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.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective:To explore the long-term survival outcomes of patients with anaplastic thyroid cancer (ATC) and analyze key factors influencing the prognosis.Methods:A retrospective analysis was conducted on the clinical and follow-up data of 77 ATC patients treated at the Sun Yat-sen University Cancer Center from March 2000 to July 2022, with tumor-specific survival as the primary endpoint. The Kaplan-Meier method was used to plot the survival curves, and univariate and multivariate Cox regression analyses were performed to identify the prognostic factors.Results:Among the 77 patients, 64 underwent surgical treatment, with 33 receiving surgery alone, 8 undergoing surgery combined with chemotherapy, 13 undergoing surgery with radiotherapy, 1 undergoing surgery with chemotherapy and radiotherapy, 2 receiving surgery combined with chemotherapy and targeted therapy, 3 receiving surgery with targeted therapy, and 4 receiving surgery with immunotherapy and targeted therapy. Among the 13 patients who did not undergo surgery, 2 received chemotherapy alone, 3 received targeted therapy alone, 1 received immunotherapy alone, 1 received chemoradiotherapy, 5 received chemotherapy combined with immunotherapy, and 1 received immunotherapy combined with targeted therapy. The median follow-up time was 8.4 months, with 58 patients (75.3%) died, and the median survival time was 6.63 months. Univariate Cox regression analysis showed that C-reactive protein, monocyte count, lymphocyte count, abnormal albumin levels, the maximum diameter of the primary tumor, BMI, and whether immunotherapy was administered were significantly associated with survival in ATC patients (all P＜0.05). Multivariate Cox regression analysis indicated that immunotherapy was an independent factor for survival in ATC patients ( HR=0.18, 95% CI: 0.05-0.62, P=0.007). Among the 40 patients admitted after 2015, the 11 patients who received immunotherapy had a median survival time of 17.2 months, which was superior to the 29 patients who did not receive this treatment (median survival time 6.2 months, P=0.03). Conclusions:ATC patients receiving immunotherapy had a better prognosis and longer survival. Additionally, elevated C-reactive protein, abnormal albumin, monocyte count, lymphocyte count, and BMI might be associated with poorer prognosis in ATC. Tailoring treatment based on the individual characteristics of ATC patients may be beneficial for their long-term survival.

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 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 In light of the high noise and inter-class imbalance encountered in the prognosis prediction of coronary heart disease,this study aims to construct an EasyEnsemble imbalanced ensemble model after LASSO feature selection and evaluate its performance.Methods Based on survey data from the National Health and Nutrition Examination Survey public database for the years 2009-2018,with follow-up data until 2019,this study aimed to predict the prognosis of coronary heart disease based on whether there was death due to the disease as the outcome.LASSO feature selection was employed to select relevant features.Subsequently,an EasyEnsemble imbalanced ensemble prediction model,as well as SMOTE+LightGBM,XGBoost,and Random Forest prediction models,were constructed using the selected features.Grid search was performed to optimize the parameters of each model.The classification performance of the models was evaluated using metrics such as AUC,precision,specificity,G-mean,and performance curves.Additionally,SHAP analysis was applied to interpret the models'results and provide insights into their interpretability.Results The EasyEnsemble model exhibited the highest overall performance,with an AUC of 0.80(95％CI:0.79～0.82),precision of 0.86(95％CI:0.78～0.93),specificity of 0.99(95％CI:0.98～0.99),and G-mean of 0.79(95％CI:0.76～0.83),as evidenced by the performance curves.Additionally,age,serum phosphorus,diabetes,and albumin were identified as important factors influencing patient prognosis.Conclusion The LASSO- EasyEnsemble imbalanced ensemble model enables accurate prognosis prediction for coronary heart disease patients,combining SHAP can help clinicians better assess disease severity and identify at-risk groups for personalized patient management.

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 explore the long-term survival outcomes of patients with anaplastic thyroid cancer (ATC) and analyze key factors influencing the prognosis.Methods:A retrospective analysis was conducted on the clinical and follow-up data of 77 ATC patients treated at the Sun Yat-sen University Cancer Center from March 2000 to July 2022, with tumor-specific survival as the primary endpoint. The Kaplan-Meier method was used to plot the survival curves, and univariate and multivariate Cox regression analyses were performed to identify the prognostic factors.Results:Among the 77 patients, 64 underwent surgical treatment, with 33 receiving surgery alone, 8 undergoing surgery combined with chemotherapy, 13 undergoing surgery with radiotherapy, 1 undergoing surgery with chemotherapy and radiotherapy, 2 receiving surgery combined with chemotherapy and targeted therapy, 3 receiving surgery with targeted therapy, and 4 receiving surgery with immunotherapy and targeted therapy. Among the 13 patients who did not undergo surgery, 2 received chemotherapy alone, 3 received targeted therapy alone, 1 received immunotherapy alone, 1 received chemoradiotherapy, 5 received chemotherapy combined with immunotherapy, and 1 received immunotherapy combined with targeted therapy. The median follow-up time was 8.4 months, with 58 patients (75.3%) died, and the median survival time was 6.63 months. Univariate Cox regression analysis showed that C-reactive protein, monocyte count, lymphocyte count, abnormal albumin levels, the maximum diameter of the primary tumor, BMI, and whether immunotherapy was administered were significantly associated with survival in ATC patients (all P＜0.05). Multivariate Cox regression analysis indicated that immunotherapy was an independent factor for survival in ATC patients ( HR=0.18, 95% CI: 0.05-0.62, P=0.007). Among the 40 patients admitted after 2015, the 11 patients who received immunotherapy had a median survival time of 17.2 months, which was superior to the 29 patients who did not receive this treatment (median survival time 6.2 months, P=0.03). Conclusions:ATC patients receiving immunotherapy had a better prognosis and longer survival. Additionally, elevated C-reactive protein, abnormal albumin, monocyte count, lymphocyte count, and BMI might be associated with poorer prognosis in ATC. Tailoring treatment based on the individual characteristics of ATC patients may be beneficial for their long-term survival.