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As the first and key step of traditional Chinese medicine (TCM)-guided drug development, lead discovery necessitates continuous exploration of new methodology for screening bioactive compounds from TCM. This work intends to establish a strategy for rapidly recognizing β2-adrenergic receptor (β2-AR) target compounds from the fruit of Siraitia grosvenorii (LHG). The method involved immobilization of β2-AR onto amino-microsphere to synthesize the receptor column, the combination of the column to high-performance liquid chromatography (HPLC) to screen bioactive compounds of LHG, the identification of the compounds by HPLC coupled with mass spectrometry (MS), and the evaluation of druggability through pharmacokinetic examination by HPLC–MS/MS. Mogroside V was screened and identified as the β2-AR-targeted bioactive compounds in LHG. This compound exhibited desired pharmacokinetic behavior including the time to reach peak plasma concentrations of 45 min, the relatively low elimination of 138.5 min, and the high bioavailability. These parameters indicated that mogroside V has a good druggability for the development of new drugs fighting β2-AR-mediated respiratory ailments like asthma. The combination of the methods in this work is probably becoming a powerful strategy for screening and early evaluating the bioactive compounds specifically binding to G-protein-coupled receptor target from complex matrices including TCM. [ABSTRACT FROM AUTHOR]

Fine particulate matter is associated with adverse health effects, but exactly which characteristics of PM2.5 are responsible for this is still widely debated. We evaluated seasonal dynamics of the composition and chemical characteristics of PM2.5 in Zhuhai, China. PM2.5 characteristics at five selected sites within Zhuhai city were analyzed. Sampling began on January 10, 2015, and was conducted for 1 year. The ambient mass concentration, carbon content (organic and elemental carbon, OC and EC), level of inorganic ions, and major chemical composition of PM2.5 were also determined. Average concentrations of PM2.5 were lower than the National Ambient Air Quality Standard (NAAQS) 24-h average of 65 μg/m3. The daily PM2.5 concentration in Zhuhai city exhibited clear seasonal dynamics, with higher daily PM2.5 concentrations in autumn and winter than in spring and summer. Carbon species (OC and EC) and water-soluble ions were the primary components of the PM2.5 fraction of particles. Apart from OC and EC, chemical species in PM2.5 were mainly composed of NH4+ and SO42−. There was a marked difference between the summer and winter periods: the concentrations of OC and EC in winter were roughly 3.4 and 4.0 times than those in summer, while NH4+, SO42−, NO3−, and Na+ were 3.2, 4.5, 28.0, and 5.7 times higher in winter than those in summer, respectively. The results of chemical analysis were consistent with three sources dominating PM2.5: coal combustion, biomass burning, and vehicle exhaust; road dust and construction; and from reaction of HCl and HNO3 with NH3 to form NH4Cl and NH4NO3. However, additional work is needed to improve the mass balance and to obtain the source profiles necessary to use these data for source apportionment. [ABSTRACT FROM AUTHOR]

Owing to the promising clinical efficacy and relatively simple composition, Shuang-Huang-Lian prescription is widely prescribed for the treatment of acute upper respiratory tract infection and acute bronchitis in practice. This necessitates the understanding of the bioactive compounds of the prescription and their binding mechanism to β2-adrenoceptor, which mediates the aforementioned ailments. In this work, a column containing immobilized β2-adrenoceptor was prepared using a diazonium salt reaction. The bioactive compound collected from the β2-adrenoceptor column was identified as chlorogenic acid by using high-performance liquid chromatography coupled with ion trap mass spectrometry. Using an injection amount dependent method, chlorogenic acid proved the binding to β2-adrenoceptor through two kinds of sites. The numbers of the sites were (1.42 ± 0.03) × 10−8 and (9.06 ± 0.49) × 10−8 M. The association constants were (2.72 ± 0.01) × 105 and (2.80 ± 0.01) × 104 M−1, respectively. Molecular docking analysis of the interaction between chlorogenic acid and β2-adrenoceptor indicated that the binding mainly occurred on Ser169, Ser173, and Phe287 of β2-adrenoceptor. These results paved the way to screen bioactive compounds of other traditional medicines by receptor chromatography. [ABSTRACT FROM AUTHOR]

The tree ring is an important carrier of the evolution of climate in the study of global change. It enjoys advantages of accurate dating, strong continuity, high resolution ratio and high reconstruction precision. This paper tested the changes of Populus euphratica tree ring and the runoff in the upper and middle reaches of the Tarim River through the monotonic trend and analyzed the response of the tree ring in the lower reaches of the Tarim River to the water supply through the combined tree ring data and the historical literature, so as to confirm the accuracy of the response of Populus euphratica tree ring to river diversion. The results were included as follows. (1) From 1957 to 2010, the radial growth of Populus euphratica in the upper and middle reaches of the Tarim River decreased gradually in the time series, which was the same as the runoff. The downtrend was significant, and | Zc | was more than 0.96. (2) From 1913 to 2000, the radial growth of Populus euphratica as a whole in the lower reaches of the Tarim River decreased. The downtrend was significant between 1973 and 2001, reaching the lowest level in the past 100 years. The formation and diversion of the Layi River was as described in the historical literature. (3) The development of the ecological water delivery project has improved the ecological environment of the lower reaches, which has been verified from the Populus euphratica tree ring in the lower reaches. However, despite the ecological water delivery project in recent years, the growth of Populus euphratica tree ring has not reached to the level before 1920, indicating that the existing ecological water delivery is of limited value in recovering desert riparian forest (4) In the analysis of the response of the Populus euphratica to the water resources, the wavelet analysis method and the historical literature review method have drawn the same conclusion. [ABSTRACT FROM AUTHOR]

Drug-protein interaction analysis is pregnant in designing new leads during drug discovery. We prepared the stationary phase containing immobilized β2-adrenoceptor ( β2 -AR) by linkage of the receptor on macroporous silica gel surface through N, N′-carbonyldiimidazole method. The stationary phase was applied in identifying antiasthmatic target of protopine guided by the prediction of site-directed molecular docking. Subsequent application of immobilized β2 -AR in exploring the binding of protopine to the receptor was realized by frontal analysis and injection amount-dependent method. The association constants of protopine to β2 -AR by the 2 methods were (1.00 ± 0.06) × 105M−1 and (1.52 ± 0.14) × 104M−1. The numbers of binding sites were (1.23 ± 0.07) × 10−7M and (9.09 ± 0.06) × 10−7M, respectively. These results indicated that β2 -AR is the specific target for therapeutic action of protopine in vivo. The target-drug binding occurred on Ser169 in crystal structure of the receptor. Compared with frontal analysis, injection amount-dependent method is advantageous to drug saving, improvement of sampling efficiency, and performing speed. It has grave potential in high-throughput drug-receptor interaction analysis. [ABSTRACT FROM AUTHOR]

Drug-protein interaction analysis has become a considerable topic in life science which includes clarifying protein functions, explaining drug action mechanisms and uncovering novel drug candidates. This work was to determine the association constants ( K A) of six drugs to β2-adrenergic receptor by injection amount-dependent method using stationary phase containing the immobilized receptor. The values of K A were calculated to be (25.85 ± 0.035) × 104 m−1 for clorprenaline, (42.51 ± 0.054) × 104 m−1 for clenbuterol, (6.67 ± 0.008) × 104 m−1 for terbutaline, (33.99 ± 0.025) × 104 m−1 for tulobuterol, (7.59 ± 0.011) × 104 m−1 for salbutamol and (78.52 ± 0.087) × 104 m−1 for bambuterol. This rank order agreed well with the data determined by zonal elution, frontal analysis and nonlinear chromatography, even using different batches of β2-AR column. A good correlation was found between the association constants by the current method and radio-ligand binding assay. Our data indicates that the injection amount-dependent method is a powerful alternative for rapid analysis of ligand-receptor interactions. [ABSTRACT FROM AUTHOR]