Triclocarban exhibits higher adipogenic activity than triclosan through peroxisome proliferator-activated receptors pathways.

Previous epidemiological and animal studies have showed the lipid metabolic disruption of antimicrobial triclocarban (TCC) and triclosan (TCS). However, the present in vivo researches were mainly devoted to the hepatic lipid metabolism, while the evidence about the impacts of TCC/TCS on the adipose tissue is very limited and the potential mechanism is unclear, especially the molecular initiation events. Moreover, little is known about the toxic difference between TCC and TCS. This study aimed to demonstrate the differential adipogenic activity of TCC/TCS as well as the potential molecular mechanism via peroxisome proliferator-activated receptors (PPARα/ß/γ). The in vitro experiment based on 3T3-L1 cells showed that TCC/TCS promoted the differentiation of preadipocytes into mature adipocytes at nanomolar to micromolar concentrations, which was approach to their human exposure levels. We revealed for the first time by reporter gene assay that TCC could activate three PPARs signaling pathways in a concentration-dependent manner, while TCS only activate PPARß. The molecular docking strategy was applied to simulate the interactions of TCC/TCS with PPARs, which explained well the different PPARs activities between TCC and TCS. TCC up-regulated the mRNA expression of three PPARs, but TCS only up-regulated PPARß and PPARγ significantly. Meanwhile, TCC/TCS also promoted the expression of adipogenic genes targeted by PPARs to different extent. The cellular and simulating studies demonstrated that TCC exerted higher adipogenic effects and PPARs activities than TCS. Our mice in vivo experiment showed that TCC could lead to adipocyte size increase, adipocyte lipid accumulation growing, fat weight and body weight gain at human-related exposure levels, and high fat diet exacerbated these effects. Moreover, male mice tended to be more susceptible to TCC induced obesogenic effect than female mice. This work highlights the potential obesogenic risks of TCC/TCS via PPARs signaling pathways, and TCC deserves more concerns for its higher activity.

Triclocarban and triclosan exacerbate high-fat diet-induced hepatic lipid accumulation at environmental related levels: The potential roles of estrogen-related receptors pathways.

Triclosan (TCS) and triclocarban (TCC) have become ubiquitous pollutants detected in human body with concentrations up to hundreds of nanomolar levels. Previous studies about the hepatic lipid accumulation induced by TCS and TCC were focused on pollutant itself, which showed weak or no effects. High-fat diet (HFD), as a known environmental factor contributing to lipid metabolism-related disorders, its synergistic action with environmental pollutants deserves concern. The present study aimed to demonstrate the combined effects and potential molecular mechanisms of TCS and TCC with HFD at cellular and animal levels. The in vitro studies showed that TCC and TCS alone had negligible impact on lipid accumulation in HepG2 cells but induced lipid deposition at nanomolar levels when co-exposure with fatty acid. TCC exhibited much higher induction effects than TCS, which was related to their differential regulatory roles in adipogenic-related genes expression. The in vivo studies showed that TCC had little influence on hepatic lipid accumulation in mice fed with normal diet (ND) but could exacerbate the lipid accumulation in mice fed with HFD. Meanwhile, TCC-induced dyslipidemia in mice fed with HFD was more significant than that fed with ND. Therefore, we speculated that TCC might increase the risk of nonalcoholic fatty liver disease (NAFLD) and atherosclerosis in HFD humans. Molecular mechanism studies showed that TCC and TCS could bind to and activate estrogen-related receptor α (ERRα) and ERRγ as well as regulate their expression. TCC had higher activity on ERRα and ERRγ than TCS, which explained partly the differential regulatory roles of two receptors in the lipid accumulation induced by TCC and TCS. This work revealed synergistic effects and molecular mechanisms of TCC and TCS with excessive fatty acid on the hepatic lipid metabolism, which provided a novel insight into the toxic mechanism of pollutants from the perspective of dietary habits.

The potential endocrine disruption mechanism of anthelmintic drug niclosamide by activating estrogen receptors and estrogen-related receptors.

Niclosamide (NIC), a helminthic drug used widely for controlling schistosomiasis, can reportedly disrupt the endocrine system. However, its underlying mechanisms are still unclear. In this study, we revealed the potential endocrine disruption mechanism of NIC by activating estrogen receptors (ERs) and estrogen-related receptors (ERRs). The binding potency of NIC with ERα, ERß and ERRγ were determined by fluorescence competitive binding assays, which shows an IC50 (the concentration of NIC needed to displace 50 % of the probe from the receptor) of 90 ± 4.1, 10 ± 1.7 nM and 0.59 ± 0.07 nM respectively. The IC50 for ERRγ is the lowest one among the three detected receptors, which is three orders of magnitude lower than the known agonist GSK4716.The transcriptional activities of NIC on ERs and ERRs were detected by MVLN cells (stably transfected with ERs reporter gene) and HeLa cells (transiently transfected with ERRs reporter gene)-based luciferase reporter gene assay. The lowest observable effective concentration (LOEC) ranked as follows: ERRγ (0.5 nM) < ERRα (10 nM) < ERs (100 nM). The maximum observed induction rate for ERRγ (294 %) was higher than that for ERRα (191 %). The maximum observed induction rate of NIC for ERs was 30 % relative to 17ß-estradiol. In addition, we simulated the interactions of NIC with ERs and ERRs by molecular docking. NIC could dock into the ligand binding pockets of ERs and ERRs and form hydrogen bonds with different amino acids. The binding energy ranked as follows: ERRγ (-8.90 kcal/mol) < ERß (-7.57 kcal/mol) < ERRα (-7.15 kcal/mol) < ERα (-6.53 kcal/mol), which implied that NIC bound to ERRγ with higher binding affinity than the other receptors. Overall, we clarify that ERRγ might be the dominant target for NIC in cells rather than ERRα and ERs. We reveal potential novel mechanisms for the endocrine disruption effects of NIC by activating both ERRs and ERs at environmentally-related nanomolar levels.

Bio-hydrogen and methane production from two-phase anaerobic digestion of food waste under the scheme of acidogenic off-gas reuse.

Anaerobic hydrolysis of food wastes sourced from bakery (T1), Chinese restaurant (T2), western-style restaurant (T3), and wet market (T4) were performed in leach bed reactors under the scheme of acidogenic off-gas reuse in methanogenic reactor. Results showed that food waste in T3 achieved the highest hydrogen production of 61.0 L/kg·VSadded. Highest activity of hydrogenase in both leachate and digestate samples confirmed the superior performance of H2 production in T3. Mixed acid fermentation with domination of acetate and butyrate was observed in all four treatments, whereas variations in quantification and speciation of the acidogenic products were closely related to the composition of substrates. High volatile solids (VS) removal (76.7%) was observed in T3 while VS reduction rates of the other treatments ranged from 37 to 55%. High COD production of 0.65 gCOD /g·VSadded together with the reuse of elevated acidogenic off-gas ensured the highest specific CH4 production of 0.42 L/g·VSadded in T3.

Selective Separation of Acetic and Hexanoic Acids across Polymer Inclusion Membrane with Ionic Liquids as Carrier.

This paper first reports on the selective separation of volatile fatty acids (VFAs) (acetic and hexanoic acids) using polymer inclusion membranes (PIMs) containing quaternary ammonium and phosphonium ionic liquids (ILs) as the carrier. The affecting parameters such as IL content, VFA concentration, and the initial pH of the feed solution as well as the type and concentration of the stripping solution were investigated. PIMs performed a much higher selective separation performance toward hexanoic acid. The optimal PIM composed of 60 wt% quaternary ammonium IL with the permeability coefficients for acetic and hexanoic acid of 0.72 and 4.38 µm s-1, respectively, was determined. The purity of hexanoic acid obtained in the stripping solution increased with an increase in the VFA concentration of the feed solution and decreasing HCl concentration of the stripping solution. The use of Na2CO3 as the stripping solution and the involvement of the electrodialysis process could dramatically enhance the transport efficiency of both VFAs, but the separation efficiency decreased sharply. Furthermore, a coordinating mechanism containing hydrogen bonding and ion exchange for VFA transport was demonstrated. The highest purity of hexanoic acid (89.3%) in the stripping solution demonstrated that this PIM technology has good prospects for the separation and recovery of VFAs from aqueous solutions.

Influence of acidogenic headspace pressure on methane production under schematic of diversion of acidogenic off-gas to methanogenic reactor.

This study investigated the effects of 12.6psi (T1), 6.3psi (T2), 3.3psi (T3) and ambient (T4) headspace pressure on the metabolic pathways in the acidogenic leach bed reactor (LBR) and overall methane recovery during two-phase anaerobic digestion of food waste. Diversion of biogas from LBR enhanced COD and soluble product generation in T2, T3 and T4 whereas, high pressure (T1) resulted in comparatively higher lactate production and low protein degradation. A pressure of 3-6psi (T2 and T3) improved the production of COD by ∼22-36%, soluble products by ∼9-43%, volatile solid reduction by ∼14-19%, and CH4 production by ∼10-31% compared with control. Besides, ∼3-6psi headspace pressure positively influenced the composition of soluble products resulting in enhanced methane recovery adding advantage to the two-phase system. A headspace pressure of ∼3-6psi is recommended to enhance the hydrolysis-acidogenesis; however, the actual hydrogen concentration should be considered.

Innovative method for increased methane recovery from two-phase anaerobic digestion of food waste through reutilization of acidogenic off-gas in methanogenic reactor.

In this study, the performance of a two-phase anaerobic digestion reactor treating food waste with the reutilization of acidogenic off-gas was investigated with the objective to improve the hydrogen availability for the methanogenic reactor. As a comparison a treatment without off-gas reutilization was also set up. Results showed that acidogenic off-gas utilization in the upflow anaerobic sludge blanket (UASB) reactor increased the methane recovery up to 38.6%. In addition, a 27% increase in the production of cumulative chemical oxygen demand (COD) together with an improved soluble microbial products recovery dominated by butyrate was observed in the acidogenic leach bed reactor (LBR) with off-gas reutilization. Of the increased methane recovery, ∼8% was contributed by the utilization of acidogenic off-gas in UASB. Results indicated that utilization of acidogenic off-gas in methanogenic reactor is a viable technique for improving overall methane recovery.

Application of rumen microbes to enhance food waste hydrolysis in acidogenic leach-bed reactors.

Effect of rumen microorganisms on hydrolysis of food waste in leach bed reactor (LBR) was investigated. LBRs were inoculated (20%, w/w) with cow manure and anaerobically digested sludge at different ratios, 0:1 (LBR-A), 1:3 (LBR-B), 1:1 (LBR-C), 3:1 (LBR-D) and 1:0 (LBR-E). High volatile solids (VS) conversion efficiency of 68% was achieved in LBR-E. Compared with LBR-A, chemical oxygen demand, total soluble products and total Kjeldahl nitrogen leaching of LBR-E were increased by 16%, 14.3% and 27%, respectively. Recovery of the highest amounts of ethanol and butyrate in LBR-E indicated that the metabolic pathway mediated by rumen microorganisms was favorable for subsequent methanogenesis. Phylogenetic analysis confirmed that the enhanced hydrolysis in LBR-E was mainly due to strong degraders, e.g. Enterobacter, Bifidobacterium thermacidophilum and Caloramator sourced from cow manure. Results demonstrate that rumen microorganisms rapidly degrade the VS and produce useful VFAs with high methane yields in subsequent methanogenesis.

A novel way to utilize hydrogen and carbon dioxide in acidogenic reactor through homoacetogenesis.

This study investigated the potential of Acetobacterium woodii, a homoacetogen, in co-culture with common acetogens for acetate production during glucose fermentation. Three types of inocula, A. woodii (AW), heat-treated sludge (HTS) and co-culture of A. woodii and heat-treated sludge (AW-HTS) were investigated. Results showed that ∼ 150 mM of glucose was almost completely converted to biomass, gases and other products in co-culture. The addition of A. woodii induced homoacetogenic fermentation in AW-HTS during the first 3 days, as evidenced by the decreased hydrogen production and acetate dominance (>90%, corresponding to 1.19 mol acetate/mol glucose) in total soluble products. However, due to the unfavorable environmental conditions, metabolic pathway in AW-HTS treatment shifted towards butyrate type at the end of the experiment. Bacterial diversity analysis indicated that species supporting growth of A. woodii were dominant during the first several days and their abundance gradually decreased until the end of experiment.