Background:
Stroke is a leading cause of adult disability that can severely compromise patients' quality of life, yet no effective medication currently exists to accelerate rehabilitation. A variety of circular RNA (circRNAs) molecules are known to function in ischemic brain injury. Lentivirus-based expression systems have been widely used in basic studies of circRNAs, but safety issues with such delivery systems have limited exploration of potential therapeutic roles for circRNAs.
Methods:
Circular RNA SCMH1 (circSCMH1) was screened from the plasma of acute ischemic stroke (AIS) patients using circRNA microarrays. Engineered RVG-circSCMH1-extracellular vesicles (RVG-circSCMH1-EVs) were generated to selectively deliver circSCMH1 to the brain. Nissl staining was used to examine infarct size. Behavioral tasks were performed to evaluate motor functions in both rodent and nonhuman primate ischemic stroke models. Golgi staining and immunostaining were used to examine neuroplasticity and glial activation. Proteomic assays and RNA-seq data combined with transcriptional profiling were used to identify downstream targets of circSCMH1.
Results:
CircSCMH1 levels were significantly decreased in plasma of AIS patients, offering significant power in predicting stroke outcomes. The decreased levels of circSCMH1 were further confirmed in the plasma and peri-infarct cortex of photothrombotic (PT) stroke mice. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that circSCMH1 treatment improved functional recovery post stroke in both mice and monkeys, and discovered that circSCMH1 enhanced the neuronal plasticity and also inhibited glial activation and peripheral immune cell infiltration. Mechanistically, circSCMH1 binds to the transcription factor MeCP2, thereby releasing repression of MeCP2 target gene transcription.
Conclusions:
RVG-circSCMH1-EVs afford protection by promoting functional recovery in the rodent and the nonhuman primate ischemic stroke models. Our study presents a potentially widely applicable nucleotide drug delivery technology and demonstrates the basic mechanism of how circRNAs can be therapeutically exploited to improve post-stroke outcomes.
A nano-Fe 3 O 4 -CoO x catalyst was prepared via a simple wet impregnation method. The nano-Fe 3 O 4 -CoO x catalyst showed good catalytic performance for the conversion of 5-hydroxymethylfurfural into 2, 5-furandicarboxylic acid (FDCA) with t-BuOOH as the oxidant. Several important reaction parameters were explored, with the highest FDCA yield of 68.6% obtained from HMF after 15 h at a reaction temperature of 80 o C. One-pot conversion of fructose into FDCA was also successful via two steps. Catalytic conversion of fructose over Fe 3 O 4 @SiO 2 -SO 3 H yielded 93.1% HMF, which was oxidized in-situ into FDCA with a yield of 59.8%. Furthermore, recycling of nano-Fe 3 O 4 -CoO x was accomplished with the help of a magnetic field. Nano-Fe 3 O 4 -CoO x showed high stability in the reaction process. The use of non-precious metals and no requirement of a base additive made this method much more economical and environmental-friendly.
In this study, a magnetically-recoverable catalyst (Fe 3 O 4 @SiO 2 -HPW) was prepared by the application of phosphotungstic acid (HPW) supported on silica-coated Fe 3 O 4 nanoparticles. The prepared samples were characterized by XRD, TEM, FT-IR, and N 2 -adsorption-desorption isotherms. The content of W in Fe 3 O 4 @SiO 2 -HPW was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and its surface acidity was determined by a potentiometric titration with n-butylamine. Fe 3 O 4 @SiO 2 -HPW showed an excellent catalytic activity for the synthesis of EMF from HMF and fructose. Under optimal reaction conditions, EMF was obtained in a high yield of 83.6% by the etherification of 5-hydroxymethylfurfural. EMF could also be synthesized directly from fructose in a yield of 54.8% via a one-pot reaction strategy. After reaction, the catalyst Fe 3 O 4 @SiO 2 -HPW could be easily separated from the reaction mixture with an external magnetic field, and it could be reused at least five times without any loss of its catalytic activity.Scheme 1 Synthesis of EMF from fructose in ethanol.
In this study, aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-diformylfuran (DFF) was studied over a magnetic catalyst [Fe 3 O 4 @SiO 2 -NH 2 -Ru(III)]. Various reaction parameters were optimized for the oxidation of HMF into DFF. A high DFF of 86.4% and HMF conversion of 99.3% were obtained after 4 h at 120 °C. More importantly, the catalyst also showed high catalytic activity in air, and high HMF conversion of 99.7% and DFF yield of 86.8% were obtained after 16 h. The high catalytic performance of Fe 3 O 4 @SiO 2 -NH 2 -Ru(III) in air makes this method much more convenient and economical. Moreover, the procedure of the catalyst recycle was simple as the Fe 3 O 4 @SiO 2 -NH 2 -Ru(III) catalyst could be readily recovered from the reaction mixture by a permanent magnet. The catalyst could be reused several times without significant loss of its catalytic activity.
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