It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mo...It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.展开更多
AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen fo...AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen for pathogenic genes and candidate pathogenic variants were obtained by bioinformatics analysis.Sanger sequencing was used for validation and familial cosegregation analysis to determine pathogenic variants.Pymol software was applied to produce a 3D structure image of the protein to analyze the structural and functional alterations of the protein.The pathogenicity of genetic variants was evaluated according to ACMG guidelines.RESULTS:The chief clinical symptoms of this proband included obvious visual impairment,protanopia and deuteranopia,peripheral punctate pigment,arteriolar attenuation,structural and functional abnormalities revealed by optical coherence tomography(OCT)and electroretinography(ERG)including thinning of the outer retinal layer,a discontinuous external limiting membrane(ELM)and ellipsoid zone(EZ),granular hyperreflective projections between the retinal pigment epithelium and the interdigitation zone,severe attenuation of photopic responses with mild reduced scotopic responses.Wholeexome sequencing revealed that the proband carried a heterozygous variant of the GUCY2D gene:c.2512C>T:p.Arg838Cys.Three-dimensional molecular structure analysis of the protein revealed that amino acid 838 was mutated from polar positively charged arginine to polar uncharged cysteine,and the spatial structure of the protein changed greatly.Sanger sequencing co-segregation analysis confirmed that such a variant was detected in neither the phenotypically normal parents nor the daughter of the proband,which was presumed to be a de novo one.The variant was determined to be pathogenic according to ACMG guidelines.The heterozygous variant at the same site was detected in the abnormal proband’s son with moderate attenuation of photopic electroretinographic responses and normal scotopic electroretinographic responses,supporting autosomal dominant inheritance.CONCLUSION:The de novo variant causing atypical autosomal dominant CRD is identified in a Chinese consanguineous family and this variant passes through this family in an autosomal dominant mode of inheritance,revealing the complex diversity and unpredictability of the inheritance mode for common single-gene genetic disease.展开更多
BACKGROUND Epigenetic regulation of leptin(LEP)plays a critical role in metabolic disorders,yet its promoter methylation patterns in lean diabetic populations remain poorly characterized.Emerging evidence suggests DNA...BACKGROUND Epigenetic regulation of leptin(LEP)plays a critical role in metabolic disorders,yet its promoter methylation patterns in lean diabetic populations remain poorly characterized.Emerging evidence suggests DNA methylation may precede clinical hyperglycemia,offering potential for early risk stratification.While obesity-associated LEP methylation is well-studied,lean Asian populations who exhibit high diabetes prevalence despite lower adiposity,represent an underexplored cohort.This study hypothesizes that LEP promoter methylation in peripheral leukocytes decreases progressively from normoglycemia to prediabetes and type 2 diabetes mellitus(T2DM),correlating inversely with serum LEP levels in lean Chinese adults[body mass index(BMI)<24 kg/m^(2)].AIM To investigate LEP promoter methylation status and its association with serum LEP levels across glycemic states in lean Chinese adults.METHODS We enrolled 392 participants including 120 normoglycemic controls,94 prediabetes[44 impaired fasting glucose(IFG)/50 impaired glucose tolerance(IGT)],178 T2DM aged 40-60 years with BMI<24 kg/m^(2).Genomic DNA from peripheral leukocytes underwent bisulfite conversion followed by methylation-specific PCR to assess CpG methylation in the LEP promoter.Serum LEP was quantified via enzyme-linked immunosorbent assay,with other parameters measured through standard assays.Statistical analyses included analysis of variance,χ²tests,and Pearson correlation(Bonferroni-corrected P value).RESULTS Methylation frequencies declined progressively:59.2%(controls)reduced to 43.6%(prediabetes;IFG:38.6%,IGT:48%)reduced to 31.5%(T2DM)(all P<0.05 vs controls;T2DM vs IGT:P=0.030).Serum LEP levels increased significantly in T2DM(16.94±4.19μg/L)vs controls(11.33±3.10μg/L;P=0.002),with intermediate values in prediabetes(IFG:13.79±3.32μg/L;IGT:12.62±4.81μg/L).A near-perfect inverse correlation between methylation and LEP levels was observed(r=-0.95,95%CI:-0.97 to-0.92,P<0.001),persisting after adjusting for age and BMI(β=-0.91,P<0.001).CONCLUSION LEP promoter hypomethylation parallels worsening glycemic status in lean Chinese adults,suggesting its potential as a blood-based epigenetic biomarker for diabetes progression,pending validation in longitudinal cohorts.展开更多
目的基于生物信息学分析HMGA2基因在脑胶质瘤中的表达和预后意义,并推断HMGA2对脑胶质瘤发生、发展的生物学功能。方法从中国脑胶质瘤基因组图谱数据库(Chinese Glioma Genome Atlas,CGGA)和癌症基因组图谱(the Cancer Genome Atlas,TC...目的基于生物信息学分析HMGA2基因在脑胶质瘤中的表达和预后意义,并推断HMGA2对脑胶质瘤发生、发展的生物学功能。方法从中国脑胶质瘤基因组图谱数据库(Chinese Glioma Genome Atlas,CGGA)和癌症基因组图谱(the Cancer Genome Atlas,TCGA)中各自获取693例和697例脑胶质瘤的基因表达数据集以及临床信息数据集,对HMGA2的不同表达状态进行研究。采用Kaplan-Meier生存曲线法和Cox分析法分析HMGA2对脑胶质瘤预后的预测价值。通过基因本体论(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析预测HMGA2可能富集的通路。将HMGA2与血管生成相关基因集进行基因集变异分析(gene set variation analysis,GSVA)。结果HMGA2在胶质瘤高级别、异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)野生型、无1p/19q共缺失的组别中高表达。生存分析显示,HMGA2较高表达脑胶质瘤患者的总生存期(overall survival,OS)显著低于HMGA2较低表达的OS(P<0.0001)。在Cox回归分析中,HMGA2表达水平是OS的独立预后因素。GO和KEGG分析显示,HMGA2富集在血管生成、内质网腔、细胞凋亡、肿瘤中的蛋白聚糖、蛋白结合、细胞外基质与受体的相互作用、焦点黏附、PI3KAKT信号通路等。GSVA结果显示HMGA2表达与血管生成呈正相关。结论HMGA2的表达与脑胶质瘤的病理级别和分子标志物密切相关,HMGA2高表达的脑胶质瘤患者预后较差,HMGA2能够影响胶质瘤的发生、发展,有望作为脑胶质瘤患者的预测标志物和治疗靶点。展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
[Objective] The aim of this study was to provide metabolic evidence for the analysis of the ecological and safety assessment of Pi-d2-transgenic rice.[Method] The main agronomic characters of Pi-d2-transgenic rice wer...[Objective] The aim of this study was to provide metabolic evidence for the analysis of the ecological and safety assessment of Pi-d2-transgenic rice.[Method] The main agronomic characters of Pi-d2-transgenic rice were observed in field experiment and the grain chemical characters and amino acid content were measured.[Results] Introduction of foreign gene Pi-d2 resulted in stably hereditable variation in agronomic characteristics in the descents.Most of the transgenic lines grew normally and orderly.Compared with the control（wild type plants）,about half of transgenic plants showed an increased or reduced plant height.There was no observable difference between transgenic plants and controls in tiller number,length of panicle,panicles per plant,seed-setting rate and 1 000-grain weight.Total amino acid content in transgenic rice was reduced,while the starch content,GC and GT were not altered in comparison with the control.[Conclusion] Introduction of foreign gene Pi-d2 has remarkable influence on plant height,while little on grain chemical characters.展开更多
目的:探究宫腔粘连(Intrauterine adhesion,IUA)患者子宫内膜组织中高迁移率族蛋白B1(High mobility group box1,HMGB1)、高迁移率族蛋白A2(High mobility group protein A2,HMGA2)和表皮生长因子受体(Epidermal growth factor receptor...目的:探究宫腔粘连(Intrauterine adhesion,IUA)患者子宫内膜组织中高迁移率族蛋白B1(High mobility group box1,HMGB1)、高迁移率族蛋白A2(High mobility group protein A2,HMGA2)和表皮生长因子受体(Epidermal growth factor receptor,EGFR)表达与病情及预后关系。方法:选取2021年8月-2023年8月本院收治的68例IUA患者(IUA组)和60例正常宫腔患者(对照组),采用免疫组化法检测HMGB1、HMGA2和EGFR表达,分析其与病情严重程度及预后不良的关系。结果:IUA组HMGB1阳性表达率低于对照组,HMGA2和EGFR阳性表达率显著升高(P<0.05)。随着病情加重,IUA患者子宫内膜组织中HMGB1阳性表达率依次降低,HMGA2和EGFR阳性表达率依次升高(P<0.05)。单因素分析显示,患者预后不良与流产史、术前月经量、粘连范围、粘连性质、HMGB1、HMGA2及EGFR表达情况有关(P<0.05),与年龄和病程无关(P>0.05)。多因素Logistic回归分析显示,流产史>3次、术前闭经、粘连范围>2/3、粘连性质肌性、HMGB1阴性表达、HMGA2及EGFR阳性表达是患者术后复发的危险因素(P<0.05)。结论:IUA患者子宫内膜组织中HMGB1低表达及HMGA2和EGFR高表达与患者病情程度及预后有关,可作为患者患病程度及不良预后的评估指标。展开更多
[Objective] The study was to analyze the phylogenesis of Anas platyrhynchos. [Method] Complete sequence of mitochondrial ND2 gene of 4 Anas platyrhynchos was determined by direct DNA sequencing based on PCR products. ...[Objective] The study was to analyze the phylogenesis of Anas platyrhynchos. [Method] Complete sequence of mitochondrial ND2 gene of 4 Anas platyrhynchos was determined by direct DNA sequencing based on PCR products. Combined with ND2 gene sequences of the Anas Linnaeus accessed in GenBank, phylogenetic tree was constructed by Neighbor-joining and maximum parsimony methods. [Result] The ND2 gene sequences of 4 Anas platyrhynchos were identical(1 041 bp in length; the nucleotide contents of A, G, T, and C were 28.91%, 13.35%, 20.75% and 36.98% respectively; A+T content approximated to that of C+G). Sequences of ND2 gene of mallard were same as spotbill duck, and had high homology with others. The phylogenetic trees indicated mallard and spotbilled duck were close in genetic relationship, both shared a haplotype; then Philippine duck, green-winged teal and northern pintail fell into branch ''A". [Conclusion] The domestic duck may be domesticated from mallard and spotbilled duck.展开更多
During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many...During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many edible plants,can ameliorate obesity by activating adipose tissue browning,but its effect on circadian clock in this process remains poorly understood.Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet(HFD)-fed wild-type(WT)mice.Moreover,dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period,which was similar to the LU-increased hepatic PER2 expressions.Hepatic peroxisome proliferators-activated receptorsα(PPARα)/recombinant retinoid X receptorα(RXRα)/fibroblast growth factor 21(FGF21)pathway was rhythmically elevated by dietary LU in HFD-fed WT mice,whereas the promotion was inhibited in Per2^(-/-)mice.Meanwhile,Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice.Further,LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^(-/-)mice.Taken together,the deletion of the core clock component Per2 impedes LUinduced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice,providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.展开更多
Magnolia officinalis is a perennial deciduous tree that has medicinal properties.The AP2/ERF gene family has a number of roles in long-term growth and metabolism.The expression of this function varies with the growth ...Magnolia officinalis is a perennial deciduous tree that has medicinal properties.The AP2/ERF gene family has a number of roles in long-term growth and metabolism.The expression of this function varies with the growth period.In this work,based on the transcriptome data of Magnolia officinalis,the complete coding gene of Magnolia officinalis was obtained,and the corresponding protein sequence was retrieved from NCBI and compared with the model plant Arabidopsis thaliana.After screening,75 protein sequences from the AP2/ERF gene family were identified and called MoAP2/ERF1–MoAP2/ERF75,followed by bioinformatics analysis.75 AP2/ERF gene families were found and classified into four subfamilies.Their protein architectures had one or more conserved AP2 domains,which were typically unstable and hydrophilic.Subcellular research revealed that it was primarily located in the nucleus.Among them,the DREB subfamily showed stronger activity in the early growth period of Magnolia officinalis,suggesting that Magnolia officinalis had stronger resistance to adversity during this period.The 15 members of the MoAP2/ERF gene family showed significant differences during different growth periods,and they regulated the gene expression of Magnolia officinalis by binding to DNA.The 15 MoAP2/ERF gene families have a wide range of physiological activities in biological processes,cellular components,and molecular functions.Including MoAP2/ERF55 can catalyze imidazole glycerol phosphate synthase activity;MoAP2/ERF39 acts as a transcriptional activator of Pti6.展开更多
BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and li...BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.展开更多
Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has bee...Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has been well-documented in prior research,molecular investigations focusing on AP2/ERF remain notably lacking in Acer paxii.This research focuses on performing an extensive genome-wide investigation to identify and characterize the AP2/ERF gene family in Acer paxii.As a result,123 ApAP2/ERFs were obtained.Phylogenetic analyses categorized the ApAP2/ERF family members into 15 subfamilies.The evolutionary traits of the ApAP2/ERFs were investigated by analyzing their chromosomal locations,conserved proteinmotifs,and gene duplication events.Moreover,investigating gene promoters revealed their potential involvement in developmental regulation,physiological processes,and stress adaptationmechanisms.Measurements of anthocyanin content revealed a notable increase in red leaves during autumn.Utilizing transcriptome data,transcriptomic profiling revealed that the majority of AP2/ERF genes in Acer paxii displayed significant differential expression between red and green leaves during the color-changing period.Furthermore,through qRT-PCR analysis,it was found that the gene expression levels of ApERF006,ApERF014,ApERF048,ApERF097,and ApERF107 were significantly elevated in red leaves.This indicates their potential participation in leaf pigmentation processes.These findings offer significant insights into the biological significance of ApAP2/ERF transcription factors and lay the groundwork for subsequent investigations into their regulatorymechanisms underlying leaf pigmentation in Acer paxii.展开更多
Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its im...Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.展开更多
BACKGROUND:With the objective of developing a locally- produced radioactive stent,the present study used in vivo animal experiments to explore apoptosis of proliferative smooth muscle cells resulting from facilitation...BACKGROUND:With the objective of developing a locally- produced radioactive stent,the present study used in vivo animal experiments to explore apoptosis of proliferative smooth muscle cells resulting from facilitation of the expression of genes caused byγ-radiation in order to prevent bile duct restenosis.We therefore explored the effects and significance ofγ-radiation on the activity of caspase-3,Fas and Bcl-2 genes in apoptosis of proliferative smooth muscle cells in the bile duct walls of dogs. METHODS:Twelve dogs were randomly divided into 2 groups(6 in each group).A postinjury bile duct stenosis model was established and radioactive 103 Pd( 103 palladium) or ordinary bile duct stents were implanted into the bile ducts.HE staining,RT-PCR and immunohistochemistry were used to detect the proliferation and apoptosis of bile duct smooth muscle cells in proliferative endomembrane and the expression of related caspase-3,Bcl-2 and Fas genes. RESULTS:The expression of caspase-3 and Fas genes in the bile duct tissues of dogs with radioactive stents was higher than that of dogs with ordinary stents.There was significant apoptosis of proliferative smooth muscle cells in the bile ducts.The expression of the Bcl-2 gene in the bile duct tissues of dogs with radioactive stents was lower than that in those with ordinary stents.There was significant apoptosis of proliferative smooth muscle cells in the dogs with low Bcl-2 gene expression. CONCLUSIONS:Radiation increases the activity of caspase-3 and Fas genes and is associated with apoptosis. The radioactive 103 Pd stent may facilitate apoptosis of proliferative smooth muscle cells in the bile ducts of dogs by activating these genes.The Bcl-2 gene expression level is correlated with the occurrence of apoptosis and the radiosusceptibility of cells.展开更多
AIM To investigate the relationship between the expression of p16 gene and the gastric carcinogenesis,depth of invasion and lymph node metastases, and to evaluate the deletion and mutation of exon 2 in p16 gene in gas...AIM To investigate the relationship between the expression of p16 gene and the gastric carcinogenesis,depth of invasion and lymph node metastases, and to evaluate the deletion and mutation of exon 2 in p16 gene in gastric carcinoma.METHODS The expression of P16 protein was examined by streptavidin-peroxidase conjugated method (S-P); the deletion and mutation of p16 gene were respectively examined by polymerase chain reaction (PCR) and polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) in gastric carcinoma.RESULTS Expression of P16 protein was detected in 96.25% (77/80) of the normal gastric mucosa, in 92.00% (45/50) of the dysplastic gastric mucosa and in 47.54% (58/122) of the gastric carcinoma. The positive rate of P16 protein expression in gastric carcinoma was significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P＜0.05). The positive rate of P16 protein expression in mucoid carcinoma 10.00% (1/ 10) was significantly lower than that in poorly differentiated carcinoma 51.22% ( 21/ 41 ),undifferentiated carcinoma 57.69% (15/26) and signet ring cell carcinoma 62.50% (10/ 16) (P＜0.05). The positive rate of p16 protein in 30 cases paired primary and lymph node metastatic gastric carcinoma: There was 46.67% (14/30) in primary gastric carcinoma, 16.67% (5/30) in lymph node metastatic gastric carcinoma. The positive rate of lymph node metastatic carcinoma was significantly lower than that of primary carcinoma (P＜0.05). There was of p16 gene mutation in exon 2, but 5 cases displayed deletion of p16 gene in exon 2 in the 25 primary gastric carcinomas.CONCLUSIONS The expression loss of P16 protein related to the gastric carcinogenesis, gastric carcinoma histopathological subtypes and lymph metastasis. The mutation of p16 gene in exon 2 may not be involved in gastric carcinogenesis. But the deletion of p16 gene in exon 2 may be involved in gastric carcinogenesis.展开更多
The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of ne...The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog （PTEN） enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated （Y444F） AAV2 vector to efficiently express a short hairpin RNA （shRNA） for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 （both carrying shRNA to PTEN） 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover,post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ～19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.展开更多
基金Israel Cancer Research FoundationSamuel Waxman Cancer Research FoundationCore funding from Tel Aviv University。
文摘It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.
基金Supported by the National Natural Science Foundation of China(No.82260206)Natural Science Foundation of Ningxia(No.2022AAC03387)+1 种基金Major Achievement Transformation Project of Ningxia Hui Autonomous Region(No.2022CJE09011)the Key Research Development Project of Ningxia Hui Autonomous Region(No.2024BEG02017).
文摘AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen for pathogenic genes and candidate pathogenic variants were obtained by bioinformatics analysis.Sanger sequencing was used for validation and familial cosegregation analysis to determine pathogenic variants.Pymol software was applied to produce a 3D structure image of the protein to analyze the structural and functional alterations of the protein.The pathogenicity of genetic variants was evaluated according to ACMG guidelines.RESULTS:The chief clinical symptoms of this proband included obvious visual impairment,protanopia and deuteranopia,peripheral punctate pigment,arteriolar attenuation,structural and functional abnormalities revealed by optical coherence tomography(OCT)and electroretinography(ERG)including thinning of the outer retinal layer,a discontinuous external limiting membrane(ELM)and ellipsoid zone(EZ),granular hyperreflective projections between the retinal pigment epithelium and the interdigitation zone,severe attenuation of photopic responses with mild reduced scotopic responses.Wholeexome sequencing revealed that the proband carried a heterozygous variant of the GUCY2D gene:c.2512C>T:p.Arg838Cys.Three-dimensional molecular structure analysis of the protein revealed that amino acid 838 was mutated from polar positively charged arginine to polar uncharged cysteine,and the spatial structure of the protein changed greatly.Sanger sequencing co-segregation analysis confirmed that such a variant was detected in neither the phenotypically normal parents nor the daughter of the proband,which was presumed to be a de novo one.The variant was determined to be pathogenic according to ACMG guidelines.The heterozygous variant at the same site was detected in the abnormal proband’s son with moderate attenuation of photopic electroretinographic responses and normal scotopic electroretinographic responses,supporting autosomal dominant inheritance.CONCLUSION:The de novo variant causing atypical autosomal dominant CRD is identified in a Chinese consanguineous family and this variant passes through this family in an autosomal dominant mode of inheritance,revealing the complex diversity and unpredictability of the inheritance mode for common single-gene genetic disease.
文摘BACKGROUND Epigenetic regulation of leptin(LEP)plays a critical role in metabolic disorders,yet its promoter methylation patterns in lean diabetic populations remain poorly characterized.Emerging evidence suggests DNA methylation may precede clinical hyperglycemia,offering potential for early risk stratification.While obesity-associated LEP methylation is well-studied,lean Asian populations who exhibit high diabetes prevalence despite lower adiposity,represent an underexplored cohort.This study hypothesizes that LEP promoter methylation in peripheral leukocytes decreases progressively from normoglycemia to prediabetes and type 2 diabetes mellitus(T2DM),correlating inversely with serum LEP levels in lean Chinese adults[body mass index(BMI)<24 kg/m^(2)].AIM To investigate LEP promoter methylation status and its association with serum LEP levels across glycemic states in lean Chinese adults.METHODS We enrolled 392 participants including 120 normoglycemic controls,94 prediabetes[44 impaired fasting glucose(IFG)/50 impaired glucose tolerance(IGT)],178 T2DM aged 40-60 years with BMI<24 kg/m^(2).Genomic DNA from peripheral leukocytes underwent bisulfite conversion followed by methylation-specific PCR to assess CpG methylation in the LEP promoter.Serum LEP was quantified via enzyme-linked immunosorbent assay,with other parameters measured through standard assays.Statistical analyses included analysis of variance,χ²tests,and Pearson correlation(Bonferroni-corrected P value).RESULTS Methylation frequencies declined progressively:59.2%(controls)reduced to 43.6%(prediabetes;IFG:38.6%,IGT:48%)reduced to 31.5%(T2DM)(all P<0.05 vs controls;T2DM vs IGT:P=0.030).Serum LEP levels increased significantly in T2DM(16.94±4.19μg/L)vs controls(11.33±3.10μg/L;P=0.002),with intermediate values in prediabetes(IFG:13.79±3.32μg/L;IGT:12.62±4.81μg/L).A near-perfect inverse correlation between methylation and LEP levels was observed(r=-0.95,95%CI:-0.97 to-0.92,P<0.001),persisting after adjusting for age and BMI(β=-0.91,P<0.001).CONCLUSION LEP promoter hypomethylation parallels worsening glycemic status in lean Chinese adults,suggesting its potential as a blood-based epigenetic biomarker for diabetes progression,pending validation in longitudinal cohorts.
文摘目的基于生物信息学分析HMGA2基因在脑胶质瘤中的表达和预后意义,并推断HMGA2对脑胶质瘤发生、发展的生物学功能。方法从中国脑胶质瘤基因组图谱数据库(Chinese Glioma Genome Atlas,CGGA)和癌症基因组图谱(the Cancer Genome Atlas,TCGA)中各自获取693例和697例脑胶质瘤的基因表达数据集以及临床信息数据集,对HMGA2的不同表达状态进行研究。采用Kaplan-Meier生存曲线法和Cox分析法分析HMGA2对脑胶质瘤预后的预测价值。通过基因本体论(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析预测HMGA2可能富集的通路。将HMGA2与血管生成相关基因集进行基因集变异分析(gene set variation analysis,GSVA)。结果HMGA2在胶质瘤高级别、异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)野生型、无1p/19q共缺失的组别中高表达。生存分析显示,HMGA2较高表达脑胶质瘤患者的总生存期(overall survival,OS)显著低于HMGA2较低表达的OS(P<0.0001)。在Cox回归分析中,HMGA2表达水平是OS的独立预后因素。GO和KEGG分析显示,HMGA2富集在血管生成、内质网腔、细胞凋亡、肿瘤中的蛋白聚糖、蛋白结合、细胞外基质与受体的相互作用、焦点黏附、PI3KAKT信号通路等。GSVA结果显示HMGA2表达与血管生成呈正相关。结论HMGA2的表达与脑胶质瘤的病理级别和分子标志物密切相关,HMGA2高表达的脑胶质瘤患者预后较差,HMGA2能够影响胶质瘤的发生、发展,有望作为脑胶质瘤患者的预测标志物和治疗靶点。
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金Supported by Program for New Century Excellent Talents in University of Ministry of Education of China(NCET-04-0907)Program for Young Scholars in Breeding from Sichuan Provincial Department of Finance(2009QNJJ-D18)~~
文摘[Objective] The aim of this study was to provide metabolic evidence for the analysis of the ecological and safety assessment of Pi-d2-transgenic rice.[Method] The main agronomic characters of Pi-d2-transgenic rice were observed in field experiment and the grain chemical characters and amino acid content were measured.[Results] Introduction of foreign gene Pi-d2 resulted in stably hereditable variation in agronomic characteristics in the descents.Most of the transgenic lines grew normally and orderly.Compared with the control（wild type plants）,about half of transgenic plants showed an increased or reduced plant height.There was no observable difference between transgenic plants and controls in tiller number,length of panicle,panicles per plant,seed-setting rate and 1 000-grain weight.Total amino acid content in transgenic rice was reduced,while the starch content,GC and GT were not altered in comparison with the control.[Conclusion] Introduction of foreign gene Pi-d2 has remarkable influence on plant height,while little on grain chemical characters.
文摘目的:探究宫腔粘连(Intrauterine adhesion,IUA)患者子宫内膜组织中高迁移率族蛋白B1(High mobility group box1,HMGB1)、高迁移率族蛋白A2(High mobility group protein A2,HMGA2)和表皮生长因子受体(Epidermal growth factor receptor,EGFR)表达与病情及预后关系。方法:选取2021年8月-2023年8月本院收治的68例IUA患者(IUA组)和60例正常宫腔患者(对照组),采用免疫组化法检测HMGB1、HMGA2和EGFR表达,分析其与病情严重程度及预后不良的关系。结果:IUA组HMGB1阳性表达率低于对照组,HMGA2和EGFR阳性表达率显著升高(P<0.05)。随着病情加重,IUA患者子宫内膜组织中HMGB1阳性表达率依次降低,HMGA2和EGFR阳性表达率依次升高(P<0.05)。单因素分析显示,患者预后不良与流产史、术前月经量、粘连范围、粘连性质、HMGB1、HMGA2及EGFR表达情况有关(P<0.05),与年龄和病程无关(P>0.05)。多因素Logistic回归分析显示,流产史>3次、术前闭经、粘连范围>2/3、粘连性质肌性、HMGB1阴性表达、HMGA2及EGFR阳性表达是患者术后复发的危险因素(P<0.05)。结论:IUA患者子宫内膜组织中HMGB1低表达及HMGA2和EGFR高表达与患者病情程度及预后有关,可作为患者患病程度及不良预后的评估指标。
基金Supported by National Key Technology R&D program(2006BAD06B06)National Infrastructure of Natural Resources for Science and Technology(2004DKA30460)~~
文摘[Objective] The study was to analyze the phylogenesis of Anas platyrhynchos. [Method] Complete sequence of mitochondrial ND2 gene of 4 Anas platyrhynchos was determined by direct DNA sequencing based on PCR products. Combined with ND2 gene sequences of the Anas Linnaeus accessed in GenBank, phylogenetic tree was constructed by Neighbor-joining and maximum parsimony methods. [Result] The ND2 gene sequences of 4 Anas platyrhynchos were identical(1 041 bp in length; the nucleotide contents of A, G, T, and C were 28.91%, 13.35%, 20.75% and 36.98% respectively; A+T content approximated to that of C+G). Sequences of ND2 gene of mallard were same as spotbill duck, and had high homology with others. The phylogenetic trees indicated mallard and spotbilled duck were close in genetic relationship, both shared a haplotype; then Philippine duck, green-winged teal and northern pintail fell into branch ''A". [Conclusion] The domestic duck may be domesticated from mallard and spotbilled duck.
文摘During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many edible plants,can ameliorate obesity by activating adipose tissue browning,but its effect on circadian clock in this process remains poorly understood.Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet(HFD)-fed wild-type(WT)mice.Moreover,dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period,which was similar to the LU-increased hepatic PER2 expressions.Hepatic peroxisome proliferators-activated receptorsα(PPARα)/recombinant retinoid X receptorα(RXRα)/fibroblast growth factor 21(FGF21)pathway was rhythmically elevated by dietary LU in HFD-fed WT mice,whereas the promotion was inhibited in Per2^(-/-)mice.Meanwhile,Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice.Further,LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^(-/-)mice.Taken together,the deletion of the core clock component Per2 impedes LUinduced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice,providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.
基金supported by the National Natural Science Foundation of China(num-ber 81202933)the Natural Science Foundation of Sichuan Province(number 2025ZNSFSC0205 and number 2022NSFSC0592)the Science and Technology Plan Project of Mianyang City(number 2018YFZJ025).
文摘Magnolia officinalis is a perennial deciduous tree that has medicinal properties.The AP2/ERF gene family has a number of roles in long-term growth and metabolism.The expression of this function varies with the growth period.In this work,based on the transcriptome data of Magnolia officinalis,the complete coding gene of Magnolia officinalis was obtained,and the corresponding protein sequence was retrieved from NCBI and compared with the model plant Arabidopsis thaliana.After screening,75 protein sequences from the AP2/ERF gene family were identified and called MoAP2/ERF1–MoAP2/ERF75,followed by bioinformatics analysis.75 AP2/ERF gene families were found and classified into four subfamilies.Their protein architectures had one or more conserved AP2 domains,which were typically unstable and hydrophilic.Subcellular research revealed that it was primarily located in the nucleus.Among them,the DREB subfamily showed stronger activity in the early growth period of Magnolia officinalis,suggesting that Magnolia officinalis had stronger resistance to adversity during this period.The 15 members of the MoAP2/ERF gene family showed significant differences during different growth periods,and they regulated the gene expression of Magnolia officinalis by binding to DNA.The 15 MoAP2/ERF gene families have a wide range of physiological activities in biological processes,cellular components,and molecular functions.Including MoAP2/ERF55 can catalyze imidazole glycerol phosphate synthase activity;MoAP2/ERF39 acts as a transcriptional activator of Pti6.
基金Supported by Special Research Plan 2023 of Chaozhou,No.202303GY05。
文摘BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.
基金supported by the National Natural Science Foundation of China[grant numbers 32271914 and 32301660]the Quality Engineering Project of Anhui Provincial Department of Education[grant number 2023zygzts007].
文摘Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has been well-documented in prior research,molecular investigations focusing on AP2/ERF remain notably lacking in Acer paxii.This research focuses on performing an extensive genome-wide investigation to identify and characterize the AP2/ERF gene family in Acer paxii.As a result,123 ApAP2/ERFs were obtained.Phylogenetic analyses categorized the ApAP2/ERF family members into 15 subfamilies.The evolutionary traits of the ApAP2/ERFs were investigated by analyzing their chromosomal locations,conserved proteinmotifs,and gene duplication events.Moreover,investigating gene promoters revealed their potential involvement in developmental regulation,physiological processes,and stress adaptationmechanisms.Measurements of anthocyanin content revealed a notable increase in red leaves during autumn.Utilizing transcriptome data,transcriptomic profiling revealed that the majority of AP2/ERF genes in Acer paxii displayed significant differential expression between red and green leaves during the color-changing period.Furthermore,through qRT-PCR analysis,it was found that the gene expression levels of ApERF006,ApERF014,ApERF048,ApERF097,and ApERF107 were significantly elevated in red leaves.This indicates their potential participation in leaf pigmentation processes.These findings offer significant insights into the biological significance of ApAP2/ERF transcription factors and lay the groundwork for subsequent investigations into their regulatorymechanisms underlying leaf pigmentation in Acer paxii.
基金partially supported by the National Natural Science Foundation of China(42177164,52474121)the Outstanding Youth Project of Hunan Provincial Department of Education(23B0008).
文摘Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.
文摘BACKGROUND:With the objective of developing a locally- produced radioactive stent,the present study used in vivo animal experiments to explore apoptosis of proliferative smooth muscle cells resulting from facilitation of the expression of genes caused byγ-radiation in order to prevent bile duct restenosis.We therefore explored the effects and significance ofγ-radiation on the activity of caspase-3,Fas and Bcl-2 genes in apoptosis of proliferative smooth muscle cells in the bile duct walls of dogs. METHODS:Twelve dogs were randomly divided into 2 groups(6 in each group).A postinjury bile duct stenosis model was established and radioactive 103 Pd( 103 palladium) or ordinary bile duct stents were implanted into the bile ducts.HE staining,RT-PCR and immunohistochemistry were used to detect the proliferation and apoptosis of bile duct smooth muscle cells in proliferative endomembrane and the expression of related caspase-3,Bcl-2 and Fas genes. RESULTS:The expression of caspase-3 and Fas genes in the bile duct tissues of dogs with radioactive stents was higher than that of dogs with ordinary stents.There was significant apoptosis of proliferative smooth muscle cells in the bile ducts.The expression of the Bcl-2 gene in the bile duct tissues of dogs with radioactive stents was lower than that in those with ordinary stents.There was significant apoptosis of proliferative smooth muscle cells in the dogs with low Bcl-2 gene expression. CONCLUSIONS:Radiation increases the activity of caspase-3 and Fas genes and is associated with apoptosis. The radioactive 103 Pd stent may facilitate apoptosis of proliferative smooth muscle cells in the bile ducts of dogs by activating these genes.The Bcl-2 gene expression level is correlated with the occurrence of apoptosis and the radiosusceptibility of cells.
基金the grant from the Teaching Committee of HunanProvince,No.97B095the"8th 5-year Plan"of Health Department of Hunan Province,No.9301
文摘AIM To investigate the relationship between the expression of p16 gene and the gastric carcinogenesis,depth of invasion and lymph node metastases, and to evaluate the deletion and mutation of exon 2 in p16 gene in gastric carcinoma.METHODS The expression of P16 protein was examined by streptavidin-peroxidase conjugated method (S-P); the deletion and mutation of p16 gene were respectively examined by polymerase chain reaction (PCR) and polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) in gastric carcinoma.RESULTS Expression of P16 protein was detected in 96.25% (77/80) of the normal gastric mucosa, in 92.00% (45/50) of the dysplastic gastric mucosa and in 47.54% (58/122) of the gastric carcinoma. The positive rate of P16 protein expression in gastric carcinoma was significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P＜0.05). The positive rate of P16 protein expression in mucoid carcinoma 10.00% (1/ 10) was significantly lower than that in poorly differentiated carcinoma 51.22% ( 21/ 41 ),undifferentiated carcinoma 57.69% (15/26) and signet ring cell carcinoma 62.50% (10/ 16) (P＜0.05). The positive rate of p16 protein in 30 cases paired primary and lymph node metastatic gastric carcinoma: There was 46.67% (14/30) in primary gastric carcinoma, 16.67% (5/30) in lymph node metastatic gastric carcinoma. The positive rate of lymph node metastatic carcinoma was significantly lower than that of primary carcinoma (P＜0.05). There was of p16 gene mutation in exon 2, but 5 cases displayed deletion of p16 gene in exon 2 in the 25 primary gastric carcinomas.CONCLUSIONS The expression loss of P16 protein related to the gastric carcinogenesis, gastric carcinoma histopathological subtypes and lymph metastasis. The mutation of p16 gene in exon 2 may not be involved in gastric carcinogenesis. But the deletion of p16 gene in exon 2 may be involved in gastric carcinogenesis.
基金supported by the Research Foundation of Jiangsu Provincial Commission of Health and Family Planning of China,No.H201653the Research Foundation of Changshu Science and Technology Bureau of China,No.CS201616
文摘The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog （PTEN） enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated （Y444F） AAV2 vector to efficiently express a short hairpin RNA （shRNA） for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 （both carrying shRNA to PTEN） 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover,post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ～19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.
