Artificial K+ Channels Formed by Pillararene-Cyclodextrin Hybrid Molecules: Tuning Cation Selectivity and Generating Membrane Potential.

A class of artificial K+ channels formed by pillararene-cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K+ over all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ > Li+ ), and is rarely observed for artificial K+ channels. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+ , and generated stable membrane potential across lipid bilayers.

Congener-specific uptake and accumulation of bisphenols in edible plants: Binding to prediction of bioaccumulation by attention mechanism multi-layer perceptron machine learning model.

Plant accumulation of phenolic contaminants from agricultural soils can cause human health risks via the food chain. However, experimental and predictive information for plant uptake and accumulation of bisphenol congeners is lacking. In this study, the uptake, translocation, and accumulation of five bisphenols (BPs) in carrot and lettuce plants were investigated through hydroponic culture (duration of 168 h) and soil culture (duration of 42 days) systems. The results suggested a higher bioconcentration factor (BCF) of bisphenol AF (BPAF) in plants than that of the other four BPs. A positive correlation was found between the log BCF and the log Kow of BPs (R2carrot = 0.987, R2lettuce = 0.801, P < 0.05), while the log (translocation factor) exhibited a negative correlation with the log Kow (R2carrot = 0.957, R2lettuce = 0.960, P < 0.05). The results of molecular docking revealed that the lower binding energy of BPAF with glycosyltransferase, glutathione S-transferase, and cytochrome P450 (-4.34, -4.05, and -3.52 kcal/mol) would be responsible for its higher accumulation in plants. Based on the experimental data, an attention mechanism multi-layer perceptron (AM-MLP) model was developed to predict the BCF of eight untested BPs by machine learning, suggesting the relatively high BCF of bisphenol BP, bisphenol PH, and bisphenol TMC (BCFcarrot = 1.37, 1.50, 1.03; BCFlettuce = 1.02, 0.98, 0.67). The prediction of BCF for ever-increasing varieties of BPs by machine learning would reduce repetitive experimental tests and save resources, providing scientific guidance for the production and application of BPs from the perspective of priority pollutants.

Congener-Specific Uptake and Metabolism of Bisphenols in Carrot Cells: Dissipation Kinetics, Biotransformation, and Enzyme Responses.

Food consumption has been considered a key pathway of bisphenol compound (BP) exposure for humans. However, there is a lack of evidence concerning their congener-specific behavior and metabolism in plants. Herein, we examined the uptake and metabolism of five BPs in plants using carrot cells. Bisphenol S (BPS) and bisphenol AF (BPAF) exhibited substantially lower dissipation rates in the cells than the other BPs, indicating a strong selectivity in the uptake and metabolism among bisphenol congeners. For a total of 23 metabolites of BPs, the predominant biotransformation pathways were found to be glycosylation, methoxylation, and conjugation, while hydroxylation, methylation, and glutathionylation were only observed for some BPs. The changes in the mRNA expression of cytochrome P450 (P450) and the activities of glycosyltransferase and glutathione S-transferase were remarkably higher in cells exposed to bisphenol F, bisphenol A, and bisphenol B than in cells exposed to BPS and BPAF, indicating congener specificity in their effects on enzymes and the associated biotransformation processes. Consequently, the potential congener-specific differences in plant uptake, metabolism, and accumulation must be considered when assessing the environmental risks posed by these commonly used plasticizers.

Phthalate esters and their metabolites in paired soil-crop systems from farmland in major provinces of eastern China: Pollution characteristics and implications for human exposure.

The extensive application of phthalate esters (PAEs) as plasticizers has raised considerable concern regarding their environmental load, but the associated occurrence of PAE metabolites has often been ignored. The soil-plant system is a vital source of human exposure to PAEs via crop intake. Here, paired soil-plant samples were collected from eastern China to investigate the occurrence characteristics of seven PAE congeners and two primary monoester phthalate metabolites (mPAEs) in farmland. The detection frequencies of PAEs and mPAEs in the investigated soil-plant systems were 100 %. The total concentrations of PAEs in the collected soil and plant samples ranged from 0.07 to 1.83 mg/kg (dw) and from 3.9 to 24 mg/kg (dw), respectively. Moreover, di-(2-ethylhexyl) phthalate, diisobutyl phthalate and di-n-butyl phthalate were the predominant PAE congeners in the farmlands of eastern China, collectively accounting for >90 % of the total concentration of PAEs. In addition, the total concentrations of the two mPAEs were markedly higher in plant samples (49 ng/g dw to 549 ng/g dw) than in soil samples (3 ng/g dw to 22 ng/g dw), indicating that PAEs are readily metabolized in plants. The hazard index (HI) values of all PAEs in all crops were <1, demonstrating that the risks of PAEs in the crops were acceptable. However, the daily intake of mPAEs from the consumption of cabbage was higher than or comparable to that of some PAEs (such as di-n-octyl phthalate). This highlights the importance of taking metabolites into consideration in further environmental investigations and risk assessments of PAEs.

Human exposure to phthalate esters in soils embodied in interregional food trade in China.

The ubiquitous occurrence of phthalate esters (PAEs) in agricultural soil results in their inevitable accumulation in crops, potentially increasing the risk of human exposure to PAEs via daily food intake. Dietary health risk of PAEs not only depends on locally produced food but also the imported food from other regions. However, the impact of interregional food trade on human dietary exposure to PAEs has been seldom assessed. Herein, we investigated the impact of interregional food trade on the dietary exposure to PAEs that contributed from soil contamination in China. The average daily dietary intake of PAEs for the Chinese general population was 24.3 µg/kg/day when assuming the total consumption of crops from local market only, while the average daily dietary intake of PAEs for the Chinese general population was decreased by 2.9% when the effects of interregional food trade were involved into the calculation. Additionally, the interregional food trade remarkably increased the daily dietary intake of PAEs in the regions of Beijing-Tianjin region (47.8%), North (21.4%) and Central (4.26%). As a result, the hazard quotient value of PAEs in the regions of Beijing-Tianjin region, North and Central increased by 29.4%, 11.0% and 5.0%, respectively, owing to the consumption of imported crops from the highly PAEs contaminated regions. In contrast, the daily intake and hazard quotient value of PAEs in the regions of Central Coast, Northwest, Northeast and South Coast decreased due to the interregional trade. These results indicated that the interregional food trade promoted the transfer of PAEs between regions and thus altered the potential risk to the local population. Overall, this study highlights the importance of taking the interregional food trade into account to provide a more accurate risk assessment of dietary exposure to pollutants.

Elevated urbanization-driven plant accumulation and human intake risks of polycyclic aromatic hydrocarbons in crops of peri-urban farmlands.

As an ubiquitous carcinogen, polycyclic aromatic hydrocarbons (PAHs) are closely related to anthropogenic activities. The process of urbanization leads to the spatial interlacing of farmlands and urbanized zones. However, field evidence on the influence of urbanization on the accumulation of PAHs in crops of peri-urban farmlands is lacking. This study comparatively investigated the urbanization-driven levels, compositions, and sources of PAHs in 120 paired plant and soil samples collected from the Yangtze River Delta in China and their species-specific human intake risks. The concentrations of PAHs in crops and soils in the peri-urban areas were 2407.92 ng g-1 and 546.64 ng g-1, respectively, which are significantly higher than those in the rural areas. The PAHs in the root were highly relevant to those in the soils (R2 = 0.63, p < 0.01), and the root bioconcentration factors were higher than 1.0, implying the contributions of root uptake to plant accumulations. However, the translocation factors in the peri-urban areas (1.57 ± 0.33) were higher than those in the rural areas (1.19 ± 0.14), indicating the enhanced influence through gaseous absorption. For the congeners, the 2- to 3-ring PAHs showed a higher plant accumulation potential than the 4- to 6-ring PAHs. Principal component analysis show that the PAHs in the peri-urban plants predominantly resulted from urbanization parameters, such as coal combustion, vehicle emissions, and biomass burning. The mean values of estimated dietary intake of PAHs from the consumption of peri-urban and rural crops were 9116 ng day-1 and 6601.83 ng day-1, respectively. The intake risks of different crops followed the order rice > cabbage > carrot > pea. Given the significant input of PAHs from urban to farmland, the influence of many anthropogenic pollutants arising from rapid urbanization should be considered when assessing the agricultural food safety.

Influence of Melatonin on Behavioral and Neurological Function of Rats with Focal Cerebral Ischemia-Reperfusion Injury via the JNK/FoxO3a/Bim Pathway.

OBJECTIVE: To investigate the influence of melatonin on behavioral and neurological function of rats with focal cerebral ischemia-reperfusion injury via the JNK/FoxO3a/Bim pathway. METHODS: One hundred and twenty healthy male SD rats were randomized into the model group (Model: the middle cerebral artery occlusion (MCAO) model was constructed and received an equal volume of normal saline containing 5% DMSO), sham operation group (Sham: received no treatment except normal feeding), and low, medium, and high dose of melatonin group (L-MT, M-MT, and H-MT intraperitoneally injected 10, 20, and 40 mg/kg melatonin 30 min after IR, respectively), with 24 rats in each group. Following 24 h of reperfusion, the rats in each of the above groups were tested for neurological deficit symptoms and behavioral changes to screen the rats included in the study. HE and TUNEL stainings were performed to observe pathological changes. Levels of oxidative stress-related indexes, inflammatory factor-related indexes, nuclear factor-κB p65 (NF-κB p65), and interferon-γ (IFN-γ) in the rat brain were measured by ELISA. The JNK/FoxO3a/Bim pathway-related proteins as well as Bcl-2, Caspase-3, and Bax were examined using Western blot. RESULTS: Detection of behavioral indicators showed that the MACO model was successfully constructed in rats. L-MT, M-MT, and L-MT groups presented reduced malondialdehyde (MDA), reactive oxygen species (ROS), tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-1ß, IFN-γ, NF-κB p65, and apoptosis compared with the Model group (P < 0.05), and the improvement degree was better in the M-MT group versus the L-HT group. Bcl-2 protein expression in the brain tissue of L-MT, M-MT, and H-MT groups increased significantly, while Bax, Caspase-3, p-JNK, p-FoxO3a, and Bim protein expression declined markedly, versus the Model group (P < 0.05). The changes of indexes were greater in the M-MT group compared with that in the L-MT group. No significant difference was observed in all the above indexes between the M-MT group and the H-MT group (P > 0.05). CONCLUSIONS: In the MACO rat model, melatonin can effectively reduce Bax and Caspase-3 levels by modulating the JNK/FoxO3a/Bim pathway, inhibit neuronal apoptosis, and alleviate neurological deficits by reducing the release of proinflammatory mediators, with anti-inflammatory and antioxidant effects. In addition, 20 mg/kg is the optimal melatonin concentration.

Effect of charge status on the ion transport and antimicrobial activity of synthetic channels.

A class of unimolecular channels formed by pillararene-gramicidin hybrid molecules are presented. The charge status of the peptide domain in these channels has a significant impact on their ion transport and antimicrobial activity. These channels exhibited different membrane-association abilities between microbial cells and mammalian cells. One of the channels displayed a higher antimicrobial activity towards S. aureus (IC50 = 0.55 µM) and negligible hemolytic toxicity, showing potential to serve as a systemic antibiotic.