Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the d...Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches.The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation,luciferase activity assays,and RNA immunoprecipitation,etc.We screened drugs sensitive to WAP four-disulfide core domain 13(WFDC13)by virtual screening and molecular docking.Results:Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells.Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies.Notably,PAN3-AS1 expression was correlated with a suppressive immune microenvironment.Moreover,we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma.In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer.Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer.Moreover,the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.Conclusion:In short,PAN3-AS1 is a valuable biomarker for diagnosis and prognosis.PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment(TME)and forecasts durable benefit from immunotherapy.Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.展开更多
It is difficult to recover chrysocolla from sulfidation flotation which is closely related to the mineral surface composition.In this study,the effects of fluoride roasting on the surface composition of chrysocolla we...It is difficult to recover chrysocolla from sulfidation flotation which is closely related to the mineral surface composition.In this study,the effects of fluoride roasting on the surface composition of chrysocolla were investigated,its impact on sulfidation flotation was explored,and the mechanisms involved in both fluoride roasting and sulfidation flotation were discussed.With CaF_(2)as the roasting reagent,Na_(2)S·9H_(2)O as the sulfidation reagent,and sodium butyl xanthate(NaBX)as the collector,the results of the flotation experiments showed that fluoride roasting improved the floatability of chrysocolla,and the recovery rate increased from 16.87%to 82.74%.X-ray diffraction analysis revealed that after fluoride roasting,approximately all the Cu on the chrysocolla surface was exposed in the form of CuO,which could provide a basis for subsequent sulfidation flotation.The microscopy and elemental analyses revealed that large quantities of"pagoda-like"grains were observed on the sulfidation surface of the fluoride-roasted chrysocolla,indicating high crystallinity particles of copper sulfide.This suggests that the effect of sulfide formation on the chrysocolla surface was more pronounced.X-ray photoelectron spectroscopy revealed that fluoride roasting increased the relative contents of sulfur and copper on the surface and that both the Cu~+and polysulfide fractions on the surface of the minerals increased.This enhances the effect of sulfidation,which is conducive to flotation recovery.Therefore,fluoride roasting improved the effect of copper species transformation and sulfidation on the surface of chysocolla,promoted the adsorption of collectors,and improved the recovery of chrysocolla from sulfidation flotation.展开更多
The discharge of micro-polluted water from sources such as agricultural runoff,urban stormwater,and treated effluents presents significant challenges to aquatic ecosystems.Constructed wetlands(CWs)have gained recog-ni...The discharge of micro-polluted water from sources such as agricultural runoff,urban stormwater,and treated effluents presents significant challenges to aquatic ecosystems.Constructed wetlands(CWs)have gained recog-nition as an eco-friendly solution for removing pollutants from various wastewater sources and are increasingly applied for micro-polluted water treatment.By reviewing 78 full-scale CW studies from Web of Science,it is summarized that the ranges of ammonium nitrogen(NH4+-N)concentrations in runoff,wastewater treatment plant effluent and polluted river were 0.1–6.6,0.3–12.3,and 0.2–41.1 mg/L,respectively.The ranges of ni-trate nitrogen concentrations were 0.2–14.2,0–5.7,and 0–2.6 mg/L,respectively.Removal efficiencies of CWs for micro-polluted water varied by CW types.The total nitrogen removal efficiencies for subsurface-flow CWs,free-water surface-flow CWs,and hybrid CWs ranged from 27.4%to 66.5%,16.8%to 89.8%,and 19.4%to 88.2%,respectively.The NH4+-N removal efficiencies ranged from 34.2%to 73.6%,38.4%to 89.4%and 13.5%to 94.2%,respectively.Additionally,other factors influencing contaminant removal efficiency such as hydraulic retention time,vegetation types,redox micro-environment and influent water quality were evaluated.Based on these findings,two strategies for improving the purification performance of CWs were proposed:the selection of incorporating electron donor substrates and the optimization of operation parameters.This paper serves as a synthesis of information to guide future research and full-scale CW applications in micro-polluted water treatment.展开更多
BACKGROUND Gastrointestinal(GI)tumors are among the most prevalent malignancies,and surgical intervention remains a primary treatment modality.However,the complexity of GI surgery often leads to prolonged recovery and...BACKGROUND Gastrointestinal(GI)tumors are among the most prevalent malignancies,and surgical intervention remains a primary treatment modality.However,the complexity of GI surgery often leads to prolonged recovery and high postoperative complication rates,which threaten patient safety and functional outcomes.Enhanced recovery after surgery(ERAS)principles have been shown to improve perioperative outcomes through evidence-based,multidisciplinary care pathways.Despite its widespread adoption,there is a paucity of research focusing specifically on optimizing ERAS-guided nursing processes in the post-anesthesia care unit(PACU)and evaluating its impact on perioperative safety in patients undergoing GI tumor surgery.This study aimed to investigate whether an ERASbased PACU nursing protocol could enhance recovery,reduce complications,and improve patient safety in this surgical population.AIM To explore the impact of optimizing the recovery room nursing process based on ERAS on the perioperative safety of patients with GI tumors.METHODS A total of 260 patients with GI tumors who underwent elective surgeries under general anesthesia in our hospital from August 2023 to August 2025 and were then observed in the recovery unit(PACU)were selected.They were randomly divided into the observation group(the PACU nursing process was optimized based on ERAS)and the control group(the conventional PACU nursing process was adopted)by the random number grouping method,with 130 cases in each group.The time of gastric tube removal,urinary catheter removal,defecation time,hospital stay,time of leaving the room after tube removal,retention time in the recovery room,occurrence of complications,satisfaction and readmission rate were compared between the two groups after entering the room.Compare the occurrence of adverse events in the PACU nursing process between the two groups.RESULTS The time of gastric tube removal,urinary catheter removal,defecation time,hospital stay,retention time in the recovery room,total incidence of complications and readmission rate in the observation group were significantly lower than those in the control group,and the satisfaction rate was higher than that in the control group(P<0.05).The occurrence of adverse events in the PACU nursing process in the observation group was lower than that in the control group(P<0.05).CONCLUSION Optimizing the PACU nursing process based on ERAS can effectively accelerate the recovery process of patients undergoing GI tumor surgery,reduce adverse events,improve nursing satisfaction,and at the same time,lower the incidence of adverse events in the PACU nursing process,providing a more refined management basis for clinical practice.展开更多
MnO_(x)-CeO_(2)catalysts for the low-temperature selective catalytic reduction(SCR)of NO remain vulnerable to water and sulfur poisoning,limting their practical applications.Herein,we report a hydrophobic-modified MnO...MnO_(x)-CeO_(2)catalysts for the low-temperature selective catalytic reduction(SCR)of NO remain vulnerable to water and sulfur poisoning,limting their practical applications.Herein,we report a hydrophobic-modified MnO_(x)-CeO_(2)catalyst that achieves enhanced NO conversion rate and stability under harsh conditions.The catalyst was synthesized by decorating MnOx crystals with amorphous CeO_(2),followed by loading hydrophobic silica on the external surfaces.The hydrophobic silica allowed the adsorption of NH_(3)and NO and diffusion of H,suppressed the adsorption of H_(2)O,and prevented SO_(2)interaction with the Mn active sites,achieving selective molecular discrimination at the catalyst surface.At 120℃,under H_(2)O and SO_(2)exposure,the optimal hydrophobic catalyst maintains 82%NO conversion rate compared with 69%for the unmodified catalyst.The average adsorption energies of NH_(3),H_(2)O,and SO_(2)decreased by 0.05,0.43,and 0.52 eV,respectively.The NO reduction pathway follows the Eley-Rideal mechanism,NH_(3)^(*)+*→NH_(2)^(*)+H^(*)followed by NH_(2)^(*)+NO^(*)→N_(2)^(*)+H_(2)O^(*),with NH_(3)dehydrogenation being the rate determining step.Hydrophobic modification increased the activation energy for H atom transfer,leading to a minor decrease in the NO conversion rate at 120℃.This work demonstrates a viable strategy for developing robust NH_(3)-S CR catalysts capable of efficient operation in water-and sulfur-rich environments.展开更多
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
基金supported by the Shandong Province Medical and Health Technology Project(202303111442).
文摘Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches.The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation,luciferase activity assays,and RNA immunoprecipitation,etc.We screened drugs sensitive to WAP four-disulfide core domain 13(WFDC13)by virtual screening and molecular docking.Results:Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells.Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies.Notably,PAN3-AS1 expression was correlated with a suppressive immune microenvironment.Moreover,we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma.In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer.Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer.Moreover,the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.Conclusion:In short,PAN3-AS1 is a valuable biomarker for diagnosis and prognosis.PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment(TME)and forecasts durable benefit from immunotherapy.Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.
基金financially supported by the National Natural Science Foundation of China(No.52374259)the Open Fund of the State Key Laboratory of Mineral Processing Science and Technology,China(No.BGRIMM-KJSKL-2023-11)the Major Science and Technology Projects in Yunnan Province,China(No.202302 AF080004)。
文摘It is difficult to recover chrysocolla from sulfidation flotation which is closely related to the mineral surface composition.In this study,the effects of fluoride roasting on the surface composition of chrysocolla were investigated,its impact on sulfidation flotation was explored,and the mechanisms involved in both fluoride roasting and sulfidation flotation were discussed.With CaF_(2)as the roasting reagent,Na_(2)S·9H_(2)O as the sulfidation reagent,and sodium butyl xanthate(NaBX)as the collector,the results of the flotation experiments showed that fluoride roasting improved the floatability of chrysocolla,and the recovery rate increased from 16.87%to 82.74%.X-ray diffraction analysis revealed that after fluoride roasting,approximately all the Cu on the chrysocolla surface was exposed in the form of CuO,which could provide a basis for subsequent sulfidation flotation.The microscopy and elemental analyses revealed that large quantities of"pagoda-like"grains were observed on the sulfidation surface of the fluoride-roasted chrysocolla,indicating high crystallinity particles of copper sulfide.This suggests that the effect of sulfide formation on the chrysocolla surface was more pronounced.X-ray photoelectron spectroscopy revealed that fluoride roasting increased the relative contents of sulfur and copper on the surface and that both the Cu~+and polysulfide fractions on the surface of the minerals increased.This enhances the effect of sulfidation,which is conducive to flotation recovery.Therefore,fluoride roasting improved the effect of copper species transformation and sulfidation on the surface of chysocolla,promoted the adsorption of collectors,and improved the recovery of chrysocolla from sulfidation flotation.
基金supported by the Natural Science Foundation of China(No.52470105)the Young Taishan Scholars Program of Shandong Province(No.358202103017).
文摘The discharge of micro-polluted water from sources such as agricultural runoff,urban stormwater,and treated effluents presents significant challenges to aquatic ecosystems.Constructed wetlands(CWs)have gained recog-nition as an eco-friendly solution for removing pollutants from various wastewater sources and are increasingly applied for micro-polluted water treatment.By reviewing 78 full-scale CW studies from Web of Science,it is summarized that the ranges of ammonium nitrogen(NH4+-N)concentrations in runoff,wastewater treatment plant effluent and polluted river were 0.1–6.6,0.3–12.3,and 0.2–41.1 mg/L,respectively.The ranges of ni-trate nitrogen concentrations were 0.2–14.2,0–5.7,and 0–2.6 mg/L,respectively.Removal efficiencies of CWs for micro-polluted water varied by CW types.The total nitrogen removal efficiencies for subsurface-flow CWs,free-water surface-flow CWs,and hybrid CWs ranged from 27.4%to 66.5%,16.8%to 89.8%,and 19.4%to 88.2%,respectively.The NH4+-N removal efficiencies ranged from 34.2%to 73.6%,38.4%to 89.4%and 13.5%to 94.2%,respectively.Additionally,other factors influencing contaminant removal efficiency such as hydraulic retention time,vegetation types,redox micro-environment and influent water quality were evaluated.Based on these findings,two strategies for improving the purification performance of CWs were proposed:the selection of incorporating electron donor substrates and the optimization of operation parameters.This paper serves as a synthesis of information to guide future research and full-scale CW applications in micro-polluted water treatment.
基金Supported by 2025 Henan Medical Education Research Project,No.WJLX2025038.
文摘BACKGROUND Gastrointestinal(GI)tumors are among the most prevalent malignancies,and surgical intervention remains a primary treatment modality.However,the complexity of GI surgery often leads to prolonged recovery and high postoperative complication rates,which threaten patient safety and functional outcomes.Enhanced recovery after surgery(ERAS)principles have been shown to improve perioperative outcomes through evidence-based,multidisciplinary care pathways.Despite its widespread adoption,there is a paucity of research focusing specifically on optimizing ERAS-guided nursing processes in the post-anesthesia care unit(PACU)and evaluating its impact on perioperative safety in patients undergoing GI tumor surgery.This study aimed to investigate whether an ERASbased PACU nursing protocol could enhance recovery,reduce complications,and improve patient safety in this surgical population.AIM To explore the impact of optimizing the recovery room nursing process based on ERAS on the perioperative safety of patients with GI tumors.METHODS A total of 260 patients with GI tumors who underwent elective surgeries under general anesthesia in our hospital from August 2023 to August 2025 and were then observed in the recovery unit(PACU)were selected.They were randomly divided into the observation group(the PACU nursing process was optimized based on ERAS)and the control group(the conventional PACU nursing process was adopted)by the random number grouping method,with 130 cases in each group.The time of gastric tube removal,urinary catheter removal,defecation time,hospital stay,time of leaving the room after tube removal,retention time in the recovery room,occurrence of complications,satisfaction and readmission rate were compared between the two groups after entering the room.Compare the occurrence of adverse events in the PACU nursing process between the two groups.RESULTS The time of gastric tube removal,urinary catheter removal,defecation time,hospital stay,retention time in the recovery room,total incidence of complications and readmission rate in the observation group were significantly lower than those in the control group,and the satisfaction rate was higher than that in the control group(P<0.05).The occurrence of adverse events in the PACU nursing process in the observation group was lower than that in the control group(P<0.05).CONCLUSION Optimizing the PACU nursing process based on ERAS can effectively accelerate the recovery process of patients undergoing GI tumor surgery,reduce adverse events,improve nursing satisfaction,and at the same time,lower the incidence of adverse events in the PACU nursing process,providing a more refined management basis for clinical practice.
基金financially sponsored by the National Natural Science Foundation of China(No.52204414)the National Energy-Saving and Low-Carbon Materials Production and Application Demonstration Platform Program,China(No.TC220H06N)+1 种基金the National Key R&D Program of China(No.2021YFC1910504)the Fundamental Research Funds for the Central Universities,China(No.FRFTP-20-097A1Z)。
文摘MnO_(x)-CeO_(2)catalysts for the low-temperature selective catalytic reduction(SCR)of NO remain vulnerable to water and sulfur poisoning,limting their practical applications.Herein,we report a hydrophobic-modified MnO_(x)-CeO_(2)catalyst that achieves enhanced NO conversion rate and stability under harsh conditions.The catalyst was synthesized by decorating MnOx crystals with amorphous CeO_(2),followed by loading hydrophobic silica on the external surfaces.The hydrophobic silica allowed the adsorption of NH_(3)and NO and diffusion of H,suppressed the adsorption of H_(2)O,and prevented SO_(2)interaction with the Mn active sites,achieving selective molecular discrimination at the catalyst surface.At 120℃,under H_(2)O and SO_(2)exposure,the optimal hydrophobic catalyst maintains 82%NO conversion rate compared with 69%for the unmodified catalyst.The average adsorption energies of NH_(3),H_(2)O,and SO_(2)decreased by 0.05,0.43,and 0.52 eV,respectively.The NO reduction pathway follows the Eley-Rideal mechanism,NH_(3)^(*)+*→NH_(2)^(*)+H^(*)followed by NH_(2)^(*)+NO^(*)→N_(2)^(*)+H_(2)O^(*),with NH_(3)dehydrogenation being the rate determining step.Hydrophobic modification increased the activation energy for H atom transfer,leading to a minor decrease in the NO conversion rate at 120℃.This work demonstrates a viable strategy for developing robust NH_(3)-S CR catalysts capable of efficient operation in water-and sulfur-rich environments.
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.
