Maternal Physiological Variations Induced by Chronic Gestational Hypoxia: 1H NMR-Based Metabolomics Study.

Metabolomics have been widely used in pregnancy-related diseases. However, physiological variations induced by chronic hypoxia during pregnancy are not well characterized. We aimed to investigate physiological variations induced by chronic hypoxia during pregnancy. A Sprague-Dawley (SD) pregnant rat model of chronic hypoxia was established. Plasma and urine metabolite profiles at different stages of the pregnancy were detected by 1H NMR (nuclear magnetic resonance). Multivariate statistical analysis was used to analyze changes in plasma and urine metabolic trajectories at different time-points. We identified hypoxia-induced changes in the levels of 30 metabolites in plasma and 29 metabolites in urine during different stages of pregnancy; the prominently affected metabolites included acetic acid, acetone, choline, citric acid, glutamine, isoleucine, lysine, and serine. Most significant hypoxia-induced changes in plasma and urine sample metabolites were observed on the 11th day of gestation. In summary, chronic hypoxia has a significant effect on pregnant rats, and may cause metabolic disorders involving glucose, lipids, amino acids, and tricarboxylic acid cycle. Metabolomics study of the effect of hypoxia during pregnancy may provide insights into the pathogenesis of obstetric disorders.

Tungsten(VI)-Copper(I)-Sulfur Cluster-Supported Metal-Organic Frameworks Bridged by in Situ Click-Formed Tetrazolate Ligands.

Six analogous two-dimensional (2D) [Tp*WS3Cu3]-based (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate) networks, namely, {[(Tp*WS3Cu3)2L3](µ3-N3)}n (2: L = 5-methyltetrazolate (Mtta); 3a: L = 5-ethyltetrazolate (Etta)) and {[(Tp*WS3Cu3)2L3]BF4}n (3b: L = Etta; 4: L = 5-propyltetrazolate (Ptta); 5: L = 5-butyltetrazolate (Btta); 6: L = 5-pentyltetrazolate (Petta)) were synthesized by reactions of [Et4N][Tp*WS3] (1), [Cu(CH3CN)4]BF4, NaN3, and NH4BF4 in different nitrile solvents (CH3(CH2)nCN, n = 0, 1, 2, 3, and 4) under solvothermal conditions. In the structures of 2-6, each alkyl tetrazolate L as a bridging ligand was generated in situ from the "click" reaction between azide and nitrile. These 2D (6,3) networks support two types of voids wherein the pendant alkyl groups are accommodated. A tetrahedron cage-like cluster [Tp*W(µ3-S)3(µ3-S')Cu3]4 (7) was also formed in some of the above reactions and can be readily separated by solvent extraction. The proportion of 7 increased with the elongation of the alkyl chains and finally became the exclusive product when heptylnitrile was employed. Further use of CuCN as a surrogate for [Cu(CH3CN)4]BF4 with the aim of introducing additional CN bridges into the network led us to isolate a tetrazolate-free compound, {[Et4N]{(Tp*WS3Cu3)[Cu2(CN)4.5]}2·2PhCH2CN}n (8·2PhCH2CN), a unique 2D network that features {(Tp*WS3Cu3)[Cu2(CN)5]}22-, {(Tp*WS3Cu3)3[Cu3(CN)7]2[Cu(CN)3]}4-, and {(Tp*WS3Cu3)[Cu4(CN)9]}26- ring subunits. Compounds 5-8 are soluble in DMF and exhibit a reverse saturable absorption and self-focusing third-order nonlinear optical (NLO) effect at 532 nm with hyperpolarizability γ values in the range of 4.43 × 10-30 to 5.40 × 10-30 esu, which are 400-500 times larger than that of their precursor 1. The results provide an interesting insight into the synergetic synthetic strategy related to the assembly of the [Tp*WS3Cu3]2+ cluster core, the "click" formation of the tetrazolate ligands, and the construction of the [Tp*WS3Cu3]2+ cluster-based 2D networks.

Diverse Tp*-Capped W-Cu-S Clusters from One-Pot Assembly Involving in Situ Thiolation of Phosphines.

In the absence/presence of S8, the one-pot assembly of [Et4N][Tp*WS3] [1; Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate] with [Cu(MeCN)4]PF6 and bis- or tetraphosphine ligands 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (dppb), and N,N,N',N'-tetrakis(diphenylphosphinomethyl)ethylenediamine (dppeda) produces six W-Cu-S clusters, namely, [(Tp*WS3Cu2Cl)2(dppe)] (2), [Tp*WS3Cu4(dppp)2(µ4-Cl)(µ-Cl)]PF6·MeCN (3·MeCN), [(Tp*WS3Cu3)2(µ4-Cl)(µ-Cl)2(dpppS2)] (4), [(Tp*WS3Cu2Cl)2(dppbS2)]·2MeCN·2H2O (5·2MeCN·2H2O), [(Tp*WS3Cu3Cl2)2(dppbS2)] (6), and [(Tp*WS3Cu3)2(Ph2PS2)3(µ6-Cl)0.5](PF6)0.5·0.75CH2Cl2 (7·0.75CH2Cl2). Compounds 2-7 are characterized by elemental analysis, IR, UV-vis, (1)H and (31)P{(1)H} NMR, electrospray ionization mass spectrometry, and X-ray crystallography. For 2, the dppe ligand bridges a pair of butterfly-shaped [Tp*WS3Cu2] cores to form a double-butterfly-shaped structure. For 4, the dppp ligand is susceptible toward S association and forms an in situ generated dpppS2 ligand, supporting an octanuclear double-half-open-cubane structure and contrasting an analogous system wherein a pentanuclear motorcycle-shaped cationic cluster 3 is formed with the absence of S8. A longer dppb ligand readily converts to S-based ligands in 5 and 6, subsequently serving as bridges between a pair of a butterfly-shaped (5) and nest-shaped (6) clusters. Further use of a tetraphosphine ligand, dppeda, in the cluster formation, with the presence of S8, leads to an unexpected ligand degradation to give the [Ph2PS2](-) anions. Three [Ph2PS2](-) anions juxtapose a pair of nest-shaped cluster cores to yield an octanuclear cluster, 7, featuring a cage to encapsulate µ6-Cl(-). The third-order nonlinear-optical (NLO) properties of 2-7 in N,N-dimethylformamide, investigated using a Z-scan technique at 532 nm, show that 2-6 have a reverse saturable absorption, while 7 has a notable saturable absorption. All of 2-7 exhibit a self-focusing effect with hyperpolarizability γ values in the range of 4.71 × 10(-30)-1.02 × 10(-29) esu, which are 440-1000 times higher than that of 1. The formation of 4-7 from 1 through the in situ thiolation of phosphine ligands presents a new approach to the design and assembly of the W-Cu-S clusters with interesting structural arrays and better NLO properties.

[Study on Chemical Composition of Zingiberis Rhizome Carbonisata].

Objective: To study the chemical constituents from Zingiberis Rhizome Carbonisata. g. Methods: Compounds were isolated by Sephadex LH-20,ODS,MCI and silica gel column chromatography. Their structures were elucidated by physicochemical property and spectral analysis. Results: 16 compounds were isolated and identified as sitost-5-en-3ß-ol acetate( 1),dibutyl phthalate( 2),4-[2-( 5-butylfuran-2-yl) ethyl]-2-methoxyphenol( 3),ß-sitosterol( 4),8-paradol( 5),10-gingerdione( 6),6-shogaol( 7),6-paradol( 8),3,5-diacetoxy-6-gingerdiol( 9),1,2-benzenediol( 10),zingiberone( 11),6-gingerol( 12),1,2,4,5-tetrahydroxybenzene( 13),stigmasterol acetate( 14),8-dehydrogingerdione( 15) and 3,5-diacetoxy-7-( 4-hydroxy-3-methoxyphenyl)-1-( 4,5-dihydroxy-3-methoxyphenyl) heptane( 16). Conclusion: All the compounds are isolated from Zingiberis Rhizome Carbonisata for the first time. And compounds 2,10,11,and13 are generated in the process of processing.

[Multicomponent Content Difference Among Different Processing Degrees of Moutan Cortex Charcoal].

Objective: To establish a method of simultaneously determining gallic acid,5-HMF,catechin and paeonol in the different processing degrees of Moutan Cortex charcoal by HPLC,and to compare the difference. Methods: The HPLC separation was carried out on a UltimateTMXB-C18column( 250 mm × 4. 6 mm,5 µm) with a mobile phase of acetonitrile and water containing 0. 5% formic acid. The flow rate was 1. 0 m L / min at 30 ℃ column temperature,and the detection wavelength was 245 nm. Results: The contents of gallic acid and 5-HMF were increased with the extension of processing time,but declined when it reached to a certain extent. And the contents of catechin and paeonol were decreased in the heating process. Conclusion: The differences of compounds content in different processing degree of Moutan Cortex charcoal were greatly. It provides a scientific basis for quality standard of Moutan Cortex charcoal.

[HPLC combined with PCA technology for analysis of five gingerol compounds in different processing degrees of ginger charcoal].

To establish a new method for simultaneously determining the content of five gingerol compounds in different processing degrees of ginger charcoal and PCA principal component analysis was conducted for analysis. Samples were analyzed on Ultimate TM XB-C18 column (4.6 mm x 250 mm, 5 µm) , with acetonitrile (A) -0.1% phosphoric acid solution (B) as mobile phase for gradient elution. Detection wavelength was set at 280 nm. The flow rate was 0.6 mL x min(-1) and the column temperature was 30 degrees C. The five compounds were separated well and showed good linearity (r ≥ 0.999 7) within the concentration ranges tested. The average value for recoveries was between 98.86% - 101.5% (RSD 1.4% - 2.9%). The contents of five compounds showed difference among different processing degrees of ginger charcoal. Zingiberone had the highest content in the standard carbon, and the content of gingerol was decreased as the deepening of processing degree. Different processing degrees of ginger charcoal were classified into three groups with PCA, and provided scientific basis for establishing the quality standards of ginger charcoal.

Dual inhibition of HY023016 based on binding properties of platelet membrane receptor subunit glycoprotein Ibα and thrombin exosites.

Thrombin has long been suggested as a desirable antithrombotic target, but anti-thrombin therapy without anti-platelet thereby has never achieved the ideal effect. HY023016 is a novel compound, in our previous study, it exerted better anti-thrombotic than dabigatran etexilate. The present study aims to illustrate the excess anti-thrombotic molecular mechanisms of HY023016 through thrombin anion exosites and the platelet membrane receptor subunit glycoprotein Ibα (GPIbα). HY023016 strongly inhibited the conversion of fibrinogen to fibrous may via blocking thrombin exosite I. We also discovered that HY023016 remarkably inhibited exosite II by a loss of affinity for the γ'-peptide of fibrinogen and for heparin. Furthermore, a solid phase binding assay revealed that HY023016 inhibited ristocetin-induced washed platelets bind to von Willebrand factor (vWF). In GST pull-down assay, HY023016 decreased the binding of recombinant vWF-A1 to GPIbα N-terminal. Thus, HY023016 provides an innovative idea for designing multi-targeted anti-thrombotic drugs and laying a scientific foundation for reducing "total thrombosis risk" in a clinical drug treatment.

Monitoring of high-density lipoprotein cholesterol level is predictive of EGFR mutation and efficacy of EGFR-TKI in patients with advanced lung adenocarcinoma.

High-density lipoprotein cholesterol (HDL-C) has an inverse association with the incidence of lung cancer. However, whether it can be used as a predictive factor in advanced lung adenocarcinoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) still remains undefined. This research aimed at studying the relationship of serum HDL-C baseline level and HDL-C kinetics to EGFR mutation, the efficacy of EGFR-TKI, and the predictive value of PFS. The presence of mutation rate in the 192 patients with lung adenocarcinoma was compared within stratified groups. Levels of baseline HDL-C and kinetics of HDL-C were analyzed retrospectively in patients treated with EGFR-TKI harboring EGFR mutation. Univariate and multivariate analyses were performed to investigate the prognostic value of HDL-C. EGFR mutation rate of HDL-C high-level group was significantly higher than that of low-level group (59.0% vs 35.6%, P=0.001). Multivariate logistic analysis showed that high-level HDL-C was an independent predictive factor for EGFR gene mutation (P=0.005; odds ratio =0.417; 95% confidence interval [CI], 0.227-0.768). Patients with a low level of HDL-C before therapy showed a progression of disease in most cases (P<0.001). According to HDL-C kinetics, patients who received EGFR-TKI treatment harboring EGFR mutation were divided into four groups. Univariate analysis showed that patients in nondecreased group had longer progression-free survival (P<0.001; hazard ratio =0.003; 95% CI, 0.001-0.018). Multivariate Cox proportional hazards model analyses showed the same result (P<0.001; hazard ratio =0.003; 95% CI, 0.001-0.018). Current results suggest that HDL-C seems to be a good independent predictive biomarker for advanced lung adenocarcinoma patients treated with the first-line EGFR-TKI. Roles of this biomarker include indicating EGFR mutation, assessing the efficacy of EGFR-TKI, and predicting the progression-free survival.

Evaluating antithrombotic activity of HY023016 on rat hypercoagulable model.

The generation of thrombus is not considered as an isolated progression without other pathologic processes, which may also enhance procoagulant state. The purpose of this study was to assess whether HY023016, a novel dabigatran prodrug and an oral direct thrombin inhibitor, or dabigatran etexilate, another thrombin inhibitor can improve the state of whole blood hypercoagulability in vitro/vivo. By using whole blood flow cytometry we explored the effects of HY023016 and dabigatran etexilate on thrombin and ADP-induced human platelet-leukocyte aggregation generated in vitro. With the method of continuous infusion of thrombin intravenous, we successfully established a rat hypercoagulable model and evaluated the effect of HY023016 or dabigatran etexilate in vivo. HY023016 was able to inhibit thrombin- or ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates in dose-dependent manner. Dabigatran etexilate was unable to affect ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates. Based on rat hypercoagulable model, dabigatran etexilate could reverse thrombin-induced circulatory system hypercoagulable state in a concentration-dependent manner. Dabigatran etexilate also inhibited electrical stimulation induced formation of arterial thrombus in rat under hypercoagulable state, and extracorporal circulation-induced formation of thrombus in dose-dependent manner. Compared with dabigatran etexilate, HY023016 showed nearly equal or even better antithrombotic activity, regardless of reversing the cycle of rat hypercoagulable state or inhibiting platelet-leukocyte aggregation. In surrmary, HY023016 could effectively improve hypercoagulable state of circulatory system.

[Characteristic of Ultrafine Particles Transferring Through Building Envelopes].

Penetration and transmission characteristics of outdoor particulate matter through building envelope structure into indoor and its influencing factors were studied by experimental and numerical simulation methods. With the aid of fast mobility particle spectrometer (fast mobility particle sizer, FMPS), particle number concentrations were measured and particle penetration rates were obtained. The effects of slit size and flow pressure on the infiltration process were studied. Compared with numerical simulation and experimental results, the trend was consistent. Experiment and simulation results showed that when the slit was 1 mm high, the penetration rate of particulates with small particle size was small. Its leading influence factor was Brownian diffusion movement, with the increase of particle size, the penetration rate increased. Particle penetration rate was enhanced with the increase of inlet pressure and particle size, but decreased with the increase of slit length. Simulation results showed that the particle penetration rate was enhanced with the increase of slit height. Among all the factors, slit height was the dominant one. When the particle size was more than 30 nm, the penetration rate was close to 1. When the slit height was reduced to 0.25 mm, the penetration rate of particles with size of near 300 nm reached the maximum of 0.93. With the increase of the particle size, particle penetration rate showed a trend of decrease, and gravity settling began to dominate. The experiment result showed that when the slit height changed, the dominant factors of particles subsidence to the wall were changed. At low concentration in a certain range, the particle number concentration had little effect on the penetration rate. The range of particle number concentration of inside and outside I/O ratio was 0.69- 0.73. The correlation coefficient R2 was 0.99. The linear correlation was obvious. The particle penetration rate in slit straight way was significantly greater than that at the corner of the channel.

[Distribution of atmospheric ultrafine particles during haze weather in Hangzhou].

Atmospheric ultrafine particles (UFPs) were monitored with fast mobility particle sizer (FMPS) in continuous haze weather and the haze fading process during December 6 to 11, 2013 in Hangzhou. Particle concentration and size distribution were studied associated with meteorological factors. The results showed that number concentrations were the highest at night and began to reduce in the morning. There was a small peak at 8 o'clock in the morning and 18 o'clock in the afternoon. It showed an obvious peak traffic source, which indicated that traffic emissions played a great role in the atmospheric pollution. During haze weather, the highest number concentration of UFPs reached 8 x 10(4) cm(-3). Particle size spectrum distribution was bimodal, the peak particle sizes were 15 nm and 100 nm respectively. Majority of UFPs were Aitken mode and Accumulation mode and the size of most particles concentrated near 100 nm. Average CMD(count medium diameter) was 85.89 nm. During haze fading process, number concentration and particles with size around 100 nm began to reduce and peak size shifted to small size. Nuclear modal particles increased and were more than accumulation mode. Average CMD was 58.64 nm. Meteorological factors such as the visibility and wind were negatively correlated with the particle number concentration. Correlation coefficient R were -0.225 and - 0.229. The humidity was correlated with number concentration. Correlation coefficient R was 0.271. The atmosphere was stable in winter and the level temperature had small correlation with number concentration. Therefore, study on distribution of atmospheric ultrafine particles during haze weather had the significance on the formation mechanism and control of haze weather.

[Ultrafine particle number concentration and size distribution of vehicle exhaust ultrafine particles].

Ultrafine particle (UFP) number concentrations obtained from three different vehicles were measured using fast mobility particle sizer (FMPS) and automobile exhaust gas analyzer. UFP number concentration and size distribution were studied at different idle driving speeds. The results showed that at a low idle speed of 800 rmin-1 , the emission particle number concentration was the lowest and showed a increasing trend with the increase of idle speed. The majority of exhaust particles were in Nuclear mode and Aitken mode. The peak sizes were dominated by 10 nm and 50 nm. Particle number concentration showed a significantly sharp increase during the vehicle acceleration process, and was then kept stable when the speed was stable. In the range of 0. 4 m axial distance from the end of the exhaust pipe, the particle number concentration decayed rapidly after dilution, but it was not obvious in the range of 0. 4-1 m. The number concentration was larger than the background concentration. Concentration of exhaust emissions such as CO, HC and NO showed a reducing trend with the increase of idle speed,which was in contrast to the emission trend of particle number concentration.

[Experimental study on the size spectra and emission factor of ultrafine particle from coal combustion].

The emission characteristics of ultrafine particles released from pulverized coal combustion were studied, the size spectra of ultrafine particles (5.6-560 nm) were measured with FMPS (fast mobility particle sizer) on a self-built aerosol experiment platform. Meanwhile, a particle dynamic evolution model was established to obtain the particle deposition rate and the emission rate through the optimized algorithm. Finally, the emission factor was calculated. The results showed that at the beginning of particle generation, the size spectra were polydisperse and complex, the initial size spectra was mainly composed of three modes including 10 nm, 30-40 nm and 100-200 nm. Among them, the number concentration of mode around 10 nm was higher than those of other modes, the size spectrum of around 100-200 nm was lognormal distributed, with a CMD (count median diameter) of around 16 nm. Then, as time went on, the total number concentration was decayed by exponential law, the CMD first increased and then tended to be stable gradually. The calculation results showed that the emission factor of particles from coal combustion under laboratory condition was (5.54 x 10(12) ± 2.18 x 10(12)) unit x g(-1).