Background: Although N6-methyladenosine (m6A) plays a very important role in different biological processes, its function in the brain has not been fully explored. Thus, we investigated the roles of the RNA demethylases Alkbh5/Fto in cerebral ischemia-reperfusion injury. Methods: We used a rat model and primary neuronal cell culture to study the role of m6A and Alkbh5/Fto in the cerebral cortex ischemic penumbra after cerebral ischemia-reperfusion injury. We used Alkbh5-shRNA and Lv-Fto ( in vitro) to regulate the expression of Alkbh5/Fto to study their regulation of m6A in the cerebral cortex and to study brain function after ischemia-reperfusion injury. Results: We found that RNA m6A levels increased consecutive to the increase of Alkbh5 expression in both the cerebral cortex of rats after middle cerebral artery occlusion, and in primary neurons after oxygen deprivation/reoxygenation. In contrast, Fto expression decreased after these perturbations. Our results suggest that knocking down Alkbh5 can aggravate neuronal damage. This is due to the demethylation of Alkbh5 and Fto, which selectively demethylate the Bcl2 transcript, preventing Bcl2 transcript degradation and enhancing Bcl2 protein expression. Conclusion: Collectively, our results demonstrate that the demethylases Alkbh5/Fto co-regulate m6A demethylation, which plays a crucial role in cerebral ischemia-reperfusion injury. The results provide novel insights into potential therapeutic mechanisms for stroke.
In this study, we isolated a plant growth-promoting Ochrobactrum with the activity of mitigating Cd toxicity to plant roots. The Ochrobactrum can be considered as a potential bioaugmentation agent that promotes plant growth, especially in some agricultural systems, or that helps in the phytoremediation of Cd-contaminated soil.
In the field of tissue engineering, polymeric materials with high biocompatibility like polylactic acid and polyglycolic acid have been widely used for fabricating living constructs. For hypopharynx tissue engineering, skeletal muscle is one important functional part of the whole organ, which assembles the unidirectionally aligned myotubes. In this study, a polyurethane (PU) scaffold with microchannel patterns was used to provide aligning guidance for the seeded human myoblasts. Due to the low hydrophilicity of PU, the scaffold was grafted with silk fibroin (PU-SF) or gelatin (PU-Gel) to improve its cell adhesion properties. Scaffolds were observed to degrade slowly over time, and their mechanical properties and hydrophilicities were improved through the surface grafting. Also, the myoblasts seeded on PU-SF had the higher proliferative rate and better differentiation compared with those on the control or PU-Gel. Our results demonstrate that polyurethane scaffolds seeded with myoblasts hold promise to guide hypopharynx muscle regeneration.
The market of available contrast agents for clinical magnetic resonance imaging (MRI) has been dominated by gadolinium (Gd) chelates based T1 contrast agents for decades. However, there are growing concerns about their safety because they are retained in the body and are nephrotoxic, which necessitated a warning by the U.S. Food and Drug Administration against the use of such contrast agents. To ameliorate these problems, it is necessary to improve the MRI efficiency of such contrast agents to allow the administration of much reduced dosages. In this study, a ten‐gram‐scale facile method is developed to synthesize organogadolinium complex nanoparticles (i.e., reductive bovine serum albumin stabilized Gd‐salicylate nanoparticles, GdSalNPs‐rBSA) with high r1 value of 19.51 mm−1 s−1 and very low r2/r1 ratio of 1.21 (B0 = 1.5 T) for high‐contrast T1‐weighted MRI of tumors. The GdSalNPs‐rBSA nanoparticles possess more advantages including low synthesis cost (≈0.54 USD per g), long in vivo circulation time (t1/2 = 6.13 h), almost no Gd3+ release, and excellent biosafety. Moreover, the GdSalNPs‐rBSA nanoparticles demonstrate excellent in vivo MRI contrast enhancement (signal‐to‐noise ratio (ΔSNR) ≈ 220%) for tumor diagnosis.
Abstract-In this paper, we develop a performance modeling technique for analyzing the time varying network layer queuing behavior of multihop wireless networks with constant bit rate (CBR) traffic. Our approach is a hybrid of a time varying adjacency matrix and a fluid flow queuing network model. Mobile network topology is modeled using time varying adjacency matrix, while node queues are modeled using fluid flow based differential equations which are solved using numerical methods. Numerical and simulation experiments show that this new approach can provide reasonably accurate results. Moreover, when compared to the computation time required in a standard discrete event simulator, the fluid flow based model is shown to be a more scalable tool. Finally, an illustrative example of our modeling technique application is given to show its capability of capturing the time varying network performance as a function of traffic load, node mobility and wireless link quality.
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