Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address thes...Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address these challenges,we propose an Uncertainty-Driven Graph Embedding-Enhanced Lateral Movement Detection framework(UGEA-LMD).First,the framework employs event-level incremental encoding on a continuous-time graph to capture fine-grained behavioral evolution,enabling newly appearing nodes to retain temporal contextual awareness even in the absence of historical interactions and thereby fundamentally mitigating the cold-start problem.Second,in the embedding space,we model the dependency structure among feature dimensions using a Gaussian copula to quantify the uncertainty distribution,and generate augmented samples with consistent structural and semantic properties through adaptive sampling,thus expanding the representation space of sparse samples and enhancing the model’s generalization under sparse sample conditions.Unlike static graph methods that cannot model temporal dependencies or data augmentation techniques that depend on predefined structures,UGEA-LMD offers both superior temporaldynamic modeling and structural generalization.Experimental results on the large-scale LANL log dataset demonstrate that,under the transductive setting,UGEA-LMD achieves an AUC of 0.9254;even when 10%of nodes or edges are withheld during training,UGEA-LMD significantly outperforms baseline methods on metrics such as recall and AUC,confirming its robustness and generalization capability in sparse-sample and cold-start scenarios.展开更多
With the rapid expansion of drone applications,accurate detection of objects in aerial imagery has become crucial for intelligent transportation,urban management,and emergency rescue missions.However,existing methods ...With the rapid expansion of drone applications,accurate detection of objects in aerial imagery has become crucial for intelligent transportation,urban management,and emergency rescue missions.However,existing methods face numerous challenges in practical deployment,including scale variation handling,feature degradation,and complex backgrounds.To address these issues,we propose Edge-enhanced and Detail-Capturing You Only Look Once(EHDC-YOLO),a novel framework for object detection in Unmanned Aerial Vehicle(UAV)imagery.Based on the You Only Look Once version 11 nano(YOLOv11n)baseline,EHDC-YOLO systematically introduces several architectural enhancements:(1)a Multi-Scale Edge Enhancement(MSEE)module that leverages multi-scale pooling and edge information to enhance boundary feature extraction;(2)an Enhanced Feature Pyramid Network(EFPN)that integrates P2-level features with Cross Stage Partial(CSP)structures and OmniKernel convolutions for better fine-grained representation;and(3)Dynamic Head(DyHead)with multi-dimensional attention mechanisms for enhanced cross-scale modeling and perspective adaptability.Comprehensive experiments on the Vision meets Drones for Detection(VisDrone-DET)2019 dataset demonstrate that EHDC-YOLO achieves significant improvements,increasing mean Average Precision(mAP)@0.5 from 33.2%to 46.1%(an absolute improvement of 12.9 percentage points)and mAP@0.5:0.95 from 19.5%to 28.0%(an absolute improvement of 8.5 percentage points)compared with the YOLOv11n baseline,while maintaining a reasonable parameter count(2.81 M vs the baseline’s 2.58 M).Further ablation studies confirm the effectiveness of each proposed component,while visualization results highlight EHDC-YOLO’s superior performance in detecting objects and handling occlusions in complex drone scenarios.展开更多
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
Alzheimer’s Disease(AD)is a progressive neurodegenerative disorder that significantly affects cognitive function,making early and accurate diagnosis essential.Traditional Deep Learning(DL)-based approaches often stru...Alzheimer’s Disease(AD)is a progressive neurodegenerative disorder that significantly affects cognitive function,making early and accurate diagnosis essential.Traditional Deep Learning(DL)-based approaches often struggle with low-contrast MRI images,class imbalance,and suboptimal feature extraction.This paper develops a Hybrid DL system that unites MobileNetV2 with adaptive classification methods to boost Alzheimer’s diagnosis by processing MRI scans.Image enhancement is done using Contrast-Limited Adaptive Histogram Equalization(CLAHE)and Enhanced Super-Resolution Generative Adversarial Networks(ESRGAN).A classification robustness enhancement system integrates class weighting techniques and a Matthews Correlation Coefficient(MCC)-based evaluation method into the design.The trained and validated model gives a 98.88%accuracy rate and 0.9614 MCC score.We also performed a 10-fold cross-validation experiment with an average accuracy of 96.52%(±1.51),a loss of 0.1671,and an MCC score of 0.9429 across folds.The proposed framework outperforms the state-of-the-art models with a 98%weighted F1-score while decreasing misdiagnosis results for every AD stage.The model demonstrates apparent separation abilities between AD progression stages according to the results of the confusion matrix analysis.These results validate the effectiveness of hybrid DL models with adaptive preprocessing for early and reliable Alzheimer’s diagnosis,contributing to improved computer-aided diagnosis(CAD)systems in clinical practice.展开更多
The increasing challenges of environmental degradation,soil erosion,and climate change have driven interest in sustainable solutions like enhanced weathering(EW)and phytoremediation.Elephant Grass(Cenchrus purpureus),...The increasing challenges of environmental degradation,soil erosion,and climate change have driven interest in sustainable solutions like enhanced weathering(EW)and phytoremediation.Elephant Grass(Cenchrus purpureus),a fast-growing perennial species,shows promise as a bioaccumulator and agent for soil weathering.This study assessed the potential of C.purpureus to improve soil quality through heavy metal(HM)uptake and EW facilitation.A 60-day greenhouse pot experiment at Jackson State University evaluated plant performance in soils amended with metabasalt rock powder at 1:1 and 2:1 rock-to-soil ratios.Biomass,growth,and HM concentrations in roots and shoots were measured via ICP-MS after wet digestion.Soil pH and magnesium(Mg)release were also monitored to assess weathering and carbon drawdown.Results showed that C.purpureus accumulated more HMs in roots at higher amendment levels,while at lower levels,metals like As,Cd,and Cr were more translocated to shoots,enhancing phytoextraction potential.High treatment favored Fe and Al uptake,possibly reducing toxic metal accumulation in edible parts.Notably,C.purpureus contributed to the weathering of 38%of metabasalt rock,leading to a 42%increase in Mg release.With high biomass,HM tolerance,and weathering capacity,C.purpureus offers a sustainable strategy for soil remediation,improved soil health,and potential support for renewable energy systems.展开更多
Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expres...Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expressed in both healthy and malignant prostate cells.This study aimed to demonstrate the relationship between pathological characteristics,survival,recurrence,and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.Methods:PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019.Inclusion criteria comprised pathological tumor stage(pT)3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm.After case selection,tissue slides were stained for EZH2 and FOXM1 antibodies,and Allred scores were calculated.Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.Results:The pT3b,ductal carcinoma component,and moderate EZH2 expression were associated with relapse(odds ratio[OR]6.21,95%confidence interval[CI]1.41-27.27,p=0.016;OR 7.29,95%CI 1.03-51.43,p=0.046;OR 5.96,95%CI 1.09-32.48,p=0.039;respectively).The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times,and the risk of death by around 9.78 times and 10.79 times,respectively.The pT3b was linked to higher death likelihood(OR 7.16,95%CI 1.38-37.23,p=0.019),while moderate EZH2 expression did not show statistical significance(OR 4.54,95%CI 0.87-23.60,p=0.072,marginally).Pathological regional lymph node stage(pN)1 had significantly higher probability of mortality than pN unknown(3.9%vs.27%,p<0.001).PCa in the neck and apex of the prostate gland increased death risk tenfold.Conclusion:Sufficient immunoexpression of EZH2,ductal carcinoma component,and neoplastic proliferation in the seminal vesicles,apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality.Clinicians should use these criteria for appropriate patient referrals,and a multicenter trial could provide accurate classifications.展开更多
Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize ...Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.展开更多
Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic ...Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.展开更多
Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration vi...Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.展开更多
The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through fu...The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.展开更多
Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factor...Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.展开更多
The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.Howev...The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.However,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood.In the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer elements.We found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)gene.Furthermore,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model.Subsequently,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency.Consistently,KLF4 expression also decreased in lung cancer tissues and cell lines.It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells.Collectively,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function.Therefore,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.展开更多
Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,...Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,development and disease.Genome-wide quantification of functional enhancers in the pig is needed.Results:We performed self-transcribing active regulatory region sequencing(STARR-seq)in the porcine kidney epithelial PK15 and testicular ST cell lines,and reliably identified 2576 functional enhancers.Most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes.Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3,which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones.This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages.Additionally,the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers.Conclusions:In summary,we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.展开更多
Objective To detect the trans-factors specifically binding to the strong enhancerelement (GPEI) in the upstream of rat glutathione S-transferase P (GST-P) gene. MethodsYeast one-hybrid system was used to screen rat...Objective To detect the trans-factors specifically binding to the strong enhancerelement (GPEI) in the upstream of rat glutathione S-transferase P (GST-P) gene. MethodsYeast one-hybrid system was used to screen rat lung MATCHMAKER cDNA library toidentify potential trans-factors that can interact with core sequence of GPEI(cGPEI).Electrophoresis mobility shift assay (EMSA) was used to analyze the binding of trans-factors to cGPEI. Results cDNA fragments coding for the C-terminal part of thetranscription factor c-Jun and rat adenine nucleotide translocator (ANT) were isolated. Thebinding of c-Jun and ANT to GPEI core sequence were confirmed. Conclusions Rat c-juntranscriptional factor and ANT may interact with cGPEI. They could play an important rolein the induced expression of GST-P gene.展开更多
Connected a segment of CMV enhancer to the front of MyoG gene promoter and then constructed the corresponding dual luciferase expression vector pGL3-CMV-MyoGpro. We set four eukaryotic expression vectors including pGL...Connected a segment of CMV enhancer to the front of MyoG gene promoter and then constructed the corresponding dual luciferase expression vector pGL3-CMV-MyoGpro. We set four eukaryotic expression vectors including pGL3-CMV, pGL3MyoGpro, pGL3-CMV-MyoGpro, and pGL3-Basic which contained CMV promoter, MyoG promoter, CMV-MyoG synthesis promoter, and a promoterless negative control, respectively. Then the four vectors and internal control Renilla luciferase report gene vector phRL-TK were transfected into bovine skeletal muscle satellite cells, mouse C2C12 cells and bovine fetal fibroblast cells to detect the promoter activity with dual luciferase report system. The results showed that CMV enhancer could significantly improve the transcription activity of bovine MyoG gene promoter in muscle satellite cells and mouse C2C12 cells, and it had certain specificity. This study provided experimental materials for increasing the high expression of exogenous gene in bovine muscle cells, and also laid the molecular theoretical basis for obtaining the high specific promoter of bovine muscle and the transgenic beef cattle.展开更多
Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and i...Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.展开更多
Muscle-derived stem cells were isolated from the skeletal muscle of Sprague-Dawley neonatal rats aged 3 days old. Cells at passage 5 were incubated in Dulbecco＇s modified Eagle＇s medium supplemented with 10% （v/v）...Muscle-derived stem cells were isolated from the skeletal muscle of Sprague-Dawley neonatal rats aged 3 days old. Cells at passage 5 were incubated in Dulbecco＇s modified Eagle＇s medium supplemented with 10% （v/v） fetal bovine serum, 20 IJg/L nerve growth factor, 20 pg/L basic fibroblast growth factor and 1% （v/v） penicillin for 6 days. Cells presented with long processes, similar to nerve cells. Connections were formed between cell processes. Immunocytochemical staining with neuron specific enolase verified that cells differentiated into neuron-like cells. Immunofluorescence cytochemistry and western blot results revealed that the expression of protein hairy enhancer of split-1 was significantly reduced. These results indicate that low expression of protein hairy enhancer of split-1 participates in the differentiation of muscle-derived stem cells into neuron-like cells.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
基金supported by the Zhongyuan University of Technology Discipline Backbone Teacher Support Program Project(No.GG202417)the Key Research and Development Program of Henan under Grant 251111212000.
文摘Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address these challenges,we propose an Uncertainty-Driven Graph Embedding-Enhanced Lateral Movement Detection framework(UGEA-LMD).First,the framework employs event-level incremental encoding on a continuous-time graph to capture fine-grained behavioral evolution,enabling newly appearing nodes to retain temporal contextual awareness even in the absence of historical interactions and thereby fundamentally mitigating the cold-start problem.Second,in the embedding space,we model the dependency structure among feature dimensions using a Gaussian copula to quantify the uncertainty distribution,and generate augmented samples with consistent structural and semantic properties through adaptive sampling,thus expanding the representation space of sparse samples and enhancing the model’s generalization under sparse sample conditions.Unlike static graph methods that cannot model temporal dependencies or data augmentation techniques that depend on predefined structures,UGEA-LMD offers both superior temporaldynamic modeling and structural generalization.Experimental results on the large-scale LANL log dataset demonstrate that,under the transductive setting,UGEA-LMD achieves an AUC of 0.9254;even when 10%of nodes or edges are withheld during training,UGEA-LMD significantly outperforms baseline methods on metrics such as recall and AUC,confirming its robustness and generalization capability in sparse-sample and cold-start scenarios.
文摘With the rapid expansion of drone applications,accurate detection of objects in aerial imagery has become crucial for intelligent transportation,urban management,and emergency rescue missions.However,existing methods face numerous challenges in practical deployment,including scale variation handling,feature degradation,and complex backgrounds.To address these issues,we propose Edge-enhanced and Detail-Capturing You Only Look Once(EHDC-YOLO),a novel framework for object detection in Unmanned Aerial Vehicle(UAV)imagery.Based on the You Only Look Once version 11 nano(YOLOv11n)baseline,EHDC-YOLO systematically introduces several architectural enhancements:(1)a Multi-Scale Edge Enhancement(MSEE)module that leverages multi-scale pooling and edge information to enhance boundary feature extraction;(2)an Enhanced Feature Pyramid Network(EFPN)that integrates P2-level features with Cross Stage Partial(CSP)structures and OmniKernel convolutions for better fine-grained representation;and(3)Dynamic Head(DyHead)with multi-dimensional attention mechanisms for enhanced cross-scale modeling and perspective adaptability.Comprehensive experiments on the Vision meets Drones for Detection(VisDrone-DET)2019 dataset demonstrate that EHDC-YOLO achieves significant improvements,increasing mean Average Precision(mAP)@0.5 from 33.2%to 46.1%(an absolute improvement of 12.9 percentage points)and mAP@0.5:0.95 from 19.5%to 28.0%(an absolute improvement of 8.5 percentage points)compared with the YOLOv11n baseline,while maintaining a reasonable parameter count(2.81 M vs the baseline’s 2.58 M).Further ablation studies confirm the effectiveness of each proposed component,while visualization results highlight EHDC-YOLO’s superior performance in detecting objects and handling occlusions in complex drone scenarios.
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
基金funded by the Deanship of Graduate Studies and Scientific Research at Jouf University under grant No.(DGSSR-2025-02-01295).
文摘Alzheimer’s Disease(AD)is a progressive neurodegenerative disorder that significantly affects cognitive function,making early and accurate diagnosis essential.Traditional Deep Learning(DL)-based approaches often struggle with low-contrast MRI images,class imbalance,and suboptimal feature extraction.This paper develops a Hybrid DL system that unites MobileNetV2 with adaptive classification methods to boost Alzheimer’s diagnosis by processing MRI scans.Image enhancement is done using Contrast-Limited Adaptive Histogram Equalization(CLAHE)and Enhanced Super-Resolution Generative Adversarial Networks(ESRGAN).A classification robustness enhancement system integrates class weighting techniques and a Matthews Correlation Coefficient(MCC)-based evaluation method into the design.The trained and validated model gives a 98.88%accuracy rate and 0.9614 MCC score.We also performed a 10-fold cross-validation experiment with an average accuracy of 96.52%(±1.51),a loss of 0.1671,and an MCC score of 0.9429 across folds.The proposed framework outperforms the state-of-the-art models with a 98%weighted F1-score while decreasing misdiagnosis results for every AD stage.The model demonstrates apparent separation abilities between AD progression stages according to the results of the confusion matrix analysis.These results validate the effectiveness of hybrid DL models with adaptive preprocessing for early and reliable Alzheimer’s diagnosis,contributing to improved computer-aided diagnosis(CAD)systems in clinical practice.
文摘The increasing challenges of environmental degradation,soil erosion,and climate change have driven interest in sustainable solutions like enhanced weathering(EW)and phytoremediation.Elephant Grass(Cenchrus purpureus),a fast-growing perennial species,shows promise as a bioaccumulator and agent for soil weathering.This study assessed the potential of C.purpureus to improve soil quality through heavy metal(HM)uptake and EW facilitation.A 60-day greenhouse pot experiment at Jackson State University evaluated plant performance in soils amended with metabasalt rock powder at 1:1 and 2:1 rock-to-soil ratios.Biomass,growth,and HM concentrations in roots and shoots were measured via ICP-MS after wet digestion.Soil pH and magnesium(Mg)release were also monitored to assess weathering and carbon drawdown.Results showed that C.purpureus accumulated more HMs in roots at higher amendment levels,while at lower levels,metals like As,Cd,and Cr were more translocated to shoots,enhancing phytoextraction potential.High treatment favored Fe and Al uptake,possibly reducing toxic metal accumulation in edible parts.Notably,C.purpureus contributed to the weathering of 38%of metabasalt rock,leading to a 42%increase in Mg release.With high biomass,HM tolerance,and weathering capacity,C.purpureus offers a sustainable strategy for soil remediation,improved soil health,and potential support for renewable energy systems.
文摘Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expressed in both healthy and malignant prostate cells.This study aimed to demonstrate the relationship between pathological characteristics,survival,recurrence,and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.Methods:PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019.Inclusion criteria comprised pathological tumor stage(pT)3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm.After case selection,tissue slides were stained for EZH2 and FOXM1 antibodies,and Allred scores were calculated.Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.Results:The pT3b,ductal carcinoma component,and moderate EZH2 expression were associated with relapse(odds ratio[OR]6.21,95%confidence interval[CI]1.41-27.27,p=0.016;OR 7.29,95%CI 1.03-51.43,p=0.046;OR 5.96,95%CI 1.09-32.48,p=0.039;respectively).The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times,and the risk of death by around 9.78 times and 10.79 times,respectively.The pT3b was linked to higher death likelihood(OR 7.16,95%CI 1.38-37.23,p=0.019),while moderate EZH2 expression did not show statistical significance(OR 4.54,95%CI 0.87-23.60,p=0.072,marginally).Pathological regional lymph node stage(pN)1 had significantly higher probability of mortality than pN unknown(3.9%vs.27%,p<0.001).PCa in the neck and apex of the prostate gland increased death risk tenfold.Conclusion:Sufficient immunoexpression of EZH2,ductal carcinoma component,and neoplastic proliferation in the seminal vesicles,apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality.Clinicians should use these criteria for appropriate patient referrals,and a multicenter trial could provide accurate classifications.
基金supported by the National Natural Science Foundation of China(grants 81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.
基金supported by the National Science Fund for Excellent Young Scholars(NSFC-82322058)the Program of National Natural Science Foundation of China(NSFC-82103929,NSFC-82273713)+10 种基金the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the National Science Fund for Distinguished Young Scholars of Hubei Province of China(2023AFA046)the Fundamental Research Funds for the Central Universities(WHU:2042022kf1205)Fundamental Research Funds for the Central Universities(WHU:2042022kf1031)for Ying Zhuthe Fundamental Research Funds for the Central Universities(2042022rc0026,2042023kf1005)for Xiao-Ping Miaothe Knowledge Innovation Program of Wuhan(whkxjsj011,2023020201010073)for Jian-Bo Tianthe Science and Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University(znpy2019060)for Yong-Chang Weithe Distinguished Young Scholars of China(NSFC-81925032)the Key Program of National Natural Science Foundation of China(NSFC-82130098)the Youth Program of National Natural Science Foundation of China(NSFC-82003547)the Program of Health Commission of Hubei Province(WJ2023M045)。
文摘Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.
基金supported by the National Natural Science Foundation of China,No.81571211(to FL)the Natural Science Foundation of Shanghai,No.22ZR1476800(to CH)。
文摘Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.
文摘The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.
基金supported by National Natural Science Foundation of China (81670874, 81500354, and 81772999)Shenzhen Science Foundation (JCYJ20160308104109234)
文摘Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.
基金the National Natural Science Foundation of China(Grant No.82072580).
文摘The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.However,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood.In the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer elements.We found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)gene.Furthermore,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model.Subsequently,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency.Consistently,KLF4 expression also decreased in lung cancer tissues and cell lines.It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells.Collectively,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function.Therefore,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.
基金supported by the National Natural Science Foundation of China(32100502)the Ministry of Agriculture of China(2016ZX08009003-006)Science&Technology Department of Yunnan Province(202102AE090039).
文摘Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,development and disease.Genome-wide quantification of functional enhancers in the pig is needed.Results:We performed self-transcribing active regulatory region sequencing(STARR-seq)in the porcine kidney epithelial PK15 and testicular ST cell lines,and reliably identified 2576 functional enhancers.Most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes.Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3,which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones.This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages.Additionally,the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers.Conclusions:In summary,we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.
基金the National Natural Science Foundation of China (Grant No. 3967017330170441) "863"Project (Grant No. 2001AA221161)+1 种基金Beijing Natural Science Foundation (7002026) High Education Science Research Foundation of China (20010023024).
文摘Objective To detect the trans-factors specifically binding to the strong enhancerelement (GPEI) in the upstream of rat glutathione S-transferase P (GST-P) gene. MethodsYeast one-hybrid system was used to screen rat lung MATCHMAKER cDNA library toidentify potential trans-factors that can interact with core sequence of GPEI(cGPEI).Electrophoresis mobility shift assay (EMSA) was used to analyze the binding of trans-factors to cGPEI. Results cDNA fragments coding for the C-terminal part of thetranscription factor c-Jun and rat adenine nucleotide translocator (ANT) were isolated. Thebinding of c-Jun and ANT to GPEI core sequence were confirmed. Conclusions Rat c-juntranscriptional factor and ANT may interact with cGPEI. They could play an important rolein the induced expression of GST-P gene.
基金Supported by the Major Special Projects of New Product Training of Transgenic Organisms(zx080072008-2008)
文摘Connected a segment of CMV enhancer to the front of MyoG gene promoter and then constructed the corresponding dual luciferase expression vector pGL3-CMV-MyoGpro. We set four eukaryotic expression vectors including pGL3-CMV, pGL3MyoGpro, pGL3-CMV-MyoGpro, and pGL3-Basic which contained CMV promoter, MyoG promoter, CMV-MyoG synthesis promoter, and a promoterless negative control, respectively. Then the four vectors and internal control Renilla luciferase report gene vector phRL-TK were transfected into bovine skeletal muscle satellite cells, mouse C2C12 cells and bovine fetal fibroblast cells to detect the promoter activity with dual luciferase report system. The results showed that CMV enhancer could significantly improve the transcription activity of bovine MyoG gene promoter in muscle satellite cells and mouse C2C12 cells, and it had certain specificity. This study provided experimental materials for increasing the high expression of exogenous gene in bovine muscle cells, and also laid the molecular theoretical basis for obtaining the high specific promoter of bovine muscle and the transgenic beef cattle.
文摘Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.
基金supported by a grant from the Distinguished Young Scholars in Universities in Liaoning Province Development Plan, No. LJQ2011090
文摘Muscle-derived stem cells were isolated from the skeletal muscle of Sprague-Dawley neonatal rats aged 3 days old. Cells at passage 5 were incubated in Dulbecco＇s modified Eagle＇s medium supplemented with 10% （v/v） fetal bovine serum, 20 IJg/L nerve growth factor, 20 pg/L basic fibroblast growth factor and 1% （v/v） penicillin for 6 days. Cells presented with long processes, similar to nerve cells. Connections were formed between cell processes. Immunocytochemical staining with neuron specific enolase verified that cells differentiated into neuron-like cells. Immunofluorescence cytochemistry and western blot results revealed that the expression of protein hairy enhancer of split-1 was significantly reduced. These results indicate that low expression of protein hairy enhancer of split-1 participates in the differentiation of muscle-derived stem cells into neuron-like cells.
