Methamphetamine (METH) is a powerful psychostimulant that is causing serious health problems worldwide owing to imprudent abuses. Recent studies have suggested that METH has deleterious effects on ...the blood–brain barrier (BBB). A few studies have also been conducted on the mechanisms whereby METH-induced oxidative stress causes BBB dysfunction. We investigated whether
N
-
tert
-butyl-α-phenylnitrone (PBN) has protective effects on BBB function against METH exposure in primary human brain microvascular endothelial cells (HBMECs). We found that METH significantly increased reactive oxygen species (ROS) generation in HBMECs. Pretreatment with PBN decreased METH-induced ROS production. With regard to BBB functional integrity, METH exposure elevated the paracellular permeability and reduced the monolayer integrity; PBN treatment reversed these effects. An analysis of the BBB structural properties, by immunostaining junction proteins and cytoskeleton in HBMECs, indicated that METH treatment changed the cellular localization of the tight (ZO-1) and adherens junctions (VE-cadherin) from the membrane to cytoplasm. Furthermore, METH induced cytoskeletal reorganization
via
the formation of robust stress fibers. METH-induced junctional protein redistribution and cytoskeletal reorganization were attenuated by PBN treatment. Our results suggest that PBN can act as a therapeutic reagent for METH-induced BBB dysfunction by inhibiting excess ROS generation.
Exposure to fine particulate matter (PM) comprising toxic compounds arising from air pollution is a major human health concern. It is linked to increased mortality and incidence of various lung ...diseases. However, the mechanisms underlying the toxic effects of PM on lung fibroblasts have not been fully explored. We used targeted quantitative metabolomics and lipidomics analysis along with cytotoxicity studies to comprehensively characterize the alterations in the metabolite profiles of human lung fibroblasts (HEL 299) upon exposure to PM2.5 and PM10. This exposure at 50 μg/mL for 72 h induced an abnormally high apoptotic response via triggering intracellular reactive oxygen species (ROS) production and mitochondrial dysfunction through an imbalance between pro- and anti-apoptotic signaling pathways. The cytotoxic effects of PM2.5 were more severe than those of PM10. Metabolomics and lipidomics analyses revealed that PM exposure triggered substantial changes in the cellular metabolite profile, which involved reduced mitochondria-related metabolites such as tricarboxylic acid (TCA) cycle intermediates, amino acids, and free fatty acids as well as increased lysoglycerophospholipids (LPLs) containing polyunsaturated fatty acids. The decrease in mitochondria-related metabolites suggested that PM exposure led to reduced TCA cycle capacity and energy production. Apoptotic and inflammatory responses as well as mitochondrial dysfunction were likely to be accelerated because of excessive accumulation of LPLs, contributing to the disruption of membrane rafts and Ca2+ homeostasis and causing increased mitochondrial ROS formation. These results provide valuable insights regarding the toxic effects of PM exposure. Our study also provides a new direction for research on PM exposure-related health disorders using different cell lines.
Display omitted
•PMs promoted apoptotic response via triggering intercellular ROS production and mitochondrial dysfunction in HEL 299 cells.•PMs induced depletion of TCA cycle intermediates, amino acids, and FFAs.•PMs induced excessive accumulations of PUFA-esterified LPC, LPE, and LPA as pro-inflammatory lipids.•PMs induced disruption of membrane properties and TCA cycle capacity through disturbances in cellular metabolism.
Linezolid is an oxazolidinone class antibiotic used for treatment infections caused by various multidrug-resistant gram-positive pathogens including enterococci. However, recently, ...linezolid-resistant isolates in animals are considered as a human health hazard. In a broiler operation system, antimicrobial resistance can be transferred to the environment and commercial broiler via the fecal–oral route. Therefore, this study was conducted to investigate the prevalence and characteristics of linezolid-resistant Enterococcus faecalis (E. faecalis) from broiler parent stock in a broiler operation system. Among 297 E. faecalis isolates from 85 flocks in 8 broiler breeder farms, the prevalence of chloramphenicol- and linezolid-resistant isolates was 0 to 12.1% and 0 to 8.0%, respectively; however, there were no significant differences between farms. Therefore, a total of 14 (4.7%) chloramphenicol- and/or linezolid-resistant E. faecalis showed resistance to 7 or more antimicrobial classes. The drug-resistance gene optrA, which can confer resistance to linezolid, tedizolid, and phenicols, was found in 8 (2.69%) isolates, and 7 (2.36%) of the 8 optrA-positive isolates co-carried the phenicol exporter gene fexA. However, E. faecalis isolates from 3 of 8 broiler breeder farms only carried the optrA and/or fexA genes. As linezolid is one of the last antimicrobial treatments of choice for multidrug-resistant gram-positive pathogens including E. faecalis, the presence of antibiotic-resistant E. faecalis in broiler breeder farms should be monitored to prevent the introduction of linezolid-resistant strains to the food chain.
Bisphenol AF (BPAF) is found in high concentrations in aquatic environments due to the increased use of thermal paper and food packaging. However, there have been relatively few toxicological studies ...and potential risk assessments of BPAF. In this study, the risk quotient (RQ) and hazard quotient (HQ) of BPAF were derived to present the safety standards for environmental risk management and protection in lakes, rivers, bays, and Italian regions. We applied the species sensitivity distribution (SSD) method based on the previous ecotoxicological data and the results of supplementary toxicity tests on BPAF. From the SSD curves, the hazardous concentration for 5 % of the species (HC5) values for the acute and chronic toxicity data were 464.75 µg/L and 3.59 µg/L, respectively, and the acute- and chronic-based predicted no-effect concentration were derived as 154.92 µg/L and 1.20 µg/L, respectively. The acute-based RQ (RQA)values of BPAF in all regions were negligible (RQ < 0.1). The chronic-based RQ (RQC) in the Xitang River (XR) and the Central Italy (CI) showed a considerably high ecological risk (12.77 and 1.29) and the Hangzhou Bay (0.21), the South and North Italy (0.79 and 0.27), and the Tamagawa River (0.13) had a medium ecological risk (0.1 < RQ < 1.0). However, the HQ values based on the tolerable daily intake for BPAF over all age groups in these regions was < 0.1, indicating the low health risk. Nonetheless, the result of this study indicates that BPAF contamination is serious in XR and CI, and their use and emissions require continuous monitoring.
•The risk quotient and hazard quotient of BPAF to protect aquatic life were derived.•The chronic-based PNEC (1.20 µg/L) derived from the SSD curve is significantly low.•The RQ value for BPAF in the Xitang River showed a high ecological risk.•BPAF levels in tap drinking water of Italy were classified as a low health risk.•The use and emission of BPAF require continuous monitoring.
Carbon nanotube buckypaper has been considered as one of the promising candidates for chemiresistive sensor applications, especially with environmental monitoring purpose due to large surface area, ...device flexibility, and the broad spectrum of responsive chemical vapor molecules. However, one of typical drawbacks in carbon-based sensors is incomplete recovery to their initial state after chemical reactions with analytes, degrading sensing reproducibility. In this work, we present a thermally stable and robust boron nitride nanotube/carbon nanotube (BNCNT) hybrid paper for self-enhanced chemiresistive sensing with full reversibility. Boron nitride nanotube (BNNT) plays an essential role in long-term reliability (33 days) at the operating temperature of 200 °C. In addition, a finite-element method was applied to understand the thermal behavior of the BNCNT network structure. The BNCNT paper-based chemiresisitve sensor exhibited highly sensitive, selective, and fully reversible responses to NO2 without external heating. Also, the sensor demonstrated the detection limit of parts per billion (ppb)-levels under strain with high reliability. With these remarkable strengths, significantly facile and cost-effective fabrication processes provide an environmental sensing platform for use in smart clothing with wearable electronics.
•Boron nitride nanotube/carbon nanotube (BNCNT)-based chemiresistive sensor with full reversibility was developed.•The BNCNT paper exhibits a highly sensitive detection to NO2 at room temperature.•The detection limit (DL) is 3.41 parts per billion (ppb) even under strained conditions with high reliability.•The BNCNT papers maintained its self-enhanced temperature of 200 °C during a long-term stability test for 33 days.•The BNNT plays a major role in the long-term reliability of maintaining a temperature of CNT networks.
Bisphenol S (BPS), an organic compound and bisphenol analog, is commonly used as a substitute for bisphenol A. BPS is widely used in epoxy glues, can coatings, and thermal receipt papers; however, ...its risks have not been fully determined and the probability of its toxicity has been continuously suggested. In this study, we conducted BPS toxicity tests on aquatic plants (acute), cladocerans (acute and chronic), and fish (chronic) to determine its adverse effects, and calculated the toxicity values. Additionally, we conducted an ecological risk assessment of BPS in freshwater ecosystems with toxicity data from previous studies using the species sensitivity distribution method and BPS exposure data from 14 rivers in four countries in Asia (China, Japan, India, and South Korea). The chronic-based risk quotient (RQ) values of BPS in one river in China and two rivers in India were > 1, indicating a high ecological risk of BPS to aquatic organisms. The other four rivers in China showed medium ecological risk (0.1 < RQ < 1) and those in Japan and South Korea showed negligible chronic risk (RQ < 0.1) to aquatic organisms. We also suggest sensitive indicators in the model organism
Danio rerio
and highlighted the importance of the development of new method of ecological risk assessment. This study could provide new information that will assist in managing BPS and bisphenol analogs in freshwater ecosystems.
Enterococcus faecalis (E. faecalis) has rapidly acquired resistance to multiple antimicrobials, and the antimicrobial resistance of E. faecalis from broiler breeders has been implicated in its ...vertical transmission to their offspring. The objective of this study was to investigate the antimicrobial resistance and genetic diversity of commensal E. faecalis isolated from the broiler breeder farms. Among a total of 229 E. faecalis isolates from 9 broiler breeder farms, the highest resistance rate was observed in tetracycline (78.2%), followed by doxycycline (58.1%) and erythromycin (43.7%), and the prevalence of antimicrobial resistance showed significant differences among the 9 broiler breeder farms (P < 0.05). The tetM gene (77.1%) and ermB gene (85.0%) were detected at the highest levels in 179 TE-and 100 E-resistant isolates, respectively. Twenty-four high-level gentamicin-resistant isolates carried aac(6″)Ie-aph(2″)-la gene, and 9 high-level ciprofloxacin-resistant isolates showed point mutations in both gyrA and parC genes. All high-level gentamicin-resistant or high-level ciprofloxacin-resistant isolates showed one of the two different virulence gene patterns, ace-asa1-efaA-gelE complex or ace-efaA-gelE complex. These results indicate that constant epidemiological monitoring at the breeder level is required to prevent the pyramidal transmission of antimicrobial-resistant E. faecalis.
Fluoranthene is a polycyclic aromatic hydrocarbon (PAH) commonly present in PAH‐contaminated soils. We studied fluoranthene catabolism and associated proteins in Mycobacterium sp. JS14, a bacterium ...isolated from a PAH‐contaminated soil in Hilo (HI, USA). Fluoranthene degrades in at least three separated pathways via 1‐indanone, 2′,3′‐dihydroxybiphenyl‐2,3,‐dicarboxylic acid, and naphthalene‐1,8‐dicarboxylic acid. Part of the diverse catabolism is converged into phthalate catabolism. An increased expression of 25 proteins related to fluoranthene catabolism is found with 1‐D PAGE or 2‐DE and nano‐LC‐MS/MS. Detection of fluoranthene catabolism associated proteins coincides well with its multiple degradation pathways that are mapped via metabolites identified. Among the up‐regulated proteins, PAH ring‐hydroxylating dioxygenase α‐subunit and β‐subunit and 2,3‐dihydroxybiphenyl 1,2‐dioxygenase are notably induced. The up‐regulation of trans‐2‐carboxybenzalpyruvate hydratase suggests that some of fluoranthene metabolites may be further degraded through aromatic dicarboxylic acid pathways. Catalase and superoxide dismutase were up‐regulated to control unexpected oxidative stress during the fluoranthene catabolism. The up‐regulation of chorismate synthase and nicotine‐nucleotide phosphorylase may be necessary for sustaining shikimate pathway and pyrimidine biosynthesis, respectively. A fluoranthene degradation pathway for Mycobacterium sp. JS14 was proposed and confirmed by proteomic study by identifying almost all the enzymes required during the initial steps of fluoranthene degradation.
Low level modular multilevel converter (MMC) is a promising candidate for medium voltage applications such as MVDC (medium voltage DC current) transmission and megawatt machine drives. Unlike ...high-level MMC using nearest level modulation (NLM), the low-level MMC using the pulse width modulation (PWM) or NLM + PWM is affected by a common mode voltage (CMV) due to a frequent change of a switching state. This CMV causes electromagnetic interference (EMI) noise, common mode current (CMC) and bearing current leading to a reduction in the efficiency and durability of the motor drive system. Therefore, this paper provides a mathematical analysis on how the switching state affects the CMV and proposes three software based CMV reduction algorithms for the low level MMC system. To reflect the characteristic of MMC modulation strategy for upper and lower reference voltage independently, two separate space vectors are used. Based on the analysis, three different CMV reduction algorithms (complete CMV reduction (CCR), DPWM CMV reduction (DCR) and partial CMV reduction (PCR)) are proposed using NLC + PWM modulation strategy. The performance of the proposed CMV reduction algorithms was verified by both simulation and experimental result.
β-hydroxybutyrate (β-OHB) has been shown to exert an anti-inflammatory activity. Apolipoprotein-E (ApoE) is strongly associated with atherosclerosis and Alzheimer's disease (AD). This study aimed to ...explore the therapeutic effect of β-OHB in the brain and the aorta of high-fat diet (HFD)-fed ApoE-deficient mice. We found in Apo-E deficient mice that β-OHB attenuated lipid deposition in the choroid plexus (ChP) and decreased amyloid plaque in the substantia nigra pars compacta. We also found decreased CD68-positive macroglia infiltration of the ChP in β-OHB-treated ApoE-deficient mice. β-OHB treatment ameliorated IgG extravasation into the hippocampal region of the brain. In vitro study using ChP mice cell line revealed that β-OHB attenuated oxidized low-density lipoprotein-induced ApoE-specific differentially expressed inflammatory ChP genes. Treatment with β-OHB reduced aortic plaque formation without affecting blood lipid profiles and decreased serum production of resistin, a well-established risk factor for both AD and atherosclerosis. Thus, the current study suggests and describes the therapeutic potential of β-OHB for the treatment of AD and atherosclerosis.
PDF
