汽车保有量的增加和能耗排放法规日益严格的限制给车辆节能减排提出了巨大挑战,网联化、智能化和电气化是提高未来交通效率和减少公路能源消耗的三大支柱。为了全面了解智能网联汽车节能减排的前沿问题与研究进展,对当前经济驾驶领域的...汽车保有量的增加和能耗排放法规日益严格的限制给车辆节能减排提出了巨大挑战,网联化、智能化和电气化是提高未来交通效率和减少公路能源消耗的三大支柱。为了全面了解智能网联汽车节能减排的前沿问题与研究进展,对当前经济驾驶领域的重点问题进行了总体概述。首先,从广义的能量转换角度总结了智能车辆节能优化技术的本质和3个过程,其中Wheels to Distance环节的车辆系统优化是挖掘汽车节能潜力的重要一环,针对其介绍了智能网联汽车节能优化问题的基本数学原理;其次,从智能运输系统的各类非同源异构数据出发,分别从人-车交互、车-车通信、车-路感知三方面阐述来源于"人-车-路"交互体系的智能信息与数据;然后,针对单车智能网联环境下的多维度信息与先进控制技术相结合的关键问题,从考虑道路坡度预测巡航控制、跟车工况预测巡航控制、智能辅助驾驶和车道变换等应用场景进行具体介绍;针对"人-车-路-云"多源异构环境下车辆行为协同节能关键科学问题,从经济驾驶、多车协同节能、道路交叉口车路协同节能和车云协同节能等方面详细介绍研究现状;并进一步介绍电气化公路系统的前瞻性研究,说明融合智能化信息的E-highway节能潜力和智能重型商用车协同节能的未来发展趋势。最后,总结并梳理智能化信息对于提升车辆节能的重要影响,并展望了其在理论与实际层面遇到的挑战。展开更多
The anti-bacterial activities of three types of di-O-caffeoylquinic acids(diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine(TCM), on Bacillus shigae growth were investigated and compared by microcal...The anti-bacterial activities of three types of di-O-caffeoylquinic acids(diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine(TCM), on Bacillus shigae growth were investigated and compared by microcalorimetry. The three types of diCQAs were 3, 4-di-O-caffeoylquinic acid(3, 4-diCQA), 3, 5-di-O-caffeoylquinic acid(3, 5-diCQA), and 4, 5-di-O-caffeoylquinic acid(4, 5-diCQA). Some qualitative and quantitative information of the effects of the three diCQAs on metabolic power–time curves, growth rate constant k, maximum heat-output power Pm, and the generation time tG, total heat output Qt, and growth inhibitory ratio I of B. shigae were calculated. In accordance with a thermo-kinetic model, the corresponding quantitative relationships of k, Pm, Qt, I and c were established. Also, the half-inhibitory concentrations of the drugs(IC50) were obtained by quantitative analysis. Based on the quantity–activity relationships and the IC50 values, the sequence of inhibitory activity was 3, 5-diCQA > 4, 5-diCQA > 3, 4-diCQA. The results illustrate the possibility that the caffeoyl ester group at C-5 is the principal group that has a higher affinity for the bacterial cell, and that the intramolecular distance of the two caffeoyl ester groups also has an important influence on the anti-bacterial activities of the diCQAs.展开更多
AIM： To improve the absorption and bioavailability of baicalin using a nanocrystal （or nanosuspension） drug delivery system. METHODS： A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to ...AIM： To improve the absorption and bioavailability of baicalin using a nanocrystal （or nanosuspension） drug delivery system. METHODS： A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo. RESULTS： The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of-34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 ug·mL-1, was much higher than the baicalin-microcrystals and the physical mixture （135 and 86.4 ug·mL- 1, respectively）. In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability （with the AUC（0-t） value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L-1·h-1, respectively）. CONCLUSION： The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure展开更多
Objective To study the rational daily administration times of Yinchenhao Decoction(YCHD)when it was used to treat experimental jaundice in rats based on pharmacodynamics/pharmacokinetics model.Methods Rats were modele...Objective To study the rational daily administration times of Yinchenhao Decoction(YCHD)when it was used to treat experimental jaundice in rats based on pharmacodynamics/pharmacokinetics model.Methods Rats were modeled by 4%1-naphthylisothiocyanate(75 mg/kg)for 48 h,then YCHD was drenched with doses of 0.324 g/kg (extract,calculated with the clinical dosage)once,0.162 g/kg twice,and 0.108 g/kg thrice a day,respectively.The total bile and the flow rate of bile were observed after the first administration;Blood samples collected from the orbital sinus at different intervals were used to investigate the levels of liver enzymes(ALT and AST)and bilirubins (TBIL and DBIL),and determine the concentration of 6,7-dimethoxycoumarin(DME)in the plasma using UPLC at the same time,then we obtained the time-effect and time-dose curves.The rational daily administration times of YCHD when treating experimental jaundice were determined based on the comprehensive analysis of time-effect and time-concentration relationships.Results Within 10 h the total bile of rats which were administered once daily(G1) was 1.65 and 1.33 times higher than that of twice and thrice(G2 and G3)a day,respectively,and the four biochemical indexes(TBIL,ALT,DBIL,and AST)of G1 decreased faster than those of G2 and G3(P<0.05).On the other hand, the blood drug level of DME when administrated once daily could maintain at a higher level for a longer time,and its Cmax and AUC0→t were higher than those of G2 and G3,which might be the main reason why its effect was the most significant.Conclusion It is more appropriate to administrate once daily when YCHD is used to treat jaundice.展开更多
AIM: To improve the absorption of thymopeptides(TH) by preparing sodium deoxycholate/phospholipid-mixed nanomicelles(SDC/PL-MMs). METHODS: TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated us...AIM: To improve the absorption of thymopeptides(TH) by preparing sodium deoxycholate/phospholipid-mixed nanomicelles(SDC/PL-MMs). METHODS: TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated using photon correlation spectroscopy(PCS), zeta potential measurement, as well as their physical stability after storage for several days. Furthermore, in situ intestinal single-pass perfusion experiments and pharmacodynamics in immunodeficient mice were performed to make a comparison with TH powders and the control drug in absorption properties. RESULTS: A narrow size distribution of nanomicelles, with a mean particle size of(149 ± 8.32) nm and a zeta potential of(-31.05 ± 2.52) mV, was obtained. The in situ intestine perfusion experiments demonstrated a significant advantage in absorption characteristics for TH compared to the other formulations, and oral administration of TH-SDC/PL-MMs potentiated an equivalent effect with i.h. TH in pharmacodynamic studies in immunodeficient mice. CONCLUSIONS: TH-SDC/PL-MMs prepared by a film dispersion method are able to improve the absorption of TH. SDC/PL-MMs might be a good approach for the more effective delivery of drugs like TH.展开更多
Background:Abnormal myocardial voltage-gated sodium channel 1.5(Nav1.5)expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion(I/R).Protein inhibitor of activated STAT Y(PI...Background:Abnormal myocardial voltage-gated sodium channel 1.5(Nav1.5)expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion(I/R).Protein inhibitor of activated STAT Y(PIASy)-mediated caveolin-3(Cav-3)small ubiquitin-related modifier(SUMO)modification affects Cav-3 binding to the Nav1.5.PIASy activity is increased after myocardial I/R,but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias.Methods:Using recombinant adeno-associated virus subtype 9(AAV9),rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA(shRNA).After two weeks,rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias.Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements.Results:PIASy was upregulated by I/R(P<0.01),with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density(P<0.01).AAV9-PIASy shRNA intraventricular injection into the rat heart down-regulated PIASy after I/R,at both mRNA and protein levels(P<0.05 vs.Scramble-shRNA+I/R group),decreased SUMO-modified Cav-3 levels,enhanced Cav-3 binding to Nav1.5,and prevented I/R-induced decrease of Nav1.5 and Cav-3co-localization in the intercalated disc and lateral membrane.PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias,which was reflected by a modest decrease in the duration of ventricular fibrillation(VF;P<0.05 vs.Scramble-shRNA+I/R group)and a significantly reduced arrhythmia score(P<0.01 vs.Scramble-shRNA+I/R group).The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia(VT),sustained VT and VF,especially at the time 5–10 min after ischemia(P<0.05 vs.Scramble-shRNA+IR group).Using in vitro human embryonic kidney 293 T(HEK293T)cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation(H/R),we confirmed that increased PIASy promot展开更多
文摘汽车保有量的增加和能耗排放法规日益严格的限制给车辆节能减排提出了巨大挑战,网联化、智能化和电气化是提高未来交通效率和减少公路能源消耗的三大支柱。为了全面了解智能网联汽车节能减排的前沿问题与研究进展,对当前经济驾驶领域的重点问题进行了总体概述。首先,从广义的能量转换角度总结了智能车辆节能优化技术的本质和3个过程,其中Wheels to Distance环节的车辆系统优化是挖掘汽车节能潜力的重要一环,针对其介绍了智能网联汽车节能优化问题的基本数学原理;其次,从智能运输系统的各类非同源异构数据出发,分别从人-车交互、车-车通信、车-路感知三方面阐述来源于"人-车-路"交互体系的智能信息与数据;然后,针对单车智能网联环境下的多维度信息与先进控制技术相结合的关键问题,从考虑道路坡度预测巡航控制、跟车工况预测巡航控制、智能辅助驾驶和车道变换等应用场景进行具体介绍;针对"人-车-路-云"多源异构环境下车辆行为协同节能关键科学问题,从经济驾驶、多车协同节能、道路交叉口车路协同节能和车云协同节能等方面详细介绍研究现状;并进一步介绍电气化公路系统的前瞻性研究,说明融合智能化信息的E-highway节能潜力和智能重型商用车协同节能的未来发展趋势。最后,总结并梳理智能化信息对于提升车辆节能的重要影响,并展望了其在理论与实际层面遇到的挑战。
基金supported the National Natural Science Foundation of China(No.81073069)
文摘The anti-bacterial activities of three types of di-O-caffeoylquinic acids(diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine(TCM), on Bacillus shigae growth were investigated and compared by microcalorimetry. The three types of diCQAs were 3, 4-di-O-caffeoylquinic acid(3, 4-diCQA), 3, 5-di-O-caffeoylquinic acid(3, 5-diCQA), and 4, 5-di-O-caffeoylquinic acid(4, 5-diCQA). Some qualitative and quantitative information of the effects of the three diCQAs on metabolic power–time curves, growth rate constant k, maximum heat-output power Pm, and the generation time tG, total heat output Qt, and growth inhibitory ratio I of B. shigae were calculated. In accordance with a thermo-kinetic model, the corresponding quantitative relationships of k, Pm, Qt, I and c were established. Also, the half-inhibitory concentrations of the drugs(IC50) were obtained by quantitative analysis. Based on the quantity–activity relationships and the IC50 values, the sequence of inhibitory activity was 3, 5-diCQA > 4, 5-diCQA > 3, 4-diCQA. The results illustrate the possibility that the caffeoyl ester group at C-5 is the principal group that has a higher affinity for the bacterial cell, and that the intramolecular distance of the two caffeoyl ester groups also has an important influence on the anti-bacterial activities of the diCQAs.
基金supported by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(Nos.20101561,NCET-11-0114)the Beijing Natural Science Foundation(No.7122176)
文摘AIM： To improve the absorption and bioavailability of baicalin using a nanocrystal （or nanosuspension） drug delivery system. METHODS： A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo. RESULTS： The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of-34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 ug·mL-1, was much higher than the baicalin-microcrystals and the physical mixture （135 and 86.4 ug·mL- 1, respectively）. In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability （with the AUC（0-t） value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L-1·h-1, respectively）. CONCLUSION： The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure
基金National Natural Science Foundation of China (81073069)
文摘Objective To study the rational daily administration times of Yinchenhao Decoction(YCHD)when it was used to treat experimental jaundice in rats based on pharmacodynamics/pharmacokinetics model.Methods Rats were modeled by 4%1-naphthylisothiocyanate(75 mg/kg)for 48 h,then YCHD was drenched with doses of 0.324 g/kg (extract,calculated with the clinical dosage)once,0.162 g/kg twice,and 0.108 g/kg thrice a day,respectively.The total bile and the flow rate of bile were observed after the first administration;Blood samples collected from the orbital sinus at different intervals were used to investigate the levels of liver enzymes(ALT and AST)and bilirubins (TBIL and DBIL),and determine the concentration of 6,7-dimethoxycoumarin(DME)in the plasma using UPLC at the same time,then we obtained the time-effect and time-dose curves.The rational daily administration times of YCHD when treating experimental jaundice were determined based on the comprehensive analysis of time-effect and time-concentration relationships.Results Within 10 h the total bile of rats which were administered once daily(G1) was 1.65 and 1.33 times higher than that of twice and thrice(G2 and G3)a day,respectively,and the four biochemical indexes(TBIL,ALT,DBIL,and AST)of G1 decreased faster than those of G2 and G3(P<0.05).On the other hand, the blood drug level of DME when administrated once daily could maintain at a higher level for a longer time,and its Cmax and AUC0→t were higher than those of G2 and G3,which might be the main reason why its effect was the most significant.Conclusion It is more appropriate to administrate once daily when YCHD is used to treat jaundice.
基金supported by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(No.20101561)Beijing Natural Science Foundation of China(No.7122176)
文摘AIM: To improve the absorption of thymopeptides(TH) by preparing sodium deoxycholate/phospholipid-mixed nanomicelles(SDC/PL-MMs). METHODS: TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated using photon correlation spectroscopy(PCS), zeta potential measurement, as well as their physical stability after storage for several days. Furthermore, in situ intestinal single-pass perfusion experiments and pharmacodynamics in immunodeficient mice were performed to make a comparison with TH powders and the control drug in absorption properties. RESULTS: A narrow size distribution of nanomicelles, with a mean particle size of(149 ± 8.32) nm and a zeta potential of(-31.05 ± 2.52) mV, was obtained. The in situ intestine perfusion experiments demonstrated a significant advantage in absorption characteristics for TH compared to the other formulations, and oral administration of TH-SDC/PL-MMs potentiated an equivalent effect with i.h. TH in pharmacodynamic studies in immunodeficient mice. CONCLUSIONS: TH-SDC/PL-MMs prepared by a film dispersion method are able to improve the absorption of TH. SDC/PL-MMs might be a good approach for the more effective delivery of drugs like TH.
基金supported by grants from the National Natural Science Foundation of China(81770824,81270239)。
文摘Background:Abnormal myocardial voltage-gated sodium channel 1.5(Nav1.5)expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion(I/R).Protein inhibitor of activated STAT Y(PIASy)-mediated caveolin-3(Cav-3)small ubiquitin-related modifier(SUMO)modification affects Cav-3 binding to the Nav1.5.PIASy activity is increased after myocardial I/R,but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias.Methods:Using recombinant adeno-associated virus subtype 9(AAV9),rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA(shRNA).After two weeks,rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias.Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements.Results:PIASy was upregulated by I/R(P<0.01),with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density(P<0.01).AAV9-PIASy shRNA intraventricular injection into the rat heart down-regulated PIASy after I/R,at both mRNA and protein levels(P<0.05 vs.Scramble-shRNA+I/R group),decreased SUMO-modified Cav-3 levels,enhanced Cav-3 binding to Nav1.5,and prevented I/R-induced decrease of Nav1.5 and Cav-3co-localization in the intercalated disc and lateral membrane.PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias,which was reflected by a modest decrease in the duration of ventricular fibrillation(VF;P<0.05 vs.Scramble-shRNA+I/R group)and a significantly reduced arrhythmia score(P<0.01 vs.Scramble-shRNA+I/R group).The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia(VT),sustained VT and VF,especially at the time 5–10 min after ischemia(P<0.05 vs.Scramble-shRNA+IR group).Using in vitro human embryonic kidney 293 T(HEK293T)cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation(H/R),we confirmed that increased PIASy promot
