Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,n...Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.展开更多
[Objectives]This study was conducted to explore the action mechanism of limonoids against Alzheimer s disease(AD)based on network pharmacology and molecular docking techniques.[Methods]Limonoid compounds were obtained...[Objectives]This study was conducted to explore the action mechanism of limonoids against Alzheimer s disease(AD)based on network pharmacology and molecular docking techniques.[Methods]Limonoid compounds were obtained through literature research(January 1942 to January 2021).Active components and potential targets of limonoids were retrieved from PubChem,TCMSP,and Swiss Target Prediction databases.AD-related targets were obtained from the GeneCards database,and intersecting targets were identified using Venny 2.1.0 to obtain the action targets of limonoids against AD.The protein-protein interaction(PPI)network was constructed using the String platform,and key targets were screened and visualized via network topology analysis with Cytoscape software.GO and KEGG pathway enrichment analyses were performed using the Metascape database,and a"drug-component-target-pathway-disease"network diagram was constructed using Cytoscape.AutoDock was empolyed for molecular docking to predict the binding properties of limonoid active components and their targets.[Results]A total of 60 limonoid compounds were obtained from literature research.Network pharmacology analysis showed 58 effective active components and 134 common targets between limonoids and AD.Key targets included AKT1(serine/threonine-protein kinase 1),TNF(tumor necrosis factor),STAT3(signal transducer and activator of transcription 3),BCL2(B-cell lymphoma 2),and EGFR(epidermal growth factor receptor).KEGG enrichment analysis revealed key signaling pathways such as pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,PI3K-Akt signaling pathway,lipid and atherosclerosis,proteoglycans in cancer,MAPK signaling pathway,and Ras signaling pathway.Molecular docking results indicated that aphanamixoid A,obacunol,cipadesin C,harpertrioate A,xylogranatin A,11-oxocneorin G,evodulone,methyl angolensate,harrpemoid B and khivorin may be key components of limonoids against AD.[Conclusions]Limonoids exert anti-Alzheimer s effects through a multi-molecule,multi-target and multi-pathway mechanism.展开更多
OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Avail...OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target proteins of MT were retrieved from the GeneCards,PharmGkb,Therapeutic Target Database,DrugBank,and Online Mendelian Inheritance in Man databases.Information regarding MT and the drug targets was compared to obtain overlapping elements.This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram.Then,a“component-target”network diagram was constructed using screened drug components and target information,via Cytoscape(Institute for Systems Biology,Seattle,WA,USA).The database for annotation,visualization,and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses.Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.RESULTS:Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory,apoptosis,and nuclear factor kappa B(NF-κB)signaling pathways.Berberine(BBR),one of the main components of HLD,inhibited the development of MT in mice.BBR reduced cell viability while increasing B-cell lymphoma 2(Bcl-2)protein expression and decreasing CD86,NF-κB,Bax,and Caspase-3 protein expression in brain vascular 2(BV2)mcroglia cells treated with morphine.Additionally,BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.CONCLUSIONS:BBR,a key component of HLD,effectively suppressed microglial activation and neuroinflammation by regulating the NF-κB and apoptosis signaling pathways,thereby delaying MT.This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.展开更多
[Objectives]To study the network pharmacology-based anticancer effect of Ardisiacrispin B for colon cancer(CRC).[Methods]The chemical structure and molecular properties of Ardisiacrispin B were assessed via the PubChe...[Objectives]To study the network pharmacology-based anticancer effect of Ardisiacrispin B for colon cancer(CRC).[Methods]The chemical structure and molecular properties of Ardisiacrispin B were assessed via the PubChem resource,while the putative target genes of Ardisiacrispin B were predicted using the PharmMapper Database.Moreover,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Ontology(GO)enrichment analyses were conducted via the WebGestalt platform.Finally,a drug-target-pathway network was built via Cytoscape to show the visual representation.[Results]Ardisiacrispin B exhibited exceptional druggability with 25 putative targets.Analyses conducted using KEGG,GO,and network methods showed that these target genes were related with inflammatory responses,cancer,and varoius other biological functions.On the basis of these findings,we further screened the correlative biotargets of Ardisiacrispin B in relation to CRC,and explored the anticancer effects of Ardisiacrispin B for the treatment of CRC through CCK8 analysis and colony formation assay.Our results confirmed that Ardisiacrispin B exhibited anti-CRC properties,and suggested 11 candidate targets of Ardisiacrispin B in the treatment of CRC.[Conclusions]Ardisiacrispin B has been demonstrated to target multiple proteins/genes and pathways,thereby forming a network that displays systematic pharmacological activities.Moreover,it has potential therapeutic value in tumor treatment,specifically in promoting the proliferation of CRC cells.展开更多
Non-alcoholic fatty liver disease(NAFLD),a chronic liver disorder closely associated with metabolic dysfunction,has become a significant global health challenge.In recent years,procyanidin B1(PB1)has demonstrated pote...Non-alcoholic fatty liver disease(NAFLD),a chronic liver disorder closely associated with metabolic dysfunction,has become a significant global health challenge.In recent years,procyanidin B1(PB1)has demonstrated potential advantages in the prevention and personalized treatment of NAFLD through multi-target and multi-pathway intervention strategies,exerting comprehensive regulatory and synergistic effects.However,its precise therapeutic mechanisms remain unclear.This study employs network pharmacology to identify key targets and potential pathways involved in the treatment of NAFLD with PB1.Additionally,molecular docking analysis is conducted to validate the reliability of these targets.The findings provide a theoretical foundation for the development of PB1 as a potential therapeutic agent for NAFLD,offering insights for future experimental and clinical research.展开更多
This study aims to explore the mechanism by which flavonoids in Crataegus pinnatifida fruit improve Alzheimer’s disease(AD)through network pharmacology and molecular docking technology.The flavonoid components presen...This study aims to explore the mechanism by which flavonoids in Crataegus pinnatifida fruit improve Alzheimer’s disease(AD)through network pharmacology and molecular docking technology.The flavonoid components present in Crataegus pinnatifida fruit were gathered from the HERB,HIT,and ETCM databases,and were further supplemented by relevant published literature.The PubChem and SwissTargetPrediction databases were utilized to predict potential targets,and a“Crataegus pinnatifida fruit-active ingredient-target”network was constructed using Cytoscape 3.9.0 software.The GeneCards database was utilized to identify targets associated with AD,which were subsequently intersected with the active targets of Crataegus pinnatifi da fruit.A protein-protein interaction(PPI)network was constructed using the STRING platform.KEGG enrichment analysis of the core targets was conducted on an online bioinformatics mapping platform,while molecular docking of the primary active components and core targets was executed using AutoDock software.Eight flavonoids and 160 potential targets were identifi ed from Crataegus pinnatifi da fruit,of which 147 targets were linked to AD.The results of the“Crataegus pinnatifi da fruit-active ingredient-target”network indicated that quercetin was the principal flavonoid active ingredient.PPI analysis revealed that SRC and EGFR were the key targets,and KEGG analysis identifi ed the main enrichment pathways as Pathways in cancer,PI3K/Akt signaling pathway,and Proteoglycans in cancer.Molecular docking confi rmed the strong binding affi nity between the core targets and the primary active ingredient.The interaction of quercetin with the key targets SRC and EGFR may represent a signifi cant mechanism by which flavonoids from Crataegus pinnatifi da fruit contribute to the improvement of AD.展开更多
Although the demand of ^(10)B separation has arisen in the 1930s,^(10)B/^(11)B are among the most difficult isotopes to separate due to the extremely similar relative atomic mass.Herein,we report an efficient separati...Although the demand of ^(10)B separation has arisen in the 1930s,^(10)B/^(11)B are among the most difficult isotopes to separate due to the extremely similar relative atomic mass.Herein,we report an efficient separation of ^(10)B isotopologue by engineering amino-galloyl synergistic materials via a selective adsorption and isotope exchange reaction,achieving a record-high single-stage separation factor of 1.048 with ^(10)B abundance up to 21.42%.^(11)B MAS NMR results and DFT calculations reveal that the galloyl groups exhibit inherent high affinity for B(OH)4-,forming tetrahedral sp^(3) B-galloyl complexes.The relatively higher ^(10)B–O bond energy of ^(10)B-galloyl complexes facilitates the isotope exchange between11B in B-galloyl complexes and ^(10)B in B(OH)_(3).Flowthrough dynamic separation in fixed-bed demonstrates the feasibility and potential of large-scale deployment of this method in real-world,suggesting a promising avenue for the exploitation of more efficient enrichment of ^(10)B for the sustainable nuclear energy and biomedical research.展开更多
Any malfunctions of the actuators of the robots have the potential to destroy the robot’s normal motion,and most of the current actuator fault diagnosis methods are difficult to meet the requirements of simplifying t...Any malfunctions of the actuators of the robots have the potential to destroy the robot’s normal motion,and most of the current actuator fault diagnosis methods are difficult to meet the requirements of simplifying the actuator modeling and solving the difficulty of fault data collection.To solve the problem of real-time diagnosis of actuator faults in the 3-PR(P)S parallel robot,the model of 3-PR(P)S parallel robot and data-driven-based method for the fault diagnosis are presented.Firstly,only the input-output relationship of the actuator is considered for modeling actuator faults,reducing the complexity of fault modeling and reducing the time consumption of parameter identification,thereby meeting the requirements of real-time diagnosis.A Simulink model of the electromechanical actuator(EMA)was constructed to analyze actuator faults.Then the short-term analysis method was employed for collecting the sample data of the slider position on the test platform of the EMA system and feature extraction.Training samples for neural networks are obtained.Furthermore,we optimized the Back Propagation(BP)neural network using the Dung Beetle Optimization Algorithm(DBO),which effectively resolved the weights and thresholds of the BP neural network.Compared to BP and Particle Swarm Optimization(PSO)-BP,the DBO-BP has better convergence,convergence rate,and the best-classifying quality.So,the classification for the different actuator faults is obviously improved.Finally,a fault diagnosis system was designed for the actuator of the 3-PR(P)S parallel robot,and the experimental results demonstrate that this system can detect actuator faults within 0.1 seconds.This work also provides the technical support for the fault-tolerant control of the 3-PR(P)S Parallel robot.展开更多
Meteor Burst Communication(MBC),a niche yet revolutionary wireless communication paradigm,exploits the transient ionized trails generated by meteors ablating in Earth’s atmosphere to enable sporadic yet resilient lon...Meteor Burst Communication(MBC),a niche yet revolutionary wireless communication paradigm,exploits the transient ionized trails generated by meteors ablating in Earth’s atmosphere to enable sporadic yet resilient long-distance radio links.Known for its exceptional resilience,robustness,and sustained connectivity,MBC holds significant promise for applications in emergency communications,remote area connectivity,military/defense systems,and environmental monitoring.However,the scientific exploration and application of MBC have long been highly challenging.In particular,under the combined influence of multiple physical field factors,the channel experiences superimposed multiple random fading effects,exhibiting bursty,highly time-varying,and strongly random characteristics.This persistent technical challenge has resulted in the absence of a practical statistical channel model for MBC to date.展开更多
In this paper,a class of quaternion-valued cellular neural networks(QVCNNS)with time-varying delays are considered.Combining graph theory with the continuation theorem of Mawhin’s coincidence degree theory as well as...In this paper,a class of quaternion-valued cellular neural networks(QVCNNS)with time-varying delays are considered.Combining graph theory with the continuation theorem of Mawhin’s coincidence degree theory as well as Lyapunov functional method,we establish new criteria on the existence and exponential stability of periodic solutions for QVCNNS by removing the assumptions for the boundedness on the activation functions and the assumptions that the values of the activation functions are zero at origin.Hence,our results are less conservative and new.展开更多
目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料...目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料和血清HMGB1、S100β水平及24 h BIS,分析脓毒症病人发生SAE的影响因素和HMGB1、S100β、BIS联合检测早期诊断SAE的临床价值。结果:SAE组病人APACHEⅡ评分、SOFA评分均明显高于非SAE组(P<0.01);SAE组血清HMGB1、S100β水平均明显高于非SAE组(P<0.01),而BIS明显低于非SAE组(P<0.01)。APACHEⅡ评分、SOFA评分和HMGB1、S100β、BIS均为脓毒症病人发生SAE的独立影响因素(P<0.01)。ROC曲线分析显示,血清HMGB1、S100β联合BIS早期诊断脓毒症病人发生SAE的AUC为0.891,敏感度为91.43%,特异度为84.62%,优于各指标独立诊断。结论:血清HMGB1、S100β联合BIS在SAE早期诊断中具有较好的临床应用价值。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
文摘Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.
基金Supported by Science and Technology Fund of Guizhou health and Health Committee(gzwkj2024-240)Anshun City Science and Technology Bureau(ASKS[2024]01).
文摘[Objectives]This study was conducted to explore the action mechanism of limonoids against Alzheimer s disease(AD)based on network pharmacology and molecular docking techniques.[Methods]Limonoid compounds were obtained through literature research(January 1942 to January 2021).Active components and potential targets of limonoids were retrieved from PubChem,TCMSP,and Swiss Target Prediction databases.AD-related targets were obtained from the GeneCards database,and intersecting targets were identified using Venny 2.1.0 to obtain the action targets of limonoids against AD.The protein-protein interaction(PPI)network was constructed using the String platform,and key targets were screened and visualized via network topology analysis with Cytoscape software.GO and KEGG pathway enrichment analyses were performed using the Metascape database,and a"drug-component-target-pathway-disease"network diagram was constructed using Cytoscape.AutoDock was empolyed for molecular docking to predict the binding properties of limonoid active components and their targets.[Results]A total of 60 limonoid compounds were obtained from literature research.Network pharmacology analysis showed 58 effective active components and 134 common targets between limonoids and AD.Key targets included AKT1(serine/threonine-protein kinase 1),TNF(tumor necrosis factor),STAT3(signal transducer and activator of transcription 3),BCL2(B-cell lymphoma 2),and EGFR(epidermal growth factor receptor).KEGG enrichment analysis revealed key signaling pathways such as pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,PI3K-Akt signaling pathway,lipid and atherosclerosis,proteoglycans in cancer,MAPK signaling pathway,and Ras signaling pathway.Molecular docking results indicated that aphanamixoid A,obacunol,cipadesin C,harpertrioate A,xylogranatin A,11-oxocneorin G,evodulone,methyl angolensate,harrpemoid B and khivorin may be key components of limonoids against AD.[Conclusions]Limonoids exert anti-Alzheimer s effects through a multi-molecule,multi-target and multi-pathway mechanism.
基金Natural Science Foundation-funded Project:Study on the Mechanism of Mechanical Stress Sensing Element Piezo Type Mechanosensitive Ion Channel Component 2 Interacting with Nuclear Receptor Subfamily 4 Group A Member 2 Mediating Traumatic Brain Injury(No.82172190)。
文摘OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target proteins of MT were retrieved from the GeneCards,PharmGkb,Therapeutic Target Database,DrugBank,and Online Mendelian Inheritance in Man databases.Information regarding MT and the drug targets was compared to obtain overlapping elements.This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram.Then,a“component-target”network diagram was constructed using screened drug components and target information,via Cytoscape(Institute for Systems Biology,Seattle,WA,USA).The database for annotation,visualization,and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses.Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.RESULTS:Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory,apoptosis,and nuclear factor kappa B(NF-κB)signaling pathways.Berberine(BBR),one of the main components of HLD,inhibited the development of MT in mice.BBR reduced cell viability while increasing B-cell lymphoma 2(Bcl-2)protein expression and decreasing CD86,NF-κB,Bax,and Caspase-3 protein expression in brain vascular 2(BV2)mcroglia cells treated with morphine.Additionally,BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.CONCLUSIONS:BBR,a key component of HLD,effectively suppressed microglial activation and neuroinflammation by regulating the NF-κB and apoptosis signaling pathways,thereby delaying MT.This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.
基金Supported by Medical Scientific Research Foundation of Guangdong Province of China(A2022479)University-Hospital Joint Fund Project of Guangzhou University of Traditional Chinese Medicine(GZYZS2024U08).
文摘[Objectives]To study the network pharmacology-based anticancer effect of Ardisiacrispin B for colon cancer(CRC).[Methods]The chemical structure and molecular properties of Ardisiacrispin B were assessed via the PubChem resource,while the putative target genes of Ardisiacrispin B were predicted using the PharmMapper Database.Moreover,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Ontology(GO)enrichment analyses were conducted via the WebGestalt platform.Finally,a drug-target-pathway network was built via Cytoscape to show the visual representation.[Results]Ardisiacrispin B exhibited exceptional druggability with 25 putative targets.Analyses conducted using KEGG,GO,and network methods showed that these target genes were related with inflammatory responses,cancer,and varoius other biological functions.On the basis of these findings,we further screened the correlative biotargets of Ardisiacrispin B in relation to CRC,and explored the anticancer effects of Ardisiacrispin B for the treatment of CRC through CCK8 analysis and colony formation assay.Our results confirmed that Ardisiacrispin B exhibited anti-CRC properties,and suggested 11 candidate targets of Ardisiacrispin B in the treatment of CRC.[Conclusions]Ardisiacrispin B has been demonstrated to target multiple proteins/genes and pathways,thereby forming a network that displays systematic pharmacological activities.Moreover,it has potential therapeutic value in tumor treatment,specifically in promoting the proliferation of CRC cells.
基金funded by Livelihood Plan Project of Department of Science and Technology of Liaoning Province(2023-MSLH-090)Department of Education of Liaoning Province(LJ212410163061).
文摘Non-alcoholic fatty liver disease(NAFLD),a chronic liver disorder closely associated with metabolic dysfunction,has become a significant global health challenge.In recent years,procyanidin B1(PB1)has demonstrated potential advantages in the prevention and personalized treatment of NAFLD through multi-target and multi-pathway intervention strategies,exerting comprehensive regulatory and synergistic effects.However,its precise therapeutic mechanisms remain unclear.This study employs network pharmacology to identify key targets and potential pathways involved in the treatment of NAFLD with PB1.Additionally,molecular docking analysis is conducted to validate the reliability of these targets.The findings provide a theoretical foundation for the development of PB1 as a potential therapeutic agent for NAFLD,offering insights for future experimental and clinical research.
基金supported by National Natural Science Foundation of China(No.82374333,No.82173961)LiaoNing Revitalization Talents Program(XLYC2203200)+5 种基金SPU Excellent Youth Program(YQ202310)SPU Youth Career Development plan(ZQN202211)Key Laboratory of polysaccharide bioactivity evaluation of TCM of Liaoning Province-Liaoning Distinguished Professor Project for Ying Jia(2017)High-level innovation and entrepreneurship team of Liaoning Province(XLYC2008029)Liaoning Provincial Department of Education Fund(LJ212410163006,LJ212410163018)Postgraduate Education and Teaching Reform Research Project of Liaoning Province in 2024(LNYJG2024251).
文摘This study aims to explore the mechanism by which flavonoids in Crataegus pinnatifida fruit improve Alzheimer’s disease(AD)through network pharmacology and molecular docking technology.The flavonoid components present in Crataegus pinnatifida fruit were gathered from the HERB,HIT,and ETCM databases,and were further supplemented by relevant published literature.The PubChem and SwissTargetPrediction databases were utilized to predict potential targets,and a“Crataegus pinnatifida fruit-active ingredient-target”network was constructed using Cytoscape 3.9.0 software.The GeneCards database was utilized to identify targets associated with AD,which were subsequently intersected with the active targets of Crataegus pinnatifi da fruit.A protein-protein interaction(PPI)network was constructed using the STRING platform.KEGG enrichment analysis of the core targets was conducted on an online bioinformatics mapping platform,while molecular docking of the primary active components and core targets was executed using AutoDock software.Eight flavonoids and 160 potential targets were identifi ed from Crataegus pinnatifi da fruit,of which 147 targets were linked to AD.The results of the“Crataegus pinnatifi da fruit-active ingredient-target”network indicated that quercetin was the principal flavonoid active ingredient.PPI analysis revealed that SRC and EGFR were the key targets,and KEGG analysis identifi ed the main enrichment pathways as Pathways in cancer,PI3K/Akt signaling pathway,and Proteoglycans in cancer.Molecular docking confi rmed the strong binding affi nity between the core targets and the primary active ingredient.The interaction of quercetin with the key targets SRC and EGFR may represent a signifi cant mechanism by which flavonoids from Crataegus pinnatifi da fruit contribute to the improvement of AD.
基金supported by the National Natural Science Foundation of China(Nos.22108181,22178233)the Fund of Science and Technology on Reactor Fuel and Materials Laboratory(No.6142A06190601)+6 种基金the National Excellent Young Scientists Fund(No.00308054A1045)the National Key R&D Program of China(No.2022YFA0912800)the Talents Program of Sichuan ProvinceDouble First Class University Plan of Sichuan Universitythe State Key Laboratory of Polymer Materials Engineering(No.sklpme 2020–03–01)the Tianfu Emei Program of Sichuan Province(No.2022EC02–00073-CG)Ministry of Education Key Laboratory of Leather Chemistry and Engineering(Sichuan University)。
文摘Although the demand of ^(10)B separation has arisen in the 1930s,^(10)B/^(11)B are among the most difficult isotopes to separate due to the extremely similar relative atomic mass.Herein,we report an efficient separation of ^(10)B isotopologue by engineering amino-galloyl synergistic materials via a selective adsorption and isotope exchange reaction,achieving a record-high single-stage separation factor of 1.048 with ^(10)B abundance up to 21.42%.^(11)B MAS NMR results and DFT calculations reveal that the galloyl groups exhibit inherent high affinity for B(OH)4-,forming tetrahedral sp^(3) B-galloyl complexes.The relatively higher ^(10)B–O bond energy of ^(10)B-galloyl complexes facilitates the isotope exchange between11B in B-galloyl complexes and ^(10)B in B(OH)_(3).Flowthrough dynamic separation in fixed-bed demonstrates the feasibility and potential of large-scale deployment of this method in real-world,suggesting a promising avenue for the exploitation of more efficient enrichment of ^(10)B for the sustainable nuclear energy and biomedical research.
文摘Any malfunctions of the actuators of the robots have the potential to destroy the robot’s normal motion,and most of the current actuator fault diagnosis methods are difficult to meet the requirements of simplifying the actuator modeling and solving the difficulty of fault data collection.To solve the problem of real-time diagnosis of actuator faults in the 3-PR(P)S parallel robot,the model of 3-PR(P)S parallel robot and data-driven-based method for the fault diagnosis are presented.Firstly,only the input-output relationship of the actuator is considered for modeling actuator faults,reducing the complexity of fault modeling and reducing the time consumption of parameter identification,thereby meeting the requirements of real-time diagnosis.A Simulink model of the electromechanical actuator(EMA)was constructed to analyze actuator faults.Then the short-term analysis method was employed for collecting the sample data of the slider position on the test platform of the EMA system and feature extraction.Training samples for neural networks are obtained.Furthermore,we optimized the Back Propagation(BP)neural network using the Dung Beetle Optimization Algorithm(DBO),which effectively resolved the weights and thresholds of the BP neural network.Compared to BP and Particle Swarm Optimization(PSO)-BP,the DBO-BP has better convergence,convergence rate,and the best-classifying quality.So,the classification for the different actuator faults is obviously improved.Finally,a fault diagnosis system was designed for the actuator of the 3-PR(P)S parallel robot,and the experimental results demonstrate that this system can detect actuator faults within 0.1 seconds.This work also provides the technical support for the fault-tolerant control of the 3-PR(P)S Parallel robot.
文摘Meteor Burst Communication(MBC),a niche yet revolutionary wireless communication paradigm,exploits the transient ionized trails generated by meteors ablating in Earth’s atmosphere to enable sporadic yet resilient long-distance radio links.Known for its exceptional resilience,robustness,and sustained connectivity,MBC holds significant promise for applications in emergency communications,remote area connectivity,military/defense systems,and environmental monitoring.However,the scientific exploration and application of MBC have long been highly challenging.In particular,under the combined influence of multiple physical field factors,the channel experiences superimposed multiple random fading effects,exhibiting bursty,highly time-varying,and strongly random characteristics.This persistent technical challenge has resulted in the absence of a practical statistical channel model for MBC to date.
基金Supported by the Innovation Platform Open Fund in Hunan Province Colleges and Universities of China(201485).
文摘In this paper,a class of quaternion-valued cellular neural networks(QVCNNS)with time-varying delays are considered.Combining graph theory with the continuation theorem of Mawhin’s coincidence degree theory as well as Lyapunov functional method,we establish new criteria on the existence and exponential stability of periodic solutions for QVCNNS by removing the assumptions for the boundedness on the activation functions and the assumptions that the values of the activation functions are zero at origin.Hence,our results are less conservative and new.
文摘目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料和血清HMGB1、S100β水平及24 h BIS,分析脓毒症病人发生SAE的影响因素和HMGB1、S100β、BIS联合检测早期诊断SAE的临床价值。结果:SAE组病人APACHEⅡ评分、SOFA评分均明显高于非SAE组(P<0.01);SAE组血清HMGB1、S100β水平均明显高于非SAE组(P<0.01),而BIS明显低于非SAE组(P<0.01)。APACHEⅡ评分、SOFA评分和HMGB1、S100β、BIS均为脓毒症病人发生SAE的独立影响因素(P<0.01)。ROC曲线分析显示,血清HMGB1、S100β联合BIS早期诊断脓毒症病人发生SAE的AUC为0.891,敏感度为91.43%,特异度为84.62%,优于各指标独立诊断。结论:血清HMGB1、S100β联合BIS在SAE早期诊断中具有较好的临床应用价值。
