Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.

Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.

Liver transplantation is a crucial treatment for end-stage liver disease,yet its complexity continues to limit clinical application.With the development of the internet and big data,artificial intelligence(AI)technologies have gradually expanded their use in liver transplantation surgery,covering donor liver evaluation,organ allocation,robot-assisted surgery,and postoperative management,demonstrating significant advantages.However,the application of AI also raises a series of ethical issues,notably fairness in resource allocation,conflicts between technical limitations and the principle of non-maleficence,ambiguous responsibility attribution,patient privacy security,and informed consent.This article systematically reviews the current applications of AI in liver transplantation surgery and the related ethical challenges,aiming to provide a reference for its rational use and sustainable development.

Objective To explore the method for grading the degree of uterine adhesion in a rat model.Methods A rat model of uterine adhesion was established using the double-injury method.Paraffin sections were observed using HE staining and Masson staining to compare morphological changes in the uterus,endometrial thickness,gland and vessel counts,uterine cavity area,and adhesion severity.Rat sections were classified into three grades based on uterine cavity area for comparative analysis.Results The average uterine cavity area and uterine cavity area/endometrial layer area were smaller in rats in the model group compared with the blank group(P＜0.01).The uterine cavity area/endometrial layer area ratio was categorized into grades Ⅰ,Ⅱ,and Ⅲ,with a significant difference among the grades(P＜0.05,P＜0.01).Conclusions The uterine cavity area/endometrial layer area ratio may reflect the grading difference in the degree of uterine adhesion in rats with uterine adhesions.This ratio may thus be used as a grading-evaluation criterion in the rat model of uterine adhesion,with implications for diagnostic grading in this model.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective To investigate whether dexmedetomidine(DEX)can inhibit the inflammatory response mediated by microglia after traumatic brain injury(TBI)in rats through the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods A TBI rat model was constructed,and successfully modeled rats were randomly separated into TBI group,low and high-dose dexmedetomidine treatment groups(DEX-L,DEX-H groups),and high-dose dexmedetomidine treatment+cGAS-STING pathway activator group(DEX-H+DMXAA group),with 18 rats in each group.Additionally,18 healthy normal rats were selected as the Control group.Rats in each group were subjected to neurobehavioral scoring(mNSS).The brain water content of rats in each group was detected.Flow cytometry was used to detect Tregs in the brain tissue of each group.ELISA was applied to detect the levels of inflammatory cytokines in brain tissue.HE staining was applied to observe brain tissue injury.TUNEL staining was applied to detect neuronal apoptosis.Immunohistochemistry was applied to detect the expression of the microglial cell marker ion calcium binding adapter molecule 1(Iba1).Western blot was applied to detect the expression of apoptosis and cGAS-STING pathway related proteins.Results Compared with the Control group,the TBI group showed structural injury to brain tissue,edema,abnormal neuronal morphology,reduced number and disordered arrangement,deep staining of nuclear folds,and blurred nucleoli,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1 β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Compared with the TBI group,the brain tissue structure of the DEX-L and DEX-H groups was slightly injuried,edema was reduced,and the morphology of neurons was relatively normal,with a small decrease in number and relatively neat arrangement,a small amount of nuclei were wrinkled and deeply stained,and most of the nucleoli were obvious,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were reduced(P＜0.05).The brain tissue structure and neuronal injury in the DEX-H+DMXAA group were more severe than the DEX-H group,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Conclusion Dexmedetomidine can inhibit the inflammatory response mediated by microglia after TBI in rats,and its mechanism of action is related to the inhibition of the cGAS-STING pathway.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective To understand the membrane protein molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in the region,and provide some evidence for rational drug use or application of efflux pump inhibitors. Methods Collected Pseudomonas aeruginosa isolated from four hospitals in the region from October 2022 to August 2023,and used SYBR-PCR method to quantitatively detect the relative mRNA expression (RE) levels of 10 membrane protein coding genes,including mexA,B,C,D,E,F,X,Y,and oprD,M. Then categorized the strains into five groups based on ceftazidime,cefepime,imipenem,and meropenem resistance phenotype combination,including the compassionate group (Group Ⅰ),Group Ⅱ with full resistance,IPM,MEM resistant,CAZ and CFP sensitive groups (Group Ⅲ),IPM resistance,MEM non-resistance (sensitive or intermediate) group (Group Ⅳ),IPM,MEM resistance,CAZ and CFP non-resistance groups (Group V).The median RE of each membrane protein-coding gene was analyzed. Results A total of 108 strains of Pseudomonas aeruginosa were collected,with 24 strains in Group Ⅰ as controls and 84 strains in the carbapenem resistant group,including 32 strains in Group Ⅱ,22 strains in Group Ⅲ,13 strains in Group Ⅳ,and 17 strains in Group Ⅴ. The expression of mexD,mexE,mexF,mexX and mexY in the drug-resistant group was higher than that in the control group,and the differences were statistically significant (U=409.5～661.0,all P<0.05). There was no statistically significant difference in mexA,mexB,mexC,oprD and oprM with the control group (U=767.0～1004.5,all P>0.05). There was no significant difference in the expression of RE genes encoding various membrane proteins among strains from different hospitals (H=0.914～7.407,all P>0.05). Among the four different phenotypes,there was no statistically significant difference in the irregular distribution of mexA and oprM RE between each group and the control group (UmexA=95.0～264.0,UoprM=143.0～331.0). The mexC RE in each group was lower than that in the control group,but the differences were not statistically significant (U=134.0～344.5,all P>0.05). MeixE and meixY RE were both higher than the control group,and the differences were statistically significant (UmexE=48.0～230.0,UmexY=83.0～184.0). MeixB was lower than the control group in group Ⅳ (U=72.0),and the differences were statistically significant (all P<0.05). MeixD and meixF showed consistent expression,with higher expression in groups Ⅲ,Ⅳ and Ⅴ compared to the control group (UmeixD=34.0～102.0,UmeixF=65.0～113.0). MeixX was expressed higher in groups Ⅱ,Ⅳ and Ⅴ compared to the control group (U=164.0,58.0,111.0),while oprD was only expressed lower in group Ⅲ than in the control group (U=140.0),with statistically significant differences (all P<0.05). Although the expression of oprD in groups Ⅱ,Ⅳ and Ⅴ was lower than that in the control group,the differences were not statistically significant (U=381.0,102.0,144.0,all P>0.05). Conclusion ExCD,mexEF and mexXY are the main membrane protein combinations of CRPA efflux pumps in Kunming area. Upregulation of mexD,E,F,X,and Y membrane protein expression enhanced efflux. The correlation between mexAB oprM efflux pump and carbapenem resistance in CRPA in this area was low. The low expression of oprD played a role in the efflux mechanism in strains that do not produce β-lactase,but there was no significant difference in low expression in enzyme producing strains.

Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P＜0.05),while AST significantly increased these thresholds in OXA-treated rats(P＜0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P＜0.05).AST restored SOD activity and reduced MDA level(P＜0.05,P＜0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P＞0.05),which were further upregulated by AST(P＜0.05,P＜0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P＜0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P＜0.01,P＜0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P＜0.05),which was attenuated by AST(P＜0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P＜0.01),which was partially reversed by AST(P＜0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P＜0.05,P＜0.01),and AST further enhanced their levels(P＜0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.

Objective To explore the pathophysiological molecular mechanism of the up-regulation of CircPDS5B level involved in premature birth.Methods The placental tissues of full-term infants(Group 1,gestational age≥37 weeks),late premature infants(Group 2,34 weeks≤gestational age<37 weeks),premature infants(Group 3,32 weeks