Exosomal miR-532-5p induced by long-term exercise rescues blood-brain barrier function in 5XFAD mice via downregulation of EPHA4.

The breakdown of the blood-brain barrier, which develops early in Alzheimer's disease (AD), contributes to cognitive impairment. Exercise not only reduces the risk factors for AD but also confers direct protection against cognitive decline. However, the exact molecular mechanisms remain elusive, particularly whether exercise can liberate the function of the blood-brain barrier. Here, we demonstrate that long-term exercise promotes the clearance of brain amyloid-ß by improving the function of the blood-brain barrier in 5XFAD mice. Significantly, treating primary brain pericytes or endothelial cells with exosomes isolated from the brain of exercised 5XFAD mice improves cell proliferation and upregulates PDGFRß, ZO-1, and claudin-5. Moreover, exosomes isolated from exercised mice exhibit significant changes in miR-532-5p. Administration or transfection of miR-532-5p to sedentary mice or primary brain pericytes and endothelial cells reproduces the improvement of blood-brain barrier function. Exosomal miR-532-5p targets EPHA4, and accordingly, expression of EphA4 is decreased in exercised mice and miR-532-5p overexpressed mice. A specific siRNA targeting EPHA4 recapitulates the effects on blood-brain barrier-associated cells observed in exercised 5XFAD mice. Overall, our findings suggest that exosomes released by the brain contain a specific miRNA that is altered by exercise and has an impact on blood-brain barrier function in AD.

Multiple roles of extracellular polymeric substance in nitrobenzene reduction by nano-sized zero-valent iron in water and their mechanism.

Extracellular polymeric substance (EPS) is secreted by many organisms and makes up a significant constituent of natural organic matter in the environment. However, nothing is known about EPS's role in the reduction of pollutants by nano-sized zero-valent iron (NZVI). This research showed that the degradation kinetics of nitrobenzene (NB) by NZVI with EPS (0.0272 ± 0.006 min-1) were 2.27 times lower than that without EPS (0.0618 ± 0.006 min-1) in the first cycle, mainly due to competition for reactive sites on the NZVI surface and the complexation of EPS with Fe(II) and Fe(III). In the second and third cycle, the degradation kinetics of NB by NZVI alone decreased obviously, while those in the presence of EPS were preserved or accelerated. Comparative studies with a quinine model compound indicated that EPS did not function as the electron shuttle to transmit electrons effectively. X-ray photoelectron spectroscopy, scanning electron microscopy and X-ray diffraction results suggested that EPS could prevent the oxidation of NZVI and even expose more effective sites on the NZVI surface, thus leading to the preservation or enhancement of NZVI reactivity in the second and third NB degradation cycles. Moreover, we found that EPS also provided colloidal stability to NZVI particles, either by steric mechanisms or electrostatic repulsion. These results indicate that EPS can play an important role in the prolongation of NZVI reactivity during standing application.

Cysteine-enhanced reductive degradation of nitrobenzene using nano-sized zero-valent iron by accelerated electron transfer.

As an aliphatic amino acid, cysteine (CYS) is diffuse in the living cells of plants and animals. However, little is known of its role in the reactivity of nano-sized zero-valent iron (NZVI) in the degradation of pollutants. This study shows that the introduction of CYS to the NZVI system can help improve the efficiency of reduction, with 30% more efficient degradation and a reaction rate constant nine times higher when nitrobenzene (NB) is used as probe compound. The rates of degradation of NB were positively correlated with the range of concentrations of CYS from 0 to 10 mmol/L. The introduction of CYS increased the maximum concentration of Fe(III) by 12 times and that of Fe(II) by four times in this system. A comparison of systems featuring only CYS or Fe(II) showed that the direct reduction of NB was not the main factor influencing its CYS-stimulated removal. The reduction in the concentration of CYS was accompanied by the generation of cystine (CY, the oxidized form of cysteine), and both eventually became stable. The introduction of CY also enhanced NB degradation due to NZVI, accompanied by the regeneration of CYS. This supports the claim that CYS can accelerate electron transfer from NZVI to NB, thus enhancing the efficiency of degradation of NB.

Drastically inhibited nZVI-Fenton oxidation of organic pollutants by cysteine: Multiple roles in the nZVI/O2/hv system.

The influence of l-cysteine, a common aliphatic amino acid, on the zero-valent iron (nZVI)/O2 photo-Fenten degradation of rhodamine B (RhB) was investigated in this study. The oxidation rate of RhB in the nZVI/O2/hv system was 91.2% after 40 min under the illumination and oxygen conditions and pH of 3, but when cysteine was introduced into the system, the oxidization process was inhibited. The removal of RhB was only about 50% after 40 min at a cysteine concentration ≥50 µM. It was shown experimentally that, under dark conditions, only 40.5% and 19.8% RhB was removed by the nZVI/O2 and nZVI/O2/cysteine systems, respectively. Electron paramagnetic resonance (EPR) and iron dissolving experiments revealed that the addition of cysteine clearly reduced the production of hydroxyl radicals (OH) and Fe2+ and Fe3+. In addition, Fourier transform infrared spectroscopy (FTIR) demonstrated that cysteine could form hydrogen bonds on the iron surface. These results indicated that the main inhibition mechanism of cysteine was the alleviation of the oxidation of nZVI to Fe2+ and Fe3+ through wrapping the nZVI particles. Moreover, cystine (the oxidized form of CYS) could partly react with OH to regenerate cysteine, which resulted in competition with RhB for OH. Another possible reason for the inhibitory effect of cysteine was the prevention of light utilization. These findings indicate a non-negligible inhibitory trait for heterogeneous Fenton process in wastewater treatment when amino acids are present.