Myocardial microRNAs (myo-miRs) are released into the circulation after acute myocardial infarction (AMI). How they impact remote organs is however largely unknown. Here we show that circulating myo-miRs are carried in exosomes and mediate functional crosstalk between the ischemic heart and the bone marrow (BM). In mice, we find that AMI is accompanied by an increase in circulating levels of myo-miRs, with miR-1, 208, and 499 predominantly in circulating exosomes and miR-133 in the non-exosomal component. Myo-miRs are imported selectively to peripheral organs and preferentially to the BM. Exosomes mediate the transfer of myo-miRs to BM mononuclear cells (MNCs), where myo-miRs downregulate CXCR4 expression. Injection of exosomes isolated from AMI mice into wild-type mice downregulates CXCR4 expression in BM-MNCs and increases the number of circulating progenitor cells. Thus, we propose that myo-miRs carried in circulating exosomes allow a systemic response to cardiac injury that may be leveraged for cardiac repair.
Permanent magnet motors with rare earth magnets are amongst the best candidates for high performance applications such as automotive. However, due to their cost and risks relating to security of supply, alternative solutions such as ferrite magnets have recently become popular. In this paper the two major design challenges of using ferrite magnets for a high torque density and high speed application, namely their low remanent flux density and low coercivity, are addressed. It is shown that a spoke type design utilizing a distributed winding may overcome the torque density challenge due to a simultaneous flux concentration and reluctance torque possibility. Furthermore, the demagnetization challenge can be overcome through careful optimization of the rotor structure, with the inclusion of non-magnetic voids on the top and bottom of the magnets. To meet the challenges of the high speed operation an extensive rotor structural analysis has been undertaken, during which electro-magnetics as well as manufacturing tolerances are taken into account. The electromagnetic studies are validated through testing of a prototype, custom built for static torque and demagnetization evaluation. The disclosed motor design surpasses the state of the art performance and cost, merging the theories into a multi-disciplinary product.
Increasing studies have demonstrated that atherosclerosis is a chronic immunoinflammatory disease, and that oxidized low-density lipoprotein (oxLDL)-specific T cells contribute to the autoimmune process in atherosclerosis. Oral administration of oxLDL, which was identified as a candidate autoantigen in atherosclerosis, was shown to induce tolerance and suppress atherogenesis. However, the precise mechanisms of mucosal tolerance induction, in particular nasal tolerance, remain unknown. In this study, we explored the effect of nasal oxLDL on atherosclerosis as well as the cellular and molecular mechanisms leading to atheroprotective responses, and then found that nasal oxLDL drastically ameliorate the initiation (47.6 %, p < 0.001) and progression (21.1 %, p = 0.001) of atherosclerosis. Most importantly, a significant 35.8 % reduction of the progression of atherosclerosis was observed in the enhanced immunization group (p < 0.001). These effects were accompanied by a significant increase in CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) and CD4(+)CD25(+)Foxp3(+) Tregs in spleens and cervical lymph nodes, together with increased transforming growth factor (TGF)-β production and suppressed T-helper cells type 1, 2, and 17 immune responses. Surprisingly, neutralization of TGF-β in vivo partially counteracted the protective effect of nasal oxLDL treatment, indicating that the presence of TGF-β was indispensable to CD4(+)LAP(+) Tregs and CD4(+)CD25(+)Foxp3(+) Tregs to acquire regulatory properties. Our studies suggest that CD4(+)LAP(+) Tregs and CD4(+)CD25(+)Foxp3(+) Tregs induced by nasal delivery of oxLDL can inhibit oxLDL-specific T cells response and ameliorate atherosclerosis process.
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