Incorporating Bioaccessibility into Inhalation Exposure Assessment of Emamectin Benzoate from Field Spraying.

The inhalation exposure of pesticide applicators and residents who live close to pesticide-treated fields is a worldwide concern in public health. Quantitative assessment of exposure to pesticide inhalation health risk highlights the need to accurately assess the bioaccessibility rather than the total content in ambient air. Herein, we developed an in vitro method to estimate the inhalation bioaccessibility of emamectin benzoate and validated its applicability using a rat plasma pharmacokinetic bioassay. Emamectin benzoate was extracted using the Gamble solution, with an optimized solid-to-liquid ratio (1/250), extraction time (24 h), and agitation (200 rpm), which obtained in vitro inhalation bioaccessibility consistent with its inhalation bioavailability in vivo (32.33%). The margin of exposure (MOE) was used to assess inhalation exposure risk. The inhalation unit exposures to emamectin benzoate of applicators and residents were 11.05-28.04 and 0.02-0.04 ng/m3, respectively, varying markedly according to the methods of application, e.g., formulations and nozzles. The inhalation risk assessment using present application methods appeared to be acceptable; however, the MOE of emamectin benzoate might be overestimated by 32% without considering inhalation bioaccessibility. Collectively, our findings contribute insights into the assessment of pesticide inhalation exposure based on bioaccessibility and provide guidance for the safe application of pesticides.

[Study on chemical constituents from Chloranthus multistachys].

To investigate the chemical constituents from the shoots of Chloranthus multistachys.All compounds wereisolated by using a combination of various chromatographic techniques including silica gel, ODS, Sephadex LH-20, reversed-phase HPLC, and other methods.Their structures were elucidated by the nuclear magnetic resonance (NMR), mass spectrometry, and other modernspectroscopies.As a result, 19 compounds were isolated from the shoots of C.multistachys and identified as zederoneepoxide(1), chlomultin C(2), curcolonol(3), sarcaglaboside A(4), zedoarofuran(5), (1E,4Z)-8-hydroxy-6-oxogermacra-1(10), 4,7(11)-trieno-12,8-lactone(6), chloranoside A(7), istanbulin A(8), (8α)-6,8-dihydroxycadina-7(11),10(15)-dien-12-oicacid-γ-lactone(9), codonolactone(10), lasianthuslactone A(11), 12,15-epoxy-5αH,9ßH-labda-8(17),13-dien-19-oicacid(12), 12R,15-dihydroxylabda-8(17),13E-dien-19-oicacid(13), N-transcinnamoyltyramine(14), trans-N-p-coumaroyltyramine(15), dibutyl phthalate (16), flavokawain A(17), bergenin(18), and enedione(19).Compounds 1, 2, 4, 7-10, 12-19 were isolated from C.multistachys for the first time and compounds 14-19 were obtained from the genus Chloranthus for the first time.

Inhalation bioaccessibility of imidacloprid in particulate matter: Implications for risk assessment during spraying.

Adverse health outcomes due to the inhalation of pesticide residues in atmospheric particulate matter (PM) are gaining global attention. Quantitative health risk assessments of pesticide inhalation exposure highlight the need to understand the bioaccessibility of pesticide residues. Herein, the inhalation bioaccessibility of imidacloprid in PM was determined using three commonly used in vitro lung modeling methods (Artificial Lysosomal Fluid, Gamble Solution, and Simulated Lung Fluid). To validate its feasibility and effectiveness, we evaluated the bioavailability of imidacloprid using a mouse nasal instillation assay. The in vitro inhalation bioaccessibility of imidacloprid was extracted using Gamble Solution with a solid-liquid ratio of 1/1000, an oscillation rate of 150 r/min, and an extraction time of 24 h, showed a strong linear correlation with its in vivo liver-based bioavailability (R2 =0.8928). Moreover, the margin of exposure was incorporated into the inhalation exposure risk assessment, considering both formulations and nozzles. The inhalation unit exposure of imidacloprid for residents was 0.95-4.09 ng/m3. The margin of exposure for imidacloprid was determined to be acceptable when considering inhalation bioaccessibility. Taken together, these results indicate that the inhalation bioaccessibility of pesticides should be incorporated into assessments of human health risks posed by PM particles.

Emamectin benzoate-induced toxicity affects intestinal epithelial integrity involving apoptosis.

The frequency presence of emamectin benzoate in agricultural production highlights the need for studying their toxicity against human intestinal epithelial barrier (IEB). Herein, we combined a Caco-2 cell model with transcriptome analysis to assess the intestinal toxicity of emamectin benzoate and its disease-causing potential. Results showed that the half maximal inhibitory concentration (IC50) of emamectin benzoate on Caco-2 cell viability after 24, 48, and 72 h of exposure were 18.1, 9.9, and 8.3 µM, respectively. Emamectin benzoate exposure enhanced the Caco-2 monolayer paracellular permeability, damaged the IEB, and increased cellular apoptosis. Key driver gene analysis of 42 apoptosis - related DEGs, identified 10 genes (XIAP, KRAS, MCL1, NRAS, PIK3CA, CYCS, MAPK8, CASP3, FADD, and TNFRSF10B) with the strongest correlation with emamectin benzoate - induced apoptosis. Transcriptomics identified 326 differentially expressed genes (DEGs, 204 upregulated and 122 downregulated). The functional terms of neurodegeneration - multiple diseases was enriched with the most number of DEGs, and the Parkinson disease pathway had the highest enrichment degree. Our findings provided support for environmental toxicology studies and the health risk assessment of emamectin benzoate.

In vivo-in vitro correlations (IVIVC) for the assessment of pyrethroid bioavailability in honey.

Bioaccessibility/bioavailability is an important factor in assessing the potential human health risk via oral exposure. However, methods for accurately predicting the bioaccessibility/bioavailability of pesticide residues are still limited, preventing accurate measurements of actual exposure to pesticide residues. In this study, pyrethroid bioavailability in honey were analysed using a mouse bioassay and bioaccessibility via in vitro methods with Tenax extraction. The results demonstrated that the combined liver plus kidney data served as an appropriate biomarker to estimate the relative bioavailability. Notably, significant in vivo-in vitro correlations (IVIVC) were observed between bioavailability and bioaccessibility (R2 = 0.7898-0.9793). Estimation of the bioavailability of honey from different nectar plants using derived IVIVC confirmed that different contents and physicochemical properties might affect its bioavailability. The findings provide insight into assessing human exposure to pesticides based on bioavailability and can decrease the uncertainty about the assessment of the risk of dietary exposure to pesticides.

Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single-center, double-blinded, randomized, placebo-controlled phase II trial.

BACKGROUND: To determine the efficacy and safety of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in Chinese adults with type 2 diabetes mellitus (T2DM). METHODS: In this single-center, double-blinded, randomized, placebo-controlled phase II trial, 91 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 45) or placebo (n = 46) three times with 4-week intervals and followed up for 48 weeks from October 2015 to December 2018. The primary endpoint was the percentage of patients with glycated hemoglobin (HbA1c) levels of < 7.0% and daily insulin reduction of ≥ 50% at 48 weeks. Additional endpoints were changes of metabolic control, islet ß-cell function, insulin resistance, and safety. RESULTS: At 48 weeks, 20% of the patients in the UC-MSCs group and 4.55% in the placebo group reached the primary endpoint (p < 0.05, 95% confidence interval (CI) 2.25-28.66%). The percentage of insulin reduction of the UC-MSCs group was significantly higher than that of the placebo group (27.78% versus 15.62%, p < 0.05). The levels of HbA1c decreased 1.31% (9.02 ± 1.27% to 7.52 ± 1.07%, p < 0.01) in the UC-MSCs group, and only 0.63% in the placebo group (8.89 ± 1.11% to 8.19 ± 1.02%, p˃0.05; p = 0.0081 between both groups). The glucose infusion rate (GIR) increased significantly in the UC-MSCs group (from 3.12 to 4.76 mg/min/kg, p < 0.01), whereas no significant change was observed in the placebo group (from 3.26 to 3.60 mg/min/kg, p ˃ 0.05; p < 0.01 between both groups). There was no improvement in islet ß-cell function in both groups. No major UC-MSCs transplantation-related adverse events occurred. CONCLUSIONS: UC-MSCs transplantation could be a potential therapeutic approach for Chinese adults with T2DM. Trial registration This study was registered on ClinicalTrials.gov (identifier: NCT02302599).

Sesquiterpenoids with neuroprotective activities from the Chloranthaceae plant Chloranthus henryi.

A rare sesquiterpenoid possessing a 6/6 bicyclic system fused with two clustered furan units and a pair of guaiane-type sesquiterpenoids were acquired from the roots of Chloranthus henryi. Their structures with absolute configurations were characterized with spectroscopic data, ECD, and X-ray diffraction analysis. All three sesquiterpenoids showed moderate neuroprotective activities on PC12 cells damaged with hydrogen peroxide.