The generation of reactive oxygen species (ROS) is an important mechanism of nanomaterial toxicity. We found that Prussian blue nanoparticles (PBNPs) can effectively scavenge ROS via multienzyme-like activity including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activity. Instead of producing hydroxyl radicals (•OH) through the Fenton reaction, PBNPs were shown to be POD mimetics that can inhibit •OH generation. We theorized for the first time that the multienzyme-like activities of PBNPs were likely caused by the abundant redox potentials of their different forms, making them efficient electron transporters. To study the ROS scavenging ability of PBNPs, a series of in vitro ROS-generating models was established using chemicals, UV irradiation, oxidized low-density lipoprotein, high glucose contents, and oxygen glucose deprivation and reperfusion. To demonstrate the ROS scavenging ability of PBNPs, an in vivo inflammation model was established using lipoproteins in Institute for Cancer Research (ICR) mice. The results indicated that PBNPs hold great potential for inhibiting or relieving injury induced by ROS in these pathological processes.

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Ten to twenty percent of newly diagnosed glioblastoma (GBM) patients initially present with multiple lesions, termed multifocal or multicentric GBM (M-GBM). The prognosis of these patients is poorer than is that of solitary GBM (S-GBM) patients. However, it is unknown whether multifocality has a genetic, epigenetic, or molecular basis. Here, we identified the genetic and epigenetic characteristics of M-GBM by performing a comprehensive analysis of multidimensional data, including imaging, genetic, epigenetic, and gene expression profiles, from 30 M-GBM cases in The Cancer Genome Atlas (TCGA) database and comparing the results with those of 173 S-GBM cases. We found that M-GBMs had no IDH1, ATRX, or PDGFRA mutations and were significantly associated with the mesenchymal subtype. We also identified the CYB5R2 gene to be hypo-methylated and overexpressed in M-GBMs. The expression level of CYB5R2 was significantly associated with patient survival in two major independent GBM cohorts, totaling 758 cases. The IDH1 mutation was markedly associated with CYB5R2 promoter methylation, but the survival influence of CYB5R2 was independent of IDH1 mutation status. CYB5R2 expression was significantly associated with collagen maturation and the catabolic process and immunoregulation pathways. These results reveal that M-GBMs have some underlying genetic and epigenetic characteristics that are associated with poor prognosis and that CYB5R2 is a new epigenetic marker for GBM prognosis.

Hydroxybenzoic acid esters (parabens) are used as preservatives in foods, cosmetics, and pharmaceuticals, which results in the exposure of humans to these compounds. Parabens and its metabolite, p-hydroxybenzoic acid (p-HB) are excreted from urine in free and conjugated forms. In this study, free and total forms (free plus conjugated) of parabens and their common metabolite, p-HB, were measured in urine samples collected from U.S. children (n = 40), Chinese children (n = 70), and Chinese adults (n = 26). The median concentrations of the sum of 6 parabens (Σparabens) in urine from U.S. and Chinese children were 54.6 and 10.1 ng/mL, respectively. The median concentration of urinary parabens measured for Chinese adults was 33.2 ng/mL, which was lower than that reported for U.S. adults. Elevated concentrations of parabens (1000-10,000 ng/mL) were found in urine from some Chinese adult females. Parabens were present predominantly (>90%) as conjugated species in urine. Among the six parabens analyzed, methyl paraben (MeP) and propyl paraben (PrP) were the predominant compounds, which accounted for 57-98% and 1.4-12%, respectively, of the total concentrations. A significant positive correlation was found between the concentrations of MeP and PrP. The geometric mean (GM) concentration of p-HB was 1380 and 2370 ng/mL for Chinese children and adults, respectively. The GM concentrations of p-HB in urine from U.S. children were 752 ng/mL for girls and 628 ng/mL for boys, which were 2-3 times lower than the concentrations determined for Chinese children. There was a significant difference in the ratios of concentrations of Σparabens and p-HB between demographic groups, which suggested the existence of various exposure routes to parabens. Based on the concentrations of urinary parabens and p-HB, the daily intake (DI) of MeP and PrP was estimated. The GM DI(MeP) estimated for Chinese children was 0.5-0.7 mg/day, which was similar to those determined for U.S. children. The GM DI(PrP) (0.2-0.5 mg/day) estimated for Chinese children was 20- to 50-fold higher than the value determined for U.S. children (0.01 mg/day). The highest exposure to parabens was found for Chinese adult females, with GM DI(MeP) and DI(PrP) of 5.9 and 1.2 mg/day, respectively. Elevated exposure to PrP was found in some Chinese adult females (27 mg/day) and children (11 mg/day).

Research funding is provided by the Ministry of Science and Technology of China [2012CB944704; 2012CB966702], the National Natural Science Foundation of China [Grant number: 31171429] and Beijing Advanced Innovation Center for Structural Biology. The authors declare no conflict of interest.