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These results of this study are of significant importance to better understand the environmental geochemical behavior of Cr(VI) with the interactions between soil minerals and microorganisms.3-Acetyldeoxynivalenol (3-Ac-DON), the acetylated derivative of deoxynivalenol (DON), has been reported to be coexisted with DON in various cereal grains. Ingestion of grain-based food products contaminated by 3-Ac-DON might exert deleterious effects on the health of both humans and animals. However, the biological toxicity of 3-Ac-DON on macrophages and the underlying mechanisms remain largely unknown. In the present study, we showed that RAW 264.7 macrophages treated with 0.75 or 1.50 μg/mL of 3-Ac-DON resulted in DNA damage and the related cell cycle arrest at G1 phase and cell death, activation of the ribotoxic stress and the endoplasmic reticulum (ER) stress responses. The 3-Ac-DON-induced cell death was accompanied by a protective autophagy, because gene silencing of Atg5 using the small interfering RNA enhanced cell death. Results of further experiments revealed a role for lysosomal membrane permeabilization in the 3-Ac-DON triggered inhibition of autophagic flux. Additional work also showed that increased lysosomal biogenesis and leakage of cathepsin B (CTSB) from lysosomes to cytosol was critical for the 3-Ac-DON-induced cell death. Importantly, 3-Ac-DON-induced DNA damage and cell death were rescued by CA-074-me, a CTSB inhibitor. Collectively, these results indicated a critical role of lysosomal membrane permeabilization in the 3-Ac-DON-induced apoptosis of RAW 264.7 macrophages.Background Child abuse and neglect (CAN) cost United States society $136 billion to $428 billion annually. Preventive interventions that reduce CAN may improve people's lives and generate economic benefits to society, but their magnitude is likely to vary greatly with assumptions about victim costs avoided through intervention. Objective We examined the implications of different assumptions about avoided victim costs in a benefit-cost analysis of Promoting First Relationships® (PFR), a 10-session attachment and strengths-based home visiting intervention. Participants and setting Participants were 247 child protection-involved but intact families in Washington State randomized to receive PFR (n = 124) or resource and referral (n = 123). Methods We monetized intervention effects on out-of-home placements and implicit effects on CAN and calculated net present values under three scenarios (1) benefits from avoided system costs, (2) additional benefits from avoided tangible victim costs, and (3) additional benefits from avoided tangible and intangible quality-of-life victim costs. For scenarios 2 and 3, we varied the CAN effect size and estimated the effect size at which PFR was reliably cost beneficial. Results PFR's societal net benefit ranged from $1 (scenario 1) to $5514 - $25,562 (scenario 2) and $7004 - $32,072 (scenario 3) (2014 USD). In scenarios 2 and 3, PFR was reliably cost beneficial at a CAN effect size of approximately -0.25. Conclusions PFR is cost beneficial assuming tangible victim costs are avoided by PFR. Research into the long-term health and economic consequences of reducing CAN in at-risk populations would contribute to comprehensive, accurate benefits models.Atmospheric fine particulate matter exposure (PM2.5) can increase the incidence and mortality of heart disease, and raise the risk of fetal congenital heart defect, which have recently drawn much attention. In this study, C57BL/6 mice were exposed to PM2.5 (approximately equivalent to 174 μg/m3) by intratracheal instillation during the gestation. After birth, 10 weeks old offspring mice were divided into four groups male exposed group (ME), female exposed group (FE), male control group (MC), female control group (FC). The pathological injury, pro-inflammatory cytokines, histone acetylation levels, and expressions of GATA-binding protein 4 (GATA4) and downstream genes were investigated. The results showed that exposure to PM2.5 in utero increased pathological damage and TNF-α and IL-6 levels in hearts of offspring mice, and effects in ME were more serious than FE. Notably, GATA4 protein levels in hearts in ME were significantly lower than that of MC, accompanied by down-regulation of histone acetyltransferase (HAT)-p300 and up-regulation of histone deacetylase-SIRT3. As GATA4 downstream genes, ratios of β-MHC gene expression to α-MHC significantly raised in ME relative to the MC. Results of chromatin immunoprecipitation (ChIP)-qPCR assay found that binding levels of acetylated histone 3 lysine 9 (H3K9ac) in GATA4 promoter region in the hearts of ME or FE were markedly decreased compared with their corresponding control groups. It suggested that maternal exposure to PM2.5 may cause cardiac injury in the offspring, heart damage of male mice was worse than female mice, in which process HAT-p300, H3K9ac, transcription factor GATA4 may play an important regulation role.The present study focuses on the determination of the occurrence and levels of per- and polyfluoroalkyl substances (PFASs) in the drinking and source water from the Philippines and Thailand. A total of 46 samples (18 commercial bottled waters, 5 drinking water from vending machine (re-fill stations) and 23 source water) were analyzed using liquid chromatography with tandem high-resolution mass spectrometry. Using the targeted method, 12 different PFASs were detected in the drinking water samples with total quantifiable PFASs (∑PFASs) levels ranging from 7.16 to 59.49 ng/L; 15 PFASs were detected in source water with ∑PFASs ranging from 15.55 to 65.65 ng/L. A 100% detection frequency was observed for perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorosulfonic acid (PFOS) in all water samples. Six other PFASs, not included in the targeted analysis, were detected using the suspect screening approach. selleck chemical For the first time, the presence of 2-(N-methylperfluorooctanesulfonamido) acetic acid (N-MeFOSAA) in drinking water is reported, and 3 novel PFASs (C5H5OF8, C6H4O2F6, and C9H2O2F16) were detected using suspect screening in source water. Combined results from target and suspect screening analysis showed that PFASs detected were predominantly (52%) short-chain (with fluorinated alkyl chain of ≤6) which could be explained by their high mobility in the environment. The detected PFASs levels in drinking water will not likely pose immediate health risk to consumers according to US EPA health advisory for PFOS and PFOA of 70 ng/L, but inclusion of bottled and drinking water from re-fill stations in monitoring programs is warranted.
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