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.

Local differential privacy (LDP), where each user perturbs her data locally before sending to an untrusted data collector, is a new and promising technique for privacy-preserving distributed data collection. The advantage of LDP is to enable the collector to obtain accurate statistical estimation on sensitive user data (e.g., location and app usage) without accessing them. However, existing work on LDP is limited to simple data types, such as categorical, numerical, and set-valued data. To the best of our knowledge, there is no existing LDP work on key-value data, which is an extremely popular NoSQL data model and the generalized form of set-valued and numerical data. In this paper, we study this problem of frequency and mean estimation on key-value data by first designing a baseline approach P rivKV within the same "perturbation-calibration" paradigm as existing LDP techniques. To address the poor estimation accuracy due to the clueless perturbation of users, we then propose two iterative solutions P rivKV M and P rivKV M + that can gradually improve the estimation results through a series of iterations. An optimization strategy is also presented to reduce network latency and increase estimation accuracy by introducing virtual iterations in the collector side without user involvement. We verify the correctness and effectiveness of these solutions through theoretical analysis and extensive experimental results.

Circular RNAs (circRNAs) are expressed at high levels in the brain and are involved in various CNS diseases. However, the potential role of circRNAs in ischemic stroke-associated neuronal injury remains largely unknown. Here, we investigated the important functions of circRNA TLK1 (circTLK1) in this process. The levels of circTLK1 were significantly increased in brain tissues in a mouse model of focal cerebral ischemia and reperfusion. Knockdown of circTLK1 significantly decreased infarct volumes, attenuated neuronal injury, and improved neurological deficits. Furthermore, circTLK1 functioned as an endogenous miR-335-3p sponge to inhibit miR-335-3p activity, resulting in the increase of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible poly (ADP-ribose) polymerase expression and a subsequent exacerbation of neuronal injury. Clinical studies confirmed increased levels of circTLK1 in the plasma of patients with acute ischemic stroke (59 males and 12 females). Our findings reveal a detrimental role of circTLK1 in ischemic brain injury.

Polypyrrole (PPy)-coated Ag composites were synthesized through an immiscible organic/inorganic biphasic system in the presence of polyvinylpyrrolidone (PVP). Highly dispersed PPy/Ag was obtained by using interface polymerization and controlling the reactive conditions. The presence of PVP could realize the effective coating of PPy on the surface of Ag. The core-shell structure was directly confirmed by transmission electron microscopy and also characterized by techniques such as Fourier transform infrared spectroscopy and X-ray diffraction. Furthermore, three-layered Au-modified PPy-coated Ag nanocomposite was prepared through the reaction of Au colloidal solution and PPy/Ag. Moreover, Au/PPy/Ag nanocomposite was immobilized on the surface of a glassy carbon electrode and applied to construct a dopamine (DA) biosensor. The biosensor exhibited a fast amperometric response to DA with the linear range from 1 × 10 -4 to 5 × 10 -3 mol/L.

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