PFOS impairs cardiac function and energy metabolism under high-fat diet: Insights into role of circulating macrophage emphasized by exposure distribution.

Per- and polyfluoroalkyl substances (PFAS), widely utilized in consumer products, have been linked to an increased risk of cardiovascular disease (CVD). With the increasing prevalence of high-fat diet, a common risk factor for CVD, the PFAS exposed populations who consume a high-fat diet will inevitably grow and may have a higher CVD risk. However, the potential toxic effect and mode of action remain elusive. We constructed a mouse model orally exposed to perfluorooctane sulfonate (PFOS), a prototypical PFAS, and fed a high-fat diet. PFOS exposure induced cardiomyopathy and structural abnormalities in the mice heart. Moreover, a characteristic of energy metabolism remodeling from aerobic to anaerobic process was observed. Interestingly, PFOS was rarely detected in heart but showed high level in serum, suggesting an indirect route of action for PFOS-caused cardiac toxicity. We further demonstrated that PFOS-caused circulating inflammation promoted metabolic remodeling and contractile dysfunction in cardiomyocytes. Wherein, PFOS stimulated the release of IL-1ß from circulating proinflammatory macrophages mediated by NF-κB and caspase-1. This study provides valuable data on PFAS-induced cardiac risks associated with exposed populations with increasing high-fat diet consumption, highlighting the significance of indirect pathways in PFOS's impact on the heart, based on the distribution of internal exposure.

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.

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.

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.

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.

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.

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.

Identification of Novel Hydrogen-Substituted Polyfluoroalkyl Ether Sulfonates in Environmental Matrices near Metal-Plating Facilities.

Environmental occurrence and behaviors of 6:2 chlorinated polyfluoroalkyl ether sulfonate (Cl-6:2 PFESA, with trade name F-53B) have been receiving increased attention recently. Nevertheless, its potential fates under diversified conditions remain concealed. In this study, susceptibility of Cl-6:2 PFESA to reductive dehalogenation was tested in an anaerobic super-reduced cyanocobalamin assay. A rapid transformation of dosed Cl-6:2 PFESA was observed, with a hydrogen-substituted polyfluoroalkyl ether sulfonate (1H-6:2 PFESA) identified as the predominant product by a nontarget screening workflow. With the aid of laboratory-purified standards, hydrogen-substituted PFESA analogues (i.e., 1H-6:2 and 1H-8:2 PFESA) were further found in river water and sediment samples collected from two separate regions near metal-plating facilities. Geometric mean concentrations of 560 pg/L (river water) and 11.1 pg/g (sediment) for 1H-6:2 PFESA and 11.0 pg/L (river water) and 7.69 pg/g (sediment) for 1H-8:2 PFESA were measured, and both analytes consisted average compositions of 1% and 0.1% among the 18 monitored per- and polyfluoroalkyl sulfonate and carboxylate pollutants, respectively. To our knowledge, this is the first to report existence of polyfluoroalkyl sulfonates with both hydrogen and ether functional group in the environment.

Chlorinated Polyfluoroalkyl Ether Sulfonic Acids in Marine Organisms from Bohai Sea, China: Occurrence, Temporal Variations, and Trophic Transfer Behavior.

F-53B, the commercial product of chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs), has been used in Chinese chrome plating industry for 30 years, and was recently identified in the environment, which caused great concerns. So far, limited investigations have been performed on their environmental occurrence, fate and impact. In this study, we demonstrated the wide occurrence of Cl-PFESAs and their trophic transfer behavior in marine organisms from Chinese Bohai Sea. 6:2 Cl-PFESA (<0.016-0.575 ng/g wet weight) was the dominant congener, and 8:2 Cl-PFESA (<0.022-0.040 ng/g) was occasionally detected. Compared to other perfluoroalkyl and polyfluoroalkyl substances (PFASs) of concern, the levels of Cl-PFESAs were relatively lower in marine organisms. Based on the comparative analysis of Cl-PFESA contamination in mollusk samples collected in 2010-2014, both the concentrations and detection frequencies of Cl-PFESAs tended to increase in this region. And this kind of chemicals were more vulnerable to be accumulated in marine organisms at relatively higher trophic levels. Similar to perfluorooctanesulfonate (PFOS) and the long chain perfluorinated carboxylates (PFCAs), 6:2 Cl-PFESA could be magnified along the food chain. Accordingly, the potential threat might be posed to the wildlife and human beings due to unintended exposure to Cl-PFESAs.

Identification of Novel Polyfluorinated Ether Sulfonates as PFOS Alternatives in Municipal Sewage Sludge in China.

A 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFAES) with the trade name F-53B, is an alternative to perfluorooctanesulfonate (PFOS) in electroplating industry that is uniquely used in China. It was developed as a mist suppressant initially in the 1970s, but the environmental behaviors and potential adverse effects of the 6:2 Cl-PFAES have only recently been investigated. In this work, the occurrence and distribution of perfluoroalkyl sulfonate (PFSA), fluorotelomer sulfonate (FTSA), and PFAES analogues were investigated in municipal sewage sludge samples collected around China. Perfluorobutane, perfluorohexane, perfluorooctane, and perfluorodecanesulfonates, 6:2 and 8:2 FTSAs, and the emerging 6:2 Cl-PFAES were detected. Moreover, 8:2 and 10:2 Cl-PFAESs were identified for the first time as new polyfluorinated contaminants using high resolution mass spectrometry. These fluorinated analytes were further quantified with the aid of commercial and laboratory-purified standards. PFOS was the predominant contaminant with a geometric mean (GM) value of 3.19 ng/g dry weight (d.w.), which was subsequently followed by 6:2 Cl-PFAES and 8:2 Cl-PFAES (GM: 2.15 and 0.50 ng/g d.w., respectively). Both 6:2 and 8:2 Cl-PFAES were positively detected as the major components in the F-53B commercial product, and discrete 6:2 Cl-PFAES/8:2 Cl-PFAES ratios in the product and sludge samples might suggest 8:2 Cl-PFAES had enhanced sorption behavior in the sludge due to the increase in hydrophobicity.

Arsenate and cadmium co-adsorption and co-precipitation on goethite.

Arsenate (As(V), AsO4(3-)) and cadmium (Cd) are among the toxic elements of most concern. Their sorption behaviors on goethite were studied by batch experiments (pH edges, isotherms and kinetics) and X-ray diffraction (XRD). Arsenic coordination environment was explored by X-ray absorbance fine structure (EXAFS) analysis. Sorption isotherms of both As(V) and Cd on goethite could be divided into the adsorption-dominated and precipitation-dominated parts, while their sorption showed different pH-dependency and sorption reversibility. Cadmium adsorption was enhanced in the presence of AsO4(3-), which could be explained by the decrease in the electrostatic potential due to the sorption of AsO4(3-) and the formation of a ternary Cd-As(V)-goethite complex. Based on the EXAFS study, AsO4(3-) adsorbed on goethite mainly formed bidentate-binuclear complex. The high loadings of Cd changed the As(V)-Fe distance and its coordination number. However, Cd did not affect the As(V) adsorption amount in the adsorption-dominated region. When As(V) and Cd formed co-precipitates, their sorption amounts were both increased. The formation of co-precipitates decreased the mobility of Cd but increased the mobility of As(V) because less As(V) was sorbed on goethite through surface complexation. This study will provide better understandings on As(V) and Cd transport and useful information on their remediation strategies.

Novel IL31RA gene mutation and ancestral OSMR mutant allele in familial primary cutaneous amyloidosis.

Primary cutaneous amyloidosis (PCA) is an itchy skin disorder associated with amyloid deposits in the superficial dermis. The disease is relatively common in Southeast Asia and South America. Autosomal dominant PCA has been mapped earlier to 5p13.1-q11.2 and two pathogenic missense mutations in the OSMR gene, which encodes the interleukin-6 family cytokine receptor oncostatin M receptor beta (OSMRbeta), were reported. Here, we investigated 29 Taiwanese pedigrees with PCA and found that 10 had heterozygous missense mutations in OSMR: p.D647V (one family), p.P694L (six families), and p.K697T (three families). The mutation p.P694L was associated with the same haplotype in five of six families and also detected in two sporadic cases of PCA. Of the other 19 pedigrees that lacked OSMR pathology, 8 mapped to the same locus on chromosome 5, which also contains the genes for 3 other interleukin-6 family cytokine receptors, including interleukin-31 receptor A (IL31RA), which can form a heterodimeric receptor with OSMRbeta through interleukin-31 signaling. In one family, we identified a point mutation in the IL31RA gene, c.1562C>T that results in a missense mutation, p.S521F, which is also sited within a fibronectin type III-like repeat domain as observed in the OSMR mutations. PCA is a genetically heterogeneous disorder but our study shows that it can be caused by mutations in two biologically associated cytokine receptor genes located on chromosome 5. The identification of OSMR and IL31RA gene pathology provides an explanation of the high prevalence of PCA in Taiwan as well as new insight into disease pathophysiology.