Potential Mechanism of Herb-Drug Interaction Mediated by Angelica dahurica: Inhibition on CYP3A Enzymes in Rats

Angelica dahurica is commonly referred to as ‘Baizhi’ in China and has been noted for its therapeutic significance. The major active ingredients of Angelica dahurica is coumarin, which is reported as a kind of potent inhibitor of cytochrome P450 enzymes (CYP450s). The aim of this study was to investigate the inhibition of CYP3A enzymes by total coumarin extract (TCE) obtained from dried root of Angelica dahurica by using in situ single pass intestinal perfusion (SPIP) and in situ liver perfusion in rats. When midazolam (MDZ) which is a substrate of CYP3A co-perfused with TCE (198 μg/mL) from Baizhi in duodenum and ileum segments, the Peff of MDZ has increased significantly compared with the MDZ single perfused group (p 0.05) (n = 6). During in situ liver perfusion study, the results demonstrated that, 3 days oral administration of TCE obtained from Baizhi could significantly reduce the elimination rate of MDZ in the perfusate (p Angelica dahurica extract co-administrated with drugs which are the substrates of CYP3A, much more attention should be paid rather than that of other CYP450 enzymes. These findings may facilitate in predicting possible herb-drug interactions (HDIs) when Angelica dahurica is used in combination with other drugs, and decrease the incidence of the CYP450-mediated HDIs.

Pampas grass-inspired FeOOH nanobelts as high performance anodes for sodium ion batteries

High-performance materials are the key to developing new alternative energy-storage systems[1-4].Sodium ion batteries(SIBs)are regarded as the promising large-scale electric energy storage owing to the high abundance and low cost of sodium resources[1,5-9].However,the sluggish kinetics of Na^(+)caused by the large-sized Na^(+)(1.02A)result in the lower energy density and unsatisfactory electrochemical properties[10-14].

Advance in Pre-Clinical Pharmacokinetics of Paeoniflorin, a Major Monoterpene Glucoside from the Root of <i>Paeonia lactiflora</i>

Paeoniflorin (PF) is one of the main bioactive components of total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora Pall. TGP exhibit various biological activities such as improvement in memory, hepatoprotection, antimutagenic properties and platelet aggregation inhibition. The aim of this paper is to review the pharmacokinetics (PK) of PF as a pure compound and in single or multiple herb(s) of traditional Chinese medicine (TCM) prescriptions. The distribution of PF or PF in TCM fitted one or two compartmental model after oral administration or intravenous injection, respectively. However, PF has a low bioavailability (BA) in rabbit (7.24%) and rat (3.24%) after oral administration. The PK profiles and BA of PF were remarkably improved when co-administered with sinomenine or glycyrrhizin acid. The PK profiles and BA of PF in Radix Paeonia Rubra (RP-R) and Jing-zhi guan-xin were improved, but in co-administration of RP-R with Radix Angelicae Sinensis, the BA was significantly reduced. PK profiles and BA of PF in Shan yao gan-cao tang or Danggui-Shaoyao-San was either remarkably improved or not. However, neither the PK profiles nor the BA of PF in Radix paeonia alba, Huangqin-tang Si ni san or Tang-Min-Ling-Wan was improved. Metabolism in the liver did not play any role in the low oral BA of PF. The low BA was thus attributed to poor permeation due to low lipophilicity, P-glycoprotein mediated efflux, intestinal bacteria and hydrolytic degradation in the intestine by the intestinal brush border lactase phlorizin hydrolase (LPH) and certain esterases. These findings show the in vivo course of PF and provide information on the maximum biological actions of PF that may help traditional Chinese herbal medicinal practitioners.

Role of Notch-1 signaling pathway in PC12 cell apoptosis induced by amyloid beta-peptide(25–35)

Recent studies have demonstrated that Notch-1 expression is increased in the hippocampus of Alzheimer＇s disease patients. We speculate that Notch-1 signaling may be involved in PC12 cell apoptosis induced by amyloid beta-peptide （25-35） （Aβ25-35）. In the present study, PC12 cells were cultured with different doses （0, 0.1, 1.0, 10 and 100 nmol/L） of N-[N-（3,5-Difluorophenacetyl）-L-alanyl]-S-phenylglycine t-butyl ester, a Notch-1 signaling pathway inhibitor, for 30 minutes. Then cultured cells were induced with Aβ25-3s for 48 hours. Pretreatment of PC12 cells with high doses of N-[N-（3,5-Difluorophenacetyl）-L-alanyl]-S-phenylglycine t-butyl ester （〉 10 nmol/L） prolonged the survival of PC12 cells after Aβ25-35 induction, decreased the expression of apoptosis-related proteins caspase-3, -8, -9, increased the activity of oxidative stress-related superoxide dismutase and catalase, inhibited the production of active oxygen, and reduced nuclear factor kappa B expression. This study indicates that the Notch-1 signaling pathway plays a pivotal role in Aβ25-35-induced PC12 apoptosis.

Extruded monolith MnO_(x)-CeO_(2)-TiO_(2) catalyst for NH_(3)-SCR of low temperature flue gas from an industry boiler:Deactivation and recovery

The selective catalytic reduction(SCR) of NO_(x) with NH_(3)(NH_(3)-SCR) technology has been widely applied for reducing NO_(x) emissions from stationary and mobile sources.In this work,the extruded monolith MnO_(x)-CeO_(2)-TiO_(2) catalyst was installed in a cement kiln for NH_(3)-SCR of NO_(x),where the flue gas temperature was 110-140℃.It is found that the monolith catalyst is severely deactivated after operating for about 200 h with almost no NO_(x) conversion at 160℃ under GHSV of 50000 h^(-1),while the fresh monolith catalyst remains 60% NO_(x) conversion.Scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS),X-ray photoelectron spectroscopy(XPS),temperature-programmed desorption of SO_(2)(SO_(2)-TPD) and thermogravimetric-differential thermal analysis(TG-DTG) experiments reveal that both MnO_(x) and CeO_(2) oxides in monolith are severely sulfated to manganese sulfate and cerium sulfate,and the external monolith walls are covered by massive ceria sulfate and little ammonium nitrate.In situ diffuse reflectance infrared Fourier trans form spectroscopy(DRIFTS) analysis demonstrates that the formation of nitrates at low temperatures is inhibited due to the occupation of active sites in MnO_(x)-CeO_(2)-TiO_(2) by sulfates,resulting in the decrease of low temperature activity.After washing with water,the activity of deactivated monolith catalyst can be partially recovered,together with significant loss of manganese and cerium from monolith.

Nano-sized alumina supported palladium catalysts for methane combustion with excellent thermal stability

Pd/Al_(2)O_(3)catalysts supported on Al_(2)O_(3)of different particle sizes were synthesized and applied in methane combustion.These catalysts were systematically characterized by Brunauer-Emmett-Teller (BET),X-ray diffraction (XRD),high resolution-transmission electron microscopy (HR-TEM),high-angle annular dark?eld-scanning transmission electron microscopy (HAADF-STEM),H_(2)-temperature-programmed reduction (H_(2)-TPR),O_(2)-temperature-programmed oxidation (O_(2)-TPO),X-ray photoelectron spectroscopy (XPS),and X-ray absorption?ne structure (XAFS).The characterization results indicated that nanosized Al_(2)O_(3)enabled the uniform dispersion of palladium nanoparticles,thus contributing to the excellent catalytic performance of these nano-sized Pd/Al_(2)O_(3)catalysts.Among them,Pd/Al_(2)O_(3)-nano-10 (Pd/Al_(2)O_(3)supported by alumina with an average particle size of 10 nm)showed superior catalytic activity and stability for methane oxidation under harsh practical conditions.It maintained excellent catalytic performance for methane oxidation for50 hr and remained stable even after harsh hydrothermal aging in 10 vol.%steam at 800℃ for 16 hr.Characterization results revealed that the strong metal-support interactions and physical barriers provided by Al_(2)O_(3)-nano-10 suppressed the coalescence ripening of palladium species,and thus contributed to the superior sintering resistance of the Pd/Al_(2)O_(3)-nano-10 catalyst.

Progress in niobium-based oxides as anode for fast-charging Li-ion batteries

With the increasing popularity of electric/hybrid vehicles and the rapid development of 3C electronics,there is a growing interest in high-rate energy storage systems.The rapid development and widespread adoption of lithiumion batteries(LIBs)can be attributed to their numerous advantages,including high energy density,high operating voltage,environmental friendliness,and lack of memory effect.However,the progress of LIBs is currently hindered by the limitations of energy storage materials,which serve as vital components.Therefore,there is an urgent need to address the development of a new generation of high-rate energy storage materials in order to overcome these limitations and further advance LIB technology.Niobium-based oxides have emerged as promising candidates for the fabrication of fast-charging Li-ion batteries due to their excellent rate capability and long lifespan.This review paper provides a comprehensive analysis of the fundamentals,methodologies,and electrochemistries of niobium-based oxides,with a specific focus on the evolution and creation of crystal phases of Nb_(2)O_(5),fundamental electrochemical behavior,and modification methods including morphology modulation,composite technology,and carbon coating.Furthermore,the review explores Nb_(2)O_(5)-derived compounds and related advanced characterization techniques.Finally,the challenges and issues in the development of niobiumbased oxides for high-rate energy storage batteries are discussed,along with future research perspectives.

基于单簇聚类的非对齐多视图异常检测算法

多视图数据广泛存在于现实,而异常也不可避免地伴随其中.现有的多视图异常检测方法针对的都是对齐的多视图场景,无法胜任更具挑战的非对齐多视图场景.为此,本文提出了4种基于单簇可能性C–均值(possibilistic C-means,PCM),即P1M(PCM,C=1)算法的非对齐多视图异常检测算法.不同于对齐的多视图场景,非对齐特性造成了样本在各视图间对应关系的缺失,以致我们无法利用在对齐场景下示例级的局部关键信息.为此,我们设法通过各视图的全局信息进行学习.本文的关键之处在于借助交替优化法为各视图分别学得一个变换矩阵,用其将各视图投影到一个公共子空间,进而在该公共子空间中用P1M学得所有训练数据对目标类的隶属度,并设置隶属度阈值,从而实现异常检测.在多个UCI数据集上的实验结果表明,本文方法能够有效应对非对齐多视图场景中的异常检测.

Alkali resistance promotion of Ce-doped vanadium-titanic- based NH3-SCR catalysts

The effect of K deactivation on V2OJWO3-TiO2 and Ce-doped V2O5/WO3-TiO2 catalysts in the selective catalytic reduction （SCR） of NOx by NH3 was studied. Ce-doped V2O5/WO3-TiO2 showed significantly higher resistance to K deactivation than V2O5/WO3-TiO2. Ce-doped V2O5/WO3-TiO2 with K/V = 4 （molar ratio） showed 90% NOx conversion at 350℃, whereas in this case V2O5/WO3-TiO2 showed no activity. The fresh and K-poisoned V2O5/WO3-TiO2 and Ce-doped V2O5/WO3-TiO2 catalysts were investigated by means of in situ diffuse reflectance infrared Fourier transform spectroscopy （DRIFTS）, NH3-temperature progress decomposition （NH3-TPD）, X-ray photoelectron spectroscopy （XPS） and H2-temperature program reduction （H2-TPR）. The effect of Ce doping on the improving resistance to K of V2O5/WO3- TiO2were discussed.

Investigation of the common intermediates over Fe-ZSM-5 in NH 3-SCR reaction at low temperature by in situ DRIFTS

The surface species formed in the reaction of NO and NO2 with pre-adsorbed NH 3 over a Fe-ZSM-5 catalyst(1.27 wt.%Fe,SiO2/Al2O3=25)at low temperature(140°C)were studied by in situ diffuse reflectance infrared Fourier transform spectroscopy(DRIFTS).Through using a background spectrum of NH3-saturated Fe-ZSM-5,we clearly observed the formation of common intermediates resulting from the reaction of NO2 or NO+O2 with pre-adsorbed NH3.This presents strong evidence that the oxidation of NO to form surface nitrates and nitrites is the key step for standard SCR at low temperature.In addition,the results suggest that in the SCR reaction at low temperature,the NH^4+ions absorbed on Brønsted acid sites are less active than NH3 adsorbed on Lewis acid sites related to Fe species.

Investigation and experimental validation of curcumin-related mechanisms against hepatocellular carcinoma based on network pharmacology

Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro validation.Methods:The predictive targets of curcumin or HCC were collected from several databases.the identified overlapping targets were crossed with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)platform.Two of the candidate pathways were selected to conduct an experimental verification.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium(MTT)assay was used to determine the effect of curcumin on the viability of Hep G2 and LO2 cells.The apoptosis and autophagy of Hep G2 cells were respectively detected by flow cytometry and transmission electron microscopy.Besides,western blot and real-time polymerase chain reaction(PCR)were employed to verify the p53 apoptotic pathway and adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)autophagy pathway.Hep G2 cells were pretreated with pifithrin-α(PFT-α)and GSK690693 for further investigation.Results:The 167 pathways analyzed by KEGG included apoptosis,autophagy,p53,and AMPK pathways.The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug,regulation of apoptotic pathway,and so on.The in vitro experiments also confirmed that curcumin can inhibit the growth of Hep G2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway.Furthermore,the protein and messenger RNA(m RNA)of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group.The damage-regulated autophagy modulator(DRAM)in the PFT-α-pretreated group was downregulated,and p62 in the GSK690693-pretreated group was upregulated.Conclusions:Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1(ULK1)autophagy pathway,in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.

A comparative study of particle size distribution from two oxygenated fuels and diesel fuel

Oxygenated fuels are known to reduce particulate matter(PM)emissions from diesel engines.In this study,100%soy methyl ester(SME)biodiesel fuel(B100)and a blend of 10%acetal denoted by A-diesel with diesel fuel were tested as oxygenated fuels.Particle size and number distributions from a diesel engine fueled with oxygenated fuels and base diesel fuel were measured using an Electrical Low Pressure Impactor(ELPI).Measurements were made at ten steady-state operational modes of various loads at two engine speeds.It was found that the geometric mean diameters of particles from SME and Adiesel were lower than that from base diesel fuel.Compared to diesel fuel,SME emitted more ultra-fine particles at rated speed while emitting less ultra-fine particles at maximum speed.Ultra-fine particle number concentrations of A-diesel were much higher than those of base diesel fuel at most test modes.

Effects of a diesel oxidation catalyst on gaseous pollutants and fine particles from an engine operating on diesel and biodiesel

The effects of a diesel oxidation catalytic （DOC） converter on diesel engine emissions were investigated on a diesel bench at various loads for two steady-state speeds using diesel fuel and B20. The DOC was very effective in hydrocarbon （HC） and CO oxidation. Approximately 90%-95% reduction in CO and 36%-70% reduction in HC were realized using the DOC. Special attention was focused on the effects of the DOC on elemental carbon （EC） and organic carbon （OC） fractions in fine particles （PM2.5） emitted from the diesel engine. The carbonaceous compositions of PM2.5 were analyzed by the method of thermal/optical reflectance （TOR）. The results showed that total carbon （TC）, OC and EC emissions for PM2.5 from diesel fuel were generally reduced by the DOC. For diesel fuel, TC emissions decreased 22%-32% after the DOC depending on operating modes. The decrease in TC was attributed to 35%-97% decrease in OC and 3%-65% decrease in EC emissions. At low load, a significant increase in the OC/EC ratio of PMz.5 was observed after the DOC. The effect of the DOC on the carbonaceous compositions in PM2.5 from B20 showed different trends compared to diesel fuel. At low load, a slight increase in EC emissions and a significant decrease in OC/EC ratio of PM2.5 after DOC were observed for B20.