α-Tocopherolquinone

Atmospheric polycyclic aromatic hydrocarbons (PAHs) and their derivatives are a global problem that influences the environment and threatens human health. To investigate the characteristics, sources, and health risk assessment of PM_2.5-bound PAHs and their derivatives, PM_2.5 were collected at an urban site in Zibo from November 5 to December 26, 2020, and the concentrations of 16 conventional PAHs, nine NPAHs, and five OPAHs in PM_2.5 were analyzed using gas chromatography-mass spectrometry. Source apportionment of PAHs and their derivatives was conducted using diagnostic ratios and a PMF model, and the health risks of PAHs and their derivatives to adult men and women were evaluated using the source-dependent incremental lifetime cancer risk (ILCR) model. The results showed that the average concentrations of ∑₁₆pPAHs, ∑₉NPAHs, and ∑₅OPAHs in PM_2.5 of Zibo City during the sampling period were (41.61 ± 13.40), (6.38 ± 5.70), and (53.20 ± 53.47) ng·m^-3, respectively. The concentrations of the three PAHs increased significantly after heating, which were 1.31, 2.04, and 5.24 times larger than those before heating. During the sampling period, Chr, BaP, and BaA were the dominant components of pPAHs; 9N-Ant and 2N-Flt + 3N-Flt were the dominant components of NPAHs; and ATQ and BZO were the dominant components of OPAHs. Source apportionment results showed that motor vehicles were the main source of PAHs and their derivatives in PM_2.5 before heating, whereas after heating, the main sources were the mixed source of coal and biomass combustion and secondary formation. The total BaP equivalent (TEQ) was 14.5 ng·m^-3 during the sampling period, and the TEQ increased significantly after heating, which was approximately 1.2 times of that before heating. Assisted by the individual PAH source apportionment results, the ILCR of PM_2.5-boundPAHs and NPAHs in Zibo City had a certain potential carcinogenic risk for adult males (1.06 × 10^-5) and females (9.32 × 10^-6). Among them, the health risks of PAHs from gasoline vehicles, diesel vehicles, and coal/biomass combustion were significantly higher than those from other emission sources.

This study aimed to prepare and assess atovaquone (ATQ)-loaded exosomes (EXO-ATQ) against Toxoplasma gondii to improve their therapeutic activities on acute and chronic phases of murine toxoplasmosis. Exosomes were isolated from a mouse macrophage cell line (J774A.1). The isolated exosomes were loaded with ATQ (EXO-ATQ), applying the co-incubation method. In vitro efficacy of EXO-ATQ against T. gondii infection was assessed in Vero cell culture. An in vivo experiment was carried out in BALB/c mice infected with RH (acute strain) and Tehran (chronic strain) of T. gondii, followed by treatment with EXO-ATQ. Their survival time and parasite load were compared with that in the suspension of ATQ (S-ATQ) as a positive control group. The in vitro study showed that exosomes improved the efficacy of ATQ, and EXO-ATQ significantly reduced intracellular proliferation of T. gondii tachyzoites compared to S-ATQ ( P  ≤  0.05). In acute experimental toxoplasmosis, the mice treated with EXO-ATQ showed a significant reduction in tachyzoites count of the peritoneal cavity and a longer survival time ( P  ≤  0.05). Furthermore, EXO-ATQ administration significantly decreased the mean number (97.3% cyst reduction) and the average size of the brain cysts of chronically infected mice with T. gondii , Tehran strain ( P  ≤  0.05). Besides, the decrease in cyst numbers was confirmed by the down-regulation of BAG1 using a real-time PCR assay. Our results implied that exosomes have the potential to be used as an efficient drug delivery system, and the loading of ATQ into the exosomes ameliorates the effect of ATQ against T. gondii . This study suggests a new strategy for improving the effectiveness of ATQ against acute and chronic phases of T. gondii .

This study is the first of its kind that suggests exosomes as a nano-carrier loaded with atovaquone (ATQ), which could be considered as a new strategy for improving the effectiveness of ATQ against acute and chronic phases of Toxoplasma gondii .