EV-COMM: A database of interspecies and intercellular interactions mediated by extracellular vesicles.

Intra- and inter-organismal interactions play a crucial role in the maintenance and function of individuals, as well as communities. Extracellular vesicles (EVs) have been identified as effective mediators for the communication both within and between species. They can carry and transport molecular cargoes to transmit biological messages. Several databases (ExoBCD, ExoCarta, EVpedia, EV-TRACK, Vesiclepedia) complied the cargoes information including DNA, RNA, protein, lipid and metabolite associated with EVs. Databases that refer to the complete records on both donor and recipient information are warranted to facilitate the understanding of the interaction across cells and species. In this study, we developed a database that compiled the records equipped with a structured process of EV-mediated interaction. The sources of donor and recipient were classified by cell type, tissues/organs and species, thus providing an extended knowledge of cell-cell, species-species interaction. The isolation and identification methods were presented for assessing the quality of EVs. Information on functional cargoes was included, where microRNA was linked to a prediction server to broaden its potential effects. Physiological and pathological context was marked to show the environment where EVs functioned. At present, a total of 1481 data records in our database, including 971 cell-cell interactions belonging to more than 40 different tissues/organs, and 510 cross-species records. The database provides a web interface to browse, search, visualize and download the interaction records. Users can search for interactions by selecting the context of interest or specific cells/species types, as well as functional cargoes. To the best of our knowledge, the database is the first comprehensive database focusing on interactions between donor and recipient cells or species mediated by EVs, serving as a convenient tool to explore and validate interactions. The Database, shorten as EV-COMM (EV mediated communication) is freely available at http://sdc.iue.ac.cn/evs/list/ and will be continuously updated.

Role of CdTe quantum dots on peripheral Immunocytes and selenoprotein P: immunotoxicity at the molecular and cellular levels.

The extensive product and application of cadmium-quantum dots (Cd-QDs), one kind of semiconductor nanomaterials, lead to prolonged exposure to the environment. Cd-QDs have shown good properties in biomedical and imaging-related fields; the safety of Cd-QDs limits the application of these materials and technologies, however. The systematic distribution of CdTe QDs in organisms has been ascertained in previous studies. Nevertheless, it is relatively less reported about the toxicity of CdTe QDs to immune macromolecules and organs. Based on this, immunocytes (including lymphocyte subsets-CD4+ T and CD8+ T cells, splenocytes) and selenoprotein P (SelP) were chosen as targets for CdTe QDs immunotoxicity studies. Results indicate that CdTe QDs induced cytotoxicity to CD4+ T cells, CD8+ T cells and splenocytes by reducing cell viability and causing apoptosis as CdTe QDs and Cd2+ enter cells. At the molecular level, the direct interaction between CdTe QDs and SelP is proved by multispectral measurements, which demonstrated the alteration of protein structure. The combined results show that CdTe QDs induced adverse effects on the immune system at the cellular and molecular levels. This research contributes to a better understanding of CdTe QDs cause harmful damage to the immune system and provides new strategies for the inhibition and treatment of health damages caused by CdTe QDs.

Application of Se-Met to CdTe QDs significantly reduces toxicity by modulating redox balance and inhibiting apoptosis.

Cadmium tellurium quantum dots (CdTe QDs) as one of the most widely used QDs have been reported the toxicity and biosafety in recent years, little work has been done to reduce their toxicity however. Based on the mechanisms of toxicity of CdTe QDs on liver target organs such as oxidative stress and apoptosis previously reported by other researchers, we investigated the mechanism of action of trace element selenium (Se) to mitigate the hepatotoxicity of CdTe QDs. The experimental results showed that Se-Met at 40-140 µg L-1 could enhance the function of intracellular antioxidant defense system and the molecular structure of related antioxidant enzymes by reduce the production of ROS by 45%, protecting the activity of antioxidants and up-regulating the expression of selenoproteins with antioxidant functions, Gpx1 increase 225% and Gpx4 upregulated 47%. In addition, Se-Met could alleviate CdTe QDs-induced apoptosis by regulating two apoptosis-inducing factors, as intracellular caspase 3/9 expression levels were reduced by 70% and 87%, decreased Ca2+ concentration, and increased mitochondrial membrane potential measurements. Overall, this study indicates that Se-Met has a significant protective effect on the hepatotoxicity of CdTe QDs. Se-Met can be applied to the preparation of CdTe QDs to inhibit its toxicity and break the application limitation.

Bisphenol P exposure in C57BL/6 mice caused gut microbiota dysbiosis and induced intestinal barrier disruption via LPS/TLR4/NF-κB signaling pathway.

Despite being one of the most world's widely used and mass-produced compounds, bisphenol A (BPA) has a wide range of toxic effects. Bisphenol P (BPP), an alternative to BPA, has been detected in many foods. The effects of BPP dietary exposure on gut microbiota and the intestinal barrier were unclear. We designed three batches of animal experiments: The first studied mice were exposed to BPP (30 µg/kg BW/day) for nine weeks and found that they gained weight and developed dysbiosis of the gut microbiota. The second, using typical human exposure levels (L, 0.3 µg/kg BW/day BPP) and higher concentrations (M, 30 µg/kg BW/day BPP; H, 3000 µg/kg BW/day BPP), caused gut microbiota dysbiosis in mice, activated the Lipopolysaccharide (LPS) /TLR4/NF-κB signaling pathway, triggered an inflammatory response, increased intestinal permeability, and promoted bacterial translocation leading to intestinal barrier disruption. The third treatment used a combination of antibiotics and alleviated intestinal inflammation and injury. This study demonstrated the mechanism of injury and concentration effects of intestinal damage caused by BPP exposure, providing reference data for BPP use and control and yielding new insights for human disease prevention.

Accumulation and ecotoxicological effects induced by combined exposure of different sized polyethylene microplastics and oxytetracycline in zebrafish.

Microplastics have been widely reported as carriers of antibiotics, yet studies investigating the combined ecotoxicology of microplastics and antibiotics on organisms is limited. In this study, different sized polystyrene plastics and oxytetracycline (OTC) were used to carry out a 30-day single and binary-combined exposure experiment of zebrafish, and the microplastics and OTC accumulation, liver histological alteration, biomarkers and transcriptomic response of zebrafish were evaluated. Our results indicated that 300 nm and 50 nm plastic particles increased the OTC accumulation in liver by 33.8% and 44.5%, respectively. Microplastics and OTC induced severe liver histological damage, and the damage is size-dependent, increasing with the decrease of microplastics sizes. The liver biomarkers indicated a different response pattern in single microplastics exposure and combined with OTC, single or co-exposure of 50 nm nano-plastics and OTC induced intense responses of integrated biomarker response values. The 50 nm nano-plastics, OTC and their combined exposure induced 1330, 2693 and 3965 significantly differentially expressed genes, respectively, in which the steroid biosynthesis pathway was significantly affected by all the three treatments. This study elucidated the size-dependent effects of microplastics and provided detailed data from histopathology to transcriptome profile, enhancing our understanding of the ecotoxicity of microplastics and OTC.

[Distribution Characteristics and Ecological Risk Assessment of Soil Heavy Metals in Baiyangdian Lake].

To understand the spatial distribution characteristics and potential ecological risk of heavy metals in soil of Baiyangdian Lake, 55 soil samples were collected and the contents of eight heavy metals (Mn, Cr, Cu, Zn, As, Cd, Pb, and Ni) were detected. The spatial variation structure and distribution pattern were analyzed using geostatistical methods (Moran index and semi-variance model). The degree of heavy metal pollution and its risk were assessed using the geoaccumulation index (Igeo) and potential ecological risk index (Eri and RI). The results showed that the average of ω(Mn), ω(Cr), ω(Cu), ω(Zn), ω(As), ω(Cd), ω(Pb), and ω(Ni) were 467.75, 43.59, 28.57, 89.04, 12.32, 0.18, 19.26, and 30.56 mg·kg-1, respectively, all of which were lower than the screening values of soil pollution risk in agricultural land. However, the contents of Cu, Zn, and Cd were significantly higher than their background values, with two highly variable elements of Cu (48.65%) and Cd (37.52%). The Moran index indicated that Mn, Cu, Cd, and Pb showed weak spatial autocorrelation. Nugget coefficients of both of Cd and Pb shown by the semi-variance model were 100%, suggesting random variation as a main spatial variation driven by anthropogenic factors. High values of soil heavy metals were mainly distributed in the southwest of Baiyangdian Lake with a significant correlation between the heavy metals. The Igeo of soil heavy metals from high to low was Cd>Cu>Zn>Ni>As>Pb>Mn>Cr. Cd pollution was the most common, in which 67.27% of the samples were lightly polluted. Ecological risk assessment revealed that the average Eri of Cd was 58.81, belonging to the middle ecological risk level, and the rest were at light ecological risk. As a whole, the RI of soil heavy metal pollution in Baiyangdian Lake was at a light ecological risk level (87.81), with the highest contribution rate of Cd to RI (66.39%). Thus, it is necessary to strengthen the control of soil heavy metal Cd pollution in Baiyangdian Lake in the future.

Molecular mechanism of two functional protein structure changes under 2,3-butanedione-induced oxidative stress and apoptosis effects in the hepatocytes.

Food security has become closely watched with the occurrence of a series of food safety incidents in recent years. The widespread adoption of 2,3-butanedione (BUT), as a food additive, is an unpreventable significant risk factor to food security. Based on this, mouse hepatocyte AML-12 cells and two functional proteins (bovine serum albumin and lysozyme) were utilized as targeted receptors to study the adverse effects of BUT at the cellular and molecular levels. Results suggested that BUT could disrupt the redox balance of AML-12 cells, reducing glutathione (GSH) activity fell to 87.18 %, which cannot offset the production of reactive oxygen species (ROS). Meanwhile, the increasement of lipid peroxidation and malondialdehyde (MDA) levels were observed. The mitochondrial membrane function was also abnormal due to the excessive accumulation of ROS and eventually leads to cell apoptosis and death. At the molecular level, the exposure of BUT could alter the skeleton and secondary structure of bovine serum albumin (BSA) and lysozyme (LYZ), and it could statically quench the intrinsic fluorescence of proteins. The combined experiments confirmed proved the potentially toxic effects of BUT accumulation on the detoxification organ, providing theoretical support for the liver diseases caused by BUT exposure, and a reference for the risk assessment of occupational exposure of BUT.

Differential aggregation of polystyrene and titanium dioxide nanoparticles under various salinity conditions and against multiple proteins types.

The interaction of nanoplastics (NPls) and engineered nanoparticles (ENPs) with organic matter and environmental pollutants is particularly important. Therefore, their behavior should be investigated under the different salinity conditions, mimicking rivers and coastal environments, to understand this phenomenon in those areas. In this work, we analyzed the elementary characteristics of polystyrene-PS (unmodified surface and modified with amino or carboxyl groups) and titanium dioxide-TiO2 nanoparticles. The effect of salinity on their colloidal properties was studied too. Also, the interaction with different types of proteins (bovine serum albumin-BSA and tilapia proteins), as well as the formation of the BSA corona and its effect on the colloidal stability of nanoparticles, were evaluated. The morphology and dispersion of sizes were more uniform in unmodified-surface PS-NPs (70.5 ± 13.7 nm) than in TiO2-NPs (131.2 ± 125.6 nm). Likewise, Rama spectroscopy allowed recognizing peaks associated with the PS phenyl group aromatic ring in unmodified-surface PS-NPs (621, 1002, 1582, and 1602 cm-1). For TiO2-NPs, the data suggest belonging to the tetragonal form, also known as rutile (445, 610 cm-1). The elevation of salinity dose-dependently decreased NP colloid stability, with more significant variation in the PS-NPs compared to TiO2-NPs. The organic matter is also involved in this phenomenon, differentially as a function of time compared to its absence (unmodified-surface PS-NPs 30 psu/TOC 5 mgL-1/24 h: 2876.6 ± 378.03 nm; unmodified-surface PS-NPs 30 psu/24 h: 2133 ± 49.57 nm). In general, the TiO2-NPs demonstrated greater affinity with all proteins tested (0.066 g/L). It was observed that morphology, size, and surface chemical modification intervene in a relevant way in the interaction of the nanoparticles with bovine serum albumin (unmodified-surface PS-NPs 298 K: 6.08E+02; 310 K: 6.63E+02; TiO2-NPs 298 K: 8.76E+02; 310 K: 1.05E+03 L mol-1) and tilapia tissues proteins (from blood, gills, liver, and brain). Their morphology and size also determined the protein corona formation and the NPs' agglomeration. These findings can provide references during knowledge transfer between NPls and ENPs.

Combined effects of micro-/nano-plastics and oxytetracycline on the intestinal histopathology and microbiome in zebrafish (Danio rerio).

Accumulated evidence has demonstrated that microplastics and oxytetracycline (OTC) affect organisms, but few studies have investigated their combined effects on aquatic organisms. In this study, adult zebrafish (Danio rerio) were exposed to single and binary-combined contamination of micro-, nano-sized polystyrene plastics and OTC for 30 days, and the intestinal histopathology, gut microbiota and antibiotic resistance genes (ARGs) of zebrafish were measured. The results showed that the intestinal epithelial damage increase with the decrease of plastic sizes. Nano-sized plastics, OTC and their combined exposure caused intestinal epithelial damage, and co-exposure with micro-sized plastics reduced the intestinal damage caused by single OTC exposure. The gut microbial communities were affected by the combined exposure to microplastics and OTC. Compared with the blank control, the relative abundance of Fusobacteria increased 12.7 % and 21.1 % in OTC combined with 45-85 µm micro-plastics (MOTC) and 40-54 nm nano-plastics (NOTC), respectively, and that of Bacteroidetes increased 26.2 % and 18.6 % in the MOTC and NOTC treatments, respectively. The effects of MOTC and NOTC on the biodiversity of the zebrafish gut microbiome were different; MOTC increased the biodiversity by 11.3 % compared with the blank control, whereas NOTC decreased the biodiversity by 8.8 % compared with the blank control. Furthermore, the abundance of ARGs in 40-54 nm nano-plastics, MOTC and NOTC treatments was increased 96.9 %, 96.6 % and 68.8 % compared with the control group, respectively. Additionally, significant differences were observed in ARGs characteristics between the micro- and nano-plastics treated groups whether combined with OTC or not. These results are essential to further understand the combined ecotoxicological effects of micro- or nano-plastics and antibiotics on aquatic organisms.

Widespread of Potential Pathogen-Derived Extracellular Vesicles Carrying Antibiotic Resistance Genes in Indoor Dust.

Extracellular vesicles (EVs) are newly recognized as important vectors for carrying and spreading antibiotic resistance genes (ARGs). However, the ARGs harbored by EVs in ambient environments and the transfer potential are still unclear. In this study, the prevalence of ARGs and mobile genetic elements (MGEs) in EVs and their microbial origins were studied in indoor dust from restaurants, kindergarten, dormitories, and vehicles. The amount of EVs ranged from 3.40 × 107 to 1.09 × 1011 particles/g dust. The length of EV-associated DNA fragments was between 21 bp and 9.7 kb. Metagenomic sequencing showed that a total of 241 antibiotic ARG subtypes encoding resistance to 16 common classes were detected in the EVs from all four fields. Multidrug, quinolone, and macrolide resistance genes were the dominant types. 15 ARG subtypes were exclusively carried and even enriched in EVs compared to the indoor microbiome. Moreover, several ARGs showed co-occurrence with MGEs. The EVs showed distinct taxonomic composition with their original dust microbiota. 30.23% of EV-associated DNA was predicted to originate from potential pathogens. Our results indicated the widespread of EVs carrying ARGs and virulence genes in daily life indoor dust, provided new insights into the status of extracellular DNA, and raised risk concerns on their gene transfer potential.

Perfluorinated compounds disrupted osmoregulation in Oryzias melastigma during acclimation to hypoosmotic environment.

Perfluorinated compounds (PFCs) are a type of ubiquitous contaminants spreading in the estuarine and coastal areas. Anadromous fish should deal with hypoosmotic challenge with PFCs stress during their migration from seawater to estuaries. However, few studies have been carried out to investigate the adverse impact of PFCs on fish osmoregulation and the underlying mechanism. In this study, Oryzias melastigma, an euryhaline fish model, were exposed to four representative PFC congeners including perfluorobutane sulfonate (PFBS), perfluorooctane sulfonates (PFOS), perfluorooctanoic acid (PFOA), and perfluorododecanoic acid (PFDoA) separately under both seawater and freshwater conditions. Histopathological changes in gills, ion homeostasis, Na+/K+-ATPase (NKA) activity, as well as the expression of related genes was detected upon exposure. Results showed that PFCs induced morphological changes in gills, disturbed the levels of major ions (Na+, Ca2+, Mg2+), and inhibited the NKA activity. Transcriptome analysis in fish gills during the acclimation to freshwater revealed that PFCs influenced the osmoregulation mainly by interfering with the endocrine system, signal transduction, as well as cellular community and motility. Validation with qRT-PCR confirmed that the mRNA expressions of osmoregulatory genes encoding hormones and receptors, as well as ion transmembrane transporters were disturbed by PFCs. Longer chain homolog (PFOS) showed a greater impact on osmoregulation than the shorter chain homolog (PFBS). Within the same carbon chain, sulfonic congener (PFOS) induced more serious injury to gills than carboxylic congener (PFOA). The interaction between PFCs and salinity varied in different adverse outcome. These results help to further understand the mechanism of how PFCs influence osmoregulation and elicit the need to assess the ecological risk of PFCs and other pollutants on anadromous migration.

Size-dependent adverse effects of microplastics on intestinal microbiota and metabolic homeostasis in the marine medaka (Oryzias melastigma).

Microplastic (MP) is an emerging environmental pollutant and exposure to MPs has been associated with numerous adverse health outcomes in both wild and laboratory animals. The toxicity of MPs depends on concentration, exposure time, chemical composition and size distribution, but the impacts of particle size remain inconclusive yet. In this study, adult marine medaka (Oryzias melastigma) were exposed to different size of polystyrene MPs (PS-MPs) with concentration of 10 mg/L for 60 days and the growth performance, lipid metabolism, immune parameters and gut microbiome were determined. Results indicated that particle size is a dominant factor causing lipid metabolism disorders and hepatic toxicity in PS-MPs-exposed fish. The bodyweight, adipocyte size and hepatic lipid contents were significantly increased in 200 µm PS-MPs-exposed fish, while 2 and 10 µm PS-MPs-exposed fish exhibited liver injury principally manifested asthepresence oflittlefibrosis and inflammation. Given that larger particles could not enter the circulatory system, the impacts of PS-MPs on intestinal microbial biota homeostasis were further investigated. The results not only showed the characterization of gut microbial communities in Oryzias melastigma, but also indicated that microbial diversity and composition were altered in gut of fish exposed to PS-MPs, in particular 200 µm PS-MPs. The differentially abundant bacterial taxa in PS-MPs-exposed fish mainly belonged to the phylum Verrucomicrobia, Firmicutes and Fusobacteria. And furthermore, increased abundance of Verrucomicrobia and Firmicutes/Bacteroidetes ratio and decreased Fusobacteria were correlated with the increased bodyweight. Intestinal microbiome should play a critical role in regulating host lipid metabolism in fish exposed to lager size of PS-MPs.

A Multi-Level Feature Fusion Network for Remote Sensing Image Segmentation.

High-resolution remote sensing image segmentation is a mature application in many industrial-level image applications and it also has military and civil applications. The scene analysis needs to be automated as much as possible with high-resolution remote sensing images. This plays a significant role in environmental disaster monitoring, forestry industry, agricultural farming, urban planning, and road analysis. This study proposes a multi-level feature fusion network (MFNet) that can integrate the multi-level features in the backbone to obtain different types of image information. Finally, the experiments in this study demonstrate that the proposed network can achieve good segmentation results in the Vaihingen and Potsdam datasets. By aiming to achieve a large difference in the scale of the target objects in remote sensing images and achieving a poor recognition result for small objects, a multi-level feature fusion solution is proposed in this study. This investigation improves the recognition results of the remote sensing image segmentation to a certain extent.

Occurrence and toxicity of perfluoroalkyl acids along the estuarine and coastal regions under varied environmental factors.

Due to the significant economic and ecological value, the increasing pollution threat to estuarine and coastal regions is of great concern. Perfluoroalkyl acids (PFAAs) are emerging pollutants which possess adverse ecological risk. In this review, we have compiled the data on the levels of PFAAs in environmental samples, mainly in estuarine and coastal zones. A worldwide map was generated to show the distribution of PFAAs. The experimental results have also been considered, which, together with those of environmental samples, has allowed us to infer about the factors that intervene in the behavior of PFAAs. The presence of PFAAs is determined primarily by the source of pollution. Salinity is as well shown as a significant condition, dependent too on the sampling environment. The analysis of PFAAs from environmental samples constitutes a fundamental tool for the surveillance of these pollutants, but the lack of homogeneity of protocols for sampling, as well as for the results presentation, limits the comparative capacity. Laboratory studies are also an essential tool in the analysis of particular aspects related to PFAAs, but many times the conditions tested are not environmentally significant. In this way, it would not be prudent to establish "paradigms" about the behavior of the PFAAs in certain areas or organisms, instead to suggest the points that can be considered fundamental for each issue addressed. The main variables that appear to intervene in estuarine and coastal regions are mainly the proximity to the source of pollution, salinity, pH, precipitation (rain) as well as types of PFAAs. All these can synergistically lead to different impacts on the ecosystem. Therefore, the particular risks of PFAAs in estuarine and coastal regions is a set of multiple variables, dependent on each sampling condition and according to the previously named parameters.

Long-term wet precipitation of PM2.5 disturbed the gut microbiome and inhibited the growth of marine medaka Oryzias melastigma.

Wet precipitation, as an important process of geochemical cycling and the most effective way of cleaning fine atmospheric particles (PM2.5), can introduce the toxic substances in the atmosphere into the water environment. The adverse effect of wet precipitation of PM2.5 on marine fish is still unclear. In this study, PM2.5 samples were collected from six locations along coastal areas of the south China sea for 30 days and used to simulate the impacts of multiday discontinuity wet precipitation of PM2.5 on marine medaka (Oryzias melastigma) in the case of 30 days discontinuity heavy rain (rainfall ≥ 7.6 mm/h and persist 1 h each day). Results showed that wet precipitation of PM2.5 significantly inhibited the body weight gain of fish. In accordance, the size and number of lipid droplets in liver of the exposed groups were lower than those in normal control (NC) group. The expressions of genes involving in lipid degradation including lipoprotein lipase gene (LPL) and carnitine palmitoyltransferase gene (CPT) were up-regulated after exposure. The composition, diversity and function of gut microbiome were affected by wet precipitation of PM2.5. PM2.5 from industrial areas that have higher concentrations of metal profiles show more obvious impacts than PM2.5 from agricultural leisure areas that possessed lower concentrations. All together, the results indicated that wet precipitation of PM2.5 can decrease the diversity of gut microbiome, affect the lipid metabolism, and finally suppress the growth of marine medaka. It confirmed the potential ecological risks of long-term rainfall in air pollution areas to the aquatic organisms.

Gut microbiota health closely associates with PCB153-derived risk of host diseases.

Although the production and use of PCB153 have been banned globally, PCB153 pollution remains because of its persistence and long half-life in the environment. There is ongoing evidence that exposure to PCB153 may influence gut microbiota health and increase the risk of host health. It is needed to illuminate whether there are associations between gut microbiota dysregulation and PCB153-induced host diseases. Importantly, it is urgently needed to find specific strains as biomarkers to monitor PCB153 pollution and associated disorders. The work aims to investigate the change of gut microbiota composition, structure and diversity and various host physiological indexes, to ravel the chain causality of PCB153, gut microbiota health and host health, and to find potential gut microbiota markers for PCB153 pollution. Here, adult female mice were administrated with PCB153. Obtained results indicated that PCB153 led to gut microbiota health deterioration. PCB153 exposure also induced obesity, hepatic lipid accumulation, abdominal adipose tissue depots and dyslipidemia in mice. Furthermore, specific gut microbiota significantly correlated with the host health indexes. This work provides support for the relationship between gut microbiota aberrance derived from PCB153 and risk of host health, and offers some indications of possible indicative functions of gut microbiota on PCB153 pollution.

Elevated bioaccumulation of PFAAs in Oryzias melastigma following the increase of salinity is associated with the up-regulated expression of PFAA-binding proteins.

Perfluoroalkyl acids (PFAAs) are widely detected in the environment, especially in estuarine and coastal areas where fluctuation of salinity occurs. Salinity alteration affected the distribution of PFAAs and even the bioaccumulation in organisms. However, the inner mechanism is still unclear. In this study, the marine medaka (Oryzias melastigma), a euryhaline fish model, was exposed to four PFAAs congeners under three different salinities (0, 15 and 35 psu). Results showed that the bioaccumulation of PFAAs increased in fish as the water salinity increased. PFAAs with longer lengths of carbon­fluorine bond showed higher bioaccumulation in the fish. Salinity did not alter the levels of PFAAs in water media, however, the uptake rate of PFAAs from gills did increase with the salinity. Further analysis of the mechanism showed that PFAA bound to branchial proteins as confirmed by fluorescence spectroscopy. Higher expressions of proteins binding to PFAAs including organic anion transporter 1 (OAT1) and fatty acid-binding protein (FABP) facilitated the uptake of PFAAs through gills in fish culturing under higher salinity. In all, our study showed that elevation of salinity can induce the expression of proteins binding to PFAAs in gills, thus facilitate the uptake of water PFAAs. Salinity fluctuation should be taken into consideration when assessing the chemical risk in the estuarine and coastal areas.

Benzo[a]pyrene at human blood equivalent level induces human lung epithelial cell invasion and migration via aryl hydrocarbon receptor signaling.

Benzo[a]pyrene (B[a]P), a typical carcinogenic polycyclic aromatic hydrocarbon, exists worldwide in vehicle exhaust, cigarette smoke and other polluted environments. Recent studies have demonstrated a strong association between B[a]P and lung cancer. However, whether B[a]P at human blood equivalent level can promote epithelial-mesenchymal transition (EMT), a crucial molecular event during cell malignant transformation, remains unclear. Besides, whether B[a]P facilitates this progress via aryl hydrocarbon receptor (AhR) signaling pathway also lacks scientific evidence. In our study, the transwell assay showed that 5 µg/L of B[a]P promoted BEAS-2B cell invasion and migration. In addition, the mRNA and protein expression levels of AhR and its target genes involved in B[a]P metabolism, such as AhR nuclear translocator, heat shock protein 90 and CYP1A1, were significantly increased by B[a]P exposure. Moreover, the mRNA expression levels of downstream regulatory factors related to both AhR signaling pathway and EMT, such as NRF2, K-RAS and hypoxia-inducible factor 1-alpha, were significantly increased. Furthermore, the expression level of the epithelial marker E-cadherin was significantly downregulated, while the mRNA expression of mesenchymal phenotype markers, N-cadherin, fibronectin and vimentin, were significantly upregulated. Notably, the above changes induced by B[a]P were significantly attenuated or even stopped by resveratrol (RSV), a natural phenol, also an AhR inhibitor, when the AhR signaling pathway was inhibited by RSV, demonstrating the regulatory role of AhR signaling pathway in B[a]P-induced EMT. In conclusion, B[a]P at the human blood equivalent level induces BEAS-2B cell invasion and migration through the AhR signaling pathway.

Sex hormones affect endothelial lipase-mediated lipid metabolism and atherosclerosis.

BACKGROUND: Endothelial lipase (EL) plays an important role in lipoprotein metabolism and atherosclerosis. To study the functional roles of EL, we recently generated transgenic (Tg) rabbits and reported that increased hepatic expression of EL in male Tg rabbits significantly reduced diet-induced hypercholesterolemia compared with non-Tg controls. This gender difference suggests that sex hormones may mediate EL functions thereby influencing lipoprotein metabolism. To examine this hypothesis, we compared the effects of orchiectomy and ovariectomy on plasma lipids and diet-induced atherosclerosis in both Tg and non-Tg rabbits. METHODS: Male rabbits were under orchiectomy whereas female rabbits were under ovariectomy. We compared plasma lipids, lipoproteins, and apolipoproteins of rabbits before and after surgery in each group fed either a chow diet or cholesterol-rich diet. RESULTS: On a chow diet, both male and female Tg rabbits showed lower plasma lipids than non-Tg counterparts and this lipid-lowering effect of EL was not affected by either orchiectomy in male or ovariectomy in female Tg rabbits. On a cholesterol diet; however, male Tg rabbits but not female Tg rabbits showed significant resistance to diet-induced hypercholesterolemia and atherosclerosis. The EL-mediated atheroprotective effect was eliminated after orchiectomy in male Tg rabbits. Female Tg rabbits showed similar levels of total cholesterol and lesion size of atherosclerosis compared with non-Tg rabbits and ovariectomy did not affect diet-induced hypercholesterolemia or atherosclerosis. CONCLUSION: These results suggest that increased EL protects against diet-induced hypercholesterolemia and atherosclerosis. The beneficial effect of EL was dependent upon the presence of androgenic hormones.

Comprehensive metabolic responses of HepG2 cells to fine particulate matter exposure: Insights from an untargeted metabolomics.

Exposure to fine particulate matter (PM2.5) increases the risk of metabolic diseases, such as cancer and cardiovascular disease. Disturbed hepatocyte metabolism accelerates the incidence and progression of metabolic diseases. However, toxic effects of PM2.5 on hepatocyte metabolism remain unclear. Accordingly, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry was used to characterize comprehensive metabolic responses of HepG2 cells to PM2.5 exposure and to discover potential therapeutic targets for PM2.5-induced metabolic dysregulation in metabolic diseases. Metabolomics revealed that exposure to liposoluble extracts of PM2.5 samples (LE) triggered substantial changes in 46 metabolic pathways, mainly involved in lipid, amino acid, nucleotide and carbohydrate metabolism, in HepG2 cells. Notably, LE exposure induced accumulation of FFAs and medium-chained acylcarnitines (6-12 carbons), but decreased levels of short-chained acylcarnitines (<5 carbons) in HepG2 cells. Meanwhile, levels of citrate/isocitrate and aconitate were decreased, while 2-hydroxyglutate and succinate accumulated in HepG2 cells treated with LE. Additionally, levels of adenosine triphosphate, guanosine triphosphate, uridine triphosphate and cytidine triphosphate were decreased; however, contents of adenosine monophosphate, guanosine monophosphate, purines and pyrimidines were increased in HepG2 cells treated with LE. Moreover, levels of glutathione, Glu-Cys, Cys-Gly, lipoic acid, methionine sulfoxide, methionine and S-adenosyl-L-methionine were increased, while those of most amino acids were decreased in HepG2 cells treated with LE. These data demonstrated that LE exposure triggered accumulation of FAAs and oncometabolites (2-hydroxyglutate and succinate), mitochondrial dysfunctions characterized by incomplete FFA oxidation and reduced energy supply from TCA cycle and oxidative phosphorylation, disturbances in methylation and redox homeostasis, and the inhibition of most amino acid metabolism in HepG2 cells. Above metabolic disorders indicates potential therapeutic targets for treating PM2.5-induced injury and diseases. To the best of our knowledge, this study provides the first evidence that LE exposure triggered accumulation of medium-chain acylcarnitines, oncometabolites, purines and pyrimidines in HepG2 cells.