Real-world experience of teriflunomide in relapsing multiple sclerosis: paramagnetic rim lesions may play a role.

Objectives: The aims of this study were to report the effectiveness and safety of teriflunomide in Chinese patients with relapsing-remitting multiple sclerosis (RRMS) and to explore the association of paramagnetic rim lesion (PRL) burden with patient outcome in the context of teriflunomide treatment and the impact of teriflunomide on PRL burden. Methods: This is a prospective observational study. A total of 100 RRMS patients treated with teriflunomide ≥3 months were included in analyzing drug persistence and safety. Among them, 96 patients treated ≥6 months were included in assessing drug effectiveness in aspects of no evidence of disease activity (NEDA) 3. The number and total volume of PRL were calculated in 76 patients with baseline susceptibility-weighted imaging (SWI), and their association with NEDA3 failure during teriflunomide treatment was investigated. Results: Over a treatment period of 19.7 (3.1-51.7) months, teriflunomide reduced annualized relapse rate (ARR) from 1.1 ± 0.8 to 0.3 ± 0.5, and Expanded Disability Status Scale (EDSS) scores remained stable. At month 24, the NEDA3% and drug persistence rate were 43.8% and 65.1%, respectively. In patients with a baseline SWI, 81.6% had at least 1 PRL, and 42.1% had ≥4 PRLs. The total volume of PRL per patient was 0.3 (0.0-11.5) mL, accounting for 2.3% (0.0%-49.0%) of the total T2 lesion volume. Baseline PRL number ≥ 4 (OR = 4.24, p = 0.009), younger onset age (OR = 0.94, p = 0.039), and frequent relapses in initial 2 years of disease (OR = 13.40, p = 0.026) were associated with NEDA3 failure. The PRL number and volume were not reduced (p = 0.343 and 0.051) after teriflunomide treatment for more than 24 months. No new safety concerns were identified in this study. Conclusion: Teriflunomide is effective in reducing ARR in Chinese patients with RRMS. Patients with less PRL burden, less frequent relapses, and relatively older age are likely to benefit more from teriflunomide, indicating that PRL might be a valuable measurement to inform clinical treatment decision.

Development of a sensitive electrochemical method to determine amitraz based on perylene tetracarboxylic acid/mesoporous carbon/Nafion@SPCEs.

A cutting-edge electrochemical method is presented for precise quantification of amitraz (AMZ), a commonly used acaricide in veterinary medicine and agriculture. Leveraging a lab-made screen-printed carbon electrode modified with a synergistic blend of perylene tetracarboxylic acid (PTCA), mesoporous carbon (MC), and Nafion, the sensor's sensitivity was significantly improved. Fine-tuning of PTCA, MC, and Nafion ratios, alongside optimization of the pH of the supporting electrolyte and accumulation time, resulted in remarkable sensitivity enhancements. The sensor exhibited a linear response within the concentration range 0.01 to 0.70 µg mL-1, boasting an exceptionally low limit of detection of 0.002 µg mL-1 and a limit of quantification of 0.10 µg mL-1, surpassing maximum residue levels permitted in honey, tomato, and longan samples. Validation with real samples demonstrated high recoveries ranging from 80.8 to 104.8%, with a relative standard deviation below 10%, affirming the method's robustness and precision. The modified PTCA/MC/Nafion@SPCE-based electrochemical sensor not only offers superior sensitivity but also simplicity and cost-effectiveness, making it a pivotal tool for accurate AMZ detection in food samples. Furthermore, beyond the scope of this study, the sensor presents promising prospects for wider application across various electrochemical analytical fields, thereby significantly contributing to food safety and advancing agricultural practices.

A potential trade-off between offense and defense in honeybee innate immunity: Reduced phagocytosis in honeybee hemocytes correlates with a protective response after exposure to imidacloprid and amitraz.

Phagocytosis "offense" is a crucial process to protect the organism from diseases and the effects of foreign particles. Insects rely on the innate immune system and thus any hindrance to phagocytosis may greatly affect their resistance to diseases and response to pathogens. The European honeybee, a valuable species due to its economic and environmental contribution, is being challenged by colony collapse disorder leading to its decline. Exposure to multiple factors including pesticides like imidacloprid and amitraz may negatively alter their immune response and ultimately make them more susceptible to diseases. In this study, we compare the effect of different concentrations and mixtures of imidacloprid and amitraz with different concentrations of the immune stimulant, zymosan A. Results show that imidacloprid and amitraz have a synergistic negative effect on phagocytosis. The lowered phagocytosis induces significantly higher hemocyte viability suggesting a negatively correlated protective mechanism "defense" from pesticide-associated damage but may not be protective from pathogens.

Assessing and mitigating foodborne acetochlor exposure induced ileum toxicity in broiler chicks: The role of omega-3 polyunsaturated fatty acids supplementation and molecular pathways analysis.

Excessive acetochlor residues present ecological and food safety challenges. Here, broiler chicks were exposed to varied acetochlor doses to first assess its effects on the gut. Subsequent dietary supplementation with omega-3 was used to assess its anti-contamination effects. Pathologically, acetochlor induced notable ileal lesions including inflammation, barrier disruption, tight junction loss, and cellular anomalies. Mechanistically, acetochlor stimulated the TNFα/TNFR1 and TLR4/NF-κB/NLRP3 pathways, promoting RIPK1/RIPK3 complex formation, MLKL phosphorylation, NLRP3 inflammasome activation, Caspase-1 activation, and GSDMD shearing with inflammatory factor release. These mechanisms elucidate ileal cell death patterns essential for understanding chicken enteritis. Omega-3 supplementation showed promise in mitigating inflammation, though its precise counteractive role remains unclear. Our findings suggest early omega-3 intervention offered protective benefits against acetochlor's adverse intestinal effects, emphasizing its potential poultry health management role. Harnessing dietary interventions' therapeutic potential will be pivotal in ensuring sustainable poultry production and food safety despite persistent environmental contaminants.

Risk assessment of airborne agricultural pesticide exposure in humans in rural China.

Continuous exposure to airborne pesticides causes their gradual accumulation in the human body, eventually posing a threat to human health. To the best of our knowledge, risk assessment study of pesticide non-occupational exposure to residents in agricultural areas has not been conducted in China. In this study, air samples (gas and dust) were collected from inside and outside residences of seven households and an area near the field in a grain-growing area (wheat and maize rotation) for eight months, and the pesticides present were examined both qualitatively and quantitatively. Using a 95% confidence interval, 9 out of 16 pesticides were detected, namely acetamiprid, acetochlor, atrazine, flucarbazone-sodium, imidacloprid, methyldisulfuron-methyl, nicosulfuron-methyl, pendimethalin, and beta-cyhalothrin, and their safety was subsequently evaluated. The results showed that the inhalation exposure of households to beta-cyhalothrin exceeded the acceptable range in the first residential, and the excess lifetime cancer risk of acetochlor inhalation exposure in six households and area around the field exceeds 1E-6, which highlights the need to strengthen preventive screening for cancer risk.

Incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease in patients with multiple sclerosis initiating disease-modifying therapies: Retrospective cohort study using a frequentist model averaging statistical framework.

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis.

Rapid and sensitive quantitation of amitraz in orange, tomato, and eggplant samples using immunochromatographic assay.

Amitraz (AMT) is a broad-spectrum formamidine insecticide and acaricide. In this study, we produced an anti-AMT monoclonal antibody (mAb) with high performance. The half-maximal inhibitory concentration of the anti-AMT mAb was 4.418 ng/mL, the cross reactivity with other insecticides was negligible, and an affinity constant was 2.06 × 109 mmol/L. Additionally, we developed an immunochromatographic assay for the rapid detection of AMT residues in oranges, tomatoes, and eggplants. The cut-off values were 2000 µg/kg in oranges and tomato samples and 1000 µg/kg in eggplant samples and the calculated limits of detection were 14.521 µg/kg, 6.281 µg/kg, and 3.518 µg/kg in oranges, tomatoes, and eggplants, respectively, meeting the detection requirements for AMT in fruits and vegetables. The recovery rates ranged between 95.8 % and 105.2 %, consistent with the recovery rates obtained via LC-MS/MS. Our developed immunochromatographic assay can effectively, accurately, and rapidly determine AMT residues in oranges, tomatoes, and eggplants.

Serum teriflunomide concentrations in routine multiple sclerosis therapy: A cross-sectional pilot study.

BACKGROUND: Teriflunomide is administered orally to treat relapsing-remitting multiple sclerosis. In this prospective pilot study, the free and total serum concentrations of teriflunomide obtained during routine health care were measured and their relationship with disease activity was evaluated. METHODS: Eighty-nine patients were included in this study. Blood samples were collected from April 2021 to February 2022, and free and total teriflunomide serum concentrations were measured. Patient assessment involved monitoring of blood counts and potential adverse effects of teriflunomide. RESULTS: In the steady-state group, total teriflunomide concentrations ranged from 14.7 to 144.2 mg/L, while free concentrations from 31.1 to 389.7 µg/L. In the non-steady-state group, the total concentration ranged from 2.2 to 59.3 mg/L, with free concentrations ranging from 6.8 to 143.5 µg/L. In the steady-state group, a significant inverse correlation was found between absolute peripheral blood lymphocyte count and both total and free teriflunomide serum concentrations. CONCLUSION: Although all patients were treated with the same dose, up to a 10-fold difference in total and free teriflunomide serum concentrations, and up to a 5-fold difference in steady-state trough concentrations were observed. This vast interindividual variability can potentially lead to toxicity or, conversely, to suboptimal therapeutic concentrations of teriflunomide, with the risk of further worsening of multiple sclerosis compensation.

Background-Free and Reversible Upconversion Hydrogel Sensing Platform for Visual Monitoring of Sulfite.

Excessive sulfite usage in food and pharmaceutical production causes respiratory and neurological diseases, underscoring the need for a sensitive and rapid quantification strategy. The portable sensing platform based on a luminescent hydrogel sensor is a powerful tool for the on-site, real-time detection of sulfite ions. However, the lack of recyclability in almost all reaction-based hydrogel sensors increases the application cost. This study constructed a reversible and upconversion nanoprobe combining upconversion nanoparticles (UCNPs) and pararosaniline (PAR) for sulfite detection. The upconversion nanoprobe was further encapsulated in a three-dimensional polyacrylamide hydrogel matrix to create a background-free, reversible hydrogel sensor. The near-infrared excitation of UCNPs avoids the autofluorescence in the hydrogel and real samples. Meanwhile, PAR serves as a specific recognition unit for sulfite ions. After the addition of sulfites, a specific reaction occurs between PAR and sulfites, leading to the recovery of characteristic emission at 540 nm, achieving sensitive detection of sulfite ions. Importantly, this specific reaction is reversible under thermal treatment, allowing the hydrogel sensor to return to its initial state and thus enabling reversible detection of sulfite ions. Furthermore, a portable sensing platform is developed to realize point-of-care, real-time quantitative detection of sulfite ions. The proposed upconversion reversible hydrogel sensor provides a new sensing strategy for the detection of hazardous substances in food and offers new insights into the preparation of reversible, highly sensitive hydrogel sensors.

Application of Simultaneous and Coupled Thermal Analysis Techniques in Studies on the Melting Process, Course of Pyrolysis and Oxidative Decomposition of Fused Triazinylacetohydrazides.

The effect of the structure of promising antioxidant agents with prospective medical use, i.e., unsubstituted and para-substituted annelated triazinylacetic acid hydrazides, on their melting points, thermal stabilities, pyrolysis and oxidative decomposition stages and the type of volatiles emitted under heating with the use of DSC and TG/DTG/FTIR/QMS methods was evaluated and discussed. The melting point of the investigated compounds increased with an enhanced number of electrons (directly correlated with their molecular weight). Melting enthalpy values were determined and presented for all the studied compounds. The pyrolysis and oxidative decomposition processes of the analysed molecules consisted of several poorly separated stages, which indicated a multi-step course of the decomposition reactions. It was found that the thermal stability of the tested compounds depended on the type of substituent at the para position of the phenyl moiety or its absence. In both atmospheres used (air and helium), the thermal stability increased in relation to R as follows: -CH3 ≤ -OCH3 < -H < -OC2H5. In an inert atmosphere, it was higher by approx. 8-18 °C than in an oxidative atmosphere. The pyrolysis was connected with the emission of NH3, HCN, HNCO, HCONH2, HCHO, CO2, CO and H2O in the case of all the tested compounds, regardless of the substituent attached. In the case of the derivative containing the para-CH3 group, para-toluidine was an additional emitted aromatic product. In turn, emissions of aniline and alcohol (methanol or ethanol) for compounds with the para-OCH3 and para-OC2H5 groups, respectively, were confirmed. In oxidative conditions, the release of NH3, NO, HCN, HNCO, HCONH2, CO2, H2O and cyanogen (for all the compounds) and para-toluidine (for the para-CH3 derivative), aniline (for para-OCH3, para-OC2H5 and unsubstituted derivatives) and acetaldehyde (for the para-OC2H5 derivative) were clearly observed. No alcohol emissions were recorded for either compound containing the para-OCH3- or para-OC2H5-substitututed phenyl ring. These results confirmed that the pyrolysis and oxidative decomposition of the investigated annelated triazinylacetohydrazides occurred according to the radical mechanism. Moreover, in the presence of oxygen, the reactions of volatiles and residues with oxygen (oxidation) and the combustion process additionally proceeded.

Visualizing the target estimand in comparative effectiveness studies with multiple treatments.

Aim: Comparative effectiveness research using real-world data often involves pairwise propensity score matching to adjust for confounding bias. We show that corresponding treatment effect estimates may have limited external validity, and propose two visualization tools to clarify the target estimand. Materials & methods: We conduct a simulation study to demonstrate, with bivariate ellipses and joy plots, that differences in covariate distributions across treatment groups may affect the external validity of treatment effect estimates. We showcase how these visualization tools can facilitate the interpretation of target estimands in a case study comparing the effectiveness of teriflunomide (TERI), dimethyl fumarate (DMF) and natalizumab (NAT) on manual dexterity in patients with multiple sclerosis. Results: In the simulation study, estimates of the treatment effect greatly differed depending on the target population. For example, when comparing treatment B with C, the estimated treatment effect (and respective standard error) varied from -0.27 (0.03) to -0.37 (0.04) in the type of patients initially receiving treatment B and C, respectively. Visualization of the matched samples revealed that covariate distributions vary for each comparison and cannot be used to target one common treatment effect for the three treatment comparisons. In the case study, the bivariate distribution of age and disease duration varied across the population of patients receiving TERI, DMF or NAT. Although results suggest that DMF and NAT improve manual dexterity at 1 year compared with TERI, the effectiveness of DMF versus NAT differs depending on which target estimand is used. Conclusion: Visualization tools may help to clarify the target population in comparative effectiveness studies and resolve ambiguity about the interpretation of estimated treatment effects.

It is time to rethink clinical trials on Bruton's tyrosine kinase inhibitors in multiple sclerosis.

The EVOLUTION trials comparing evobrutinib and teriflunomide in multiple sclerosis revealed unexpected negative results, challenging the choice of the annualized relapse rate (ARR) as the primary outcome. While monoclonal antibodies effectively control inflammation, the focus on ARR may not capture the long-term disability progression addressed by Bruton's tyrosine kinase inhibitors (BTKi). This letter questions the suitability of teriflunomide as a comparator due to low relapse rates in the control group, possibly stemming from patient selection bias. The author advocates for a reevaluation of study design, outcomes, and comparators in multiple sclerosis research, emphasizing the need for new approaches to address disease activity and disability progression. It is time to rethink clinical trials on Bruton's tyrosine kinase inhibitors in multiple sclerosis.

Phytotoxic phenols from the needles of Cedrus deodara.

During the course of screening for anti-seed germination phytochemicals, the methanol fraction of the Cedrus deodara fresh needles showed potent activity. Bioactivity-guided fractionation led to the isolation of thirty-eight phenolic compounds. Four ones were identified as previously undescribed including (7S,8S)-3-methoxy-9'-acetoxy-3',7-epoxy-8,4'-oxyneoligna-4,9-diol (7), (7S,8R)-dihydro-3'-hydroxy-8-acetoxymethyl-7-(4-hydroxy-3-methoxy-phenyl)-1'-benzofuranpropanol (10), (8S)-4,9,9'-trihydroxy-3,3'-dimethoxy-8,4'-oxyneolignan (11) and (7S,8S)-4,7,9'-trihydroxy-3,3'-dimethoxy-9-acetoxy-8,4'-oxyneolignan (16), respectively. The potential phytotoxic effects of these compounds on the seed germination and root elongation of Arabidopsis thaliana were evaluated by the filter paper assay developed in our laboratory. Bioassay results indicated that caffeic acid (36) displayed most significant inhibitory activities against the seed germination and root elongation of A. thaliana, stronger than those of the commercial herbicides acetochlor and glyphosate at the same concentration of 200 µg/mL. Ditetrahydrofuran lignan (1), dihydrochalcone (25), and eight simple phenols (28, 29, 31, 33-35, 37 and 38) completely inhibited the seed germination of A. thaliana at the concentration of 400 µg/mL, which were as active as acetochlor. Dihydroflavone (21) and the simple phenols 32-34 displayed stronger inhibitory effects on the root elongation of A. thaliana than that of glyphosate. The inhibitory effects of these active compounds on the seed germination and root elongation of Amaranthus tricolor and Lactuca sativa were evaluated as well. The phytotoxic activity of 11, 16, 22, 25, 31, 34, 37 and 38 were detected for the first time. In addition, the structure-activity relationships of the same class of these phytochemicals were discussed.

Determination of acetochlor by UPLC-MS3 in cells and its application to a cellular pharmacokinetic study.

The aim of this work was to develop a fast, simple, and reliable UPLC-MS3 method for the sensitive detection of acetochlor in biological samples. In MS3 mode, the ion transition m/z 270.1 â†’ 224.1→148.1 was chosen for quantification with butachlor as the internal standard. In the UPLC system, separation was performed on a UPLC column (2.1 × 50 mm ID, 1.7 µm) with 0.1 % FA in water and acetonitrile as mobile phases. After simple protein precipitation via acetonitrile, the method was well validated with good linearity (0.5-20 ng/mL, r > 0.995), accuracy (-3.70 %-2.98 %), and precision (<15 %). The selectivity and sensitivity were improved obviously in MS3 mode than that in MRM mode. The developed UPLC-MS3 method was successfully applied to the cellular pharmacokinetics study of acetochlor in MCF-7 cells.

Hepatic effects of acetochlor chiral isomers in zebrafish and L02 cells.

The pesticide acetochlor (ACT) is a chiral isomer commonly detected in the global environment, yet its specific impacts on liver function remain poorly understood. We utilized zebrafish and L02 cells as research models to comprehensively investigate how ACT and its chiral isomers affect the liver. Our investigations unveiled that the R, Rac, and S isomers of ACT disrupt hepatic lipid transport, catabolism, and synthesis, leading to delayed yolk sac absorption and the accumulation of lipids in zebrafish embryos. These isomers induce oxidative stress in the liver of zebrafish embryos, reducing antioxidant levels and enzyme activity. The accumulated lipids in the liver render it susceptible to oxidative stress, further exacerbating hepatocyte damage. Hepatocyte damage manifests as extensive vacuolization of liver cells and alterations in liver morphology, which are induced by R, Rac, and S. Furthermore, we elucidated the molecular mechanisms underpinning the disturbance of hepatic lipid metabolism by R, Rac, and S in L02 cells. These compounds stimulate lipid synthesis through the upregulation of the AMPK/SREBP-1c/FAS pathway while inhibiting lipolysis via downregulation of the PPAR-α/CPT-1a pathway. Remarkably, our results highlight that S exhibits significantly higher hepatotoxicity in comparison to R. This study provides valuable insights into the hepatic effects of ACT chiral isomers.

Contrasting roles of cytochrome P450s in amitraz and chlorfenapyr resistance in the crop pest Tetranychus urticae.

The molecular mechanisms of amitraz and chlorfenapyr resistance remain only poorly understood for major agricultural pests and vectors of human diseases. This study focusses on a multi-resistant field strain of the crop pest Tetranychus urticae, which could be readily selected in the laboratory to high levels of amitraz and chlorfenapyr resistance. Toxicity experiments using tralopyril, the active toxophore of chlorfenapyr, suggested decreased activation as a likely mechanism underlying resistance. Starting from the same parental strain, transcriptome profiling revealed that a cluster of detoxifying genes was upregulated after amitraz selection, but unexpectedly downregulated after chlorfenapyr selection. Further functional validation associated the upregulation of CYP392A16 with amitraz metabolism and the downregulation of CYP392D8 with reduced activation of chlorfenapyr to tralopyril. Genetic mapping (QTL analysis by BSA) was conducted in an attempt to unravel the genetic mechanisms of expression variation and resistance. This revealed that chlorfenapyr resistance was associated with a single QTL, while 3 QTLs were uncovered for amitraz resistance. Together with the observed contrasting gene expression patterns, we argue that transcriptional regulators most likely underly the distinct expression profiles associated with resistance, but these await further functional validation.

Adsorption of acetochlor-contaminated water systems using novel P-doped biochar: Effects, application, and mechanism.

Given the serious threat of acetochlor (ACT) to the aquatic ecological environment, designing wastewater treatment-oriented adsorbents for the sustainable remediation of actual ACT-contaminated water is a promising yet challenging strategy. Herein, a novel P-doped biochar (PBC-800) with a high adsorption capacity (51.34 mg g-1) and a rapid reaction rate (47.35 mg g-1 h-1) for ACT was prepared through pyrolyzing of rice straw biomass pre-impregnated with potassium dihydrogen phosphate (KH2PO4). Additionally, P-doped biochars synthesized at different pyrolysis temperatures exhibited significant variations in ACT adsorption performance, which was mainly ascribed to the distinction between hydrophilicity and sp2 conjugate C (ID/IG = 0.84-1.08). The adsorption behavior of ACT on PBC-800 followed the Elovich kinetics and Freundlich adsorption isotherm models. Thermodynamic calculations indicated that the adsorption of ACT by PBC-800 was a spontaneously disordered decreasing exothermic process. Besides, PBC-800 exhibited a powerful anti-interference for ACT adsorption within complex water matrices, highlighting its potential for various of practical applications. Through characterization analysis and further experiments, it was proved that the excellent adsorption performance of PBC-800 on ACT was ascribed to a combination of physical and chemical adsorption mechanisms, including 57.5% pore filling, 23.4% hydrophobic interaction, 12.7% π-π interaction, and 6.4% hydrogen bonding. Moreover, PBC-800 exerted a prominent adhesion impact upon Gram-positive and negative bacteria at 3 h. This study offers a new idea for the utilization of agricultural residues and provides insights into the mechanism of ACT adsorption through its derived biochar.

Stereoselective toxicity of acetochlor chiral isomers on the nervous system of zebrafish larvae.

Acetochlor (ACT) is a widely detected pesticide globally, and the neurotoxic effects of its chiral isomers on humans and environmental organisms remain uncertain. Zebrafish were used to study the neurotoxicity of ACT and its chiral isomers. Our study reveals that the R-ACT, Rac-ACT, and S-ACT induce neurotoxicity in zebrafish larvae by impairing vascular development and disrupting the blood-brain barrier. These detrimental effects lead to apoptosis in brain cells, hindered development of the central nervous system, and manifest as altered swimming behavior and social interactions in the larvae. Importantly, the neurotoxicity caused by the S-ACT exhibits the most pronounced impact and significantly diverges from the effects induced by the R-ACT. The neurotoxicity associated with the Rac-ACT falls intermediate between that of the R-ACT and S-ACT. Fascinatingly, we observed a remarkable recovery in the S-ACT-induced abnormalities in BBB, neurodevelopment, and behavior in zebrafish larvae upon supplementation of the Wnt/ß-catenin signaling pathway. This observation strongly suggests that the Wnt/ß-catenin signaling pathway serves as a major target of S-ACT-induced neurotoxicity in zebrafish larvae. In conclusion, S-ACT significantly influences zebrafish larval neurodevelopment by inhibiting the Wnt/ß-catenin signaling pathway, distinguishing it from R-ACT neurotoxic effects.