Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective:To analyze the influence of forming direction on the surface characteristics,elastic modulus,bending strength and fracture toughness of printed parts and the relationship between forming direction and force direction,and to provide scientific basis and guidance for the clinical applica-tion of oral denture base resin materials.Methods:The 3D printing technology was used to print denture base resin samples.The shape and size of the samples referred to the current standard for testing conven-tional denture base materials.The samples used for physical performance testing were cylindrical(with a diameter of 15 mm and a thickness of 1 mm)and printed at different angles along the Z axis(0°,45°,90°).Scanning electron microscope was used to observe the microscopic topography of the different sam-ples.The color stability of different samples was observed by color stabilizer.The surface roughness of the samples was analyzed by using surface roughness tester.The Vickers hardness was measured to ana-lyze the hardness of the samples.The samples used for mechanical performance testing were rectangular(elastic modulus and bending strength:A length of 64 mm,a width of 10 mm,and a height of 3.3 mm;fracture toughness:A length of 39 mm,a width of 8 mm,and a height of 4 mm),divided into two groups:W group and H group.The W group was printed from the bottom up along the Z axis with the length × width as the bottom surface parallel to the X,Y axis plane,while the H group printed from the bottom up along the Z axis with the length × height as the bottom surface parallel to the X,Y axis plane.The forming angles of both groups were equally divided into 0°,45°,and 90°.The elastic modulus,bending strength and fracture toughness of different samples were studied through universal mechanical testing machine.SPSS 22.0 software was used for statistical analysis.Results:The microscopic topogra-phy and roughness of different samples were closely related to the printing direction,with significant differences between the 0°,45°,and 90° specimens.The 0° specimens had the smoothest surface(roughness＜1 μm).The surface of the 45 ° specimen was the roughest(roughness＞3 μm).The microhardness of the 0° sample was the best[(196.13±0.20)MPa],with a significant difference com-pared with the 90° sample[(186.62±4.81)MPa,P＜0.05].The mechanical properties of different samples were also closely related to the printing direction.The elastic modulus,bending strength,and fracture toughness of the 45° samples in the W group were the highest compared with the other groups.The results of elastic modulus showed that in the H group,the 45° specimens had the highest elastic mo-dulus,which was significantly different from the 0° and 90° specimens(P＜0.05).The elastic modulus of 0° and 45° specimens in the W group were higher than those in 90° specimens(P＜0.05).The bending strength results showed that there was no significant difference between the specimens from dif-ferent angles in the H group.The bending strength of the 90° specimens in the W group was the smallest,and there was a significant difference between 90° and the 0° and 45° specimens(P＜0.05);And the bendind strength of the 0° and 45° specimens in the W group was significantly higher than that of the 0° and 45° specimens in the H group(P＜0.05).The fracture toughness results showed that the fracture toughness of the H group specimens was lower than 1.9 MPa m1/2,which was specified in the denture base standard.The 45° samples in the W group were the highest,with significant differences compared with the 0° and 90° samples(P＜0.05).And the 90° samples of the W group specimens were lower than 1.9 MPa m1/2.And the fracture toughness of the 45° specimen in the W group was significantly higher than that of all the specimens in the H group(P＜0.05).Conclusion:The 0° samples had rela-tively better physical properties.The 45° samples had the best mechanical properties.But the fracture toughness of specimens(H group and 90° samples of W group)did not yet meet clinical requirements.That indicated that the characteristics of the 3D printing denture base resin were affected by the printing direction.Only when the performance of the printed samples in all directions met the minimum require-ments of the standard,they could be used in clinical practice.

Emerging evidence suggests that ferroptosis,an iron-dependent form of regulated cell death,plays a criti-cal role in the genesis of liver fibrosis through inducing hepatic stellate cell(HSC)ferroptosis to inhibit liver fibrosis or inducing hepatic ferroptosis to potentiates liver fibrosis.Pharmacologically targeting at ferroptosis with its inducers can slow down the progression of liver fibrosis in vitro and in vivo model.This review suggests that pharmacological in-duction of HSC ferroptosis might be used as a potential novel targeted therapy for the treatment of liver fibrosis.

Objective To observe the changes in serum levels of interleukin-17(IL-17)and secretory pro-tein Dickkopf-1(DKK-1)in patients with spinal fracture and spinal cord injury,and to explore their predictive value for poor prognosis.Methods A total of 133 patients with spinal fractures and spinal cord injury who un-derwent spinal canal decompression surgery at the hospital from October 2018 to August 2022 were regarded as the study group.According to the american spinal injury association(ASIA)neurological function level,they were separated into the good prognosis group(80 cases)and the poor prognosis group(53 cases).Anoth-er 128 patients with simple spinal fractures who underwent spinal canal decompression surgery in the hospital were collected as the control group.Clinical data of patients with spinal fractures and spinal cord injury were collected.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum IL-17 and DKK-1 levels in all patients.Logistic regression was used to analyze factors influencing the prognosis of patients.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum IL-17 and DKK-1 levels for poor prognosis in patients.Results The serum levels of IL-17[(23.18±4.85)μg/mL vs.(12.97±3.91)pg/mL]and DKK-1[(2.48±0.41)ng/mL vs.(1.37±0.26)ng/mL]in the study group were higher than those in the control group,and the differences were statistically significant(P＜0.05).The serum IL-17[(26.61±4.85)pg/mL vs.(20.91±3.81)pg/mL]and DKK-1 levels[(2.83±0.48)ng/mL vs.(2.25±0.39)ng/mL]in the poor prognosis group were obviously higher than those in the good prognosis group,and the differences were statistically significant(P＜0.001).The independent risk factors for poor prognosis in patients included IL-17 and DKK-1(P＜0.05).The area under the curve(AUC)of serum IL-17,DKK-1 and their combined diagnosis for poor prognosis in patients was 0.822(95％CI:0.746-0.883),0.796(95％CI:0.718-0.861),and 0.910(95％CI:0.848-0.953),respectively.The diagnostic efficacy of the combination was higher than those of single detection(Z=2.034,P=0.042;Z=2.422,P=0.015).Conclusion Serum IL-17 and DKK-1 levels are elevated in patients with spinal fracture combined with spinal cord injury,and both have diagnostic value for the prognosis of the patients.

Objective To explore the improving effect of eicosapentaenoic acid(EPA)on the skeletal muscle insulin resistance in obese rats by regulating the p38 MAPK signaling pathway.Methods Fifty male Wistar rats were randomly divided into the control group,model group,inhibitor group,EPA group and inhibi-tor+EPA group,10 cases in each group.The intervention lasted for 6 weeks.The inhibitor group was given 1 mg/kg p38 MAPK inhibitor SB203580 by gavage.The EPA group was given 70 mg/kg EPA by gavage,the in-hibitor+EPA group was given SB203580+EPA by gavage,and the model group and control group were given equal volume of saline.The levels of fasting blood-glucose,fasting serum insulin,glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)in the skeletal muscles were deter-mined.The rat insulin resistance degree was evaluated by using the intraperitoneal glucose tolerance test(IPGTT)and insulin tolerance test(ITT).The protein and mRNA expression levels of phosphorylation p38 in the rat skeletal muscle tissues were detected by Western blot and qRT-PCR.Results Compared with the control group,the body weight,epididymal fat wet weight,fasting blood-glucose and insulin levels,IPGTT and ITT blood glucose levels,and MDA content in the model group were significantly increased,the GSH-Px and SOD activities were significantly decreased,and the relative expression levels of p-p38 protein and p38 mRNA expression in skeletal muscle tissues were significantly increased(P＜0.05).Compared with the model group,the body weight and epididymal fat wet weight in the EPA group and inhibitor+EPA group were sig-nificantly decreased,while the fasting blood-glucose,fasting serum insulin,IPGTT and ITT blood glucose lev-els and MDA contents in the inhibitor group and EPA group were significantly decreased,the activities of GSH-Px and SOD were significantly increased,and the relative expression level of p-p38 protein in skeletal muscle tissues was significantly decreased(P＜0.05).However,the expression of p38 mRNA in skeletal muscle tissues had no significant change(P＞0.05).Conclusion EPA alleviates the oxidative stress possibly by inhibiting p38 MAPK signaling pathway,thus improves the skeletal muscle insulin resistance of obese rats.