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Severe pain in patients can be alleviated by morphine treatment. However, long-term morphine treatment induces analgesic tolerance and the molecular mechanism of morphine analgesic intolerance is still not fully elucidated. Therefore, a novel target for improving morphine analgesic tolerance is required. Whole-genome sequencing showed that circNf1 is highly expressed in the dorsal horns of morphine-treated rats. Circular RNAs (circRNAs) are known to be unique and conserved cellular molecules that are mostly present in cytoplasm and participate in various biochemical processes with different functions. Therefore, we focused on exploring the molecular mechanism by which circNf1 contributes to morphine analgesic tolerance.CircRNA sequencing revealed differential expression of circRNAs after morphine treatment, and bioinformatics software programs (miRNAda, PicTar, and RNAhybrid) were used to predict possible mRNAs and binding sites. RNA binding protein immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP), fluorescence in situ hybridization (FISH), western blotting, biotin-coupled probe pull-down assay, luciferase assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to detect and measure the expression levels of circRNAs, mRNAs, and proteins. Intrathecal injections of small interfering RNAs (siRNAs), microRNA (miRNA) agomirs, and functional virus microinjections were administered to artificially mediate the expression of molecules. Tail immersion and hotplate tests were performed to evaluate morphine analgesic tolerance.Morphine-induced circNf1 expression was high in the spinal cord. RIP-PCR and luciferase assay data showed that circNf1 could combine with both miR-330-3p and miR-665, and FISH showed that circNf1 co-localized with miR-330-3p and miR-665. qRT-PCR assay showed downregulation of miR-330-3p and miR-665 in morphine-treated rats; western blotting results showed that CXCL12 increased after morphine treatment, however, the upregulation of CXCL12 could be alleviated after the intrathecal injection of miR-330-3p as well as miR-665 agomir. qRT-PCR indicated that circNf1 can bind to CXCL12 promoter, the increased circNf1 can enhance CXCL12 mRNA in naïve rats, and inhibition of circNf1 can alleviate the upregulation of CXCL12 mRNA in morphine-treated rats. Behavioral tests revealed that inhibition of circNf1 and CXCL12 and the enhancement of miR-330-3p and miR-665 can alleviate morphine analgesic tolerance.Our study indicates a novel pathway that can contribute to morphine analgesic tolerance, the circRNA to cytokine pathway, in which circNf1 functions as a sponge for miR-330-3p and miR-665 and induces the upregulation of CXCL12 at both transcriptional and translational levels in morphine-treated rats.

The synthesis of two-dimensional (2D) zeolites has garnered attention due to their superior properties for applications that span catalysis to selective separations. Prior studies of 2D zeolite catalysts demonstrated enhanced mass transport for improved catalyst lifetime and selectivity. Moreover, the significantly higher external surface area of 2D materials allows for reactions of bulky molecules too large to access interior pores. There are relatively few protocols for preparing 2D materials, owing to the difficultly of capping growth in one direction to only a few unit cells. To accomplish this, it is often necessary to employ complex, commercially unavailable organic structure-directing agents (OSDAs) prepared via multistep synthesis. However, a small subset of zeolite structures exist as naturally layered materials where postsynthesis steps can be used to exfoliate samples and produce ultrathin 2D nanosheets. In this study, we selected a common layered zeolite, the MWW framework, to explore methods of preparing 2D nanosheets via one-pot synthesis in the absence of complex organic templates. Using a combination of high-resolution microscopy and spectroscopy, we show that 2D MMW-type layers with an average thickness of 3.5 nm (ca. 1.5 unit cells) can be generated using the surfactant cetyltrimethylammonium (CTA), which operates as a dual OSDA and exfoliating agent to affect Al siting and to eliminate the need for postsynthesis exfoliation, respectively. We tested these 2D catalysts using a model reaction that assesses external (surface) Bronsted acid sites and observed a marked increase in the conversion relative to three-dimensional MWW (MCM-22) and 2D layers prepared from postsynthesis exfoliation (ITQ-2). Collectively, our findings identify a facile and effective route to directly synthesize 2D MWW-type materials, which may prove to be more broadly applicable to other layered zeolites.

Traditional training for percutaneous renal access (PCA) relies on apprenticeship, which raises concerns about patient safety, limited training opportunities, and inconsistent quality of feedback. In this study, we proposed the development of a novel augmented reality (AR) simulator for ultrasound (US)-guided PCA and evaluated its validity and efficacy as a teaching tool. Our AR simulator allows the user to practice PCA on a silicone phantom using a tracked needle and US probe emulator under the guidance of simulated US on a tablet screen. 6 Expert and 24 novice participants were recruited to evaluate the efficacy of our simulator. Experts highly rated the realism and usefulness of our simulator, reflected by the average face validity score of 4.39 and content validity score of 4.53 on a 5-point Likert scale. Comparisons with a Mann–Whitney U test revealed significant differences $$(p