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Metabolic dysregulation of neurons is associated with diverse human brain disorders. Metabolic reprogramming occurs during neuronal differentiation, but it is not fully understood which molecules regulate metabolic changes at the early stages of neurogenesis. In this study, we report that miR-124 is a driver of metabolic change at the initiating stage of human neurogenesis. Proteome analysis has shown the oxidative phosphorylation pathway to be the most significantly altered among the differentially expressed proteins (DEPs) in the immature neurons after the knockdown of miR-124. In agreement with these proteomics results, miR-124-depleted neurons display mitochondrial dysfunctions, such as decreased mitochondrial membrane potential and cellular respiration. Moreover, morphological analyses of mitochondria in early differentiated neurons after miR-124 knockdown result in smaller and less mature shapes. Lastly, we show the potential of identified DEPs as novel metabolic regulators in early neuronal development by validating the effects of GSTK1 on cellular respiration. GSTK1, which is upregulated most significantly in miR-124 knockdown neurons, reduces the oxygen consumption rate of neural cells. Collectively, our data highlight the roles of miR-124 in coordinating metabolic maturation at the early stages of neurogenesis and provide insights into potential metabolic regulators associated with human brain disorders characterized by metabolic dysfunctions., (© 2024. The Author(s).)

Objectives: The aim of this meta-analysis was to evaluate whether a lidocaine patch is beneficial for postoperative pain as an option for multimodal analgesia., Methods: Information was obtained from PubMed, Embase, and the Cochrane Central Register of Controlled Trials for clinical randomized controlled trials of lidocaine patches for postoperative pain (as of March 2022). Two researchers independently completed study screening, risk bias assessment, and data extraction. Review Manager (version 5.4, Cochrane Collaboration) was used to conduct the meta-analysis. The evaluation metrics were postoperative pain scores, opioid consumption, and patient satisfaction., Results: Sixteen randomized controlled trials were included, and data from 918 patients were available. Pain scores differed between the 2 groups at 12, 24, and 48 hours postoperatively, and the pain scores of the lidocaine patch group were significantly lower (mean difference [MD]=-1.32 [95% CI, -1.96 to -0.68], P <0.0001; I2 =92%) at 12 hours after the operation; (MD=-1.23 [95% CI, -1.72 to -0.75], P <0.00001; I2 =92%) at 24 hours after the operation; and (MD=-0.25 [95% CI,-0.29 to -0.21], P <0.00001; I2 =98%) at 48 hours after the operation. In addition, the lidocaine patch group had decreased opioid requirements (MD=-3.57 [95% CI, -5.06 to -2.09], P <0.00001; I2 =96%). The lidocaine patch group seemed to be more satisfied, but there was no statistically significant difference (risk ratio, 1.50 [95% CI, 0.74 to 3.05], P =0.26) between the groups., Discussion: Lidocaine patches are beneficial for postoperative pain and can be used in multimodal analgesia to reduce opioid use, but there is no significant increase in patient satisfaction with pain control. More data are needed to support this conclusion due to the large heterogeneity in the present study., Competing Interests: Supported by the National Natural Science Foundation of China (No.82171186) and Natural Science Foundation of Fujian Province (No.2021J01397). The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

RNAs are versatile molecules that are primarily involved in gene regulation and can thus be widely used to advance the fields of therapeutics and diagnostics. In particular, circular RNAs which are highly stable, have emerged as strong candidates for use on next-generation therapeutic platforms. Endogenous circular RNAs control gene regulatory networks by interacting with other biomolecules or through translation into polypeptides. Circular RNAs exhibit cell-type specific expression patterns, which can be altered in tissues and body fluids depending on pathophysiological conditions. Circular RNAs that are aberrantly expressed in diseases can function as biomarkers or therapeutic targets. Moreover, exogenous circular RNAs synthesized in vitro can be introduced into cells as therapeutic molecules to modulate gene expression networks in vivo . Depending on the purpose, synthetic circular RNA sequences can either be identical to endogenous circular RNA sequences or artificially designed. In this review, we introduce the life cycle and known functions of intracellular circular RNAs. The current stage of endogenous circular RNAs as biomarkers and therapeutic targets is also described. Finally, approaches and considerations that are important for applying the available knowledge on endogenous circular RNAs to design exogenous circular RNAs for therapeutic purposes are presented.