Objective:The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule(LTC)on ischemic stroke rats.Methods:Twenty-six rats were randomly divided into four...Objective:The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule(LTC)on ischemic stroke rats.Methods:Twenty-six rats were randomly divided into four groups,including sham group,sham+LTC group,MCAO group,and MCAO+LTC group.Ischemic stroke rats were simulated by middle cerebral artery occlusion(MCAO),and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days.LTC therapy was validated in terms of neurobehavioral abnormality evaluation,cerebral infarct area,and histological assessments.The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis,aiming to finding the molecules in respond to the surgery or LTC treatment.Results:Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats.The interstitial edema,atrophy,and pyknosis of glial and neuronal cells occurred in the infarcted area,core area,and marginal area of cerebral cortex were improved after LTC treatment.A total of 13 potential biomarkers were observed,and Youden index of 11 biomarkers such as LysoPC,SM,and PE were more than 0.7,which were involved in neuroprotective process.The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism,together with nicotinate and nicotinamide metabolism.Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC.Conclusion:The present study could provide evidence that metabolomics,as systematic approach,revealed its capacity to evaluate the holistic efficacy of TCM,and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.展开更多
The study of the development cost of general aviation aircraft is limited by small samples with many cost-driven factors. This paper investigates a parametric modeling method for prediction of the development cost of ...The study of the development cost of general aviation aircraft is limited by small samples with many cost-driven factors. This paper investigates a parametric modeling method for prediction of the development cost of general aviation aircraft. The proposed technique depends on some principal components, acquired by utilizing P value analysis and gray correlation analysis. According to these principal components, the corresponding linear regression and BP neural network models are established respectively. The feasibility and accuracy of the P value analysis are verified by comparing results of model fitting and prediction. A sensitivity analysis related to model precision and suitability is discussed in detail. Results obtained in this study show that the proposed method not only has a certain degree of versatility, but also provides a preliminary prediction of the development cost of general aviation aircraft.展开更多
Obtaining accurate development cost estimation results of general aviation aircraft is crucial for companies to adopt the best strategy in the development process.To address this problem,this paper proposes a combinat...Obtaining accurate development cost estimation results of general aviation aircraft is crucial for companies to adopt the best strategy in the development process.To address this problem,this paper proposes a combination of three commonly used single prediction methods.The optimal weight values of the three single prediction methods are determined by utilizing the shortest ideal point method.Ten cost datasets collected from literature are utilized for fitting and testing the combined prediction method,and the weight coefficients of the three individual prediction methods are calculated as 0.6859,0.0035 and 0.3106,respectively.The results of this study indicate that the developed method has better fitting and estimation accuracy than that of the three individual methods,with average fitting and predicting error values of 2.60%and 6.43%,respectively.Additionally,the cost data of military and civil aircraft development from literature are collected for verification.The results further confirm that the proposed method is not only superior to the single prediction methods in terms of high precision but has wider applications.More importantly,this research can provide important reference for general aviation aircraft companies in term of product cost planning and corporate sales strategies.展开更多
Helicobacter pylori(H.pylori),creating a global infection rate over 50%,presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo.To improve the eradication efficacy,here...Helicobacter pylori(H.pylori),creating a global infection rate over 50%,presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo.To improve the eradication efficacy,herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG,calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer.RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H.pylori infection sites,and then effectively destroyed the architecture of H.pylori biofilms,killed dispersed H.pylori and inhibited the re-adhesion of residual bacteria(called biofilms eradication tetralogy).Moreover,RHL/Cl-Ch-cal activated the host immune response to H.pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells.Finally,RHL/Cl-Ch-cal killed the intracellular H.pylori through recovering the lysosomal acidification and assisting degradation.In experiments,RHL/Cl-Ch-cal demonstrated prominent anti-H.pylori efficacy in the classical H.pylori-infected mice model.Therefore,the study provides a“comprehensive attack”strategy for anti-H.pylori therapies including biofilms eradication tetralogy,immune activation and intracellular bacteria killing.展开更多
Four new diterpenoids including one cis clerodane-type(1) and three highly oxygenated labdane-type diterpenes(2–4) were isolated from the aerial parts of Leonurus macranthus. Their structures were elucidated on the b...Four new diterpenoids including one cis clerodane-type(1) and three highly oxygenated labdane-type diterpenes(2–4) were isolated from the aerial parts of Leonurus macranthus. Their structures were elucidated on the basis of spectroscopic data(NMR, UV, IR, and MS). Compound 1 represents the first example of cis clerodane-type diterpene in the plants of Leonurus genus. Compounds 1 and 4 exhibited weak inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC_(50) values of 35.8 ± 3.6 mmol/L and 48.6 ± 4.8 mmol/L,展开更多
基金financially supported by the National Natural Science Foundation of China(81573572,81530097,32101957)the National Key R&D Program of China(2022YFC2010104)Agricultural Science and Technology Innovation Program of Institute of Food Science and Technology,Chinese Academy of Agricultural Sciences(CAAS-ASTIP-Q2022-IFST-08)。
文摘Objective:The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule(LTC)on ischemic stroke rats.Methods:Twenty-six rats were randomly divided into four groups,including sham group,sham+LTC group,MCAO group,and MCAO+LTC group.Ischemic stroke rats were simulated by middle cerebral artery occlusion(MCAO),and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days.LTC therapy was validated in terms of neurobehavioral abnormality evaluation,cerebral infarct area,and histological assessments.The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis,aiming to finding the molecules in respond to the surgery or LTC treatment.Results:Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats.The interstitial edema,atrophy,and pyknosis of glial and neuronal cells occurred in the infarcted area,core area,and marginal area of cerebral cortex were improved after LTC treatment.A total of 13 potential biomarkers were observed,and Youden index of 11 biomarkers such as LysoPC,SM,and PE were more than 0.7,which were involved in neuroprotective process.The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism,together with nicotinate and nicotinamide metabolism.Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC.Conclusion:The present study could provide evidence that metabolomics,as systematic approach,revealed its capacity to evaluate the holistic efficacy of TCM,and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.
基金supported by the National Postdoctoral Program for Innovative Talents, Postdoctoral Science Foundation of China (No. 2017M610740)supports from Hefei General Aviation Research Institute, Beihang University
文摘The study of the development cost of general aviation aircraft is limited by small samples with many cost-driven factors. This paper investigates a parametric modeling method for prediction of the development cost of general aviation aircraft. The proposed technique depends on some principal components, acquired by utilizing P value analysis and gray correlation analysis. According to these principal components, the corresponding linear regression and BP neural network models are established respectively. The feasibility and accuracy of the P value analysis are verified by comparing results of model fitting and prediction. A sensitivity analysis related to model precision and suitability is discussed in detail. Results obtained in this study show that the proposed method not only has a certain degree of versatility, but also provides a preliminary prediction of the development cost of general aviation aircraft.
基金the National Postdoctoral Program for Innovative Talents,Postdoctoral Science Foundation of China(No.2017M610740)the supports from Hefei General Aviation Research Institute,Beihang University。
文摘Obtaining accurate development cost estimation results of general aviation aircraft is crucial for companies to adopt the best strategy in the development process.To address this problem,this paper proposes a combination of three commonly used single prediction methods.The optimal weight values of the three single prediction methods are determined by utilizing the shortest ideal point method.Ten cost datasets collected from literature are utilized for fitting and testing the combined prediction method,and the weight coefficients of the three individual prediction methods are calculated as 0.6859,0.0035 and 0.3106,respectively.The results of this study indicate that the developed method has better fitting and estimation accuracy than that of the three individual methods,with average fitting and predicting error values of 2.60%and 6.43%,respectively.Additionally,the cost data of military and civil aircraft development from literature are collected for verification.The results further confirm that the proposed method is not only superior to the single prediction methods in terms of high precision but has wider applications.More importantly,this research can provide important reference for general aviation aircraft companies in term of product cost planning and corporate sales strategies.
基金supported by National Natural Science Foundation of China (Nos. 81773659 and 81973264)Guangdong Basic and Applied Basic Research Foundation (Nos. 2019A1515011954, 2020A1515010593 and 2021A1515012621, China)Guangdong Provincial Key Laboratory of Construction Foundation (No. 2019B030301005, China)
文摘Helicobacter pylori(H.pylori),creating a global infection rate over 50%,presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo.To improve the eradication efficacy,herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG,calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer.RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H.pylori infection sites,and then effectively destroyed the architecture of H.pylori biofilms,killed dispersed H.pylori and inhibited the re-adhesion of residual bacteria(called biofilms eradication tetralogy).Moreover,RHL/Cl-Ch-cal activated the host immune response to H.pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells.Finally,RHL/Cl-Ch-cal killed the intracellular H.pylori through recovering the lysosomal acidification and assisting degradation.In experiments,RHL/Cl-Ch-cal demonstrated prominent anti-H.pylori efficacy in the classical H.pylori-infected mice model.Therefore,the study provides a“comprehensive attack”strategy for anti-H.pylori therapies including biofilms eradication tetralogy,immune activation and intracellular bacteria killing.
基金financially supported by the National Natural Science Foundation of China (Nos. 81573572, 81530097)New Century Excellent Talents in University (No. NCET-13-0693)
文摘Four new diterpenoids including one cis clerodane-type(1) and three highly oxygenated labdane-type diterpenes(2–4) were isolated from the aerial parts of Leonurus macranthus. Their structures were elucidated on the basis of spectroscopic data(NMR, UV, IR, and MS). Compound 1 represents the first example of cis clerodane-type diterpene in the plants of Leonurus genus. Compounds 1 and 4 exhibited weak inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC_(50) values of 35.8 ± 3.6 mmol/L and 48.6 ± 4.8 mmol/L,
