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Abstract Background Protein aggregates can be found in peripheral organs, such as the heart, kidney, and pancreas, but little is known about the impact of peripherally misfolded proteins on neuroinflammation and brain functional recovery following ischemic stroke. Methods Here, we studied the ischemia/reperfusion (I/R) induced brain injury in mice with cardiomyocyte-restricted overexpression of a missense (R120G) mutant small heat shock protein, αB-crystallin (CryAB R120G ), by examining neuroinflammation and brain functional recovery following I/R in comparison to their non-transgenic (Ntg) littermates. To understand how peripherally misfolded proteins influence brain functionality, exosomes were isolated from CryAB R120G and Ntg mouse blood and were used to treat wild-type (WT) mice and primary cortical neuron-glia mix cultures. Additionally, isolated protein aggregates from the brain following I/R were isolated and subjected to mass-spectrometric analysis to assess whether the aggregates contained the mutant protein, CryAB R120G . To determine whether the CryAB R120G misfolding can self-propagate, a misfolded protein seeding assay was performed in cell cultures. Results Our results showed that CryAB R120G mice exhibited dramatically increased infarct volume, delayed brain functional recovery, and enhanced neuroinflammation and protein aggregation in the brain following I/R when compared to the Ntg mice. Intriguingly, mass-spectrometric analysis of the protein aggregates isolated from CryAB R120G mouse brains confirmed presence of the mutant CryAB R120G protein in the brain. Importantly, intravenous administration of WT mice with the exosomes isolated from CryAB R120G mouse blood exacerbated I/R-induced cerebral injury in WT mice. Moreover, incubation of the CryAB R120G mouse exosomes with primary neuronal cultures induced pronounced protein aggregation. Transduction of CryAB R120G aggregate seeds into cell cultures caused normal CryAB proteins to undergo dramatic aggregation and form large aggregates, suggesting self-propagation of CryAB R120G misfolding in cells. Conclusions These results suggest that peripherally misfolded proteins in the heart remotely enhance neuroinflammation and exacerbate brain injury following I/R likely through exosomes, which may represent an underappreciated mechanism underlying heart-brain crosstalk. 

Cobalt( ii ) ions were adsorbed to the surface of rod-shape anatase TiO 2 nanocrystals and subsequently heated to promote ion diffusion into the nanocrystal. After removal of any remaining surface bound cobalt, a sample consisting of strictly cobalt-doped TiO 2 was obtained and characterized with powder X-ray diffraction, transmission electron microscopy, UV-visible spectroscopy, fluorescence spectroscopy, X-ray photoelectron spectroscopy, SQUID magnetometry, and inductively-coupled plasma atomic emission spectroscopy. The nanocrystal morphology was unchanged in the process and no new crystal phases were detected. The concentration of cobalt in the doped samples linearly correlates with the initial loading of cobalt( ii ) ions on the nanocrystal surface. Thin films of the cobalt doped TiO 2 nanocrystals were prepared on indium-tin oxide coated glass substrate, and the electrical conductivity increased with the concentration of doped cobalt. Magnetic measurements of the cobalt-doped TiO 2 nanocrystals reveal paramagnetic behavior at room temperature, and antiferromagnetic interactions between Co ions at low temperatures. Antiferromagnetism is atypical for cobalt-doped TiO 2 nanocrystals, and is proposed to arise from interstitial doping that may be favored by the diffusional doping mechanism. 

Hollow Mn₃O₄nanoparticles (diameter=31 nm, cavity diameter=16 nm, and shell thickness=7 nm) were attached to the surface of multiwall carbon nanotubes (MWCNT). A suspension of hollow Mn₃O₄/MWCNT with Nafion™ was dropcast onto a glassy carbon electrode, and the electrochemical reduction of oxygen in aqueous solution was investigated with this electrode. We assess the role of MWCNT, hollow Mn₃O₄, and Nafion™ in the performance of the electrode, and investigate the kinetics of the oxygen reduction reaction. The electrode exhibits outstanding performance in measures of cathodic current density and onset potential, and performed similarly well in acidic, neutral, and alkaline conditions.