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Aims: Nerve injury‐induced maladaptive changes in gene expression in the spinal neurons are essential for neuropathic pain genesis. Circular RNAs (ciRNA) are emerging as key regulators of gene expression. Here, we identified a nervous‐system‐tissues‐specific ciRNA‐Kat6 with conservation in humans and mice. We aimed to investigate whether and how spinal dorsal horn ciRNA‐Kat6b participates in neuropathic pain. Methods: Unilateral sciatic nerve chronic constrictive injury (CCI) surgery was used to prepare the neuropathic pain model. The differentially expressed ciRNAs were obtained by RNA‐Sequencing. The identification of nervous‐system‐tissues specificity of ciRNA‐Kat6b and the measurement of ciRNA‐Kat6b and microRNA‐26a (miRNA‐26a) expression level were carried out by quantitative RT‐PCR. The ciRNA‐Kat6b that targets miRNA‐26a and miRNA‐26a that targets Kcnk1 were predicted by bioinformatics analysis and verified by in vitro luciferase reports test and in vivo experiments including Western‐blot, immunofluorescence, and RNA–RNA immunoprecipitation. The correlation between neuropathic pain and ciRNA‐Kat6b, miRNA‐26a, or Kcnk1 was examined by the hypersensitivity response to heat and mechanical stimulus. Results: Peripheral nerve injury downregulated ciRNA‐Kat6b in the dorsal spinal horn of male mice. Rescuing this downregulation blocked nerve injury‐induced increase of miRNA‐26a, reversed the miRNA‐26a‐triggered decrease of potassium channel Kcnk1, a key neuropathic pain player, in the dorsal horn, and alleviates CCI‐induced pain hypersensitivities. On the contrary, mimicking this downregulation increased the miRNA‐26a level and decreased Kcnk1 in the spinal cord, resulting in neuropathic pain‐like syndrome in naïve mice. Mechanistically, the downregulation of ciRNA‐Kat6b reduced the accounts of miRNA‐26a binding to ciRNA‐Kat6b, and elevated the binding accounts of miRNA‐26a to the 3′ untranslated region of Kcnk1 mRNA and degeneration of Kcnk1 mRNA, triggering in the reduction of KCNK1 protein in the dorsal horn of neuropathic pain mice. Conclusion: The ciRNA‐Kat6b/miRNA‐26a/Kcnk1 pathway in dorsal horn neurons regulates the development and maintenance of neuropathic pain, ciRNA‐Kat6b may be a potential new target for analgesic and treatment strategies. [ABSTRACT FROM AUTHOR]

Xylella fastidiosa causes Pierce's disease (PD) on grapevines, leading to significant economic losses in grape and wine production. To further our understanding of X. fastidiosa virulence on grapevines, we examined the PD1311 gene, which encodes a putative acyl-coenzyme A (acyl-CoA) synthetase, and is highly conserved across Xylella species. It was determined that PD1311 is required for virulence, as the deletion mutant, ΔPD1311, was unable to cause disease on grapevines. The ΔPD1311 strain was impaired in behaviours known to be associated with PD development, including motility, aggregation and biofilm formation. ΔPD1311 also expressed enhanced sensitivity to H2O2 and polymyxin B, and showed reduced survival in grapevine sap, when compared with wild-type X. fastidiosa Temecula 1 (TM1). Following inoculation, ΔPD1311 could not be detected in grape shoots, which may be related to its altered growth and sensitivity phenotypes. Inoculation with ΔPD1311 2 weeks prior to TM1 prevented the development of PD in a significant fraction of vines and eliminated detectable levels of TM1. In contrast, vines inoculated simultaneously with TM1 and ΔPD1311 developed disease at the same level as TM1 alone. In these vines, TM1 populations were distributed similarly to populations in TM1-only inoculated plants. These findings suggest that, through an indirect mechanism, pretreatment of vines with ΔPD1311 suppresses pathogen population and disease. [ABSTRACT FROM AUTHOR]