Competitive-like binding between carbon black and CTNNB1 to ΔNp63 interpreting the abnormal respiratory epithelial repair after injury.

Airway epithelium is extraordinary vulnerable to damage owning to continuous environment exposure. Subsequent repair is therefore essential to restore the homeostasis of respiratory system. Disruptions in respiratory epithelial repair caused by nanoparticles exposure have been linked to various human diseases, yet implications in repair process remain incompletely elucidated. This study aims to elucidate the key stage in epithelial repair disturbed by carbon black (CB) nanoparticles, highlighting the pivotal role of ΔNp63 in mediating the epithelium repair. A competitive-like binding between CB and beta-catenin 1 (CTNNB1) to ΔNp63 is proposed to elaborate the underlying toxicity mechanism. Specifically, CB exhibits a remarkable inhibitory effect on cell proliferation, leading to aberrant airway epithelial repair, as validated in air-liquid culture. ΔNp63 drives efficient epithelial proliferation during CB exposure, and CTNNB1 was identified as a target of ΔNp63 by bioinformatics analysis. Further molecular dynamics simulation reveals that oxygen-containing functional groups on CB disrupt the native interaction of CTNNB1 with ΔNp63 through competitive-like binding pattern. This process modulates CTNNB1 expression, ultimately restraining proliferation during respiratory epithelial repair. Overall, the current study elucidates that the diminished interaction between CTNNB1 and ΔNp63 impedes respiratory epithelial repair in response to CB exposure, thereby enriching the public health risk assessment on CB-related respiratory diseases.

Exploring Prenatal Exposure to Halogenated Compounds and Its Relationship with Birth Outcomes Using Nontarget Analysis.

Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks.

Association between famine exposure during infancy and childhood and the risk of chronic kidney disease in adulthood.

BACKGROUND: Famine exposure in childhood is proven to be associated with multiple chornic disease in adult but has not been studied with chronic kidney disease (CKD). AIMS: This study was conducted to identify the relationship between famine exposure during infancy and childhood - specifically, the Chinese famine of 1959-1961 - and the risk of adult-onset chronic kidney disease (CKD) among Chinese individuals. METHODS: This study included 2937 individuals from the Qingdao Diabetes Prevention Program. They were stratified by birth year into infancy-exposed (1956-1958), childhood-exposed (1950-1955) and unexposed (1963-1971) groups. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR of <90 mL/min/1.73 m2 . RESULTS: The mean eGFR values for the infancy-exposed and childhood-exposed groups were 107.23 ± 12.53 and 103.23 ± 12.44 mL/min/1.73 m2 , respectively, both of which were lower than that of the unexposed group (114.82 ± 13.39 mL/min/1.73 m2 ; P < 0.05). In the crude model, the odds ratio (OR) for CKD was 2.00 (95% confidence interval (CI): 1.39-2.88) in the infancy-exposed group and 2.92 (95% CI: 2.17-3.93) in the childhood-exposed group. Further adjustments for urban/rural residence, body mass index, age, current smoking, type 2 diabetes, systolic blood pressure, diastolic blood pressure and total cholesterol did not significantly alter the association between famine exposure and CKD. The corresponding ORs were 1.71 (95% CI: 1.17-2.50) and 2.48 (95% CI: 1.81-3.40) for the infancy-exposed and childhood-exposed groups respectively. CONCLUSIONS: Famine exposure during infancy and childhood is associated with a long-term decline in eGFR and an increased adult-onset CKD risk. Early intervention for high-risk individuals may mitigate the risk of adult-onset CKD.

Association between phthalate metabolite mixture in neonatal cord serum and birth outcomes.

Prenatal exposure to phthalates (PAEs) is ubiquitous among Chinese neonates. PAEs entering the body will be transformed to various hydrolyzed and oxidated PAE metabolites (mPAEs). PAEs and mPAEs exposure may lead to adverse birth outcomes through disruption of multiple hormone signaling pathways, induction of oxidative stress, and alterations in intracellular signaling processes. In this study, the concentrations of 11 mPAEs in 318 umbilical cord serum samples from neonates in Jinan were quantified with HPLC-ESI-MS. Multiple linear regression, Bayesian kernel machine regression, and quantile g-computation models were utilized to investigate the effects of both individual mPAE and mPAE mixture on birth outcomes. Stratified analysis was performed to explore whether these effects were gender-specific. mPAE mixture was negatively associated with birth length (BL) z-score, birth weight (BW) z-score, head circumference (HC) z-score, and ponderal index (PI). Mono(2-ethylhexyl) phthalate (MEHP) manifested negative associations with BL(z-score), BW(z-score), HC(z-score), and PI, whereas mono(2-carboxymethylhexyl) phthalate (MCMHP) was negatively associated with BW(z-score) and PI within the mPAE mixture. Stratified analysis revealed that the negative associations between mPAE mixture and four birth outcomes were attenuated in female infants, while the positive impact of mono(2-ethyl-5carboxypentyl) phthalate (MECPP) on BL(z-score) and BW(z-score) could be detected only in females. In summary, our findings suggest that prenatal exposure to phthalates may be associated with intrauterine growth restriction, and these effects vary according to the gender of the infant.

Marine-Derived Alternariol Monomethyl Ether Alleviates Ovalbumin-Induced Food Allergy by Suppressing MAPK and NF-κB Signaling Pathways of Mast Cells.

The prevalence of food allergies has grown dramatically over the past decade. Recently, studies have shown the potential of marine substances to alleviate food allergies. We utilized a rat basophilic leukemia (RBL)-2H3 model to evaluate the antiallergic effects of alternariol monomethyl ether (AME) extracted from marine fungi Alternaria sp. Our results showed that AME attenuated food allergy symptoms in mice and reduced histamine release in serum. The population of mast cells in the spleen and mesenteric lymph nodes was considerably reduced. Moreover, in vitro assays also revealed that AME inhibited the release of ß-hexosaminidase and histamine. Transcriptomic analysis uncovered that AME regulated gene expression associated with mast cells. Additionally, Western blotting demonstrated that AME suppressed mast cell activation by modulating MAPK and NF-κB signaling pathways. Taken together, these findings provide a theoretical basis for the potential antiallergic use of marine-derived compounds in the development of functional foods.

Hepatotoxicity assessment investigations on PFASs targeting L-FABP using binding affinity data and machine learning-based QSAR model.

Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants that have been detected in various environmental media and human serum, but their safety assessment remains challenging. PFASs may accumulate in liver tissues and cause hepatotoxicity by binding to liver fatty acid binding protein (L-FABP). Therefore, evaluating the binding affinity of PFASs to L-FABP is crucial in assessing the potential hepatotoxic effects. In this study, two binding sites of L-FABP were evaluated, results suggested that the outer site possessed high affinity to polyfluoroalkyl sulfates and the inner site preferred perfluoroalkyl sulfonamides, overall, the inner site of L-FABP was more sensitive to PFASs. The binding affinity data of PFASs to L-FABP were used as training set to develop a machine learning model-based quantitative structure-activity relationship (QSAR) for efficient prediction of potentially hazardous PFASs. Further Bayesian Kernel Machine Regression (BKMR) model disclosed flexibility as the determinant molecular property on PFASs-induced hepatotoxicity. It can influence affinity of PFASs to target protein through affecting binding conformations directly (individual effect) as well as integrating with other molecular properties (joint effect). Our present work provided more understanding on hepatotoxicity of PFASs, which could be significative in hepatotoxicity gradation, administration guidance, and safer alternatives development of PFASs.

Integrated Bioinformatics Analysis for the Identification of Key lncRNAs, mRNAs, and Potential Drugs in Clear Cell Renal Cell Carcinomas.

Purpose: The overall survival of clear cell renal cell carcinoma (ccRCC) is poor. Markers for early detection and progression could improve disease outcomes. This study aims to reveal the potential pathogenesis of ccRCC by integrative bioinformatics analysis and to further develop new therapeutic strategies. Patients and Methods: RNA-seq data of 530 ccRCC cases in TCGA were downloaded, and a comprehensive analysis was carried out using bioinformatics tools. Another 14 tissue samples were included to verify the expression of selected lncRNAs by qRT-PCR. DGIdb database was used to screen out potential drugs, and molecular docking was used to explore the interaction and mechanism between candidate drugs and targets. Results: A total of 58 differentially expressed lncRNAs (DElncRNAs) and 660 differentially expressed mRNAs (DEmRNAs) were identified in ccRCC. LINC02038, FAM242C, LINC01762, and PVT1 were identified as the optimal diagnostic lncRNAs, of which PVT1 was significantly correlated with the survival rate of ccRCC. GO analysis of cell components showed that DEmRNAs co-expressed with 4 DElncRNAs were mainly distributed in the extracellular area and the plasma membrane, involved in the transport of metal ions, the transport of proteins across membranes, and the binding of immunoglobulins. Immune infiltration analysis showed that MDSC was the most correlated immune cells with PVT1 and key mRNA SIGLEC8. Validation analysis showed that GABRD, SIGLEC8 and CDKN2A were significantly overexpressed, while ESRRB, ELF5 and UMOD were significantly down-regulated, which was consistent with the expression in our analysis. Furthermore, 84 potential drugs were screened by 6 key mRNAs, of which ABEMACICLIB and RIBOCICLIB were selected for molecular docking with CDKN2A, with stable binding affinity. Conclusion: In summary, 4 key lncRNAs and key mRNAs of ccRCC were identified by integrative bioinformatics analysis. Potential drugs were screened for the treatment of ccRCC, providing a new perspective for disease diagnosis and treatment.

Identification of lower brominated bisphenol A analogs as the photooxidation products of tetrabromobisphenol A bis(2,3-dibromopropyl) ether (TBBPA-BDBPE).

The transformation products and mechanism of tetrabromobisphenol A (TBBPA) derivatives are still largely unknown compared with TBBPA. In this paper, sediment, soil and water samples (15 sites, 45 samples) collected in a river flowing through brominated flame retardant manufacturing zone were analyzed to determine TBBPA derivatives, byproducts, and transformation products. TBBPA derivatives and byproducts were detected with concentrations ranging from none detection to 1.1 × 104 ng/g dw and with detection frequencies of 0-100 % in all samples. The concentrations of TBBPA derivatives such as TBBPA bis(2,3-dibromopropyl) ether (TBBPA-BDBPE) and TBBPA bis(allyl ether) in sediment and soil samples were higher than that of TBBPA. In addition, the occurrence of various unknown bromobisphenol A allyl ether analogs in the samples was further confirmed by using 11 synthesized analogs, which might be produced during the waste treatment process of the factories. The possible transformation pathways of TBBPA-BDBPE were revealed for the first time by using UV/base/persulfate (PS) as designed photooxidation waste treatment system in the laboratory. Ether bond cleavage, debromination, and ß-scission contributed to the transformation of TBBPA-BDBPE and the occurrence of transformation products in the environment. The concentrations of the transformation products of TBBPA-BDBPE ranged from none detection to 3.4 × 102 ng/g dw. These data provide new insights into the fate of TBBPA derivatives in environmental compartments.

Human health risk assessment of 6:2 Cl-PFESA through quantitative in vitro to in vivo extrapolation by integrating cell-based assays, an epigenetic key event, and physiologically based pharmacokinetic modeling.

Human health risk assessment of chemicals is essential but often relies on time-consuming and animal and labor-extensive procedures. Here, we develop a population-based, quantitative in vitro to in vivo extrapolation (QIVIVE) approach which depended on cellular effects monitored by in vitro assays, considered chemical internal concentration determined by LC-MS/MS, extrapolated into in vivo target tissue concentration through physiologically based pharmacokinetic (PBPK) modelling, and assessed populational health risk using in silico modelling. By applying this QIVIVE approach to 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), as a representative of the emerging pollutants, we find that 6:2 Cl-PFESA disturbed lipid homeostasis in HepG2 cells through enhancement of lipid accumulation and fatty acid ß-oxidation, during which miR-93-5p served as a key event towards toxicity and thus, could serve as an efficient toxicity marker for risk assessment; further, the disruption potency of lipid homeostasis of 6:2 Cl-PFESA for the most of studied populations in China might be of moderate concern. Together, our approach improved the reliability of QIVIVE during human health risk assessment, which can readily be used for other chemicals.

Binding, activity and risk assessment of bisphenols toward farnesoid X receptor pathway: In vitro and in silico study.

Bisphenols have been identified as emerging environmental pollutants of high concern with potential adverse effects through interactions with receptor-mediated pathways. However, their potential mechanism of action and health risks through the farnesoid X receptor (FXR) pathway remain poorly understood. In the present study, we aimed to explore the potential disruption mechanism of bisphenols through the FXR signalling pathway. Receptor binding assays showed that bisphenols bound to FXR directly, with tetrabromobisphenol A (TBBPA; 34-fold), tetrachlorobisphenol A (TCBPA; 8.7-fold), bisphenol AF (BPAF; 2.0-fold), and bisphenol B (BPB; 1.9-fold) showing a significantly stronger binding potency than bisphenol A (BPA). In receptor transcriptional activity assays, bisphenols showed agonistic activity toward FXR, with BPAF, BPB, and bisphenol F (BPF) exhibiting higher activity than BPA, but TBBPA and TCBPA showing significantly weaker activity than BPA. Molecular docking results indicated that the number of hydrogen bonds dictated their binding strength. Intracellular concentrations of bisphenols were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in receptor activity assays, and it was found that the intracellular concentrations of TBBPA and TCBPA were 40-fold lower than those of BPA. Using the bioactivity concentrations in the FXR receptor activity assay, the liver concentrations of bisphenols were estimated using physiologically-based pharmacokinetic (PBPK) models through their serum concentrations, and the hazard quotient (HQ) values were calculated. The results suggest a potentially high concern for the risk of activating the FXR pathway for some populations with high exposure. Overall, these results indicate that bisphenols can bind to and activate FXR receptors, and that the activation mechanism is dependent on cellular uptake and binding strength. This study provides important information regarding the exposure risk of bisphenols, which can promote the development of environmentally friendly bisphenols.

Long term toxicities following developmental exposure to perfluorooctanoic acid: Roles of peroxisome proliferation activated receptor alpha.

Perfluorooctanoic acid (PFOA) is a widespread persistent organic pollutant. Fertile chicken eggs were exposed to PFOA and incubated to hatch. At three time points post hatch (0-, 1- and 3-months old), chickens were subjected to electrocardiography and sacrificed. Serum was subjected to LC-MS/MS for PFOA concentration, and organs were subjected to histopathological assessments. Additionally, PPARα-silencing lentivirus was co-applied with PFOA exposure, and the corresponding phenotypes were evaluated. Western blotting was performed to assess expressions of FABPs and pSMAD2 in heart and liver samples. Considerable amount of PFOA were detected in hatchling chicken serum, but not in one-month-old or three-month-old chicken serum. PFOA exposure resulted in developmental cardiotoxicity and hepatotoxicity in hatchling chickens. Meanwhile, one-month-old chickens still exhibited elevated heart rate, but classical cardiac remodeling (thicker right ventricular wall) were observed in exposed animals. Three-month-old chickens exhibited similar results as one-month-old ones. PPARα silencing only had partial protective effects in hatchling chickens, but the protective effects seemed to increase as chickens aged. Western blotting results indicated that L-FABP was involved in PFOA-induced hepatotoxicity, while pSMAD2 was involved in PFOA-induced cardiotoxicity. In summary, developmental exposure to PFOA resulted in persistent cardiotoxicity, but not hepatotoxicity. PPARα participates in both cardiotoxicity and hepatotoxicity.

Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues.

Triclosan (TCS) is a widespread antimicrobial agent that is associated with many adverse health outcomes. Its gut toxicity has been attributed to the molecular modifications mediated by commensal microbes, but microbial transformations of TCS derivatives in the gut lumen are still largely unknown. Aromatic hydroxylation is the predominant oxidative metabolism of TCS that linked to its toxicological effects in host tissues. Here, we aimed to reveal the biological fates of hydroxyl-TCS (OH-TCS) in the colon, where intestinal microbes mainly reside. Unlike the profiles generated via host metabolism, OH-TCS species remain unconjugated in human stools from a cohort study. Through tracking molecular compositions in mouse intestinal tract, elevated abundance of free-form OH-TCS while reduced abundance of conjugated forms was observed in the colon digesta and mucosa. Using antibiotic-treated and germ-free mice, as well as in vitro approaches, we demonstrate that gut microbiota-encoded enzymes efficiently convert glucuronide/sulfate-conjugated OH-TCS, which are generated from host metabolism, back to their bioactive free-forms in colon tissues. Thus, host-gut microbiota metabolic interactions of TCS derivatives were proposed. These results shed light on the crucial roles of microbial metabolism in TCS toxicity, and highlight the importance of incorporating gut microbial transformations in health risk assessment of environmental chemicals.

Thin-layer chromatography coupled with HPLC-DAD/UHPLC-HRMS for target and non-target determination of emerging halogenated organic contaminants in animal-derived foods.

In this study, a simple, solvent-saving, and sensitive method was established using high-performance liquid chromatography coupled with high-resolution mass spectrometry to quantitively determine 16 emerging halogenated organic contaminants (HOCs), including polyhalogenated carbazoles, halogenated phenols, and tetrabromobisphenol-A analogs, and to qualitatively identify non-target HOCs in animal-derived food samples. The sample extracts were physically frozen to remove most lipids and further purified by thin-layer chromatography according to the targets polarity. The method detection limit and method quantification limit of 16 HOCs were in the range of 0.003-9.168 and 0.010-30.601 ng·g-1 dry weight, respectively. The recoveries were within 69.1-111.0 %, the intra/inter-day precisions were 0.1-6.1 % and 0.1-6.7 %, and the matrix effects were between -12.1 and 10.8 %, all within the acceptable range. Finally, 16 HOCs were detected in nine actual samples in range of not detected-307.22 ng·g-1 dry weight. Moreover, five bromides and two chlorides were identified by using non-target analysis in animal-derived foods.

Insight into the dynamic microbial community and core bacteria in composting from different sources by advanced bioinformatics methods.

Microbial communities are important for high composting efficiency and good quality composts. This study was conducted to compare the changes of physicochemical and bacterial characteristics in composting from different raw materials, including chicken manure (CM), duck manure (DM), sheep manure (SM), food waste (FW), and vegetable waste (VW). The role and interactions of core bacteria and their contribution to maturity in diverse composts were analyzed by advanced bioinformatics methods combined sequencing with co-occurrence network and structural equation modeling (SEM). Results indicated that there were obviously different bacterial composition and diversity in composting from diverse sources. FW had a low pH and different physiochemical characteristics compared to other composts but they all achieved similar maturity products. Redundancy analysis suggested total organic carbon, phosphorus, and temperature governed the composition of microbial species but key factors were different in diverse composts. Network analysis showed completely different interactions of core bacterial community from diverse composts but Thermobifida was the ubiquitous core bacteria in composting bacterial network. Sphaerobacter and Lactobacillus as core genus were presented in the starting mesophilic and thermophilic phases of composting from manure (CM, DM, SM) and municipal solid waste (FW, VW), respectively. SEM indicated core bacteria had the positive, direct, and the biggest (> 80%) effects on composting maturity. Therefore, this study presents theoretical basis to identify and enhance the core bacteria for improving full-scale composting efficiency facing more and more organic wastes.

Bioconversion of food waste to crayfish feed using solid-state fermentation with yeast.

In order to realize the value-added utilization of food waste (FW), the preparation of crayfish (Procambarus clarkii) feed by yeast fermentation was investigated. Firstly, the suitable fermentation condition was obtained through a single factor experiment as follows: the initial moisture of the FW was adjusted to 60% with bran and inoculated with a 2% yeast mixture (Saccharomyces cerevisiae, Candida utilis, and Yarrowia lipolytica, 3:2:1) followed by aerobic solid-state fermentation for 7 days. The crude protein and acid-soluble protein contents in the fermented feed were 25.14% and 5.16%, which were increased by 8% and 140.67%, respectively. The crude fat content was 0.74%, decreased by 68.29%. The content of antioxidant glutathione (571.78 µg/g) increased 63.33%, and the activities of protease and amylase increased nearly 9 and 3 times, respectively. The maximum degradation rates of aflatoxin B1, zearalenone, and deoxynivalenol were 63.83%, 77.52%, and 80.16%, respectively. The fermented feeds were evaluated by substituting (0%, 10%, 30%, 50%, and 100%) commercial diet for crayfish (30-day culture period). When the replacement proportion was 30%, the weight gain of crayfish reached 44.87% (initial body weight 13.98 ± 0.41 g), which was significantly increased by 10.25% compared with the control (p = 0.0005). In addition, the lysozyme and SOD enzyme activities in crayfish hepatopancreas were also increased significantly. Our findings suggest that yeast-fermented feed from FW can replace 30% of crayfish's conventional diet, which may improve crayfish's antioxidant capacity and enhance non-specific immunity by providing molecules such as glutathione.

Nontarget Identification of Novel Per- and Polyfluoroalkyl Substances in Cord Blood Samples.

Per- and polyfluoroalkyl substances (PFASs) can penetrate the placental barrier and reach embryos through cord blood, probably causing adverse birth outcomes. Therefore, novel PFASs identification in cord blood and their relationships with birth outcomes are essential to evaluate prenatal exposure risk of PFASs. Herein, 16 legacy and 12 novel PFASs were identified in 326 cord blood samples collected from pregnant women in Jinan, Shandong, China. The presence of perfluoropolyether carboxylic acids, hydrogen-substituted polyfluoroetherpropane sulfate, and 3:3 chlorinated polyfluoroalkyl ether alcohol in cord blood was reported for the first time. Two extensive OECD (Organization for Economic Co-operation and Development)-defined PFASs named fipronil sulfone and 2-chloro-6-(trifluoromethyl)pyridine-3-ol were also identified. Quantification results showed that the emerging and OECD-defined PFASs separately accounted for 9.4 and 9.7% of the total quantified PFASs, while the legacy PFOA, PFOS, and PFHxS were still the most abundant PFASs with median concentrations of 2.12, 0.58, and 0.37 ng/mL, respectively. Several PFASs (C9-C12 PFCAs, C6-C8 PFSAs, and 6:2 Cl-PFESA) showed significantly higher levels for older maternities than younger ones. PFHxS levels were positively associated with birth weight and ponderal index (p < 0.05). The results provide comprehensive information on the presence and exposure risks of several novel PFASs during the early life stage.

Inhaled tire-wear microplastic particles induced pulmonary fibrotic injury via epithelial cytoskeleton rearrangement.

Tire wear microplastic particles (TWMPs) are emerging microplastic pollutants that have gained increasing attention lately. However, the health effect of inhaled airborne TWMPs has never been explored before and may already be included in particulate matter morbidity and mortality. Here, we endeavored to address the preliminary study of TWMP inhalation-induced pulmonary toxic effects and its epigenetic mechanisms in C57BL/6 mice. As a result, restricted ventilatory dysfunction and fibrotic pathological changes were observed in TWMP-treaded mice. Further research found that attenuation of miR-1a-3p plays an important role in TWMP-induced lung injury. Results from in vitro study confirmed that cytoskeleton regulatory gene twinfilin-1 was one of the target genes of miR-1a-3p, and involved in cytoskeleton rearrangement caused by TWMP exposure. Mechanistically, miR-1a-3p inhibited the F-actin formation by targeting cytoskeletal regulatory proteins twinfilin-1, leading to TWMP-induced pulmonary fibrotic injury. While we are in the very early stages of explaining the role of epigenetics in TWMP-induced lung injury, the potential for the use of epigenetic marks as biomarkers is high and discoveries made in this field will likely bring us closer to better understanding this crucial mechanism.

Occurrence and distribution of organophosphate flame retardants in seawater and sediment from coastal areas of the East China and Yellow Seas.

Organophosphates (OPEs) are manmade organic pollutants that are widely used as flame retardants, plasticizers, and antifoaming and hydraulic agents. In this study, seven OPEs in seawater and sediment from the Yellow Sea and East China Sea were determined to study the distribution and diffusion behavior, and to evaluate the environmental risks. The ΣOPEs in the seawater and sediments ranged from below the method detection limit (1.0, indicating high ecological risks to aquatic organisms.

Hexafluoropropylene oxide dimer acid (HFPO-DA) induced developmental cardiotoxicity and hepatotoxicity in hatchling chickens: Roles of peroxisome proliferator activated receptor alpha.

Hexafluoropropylene oxide dimer acid (HFPO-DA) is a perfluorooctanoic acid (PFOA) substitute. In the current study, potential developmental cardiotoxicity and hepatotoxicity following HFPO-DA exposure in chicken embryo has been investigated, focusing on the roles of peroxisome proliferator activated receptor alpha (PPARα), the major molecular target in PFOA-induced toxicities. HFPO-DA was exposed to fertile chicken eggs via air cell injection, morphology and function of the target organs (heart and liver) in hatchlings were investigated with histopathology and electrocardiography, and the serum levels of HFPO-DA had been measured with quadrupole-time of flight liquid chromatograph-mass spectrometer (Q-TOF LC/MS). Additionally, lentivirus-mediated in ovo PPARα silencing was used to assess the roles of PPARα in HFPO-DA induced developmental toxicities. The results indicated that developmental exposure to HFPO-DA induced developmental cardiotoxicity, including thinned right ventricular wall and elevated heart rates, similar to those observed with PFOA exposure, as well as developmental hepatotoxicity in the form of steatosis. Silencing of PPARα alleviated such effects, suggesting participation of PPARα in HFPO-DA induced developmental toxicities in chicken embryo. Moreover, enhanced expression of PPARα downstream genes, cluster of differentiation 36 (CD36) and enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), were observed in HFPO-DA exposed animal heart tissues, which can be abolished by PPARα silencing. On the other hand, liver-type fatty acid binding protein (L-FABP) and CD36 expression were effectively enhanced in exposed liver tissues, but not EHHADH, suggesting differential mechanism of toxicity in heart and liver tissues. In summary, developmental exposure to HFPO-DA induced developmental cardiotoxicity and hepatotoxicity in hatchling chickens similar to PFOA, and PPARα still participates in such toxicities, with some differential downstream gene regulations in different organs. Further investigation on HFPO-DA-induced developmental toxicities is guaranteed.