contaminated soils.

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