Silver nanoparticles (AgNPs) have tremendous potentials in medical devices due to their excellent antimicrobial properties. Blood compatibility should be investigated for AgNPs due to the potential blood contact. However, so far, most studies are not systematic and have not provided insights into the mechanisms for blood compatibility of AgNPs. In this study, we have investigated the blood biological effects, including hemolysis, lymphocyte proliferation, platelet aggregation, coagulation and complement activation, of 20 nm AgNPs with two different surface coatings (polyvinyl pyrrolidone and citrate). Our results have revealed AgNPs could elicit hemolysis and severely impact the proliferation and viability of lymphocytes at all investigated concentrations (10, 20, 40 μg/mL). Nevertheless, AgNPs didn’t show any effect on platelet aggregation, coagulation process, or complement activation at up to ~40 μg/mL. Proteomic analysis on AgNPs plasma proteins corona has revealed that acidic and small molecular weight blood plasma proteins were preferentially adsorbed onto AgNPs, and these include some important proteins relevant to hemostasis, coagulation, platelet, complement activation and immune responses. The predicted biological effects of AgNPs by proteomic analysis are mostly consistent with our experimental data since there were few C3 components on AgNPs and more negative than positive factors involving platelet aggregation and thrombosis.

Aims: PTEN-putative kinase 1 (PINK1)-Parkin-mediated mitophagy is crucial for the clearance of damaged mitochondria. However, the mechanisms underlying PINK1-Parkin-mediated mitophagy are not fully understood. The goal of this study is to identify new regulators and to elucidate the regulatory mechanisms of mitophagy. Results: Quantitative mitochondrial proteomic analysis revealed that 63 proteins showed increased levels and 36 proteins showed decreased levels in cells subjected to carbonyl cyanide m -chlorophenyl hydrazone (CCCP) treatment. Peroxiredoxin 6 (PRDX6 or Prx6), a unique member of the ubiquitous PRDX family, was recruited to depolarized mitochondria. Reactive oxygen species (ROS) generated by CCCP promoted PRDX6 accumulation and PINK1 stabilization in damaged mitochondria and induced mitophagy. In addition, depletion of PRDX6 resulted in the stabilization of PINK1, accumulation of autophagic marker, p62, translocation of Parkin to mitochondria, and lipidation of microtubule-associated protein 1 light chain 3. Furthermore, these events were blocked upon supplementation with antioxidant N -acetyl- l -cysteine or depletion of PINK1. Innovation: This is the first study to demonstrate that PRDX6 is the only member of the PRDX family that relocates to damaged mitochondria, where it plays a crucial role in the initial stage of mitophagy by controlling ROS homeostasis. Conclusion: ROS induce the recruitment of PRDX6 to mitochondria, where PRDX6 controls ROS homeostasis in the initial step of PINK1-Parkin-mediated mitophagy. Our study provides new insight into the initial regulatory mechanisms of mitophagy and reveals the protective role of PRDX6 in the clearance of damaged mitochondria. Antioxid. Redox Signal. 24, 486–501.

Biodegradable polylactic acid (PLA) plastics have been praised as an effective solution to the global pollution caused by petroleum-based plastics, and their widespread use in food packaging and disposable tableware has resulted in increased oral exposure to PLA microplastics (PLA-MPs). Despite their eco-friendly and biodegradable reputation, the in vivo behaviors of PLA-MPs concerning fermentation, carbon cycle, and adverse effects remain unknown. Here, we showed that gut microbiota from the colon can effectively degrade the PLA-MPs by secreting esterase FrsA, whereas esterase FrsA-producing bacteria were identified to dominate this behavior in male C57BL/6 mice. Using isotope tracing and multiomics techniques, we uncovered that ¹³ C-labeled PLA-MPs were incorporated into the carbon cycle of gut microbiota as a carbon source. Meanwhile, these degraded PLA-MPs fragments entered the succinate pathway of the tricarboxylic acid cycle within gut epithelial cells. These processes altered the metabolic phenotype of the gut, resulting in the decreased linear short-chain fatty acids that are primary energy sources of the gut epithelium. Furthermore, we found that exposure of PLA-MPs significantly reduced the appetite and body weight of mice. Our findings present an overall process of biodegradable plastics within hosts, with the focus on the entire double carbon cycle of PLA-MPs in the gut, which offers indispensable insights into the potential impact of exposure to PLA-MPs.