Strategy for Fluorescence/Photoacoustic Signal Maximization Using Dual-Wavelength-Independent Excitation.

Dual-mode imaging of fluorescence-photoacoustics has emerged as a promising technique for biomedical applications. However, conventional dual-mode imaging is based on single-wavelength excitation, which often results in opposing fluorescence and photoacoustic signals due to competing photophysical processes in one agent, rendering the maximization of both signals infeasible. To meet this challenge, we herein propose a new strategy by using the dual-excitation approach, where one excitation wavelength generates a fluorescence signal and the other produces a photoacoustic signal, thus achieving simultaneous maximization of both signals in one fluorescence-photoacoustic molecule. Based on this strategy, three dye molecules were employed for comparison, and it was surprising to find that QHD dye with two types of excitation wavelengths could generate fluorescence and photoacoustic signals, respectively. Furthermore, this strategy was successfully implemented in dual-mode imaging of rheumatoid arthritis mice. Importantly, this study emphasizes a new design guideline for the maximization of fluorescence-photoacoustic signals by using dual-wavelength-independent excitation.

Visualization of Lysosomal Dynamics during Autophagy by Fluorescent Probe.

Lysosomes are one of the important organelles within cells, and their dynamic movement processes are associated with many biological events. Therefore, real-time monitoring of lysosomal dynamics processes has far-reaching implications. A lysosome-targeted fluorescent probe N(CH2)3-BD-PZ is proposed for real-time monitoring of lysosomal kinetic motility. Using this probe, the dynamic process of lysosomes under starvation induction was successfully explored through fluorescence imaging. Importantly, we observed a new pattern of lysosomal dynamic movement, in which an irregular lysosome was slowly cleaved into two different-sized touching lysosomes and then fused to form a new round lysosome. This research provides a powerful fluorescence tool to understand the dynamic motility of intracellular lysosomes under fluorescence imaging.

A Lightweight Recurrent Grouping Attention Network for Video Super-Resolution.

Effective aggregation of temporal information of consecutive frames is the core of achieving video super-resolution. Many scholars have utilized structures such as sliding windows and recurrences to gather the spatio-temporal information of frames. However, although the performances of constructed video super-resolution models are improving, the sizes of the models are also increasing, exacerbating the demand on the equipment. Thus, to reduce the stress on the device, we propose a novel lightweight recurrent grouping attention network. The parameters of this model are only 0.878 M, which is much lower than the current mainstream model for studying video super-resolution. We have designed a forward feature extraction module and a backward feature extraction module to collect temporal information between consecutive frames from two directions. Moreover, a new grouping mechanism is proposed to efficiently collect spatio-temporal information of the reference frame and its neighboring frames. The attention supplementation module is presented to further enhance the information gathering range of the model. The feature reconstruction module aims to aggregate information from different directions to reconstruct high-resolution features. Experiments demonstrate that our model achieves state-of-the-art performance on multiple datasets.

Genome-wide analysis of MdPLATZ genes and their expression during axillary bud outgrowth in apple (Malus domestica Borkh.).

BACKGROUND: Branching is a plastic character that affects plant architecture and spatial structure. The trait is controlled by a variety of plant hormones through coordination with environmental signals. Plant AT-rich sequence and zinc-binding protein (PLATZ) is a transcription factor that plays an important role in plant growth and development. However, systematic research on the role of the PLATZ family in apple branching has not been conducted previously. RESULTS: In this study, a total of 17 PLATZ genes were identified and characterized from the apple genome. The 83 PLATZ proteins from apple, tomato, Arabidopsis, rice, and maize were classified into three groups based on the topological structure of the phylogenetic tree. The phylogenetic relationships, conserved motifs, gene structure, regulatory cis-acting elements, and microRNAs of the MdPLATZ family members were predicted. Expression analysis revealed that MdPLATZ genes exhibited distinct expression patterns in different tissues. The expression patterns of the MdPLATZ genes were systematically investigated in response to treatments that impact apple branching [thidazuron (TDZ) and decapitation]. The expression of MdPLATZ1, 6, 7, 8, 9, 15, and 16 was regulated during axillary bud outgrowth based on RNA-sequencing data obtained from apple axillary buds treated by decapitation or exogenous TDZ application. Quantitative real-time PCR analysis showed that MdPLATZ6 was strongly downregulated in response to the TDZ and decapitation treatments, however, MdPLATZ15 was significantly upregulated in response to TDZ, but exhibited little response to decapitation. Furthermore, the co-expression network showed that PLATZ might be involved in shoot branching by regulating branching-related genes or mediating cytokinin or auxin pathway. CONCLUSION: The results provide valuable information for further functional investigation of MdPLATZ genes in the control of axillary bud outgrowth in apple.

Chromatin-associated OGT promotes the malignant progression of hepatocellular carcinoma by activating ZNF263.

Reversible and dynamic O-GlcNAcylation regulates vast networks of highly coordinated cellular and nuclear processes. Although dysregulation of the sole enzyme O-GlcNAc transferase (OGT) was shown to be associated with the progression of hepatocellular carcinoma (HCC), the mechanisms by which OGT controls the cis-regulatory elements in the genome and performs transcriptional functions remain unclear. Here, we demonstrate that elevated OGT levels enhance HCC proliferation and metastasis, in vitro and in vivo, by orchestrating the transcription of numerous regulators of malignancy. Diverse transcriptional regulators are recruited by OGT in HCC cells undergoing malignant progression, which shapes genome-wide OGT chromatin cis-element occupation. Furthermore, an unrecognized cooperation between ZNF263 and OGT is crucial for activating downstream transcription in HCC cells. We reveal that O-GlcNAcylation of Ser662 is responsible for the chromatin association of ZNF263 at candidate gene promoters and the OGT-facilitated HCC malignant phenotypes. Our data establish the importance of aberrant OGT activity and ZNF263 O-GlcNAcylation in the malignant progression of HCC and support the investigation of OGT as a therapeutic target for HCC.

ASSVd infection inhibits the vegetative growth of apple trees by affecting leaf metabolism.

Apple scar skin viroid (ASSVd) can infect apple trees and cause scar skin symptoms. However, the associated physiological mechanisms are unclear in young saplings. In this study, ASSVd-infected and control 'Odysso' and 'Tonami' apple saplings were examined to clarify the effects of ASSVd on apple tree growth and physiological characteristics as well as the leaf metabolome. The results indicated that leaf ASSVd contents increased significantly after grafting and remained high in the second year. Leaf size, tree height, stem diameter, branch length, and leaf photosynthetic efficiency decreased significantly in viroid-infected saplings. In response to the ASSVd infection, the chlorophyll a and b contents decreased significantly in 'Odysso', but were unchanged in 'Tonami'. Moreover, the N, P, K, Fe, Mn, and Ca contents decreased significantly in the leaves of viroid-infected 'Odysso' or 'Tonami'. Similarly, the CAT and POD contents decreased significantly in the viroid-infected saplings, but the SOD content increased in the viroid-infected 'Tonami' saplings. A total of 15 and 40 differentially abundant metabolites were respectively identified in the metabolome analyses of 'Odysso' and 'Tonami' leaves. Specifically, in the viroid-infected 'Odysso' and 'Tonami' samples, the L-2-aminobutyric acid, 6″-O-malonyldaidzin, and D-xylose contents increased, while the coumarin content decreased. These metabolites are related to the biosynthesis of isoflavonoids and phenylpropanoids as well as the metabolism of carbohydrates and amino acids. These results imply that ASSVd affects apple sapling growth by affecting physiological characteristics and metabolism of apple leaves. The study data may be useful for future investigations on the physiological mechanisms underlying apple tree responses to ASSVd.

Volatile metabolome and floral transcriptome analyses reveal the volatile components of strongly fragrant progeny of Malus × robusta.

Floral fragrance is an important trait that contributes to the ornamental properties and pollination of crabapple. However, research on the physiological and molecular biology of the floral volatile compounds of crabapple is rarely reported. In this study, metabolomic and transcriptomic analyses of the floral volatile compounds of standard Malus robusta flowers (Mr), and progeny with strongly and weakly fragrant flowers (SF and WF, respectively), were conducted. Fifty-six floral volatile compounds were detected in the plant materials, mainly comprising phenylpropane/benzene ring-type compounds, fatty acid derivatives, and terpene compounds. The volatile contents were significantly increased before the early flowering stage (ES), and the contents of SF flowers were twice those of WF and Mr flowers. Odor activity values were determined for known fragrant volatiles and 10-11 key fragrant volatiles were identified at the ES. The predominant fragrant volatiles were methyl benzoate, linalool, leaf acetate, and methyl anthranilate. In the petals, stamens, pistil, and calyx of SF flowers, 26 volatiles were detected at the ES, among which phenylpropane/benzene ring-type compounds were the main components accounting for more than 75% of the total volatile content. Functional analysis of transcriptome data revealed that the phenylpropanoid biosynthesis pathway was significantly enriched in SF flowers. By conducting combined analyses between volatiles and differentially expressed genes, transcripts of six floral scent-related genes were identified and were associated with the contents of the key fragrant volatiles, and other 23 genes were potentially correlated with the key volatile compounds. The results reveal possible mechanisms for the emission of strong fragrance by SF flowers, and provide a foundation for improvement of the floral fragrance and development of new crabapple cultivars.

Teacher cognition in teaching intercultural communicative competence: A qualitative study on preservice Chinese language teachers in Hong Kong SAR, China.

The purpose of this study is to examine preservice Chinese language teachers' cognition in teaching intercultural communicative competence. In the study we collected data through in-depth interviews with seven preservice teachers in a Master of Education program (Teaching Chinese as a Second Language, TCSL) at a university in Hong Kong SAR, China. The findings indicated that the participants had a relatively positive attitude and inclination toward the development of students' intercultural communicative competence, while their conceptualizations of culture tended to be static and ambiguous. In addition, the participants' objectives in teaching intercultural communicative competence were found to be more attitude-than knowledge- or skill-oriented. The study offers valuable insights that preservice language teachers' cognition plays a crucial role in their future professional development and calls for curricular innovations with intercultural aims in teacher education programs.

Physiological and transcriptome analyses reveal the response of Ammopiptanthus mongolicus to extreme seasonal temperatures in a cold plateau desert ecosystem.

Ammopiptanthus mongolicus is the only evergreen broad-leaved shrub present in arid areas of Northwest China and plays an important role in maintaining the stability of the local desert ecosystem. It can survive under extreme temperatures (e.g., extreme low temperature: - 24.8 °C and extreme high temperature: 37.7 °C). To understand the gene expression-physiological regulation network of A. mongolicus in extreme temperature environments, we monitored the changes in gene expression and photosynthetic traits of the leaves. The results showed that at low temperatures, the net photosynthetic rates (A), Fv'/Fm' and electron transport rate (ETR) decreased, the Fv/Fm ratio was only 0.32, and the proportion of nonregulatory heat dissipation Y(NO) increased. Based on a KEGG analysis of the differentially expressed genes, 15 significantly enriched KEGG pathways were identified, which were mainly related to circadian rhythm, photosynthesis, lipid metabolism, carbohydrate metabolism, plant hormones and other life activities. At high temperatures, the A value increased, and the proportion of regulatory energy dissipation Y(NPQ) increased. The KEGG analysis identified 24 significantly enriched KEGG pathways, which are mainly related to circadian rhythm, carbon sequestration of photosynthesis, carotenoid biosynthesis, secondary metabolites, cofactors and vitamin metabolism. In general, at the expense of photosynthesis, A. mongolicus can ensure the survival of leaves by increasing Y(NO) levels, regulating the circadian rhythm, increasing the synthesis of unsaturated fatty acids and changing the role of plant hormones. Under high-temperature stress, a high photosynthetic capacity was maintained by adjusting the stomatal conductance (gsw), increasing Y(NPQ), consuming excess light energy, continuously assembling and maintaining PSII, and changing the production of antioxidants.

Whole genome re-sequencing and transcriptome reveal an alteration in hormone signal transduction in a more-branching mutant of apple.

Branch number is an important trait in grafted apple breeding and cultivation. To provide new information on molecular mechanisms of apple branching, whole reduced-representation genomes and transcriptome of a wild-type (WT) apple (Malus spectabilis) and its more-branching (MB) mutant at the branching stage were examined in this study. Comparison of WT and MB genomes against the Malus domestica reference genome identified 14,908,939 single nucleotide polymorphisms (SNPs) and 173,315 insertions and deletions (InDels) in WT and 1,483,221 SNPs and 1,725,977 InDels in MB. Analysis of the genetic variation between MB and WT revealed 1,048,575 SNPs and 37,327 InDels. Among them, 24,303 SNPs and 891 InDels mapped to coding regions of 5,072 and 596 genes, respectively. GO and KEGG functional annotation of 3,846 and 944 genes, respectively, identified 32 variant genes related to plant hormone signal transduction that were involved in auxin, cytokinin, gibberellin, abscisic acid, ethylene, and brassinosteroid pathways. The transcriptome pathways of plant hormone signal transduction and zeatin biosynthesis were also significantly enriched during MB branching. Furthermore, transcriptome data suggested the regulatory roles of auxin signaling, increase of cytokinin and genes of cytokinin synthesis and signaling, and the suppressed abscisic acid signaling. Our findings suggest that branching development in apple is regulated by plant hormone signal transduction.

Controlling Rheology of Fluid Interfaces through Microblock Length of Sequence-Controlled Amphiphilic Copolymers.

Previous studies have demonstrated that films of sequence-controlled amphiphilic copolymers display contact angles that depend on microblock size. This suggests that microblock length may provide a means of tuning surface and interfacial properties. In this work, the interfacial rheology of a series of sequence-controlled copolymers, prepared through the addition of bicyclo[4.2.0]oct-1(8)-ene-8-carboxamide (monomer A) and cyclohexene (monomer B) to generate sequences up to 24 monomeric units composed of (A m B n ) i microblocks, where m, n, and i range from 1 to 6. Interfacial rheometry is used to measure the mechanical properties of an air-water interface with these copolymers. As the microblock size increases, the interfacial storage modulus, G', increases, which may be due to an increase in the size of interfacial hydrophobic domains. Small-angle X-ray scattering shows that the copolymers have a similar conformation in solution, suggesting that any variations in the mechanics of the interface are due to assembly at the interface, and not on solution association or bulk rheological properties. This is the first study demonstrating that microblock size can be used to control interfacial rheology of amphiphilic copolymers. Thus, the results provide a new strategy for controlling the dynamics of fluid interfaces through precision sequence-controlled polymers.

Systematic review and meta-analysis of the sedative effects and safety of dexmedetomidine in patients after cardiac surgery.

BACKGROUND: In order to increase the sample size and improve the test efficiency from a statistical perspective, we conducted a combined analysis of multiple results from similar studies. In this study, we conducted a meta-analysis to investigate the sedative effect of dexmedetomidine on patients after cardiac surgery, so as to provide theoretical basis and help for clinical treatment of cardiac diseases. METHODS: The Boolean logic search method was employed to search online databases for publications, with "dexmedetomidine", "cardiac surgery", "competitive antagonist", and "analgesic sedation" used as keywords. In addition, the literature was screened for comparative studies on the use of midazolam and propofol as controls. The Newcastle-Ottawa Scale (NOS) of Cochrane Collaborative Network was used to evaluate the pathological control studies in Meta-analysis, and the star rating system (out of 9 stars) was used to measure the results from the subjects, cases and groups. Finally, a meta-analysis was performed with Review Manager software (Cochrane). RESULTS: Thirteen references containing mostly low-risk biases (medium-high quality) were included in this study. The meta-analysis showed no statistically obvious heterogeneity in the mechanical ventilation time (MVT) between patients in the control group (group A) or patients in the experimental group (group B) (Chi2=74.71; I2=92%; P<0.00001), showing no statistical significance (Z=1.57; P=0.12). Heterogeneity was found as a complication in both groups (Chi2=14.82; I2=60%; P=0.02), but fewer complications were observed in group B (Z=2.06, P=0.04). The sedative effect displayed by patients from the 2 groups during the induction of anesthesia was statistically heterogeneous (Chi2=6.45; I2=38%; P=0.17), but the sedative effect in group B was shown to be greater (Z=3.31, P=0.0009). CONCLUSIONS: Dexmedetomidine can significantly reduce the mechanical ventilation time and the incidence of complications in patients after cardiac surgery, and has a high safety and good sedative effect on patients.

Using cross efficiency method integrating regret theory and WASPAS to evaluate road safety performance of Chinese provinces.

Currently, the road safety performance of a national- or province-level is absorbing much attention from practitioners and academics. A variety of models based on Data Envelopment Analysis (DEA) have been presented to appraise road safety performance in previous literature. However, the main weakness of these methods is that the decision-maker's psychological behavior is neglected. Besides, Cross Efficiency Method (CEM) adopts the weighted average to aggregate the cross efficiencies which may lead to information loss. To address these limitations, a hybrid road safety evaluation model was constructed by integrating CEM, regret theory, and Weighted Aggregated Sum Product Assessment (WASPAS) to appraise the road safety performance of Chinese provinces. In the presented model, regret theory is employed to depict the psychological behavior of the decision-maker. Then entropy weight method is utilized to calculate the weight of self-evaluation and peer-evaluation. To reduce information loss, WASPAS is adopted to fuse the cross efficiencies and derive the ranking of decision-making units. Finally, the presented model is employed to assess the road safety efficiency in the province of mainland China. The results show that the mean of road safety efficiency score for the eastern, central, and western areas is gradually decreasing. Furthermore, the outcomes of a comparative analysis represent that the results obtained by the proposed model outperform the CEM and DEA road safety model.

Molecular mechanism of MdWUS2-MdTCP12 interaction in mediating cytokinin signaling to control axillary bud outgrowth.

Shoot branching is an important factor that influences the architecture of apple trees and cytokinin is known to promote axillary bud outgrowth. The cultivar 'Fuji', which is grown on ~75% of the apple-producing area in China, exhibits poor natural branching. The TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) family genes BRANCHED1/2 (BRC1/2) are involved in integrating diverse factors that function locally to inhibit shoot branching; however, the molecular mechanism underlying the cytokinin-mediated promotion of branching that involves the repression of BRC1/2 remains unclear. In this study, we found that apple WUSCHEL2 (MdWUS2), which interacts with the co-repressor TOPLESS-RELATED9 (MdTPR9), is activated by cytokinin and regulates branching by inhibiting the activity of MdTCP12 (a BRC2 homolog). Overexpressing MdWUS2 in Arabidopsis or Nicotiana benthamiana resulted in enhanced branching. Overexpression of MdTCP12 inhibited axillary bud outgrowth in Arabidopsis, indicating that it contributes to the regulation of branching. In addition, we found that MdWUS2 interacted with MdTCP12 in vivo and in vitro and suppressed the ability of MdTCP12 to activate the transcription of its target gene, HOMEOBOX PROTEIN 53b (MdHB53b). Our results therefore suggest that MdWUS2 is involved in the cytokinin-mediated inhibition of MdTCP12 that controls bud outgrowth, and hence provide new insights into the regulation of shoot branching by cytokinin.

Simultaneous detection of Cys/Hcy and H2S through distinct fluorescence channels.

Hydrogen sulfide (H2S), cysteine (Cys) and homocysteine (Hcy) play critical roles in human pathologies and there are close interconnections between them in their generation and metabolism in living systems. To elucidate their complex interplay networks, single-molecule fluorescent probes enabling simultaneous detection of H2S and Cys/Hcy from distinct emission channels have been becoming indispensable tools. In this report, we have rationally developed a novel fluorescent probe, NC, for H2S and Cys/Hcy by integrating an amino 7-nitro-1, 2, 3-benzoxadiazole (NBD) moiety and an azide group into the coumarin platform. NC exhibited good selectivity and sensitivity for the discriminatory detection of H2S and Cys/Hcy, and its capability for imaging of intracellular H2S and Cys/Hcy was proved.

Aggregation-enhanced emission enables phenothiazine coumarin as a robust ratiometric fluorescent for rapid and selective detection of HClO.

By taking advantage of phenothiazine moiety as an electron-donating group, a novel donor-acceptor (D-A) type coumarin dye, PTZ-Et, was developed. The introduction of phenothiazine moiety not only caused emission red-shifting and Stokes shift enlarging, but also endowed PTZ-Et with significant aggregation-enhanced emission (AEE) features, thereby enabled PTZ-Et as a robust ratiometric fluorescent probe for HClO detection. Upon oxidation of the sulfur atom on phenothiazine into sulfoxide, PTZ-Et displayed remarkable ratiometric fluorescence response (over 150 folds variations of F534/F626) toward HClO with rapid response time (<30 s) and ultra-sensitivity (LOD = 15 nM). Additionally, the corresponding sensing mechanism of PTZ-Et for HClO was fully elucidated through the successful purification and well characterization (1H NMR, 13C NMR, HRMS, and single crystal data) of the corresponding reaction product between PTZ-Et and HClO. Significantly, PTZ-Et was capable of monitoring both exogenous and endogenous HClO in living RAW 264.7 cells by ratiometric fluorescence imaging.

Role of Cytokinin, Strigolactone, and Auxin Export on Outgrowth of Axillary Buds in Apple.

Shoot branching is regulated by phytohormones, including cytokinin (CK), strigolactone (SL), and auxin in axillary buds. The correlative importance of these phytohormones in the outgrowth of apple axillary buds remains unclear. In this study, the outgrowth dynamics of axillary buds of a more-branching mutant (MB) and its wild-type (WT) of Malus spectabilis were assessed using exogenous chemical treatments, transcriptome analysis, paraffin section, and reverse transcription-quantitative PCR analysis (RT-qPCR). High contents of CK and abscisic acid coincided in MB axillary buds. Exogenous CK promoted axillary bud outgrowth in the WT but not in MB, whereas exogenous gibberellic had no significant effect on bud outgrowth in the WT. Functional analysis of transcriptome data and RT-qPCR analysis of gene transcripts revealed that MB branching were associated with CK signaling, auxin transport, and SL signaling. Transcription of the SL-related genes MsMAX1, MsD14, and MsMAX2 in the axillary buds of MB was generally upregulated during bud outgrowth, whereas MsBRC1/2 were generally downregulated both in WT and MB. Exogenous SL inhibited outgrowth of axillary buds in the WT and the apple varieties T337, M26, and Nagafu 2, whereas axillary buds of the MB were insensitive to SL treatment. Treatment with N-1-naphthylphalamic acid (NPA; an auxin transport inhibitor) inhibited bud outgrowth in plants of the WT and MB. The transcript abundance of MsPIN1 was generally decreased in response to NPA and SL treatments, and increased in CK and decapitation treatments, whereas no consistent pattern was observed for MsD14 and MsMAX2. Collectively, the present results suggest that in apple auxin transport from the axillary bud to the stem may be essential for the outgrowth of axillary buds, and at least, is involved in the process of bud outgrowth.

MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5.

Dysfunctions of gene transcription and translation in the nociceptive pathways play the critical role in development and maintenance of chronic pain. Circular RNAs (circRNAs) are emerging as new players in regulation of gene expression, but whether and how circRNAs are involved in chronic pain remain elusive. We showed here that complete Freund's adjuvant-induced chronic inflammation pain significantly increased circRNA-Filip1l (filamin A interacting protein 1-like) expression in spinal neurons of mice. Blockage of this increase attenuated complete Freund's adjuvant-induced nociceptive behaviors, and overexpression of spinal circRNA-Filip1l in naive mice mimicked the nociceptive behaviors as evidenced by decreased thermal and mechanical nociceptive threshold. Furthermore, we found that mature circRNA-Filip1l expression was negatively regulated by miRNA-1224 via binding and splicing of precursor of circRNA-Filip1l (pre-circRNA-Filip1l) in the Argonaute-2 (Ago2)-dependent manner. Increase of spinal circRNA-Filip1l expression resulted from the decrease of miRNA-1224 expression under chronic inflammation pain state. miRNA-1224 knockdown or Ago2 overexpression induced nociceptive behaviors in naive mice, which was prevented by the knockdown of spinal circRNA-Filip1l. Finally, we demonstrated that a ubiquitin protein ligase E3 component n-recognin 5 (Ubr5), validated as a target of circRNA-Filip1l, plays a pivotal role in regulation of nociception by spinal circRNA-Filip1l. These data suggest that miRNA-1224-mediated and Ago2-dependent modulation of spinal circRNA-Filip1l expression regulates nociception via targeting Ubr5, revealing a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain.SIGNIFICANCE STATEMENT circRNAs are emerging as new players in regulation of gene expression. Here, we found that the increase of circRNA-Filip1l mediated by miRNA-1224 in an Ago2-dependent way in the spinal cord is involved in regulation of nociception via targeting Ubr5 Our study reveals a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain.