Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predi...Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predicted by PubChem and Swiss Target Prediction databases,and the targets of KOA were obtained by DisGeNET,OMIM,and GeneCards databases.Then,the targets of quercetin and KOA were intersected to find the potential targets of quercetin against KOA.The protein–protein interaction network was constructed through the STRING database,and the core targets were screened.Gene ontology(GO)functions enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DAVID database.The drug–target–pathway–disease network was constructed by Cytoscape software,and the molecular docking verification was performed by Vina.Results There were 49 potential targets for quercetin against KOA,including 10 core targets.GO functions enrichment analysis showed that the biological process of quercetin against KOA mainly involved the negative regulation of apoptotic process,collagen catabolic process,and extracellular matrix disassembly.KEGG pathway enrichment analysis showed that quercetin against KOA was closely related to PI3K-Akt signaling pathway,Rap 1 signaling pathway,FoxO signaling pathway,Ras signaling pathway,TNF signaling pathway,and ErbB signaling pathway.The results of molecular docking showed that the binding energies between ligand and receptors were less than−5 kcal·mol−1.Conclusions The molecular mechanism of quercetin against KOA involves many targets and pathways,which can regulate the proliferation and apoptosis of chondrocytes,degradation of extracellular matrix,and inflammatory reaction.Quercetin can stably bind to the active pockets of core target proteins,thereby exerting the effect against KOA.展开更多
Objective The resting-state functional magnetic resonance imaging(rs-f MRI)method was used to observe brain activity and its functional connection upon electroacupuncture stimulation at bilateral uterine acupoints(EX-...Objective The resting-state functional magnetic resonance imaging(rs-f MRI)method was used to observe brain activity and its functional connection upon electroacupuncture stimulation at bilateral uterine acupoints(EX-CA1),as well as to investigate the mechanism of acupuncture in the treatment of gynecological diseases.Methods Twenty-two healthy female subjects were stimulated by electroacupuncture at bilateral uterine acupoints;rs-f MRI data of the brain were acquired and standardized.Degree centrality(DC),amplitude of low-frequency fluctuation(ALFF),and regional homogeneity(ReHo)were used to analyze local spontaneous brain activity via acupuncture.An independent component analysis was used to evaluate the functional connectivity of the resting brain networks after acupuncture.Results Analytical results showed that the neural activity intensity of the precuneus lobe,orbitofrontal cortex,lingual gyrus,amygdala,and posterior central gyrus decreased after acupuncture(voxel P<0.001,cluster P<0.05).Functional connectivity analysis revealed weakened auditory and right frontal-parietal networks(voxel P<0.001,cluster P<0.05),enhanced visual network(voxel P<0.001,cluster P<0.05),and synergistic auditory network and hypothalamic-pituitary system.Conclusion Significant differences in neural activity and functional connectivity in specific brain regions were observed after acupuncture intervention at uterine acupoints;the hypothalamic-pituitary system also showed various active states in different brain regions.It is speculated that the effective mechanism of acupuncture at uterine acupoints is related to the regulation of reproductive hormones,emotional changes,and somatic sensations.Therefore,the methods used in this study could clarify the neural mechanism of uterine-point acupuncture in the treatment of gynecological diseases and may serve as a reference for other studies pertaining to acupuncture.展开更多
Objective To investigate the human body’s complex system,and classify and characterize the human body’s health states with“a comprehensive integrated method from qualitative to quantitative”.Methods This paper int...Objective To investigate the human body’s complex system,and classify and characterize the human body’s health states with“a comprehensive integrated method from qualitative to quantitative”.Methods This paper introduces the concept of“order parameters”and proposes a method for establishing an order parameter model of gas discharge visualization(GDV)based on the principle of“mastering both permanence and change(MBPC)”.The method involved the fol-lowing three steps.First,average luminous intensity(I)and average area(S)of the GDV im-ages were calculated to construct the phase space,and the score of the health questionnaire was calculated as the health deviation index(H).Second,the k-means++clustering method was employed to identify subclasses with the same health characteristics based on the data samples,and to statistically determine the symptom-specific frequencies of the subclasses.Third,the distance(d)between each sample and the“ideal health state”,which determined in the phase space of each subclass,was calculated as an order parameter describing the health imbalance,and a linear mapping was established between the d and the H.Further,the health implications of GDV signals were explored by analyzing subclass symptom profiles.We also compare the mean square error(MSE)with classification methods based on age,gen-der,and body mass index(BMI)indices to verify that the phase space possesses the ability to portray the health status of the human body.Results This study preliminarily tested the reliability of the order parameter model on data samples provided by 20 participants.Based on the discovered linear law,the current model can use d calculated by measuring the GDV signal to predict H(R^(2)>0.77).Combined with the symptom profiles of the subclasses,we explain the classification basis of the phase space based on the pattern identification.Compared with common classification methods based on age,gender,BMI,etc.,the MSE of phase space-based classification was reduced by an order of magnitude.Conclusion In this study,the GDV order parameter model based on MBPC can identify sub-classes and characterize individual health levels,and explore the TCM health meanings of the GDV signals by using subjective-objective methods,which holds significance for establishing mathematical models from TCM diagnosis principles to interpret human body signals.展开更多
Manganese-catalyzed C—C bond cleavage of cyclobutanols has attracted great attention due to the high abundance and cheap and eco-friendly behaviour.A manganese-catalyzed ring-opening C—C bond fluorination of cyclobu...Manganese-catalyzed C—C bond cleavage of cyclobutanols has attracted great attention due to the high abundance and cheap and eco-friendly behaviour.A manganese-catalyzed ring-opening C—C bond fluorination of cyclobutanols is reported.Under mild conditions,the reaction provides a straightforward access to γ-fluorinated ketones using 10 mol% Mn(OAc)_(2) as catalyst and electrophilic fluorination reagent,which was generated in situ from HF·Et 3N and PhIO,as fluorine source.The reaction has an excellent functional-group tolerance and displays a broad substrate scope,affording the corresponding products in 50%~76%yields.展开更多
基金funded by the Project of Chinese Medicine Science and Technology Development Planning in Shandong Province(2017-018)the Project of Scientific Research and Development Plan of Colleges and Universities in Shandong Province(J18KB130)the Project of the First Batch of Excellent Scientific Research and Innovation Team in Shandong University of Chinese Medicine(220316).
文摘Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predicted by PubChem and Swiss Target Prediction databases,and the targets of KOA were obtained by DisGeNET,OMIM,and GeneCards databases.Then,the targets of quercetin and KOA were intersected to find the potential targets of quercetin against KOA.The protein–protein interaction network was constructed through the STRING database,and the core targets were screened.Gene ontology(GO)functions enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DAVID database.The drug–target–pathway–disease network was constructed by Cytoscape software,and the molecular docking verification was performed by Vina.Results There were 49 potential targets for quercetin against KOA,including 10 core targets.GO functions enrichment analysis showed that the biological process of quercetin against KOA mainly involved the negative regulation of apoptotic process,collagen catabolic process,and extracellular matrix disassembly.KEGG pathway enrichment analysis showed that quercetin against KOA was closely related to PI3K-Akt signaling pathway,Rap 1 signaling pathway,FoxO signaling pathway,Ras signaling pathway,TNF signaling pathway,and ErbB signaling pathway.The results of molecular docking showed that the binding energies between ligand and receptors were less than−5 kcal·mol−1.Conclusions The molecular mechanism of quercetin against KOA involves many targets and pathways,which can regulate the proliferation and apoptosis of chondrocytes,degradation of extracellular matrix,and inflammatory reaction.Quercetin can stably bind to the active pockets of core target proteins,thereby exerting the effect against KOA.
基金National Nature Science Foundation of China(61872225)Natural Science Foundation of Shandong Province(ZR2020KF013,ZR2020ZD44,ZR2019ZD04,and ZR2020QF043)+1 种基金Introduction and Cultivation Program for Young Creative Talents in Colleges and Universities of Shandong Province(2019-173)Special Fund of Qilu Health and Health Leading Talents Training Project。
文摘Objective The resting-state functional magnetic resonance imaging(rs-f MRI)method was used to observe brain activity and its functional connection upon electroacupuncture stimulation at bilateral uterine acupoints(EX-CA1),as well as to investigate the mechanism of acupuncture in the treatment of gynecological diseases.Methods Twenty-two healthy female subjects were stimulated by electroacupuncture at bilateral uterine acupoints;rs-f MRI data of the brain were acquired and standardized.Degree centrality(DC),amplitude of low-frequency fluctuation(ALFF),and regional homogeneity(ReHo)were used to analyze local spontaneous brain activity via acupuncture.An independent component analysis was used to evaluate the functional connectivity of the resting brain networks after acupuncture.Results Analytical results showed that the neural activity intensity of the precuneus lobe,orbitofrontal cortex,lingual gyrus,amygdala,and posterior central gyrus decreased after acupuncture(voxel P<0.001,cluster P<0.05).Functional connectivity analysis revealed weakened auditory and right frontal-parietal networks(voxel P<0.001,cluster P<0.05),enhanced visual network(voxel P<0.001,cluster P<0.05),and synergistic auditory network and hypothalamic-pituitary system.Conclusion Significant differences in neural activity and functional connectivity in specific brain regions were observed after acupuncture intervention at uterine acupoints;the hypothalamic-pituitary system also showed various active states in different brain regions.It is speculated that the effective mechanism of acupuncture at uterine acupoints is related to the regulation of reproductive hormones,emotional changes,and somatic sensations.Therefore,the methods used in this study could clarify the neural mechanism of uterine-point acupuncture in the treatment of gynecological diseases and may serve as a reference for other studies pertaining to acupuncture.
基金Program of Office of Science and Technology Development,Peking University(3124-2021|-L-w6).
文摘Objective To investigate the human body’s complex system,and classify and characterize the human body’s health states with“a comprehensive integrated method from qualitative to quantitative”.Methods This paper introduces the concept of“order parameters”and proposes a method for establishing an order parameter model of gas discharge visualization(GDV)based on the principle of“mastering both permanence and change(MBPC)”.The method involved the fol-lowing three steps.First,average luminous intensity(I)and average area(S)of the GDV im-ages were calculated to construct the phase space,and the score of the health questionnaire was calculated as the health deviation index(H).Second,the k-means++clustering method was employed to identify subclasses with the same health characteristics based on the data samples,and to statistically determine the symptom-specific frequencies of the subclasses.Third,the distance(d)between each sample and the“ideal health state”,which determined in the phase space of each subclass,was calculated as an order parameter describing the health imbalance,and a linear mapping was established between the d and the H.Further,the health implications of GDV signals were explored by analyzing subclass symptom profiles.We also compare the mean square error(MSE)with classification methods based on age,gen-der,and body mass index(BMI)indices to verify that the phase space possesses the ability to portray the health status of the human body.Results This study preliminarily tested the reliability of the order parameter model on data samples provided by 20 participants.Based on the discovered linear law,the current model can use d calculated by measuring the GDV signal to predict H(R^(2)>0.77).Combined with the symptom profiles of the subclasses,we explain the classification basis of the phase space based on the pattern identification.Compared with common classification methods based on age,gender,BMI,etc.,the MSE of phase space-based classification was reduced by an order of magnitude.Conclusion In this study,the GDV order parameter model based on MBPC can identify sub-classes and characterize individual health levels,and explore the TCM health meanings of the GDV signals by using subjective-objective methods,which holds significance for establishing mathematical models from TCM diagnosis principles to interpret human body signals.
基金Project supported by the National Natural Science Foundation of China(Nos.92156008,22161142016)the Taishan Scholar Program at Shandong Provincethe Natural Science Foundation of Shandong Province(No.ZR2020QB018)。
文摘Manganese-catalyzed C—C bond cleavage of cyclobutanols has attracted great attention due to the high abundance and cheap and eco-friendly behaviour.A manganese-catalyzed ring-opening C—C bond fluorination of cyclobutanols is reported.Under mild conditions,the reaction provides a straightforward access to γ-fluorinated ketones using 10 mol% Mn(OAc)_(2) as catalyst and electrophilic fluorination reagent,which was generated in situ from HF·Et 3N and PhIO,as fluorine source.The reaction has an excellent functional-group tolerance and displays a broad substrate scope,affording the corresponding products in 50%~76%yields.
