Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum ph...Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.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
Dear Editor,In vivo bioluminescence imaging(BLI)models of virus infection possess unique advantages over conventional assays.For instance,the BLI model enables rapid and real-time detection of viral load and dissemina...Dear Editor,In vivo bioluminescence imaging(BLI)models of virus infection possess unique advantages over conventional assays.For instance,the BLI model enables rapid and real-time detection of viral load and dissemination in the same animal over time(Mehle,2015;Wen et al.,2022).展开更多
Numerical weather prediction of wind speed requires statistical postprocessing of systematic errors to obtain reliable and accurate forecasts.However,use of postprocessing models is often undesirable for extreme weath...Numerical weather prediction of wind speed requires statistical postprocessing of systematic errors to obtain reliable and accurate forecasts.However,use of postprocessing models is often undesirable for extreme weather events such as gales.Here,we propose a postprocessing algorithm based on a gale-aware deep attention network to simultaneously improve wind speed forecasts and gale area warnings.Specifically,the algorithm includes both a galeaware loss function that focuses the model on potential gale areas,and an observation station supervision strategy that alleviates the problem of missing extreme values caused by data gridding.The effectiveness of the proposed model was verified by using data from 235 wind speed observation stations.Experimental results show that our model can produce wind speed forecasts with a root-mean-square error of 1.1547 m s^(-1),and a Hanssen–Kuipers discriminant score of 0.517,performance that is superior to that of the other postprocessing algorithms considered.展开更多
Influenza A virus(IAV)poses a global public health concern and remains an imminent threat to human health.Emerging antiviral resistance to the currently approved influenza drugs emphasizes the urgent need for new ther...Influenza A virus(IAV)poses a global public health concern and remains an imminent threat to human health.Emerging antiviral resistance to the currently approved influenza drugs emphasizes the urgent need for new therapeutic entities against IAV.Allopregnanolone(ALLO)is a natural product that has been approved as an antidepressant drug.In the present study,we repurposed ALLO as a novel inhibitor against IAVs.Mechanistic studies demonstrated that ALLO inhibited virus replication by interfering with the nucleus translocation of viral nucleoprotein(NP).In addition,ALLO showed significant synergistic activity with compound 16,a hemagglutinin inhibitor of IAVs.In summary,we have identified ALLO as a novel influenza virus inhibitor targeting NP,providing a promising candidate that deserves further investigation as a useful anti-influenza strategy in the future.展开更多
基金supported by Key R&D Project in Shandong ProvinceChina(Grant number:2020CXGC010505)+2 种基金Qingdao Science and Technology Demonstration Program for the Benefit of the PeopleShandong ProvinceChina(Grant number:23-7-8-smjk-3-nsh)。
文摘Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.
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supported by the National Natural Science Foundation of China (82104134)the Open Research Fund Program of the State Key Laboratory of Virology of China (2022IOV003)。
文摘Dear Editor,In vivo bioluminescence imaging(BLI)models of virus infection possess unique advantages over conventional assays.For instance,the BLI model enables rapid and real-time detection of viral load and dissemination in the same animal over time(Mehle,2015;Wen et al.,2022).
基金Supported by the National Natural Science Foundation of China (62106169)。
文摘Numerical weather prediction of wind speed requires statistical postprocessing of systematic errors to obtain reliable and accurate forecasts.However,use of postprocessing models is often undesirable for extreme weather events such as gales.Here,we propose a postprocessing algorithm based on a gale-aware deep attention network to simultaneously improve wind speed forecasts and gale area warnings.Specifically,the algorithm includes both a galeaware loss function that focuses the model on potential gale areas,and an observation station supervision strategy that alleviates the problem of missing extreme values caused by data gridding.The effectiveness of the proposed model was verified by using data from 235 wind speed observation stations.Experimental results show that our model can produce wind speed forecasts with a root-mean-square error of 1.1547 m s^(-1),and a Hanssen–Kuipers discriminant score of 0.517,performance that is superior to that of the other postprocessing algorithms considered.
基金the National Natural Science Foundation of China(No.82104134)the Natural Science Foundation of Shandong Province,China(No.ZR2020MH383)+2 种基金the Major Basic Program of Natural Science Foundation of Shandong Province(No.ZR2021ZD17)the Jinan Independent Training Innovative Team(No.2021GXRC028)the Open Research Fund Program of the State Key Laboratory of Virology of China(No.2022IOV003).
文摘Influenza A virus(IAV)poses a global public health concern and remains an imminent threat to human health.Emerging antiviral resistance to the currently approved influenza drugs emphasizes the urgent need for new therapeutic entities against IAV.Allopregnanolone(ALLO)is a natural product that has been approved as an antidepressant drug.In the present study,we repurposed ALLO as a novel inhibitor against IAVs.Mechanistic studies demonstrated that ALLO inhibited virus replication by interfering with the nucleus translocation of viral nucleoprotein(NP).In addition,ALLO showed significant synergistic activity with compound 16,a hemagglutinin inhibitor of IAVs.In summary,we have identified ALLO as a novel influenza virus inhibitor targeting NP,providing a promising candidate that deserves further investigation as a useful anti-influenza strategy in the future.