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Moderately to well-preserved radiolarians have been extracted from nine greyish green and purplish-red bedded cherts in the mud-matrix melange of the eastern Yarlung-Zangbo Suture Zone (YZSZ) at Jinlang Section, Zedong, southern Xizang (Tibet). Forty-two species belonging to 27 genera, including Middle Jurassic characteristic species such as Laxtorum (?) jurassicum Isozaki and Matsuda, Laxtorum (?) hichisoense Isozaki and Matsuda, Stichocapsa japonica Yao, Stichocapsa robusta Matsuoka, Parahsuum (?) magnum Takemura, Sella chrafatensis (El Kadiri), and Unuma typicus Ichikawa and Yao are recognized and three assemblages, Laxtorum (?) jurassicum Assemblage (Aalenian), Quarticella ovalis Assemblage (late Bajocian), and Stichocapsa robusta Assemblage (middle Bathonian) are established in ascending order. These assemblages can be well correlated to the Middle Jurassic Unitary Association (UA) Zones (Baumgartner et al., 1995) in west Tethys and coeval biozones in Japan and provide reliable age information for the Middle Jurassic stratigraphic correlation of the pelagic sediments along the YZSZ.

3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid (BCAA)-associated mammalian target of rapamycin complex 1 (mTORC1) activation. Previous studies have demonstrated the therapeutic effects of BT2 on arthritis, liver cancer, and kidney injury. However, the effects of BT2 on ulcerative colitis (UC) are unknown.To investigate the anti-UC effects of BT2 and the underlying mechanism.Mouse UC models were created through the administration of 3.5% dextran sodium sulfate (DSS) for 7 d. The mice in the treated groups were administered salazosulfapyridine (300 mg/kg) or BT2 (20 mg/kg) orally from day 1 to day 7. At the end of the study, all of the mice were sacrificed, and colon tissues were removed for hematoxylin and eosin staining, immunoblot analyses, and immunohistochemical assays. Cytokine levels were measured by flow cytometry. The contents of BCAAs including valine, leucine, and isoleucine, in mouse serum were detected by liquid chromatography-tandem mass spectrometry, and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing.Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice. BT2 also reduced the production of the proinflammatory cytokines interleukin 6 (IL-6), IL-9, and IL-2 and increased the anti-inflammatory cytokine IL-10 level. In addition, BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice. Furthermore, high-throughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis. Compared with the DSS group, BT2 treatment increased the ratio ofOur results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.

Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.

A hypersensitivity response akin to immune reconstitution inflammatory syndrome (IRIS) has been proposed as a mechanism responsible for anti-PD-1 therapy-induced tuberculosis. IRIS is associated with enhanced activation of IL-17A-expressing CD4 + T cells (Th17). Gut microbiota is thought to be linked to pulmonary inflammation through the gut-lung axis. We used ImmuCellAI to investigate the T cell population in lung cancer and tuberculosis samples. Then, we applied flow cytometry to monitor the expression levels of the Th17 cell activation marker CD38 in the peripheral blood of a patient experiencing adverse events, including tuberculosis, in response to pembrolizumab. The gut microbiome was examined by 16S rRNA sequencing to examine the alterations caused by pembrolizumab. The percentage of Th17 cells was increased in both lung cancer and tuberculosis. FACS analysis showed that pembrolizumab induced substantial CD38 expression in Th17 cells. The patient’s fecal samples showed that the diversity of the gut microbiota was significantly increased in response to the pembrolizumab cycle. One enriched genus was Prevotella, which has previously been linked to lung inflammation and Th17 immune activation. The observed Th17 activation in our patient was consistent with a role of Th17-mediated IRIS in pembrolizumab-triggered tuberculosis. Pembrolizumab might trigger airway inflammation with a Th17 phenotype through microbiota interactions in the gut-lung axis.

Cette proposition de communication a pour but d’expliquer comment la prosodie émotionnelle, en passant par le principe phonographique, est représentée par la substance graphique dans un texte multimodal doté de moindre de littéralité comme la BD. Les modèles de mesure des variations matérielles de la prosodie des émotions basiques (colère, tristesse, joie, peur et surprisse) permettent de construire un protocole dans le codage d’une émotion selon les changements de paramètres acoustiques et ainsi de comprendre les variations prosodiques à représenter graphiquement. Après avoir cité les exemples concrets des représentations graphiques des émotions basiques dans les BD francobelges, nous pouvons en conclure que le codage idéographique dans la BD se compose de deux phénomènes :diagramme et icône. Cette notation présentant quelque consensus de configurations graphiques, reste néanmoins imparfaite, non-conventionnelle, mais laisse le libre choix aux auteurs.

A rapid and high sensitive ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of notoginsenoside R1 and ginsenoside Re in rat plasma was developed. The analytes and internal standard, digoxin, were extracted from rat plasma via protein precipitation with methanol and separated on an Phenomenex Gemini C18 column within 2 min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring and positive ion mode. The precursor to product ion transitions monitored for notoginsenoside R1, ginsenoside Re, and internal standard were m/z 955.5→775.5, 969.6→789.1, and 803.6→283.1, respectively. The assay was validated with linear range of 1.9-380 ng/mL for notoginsenoside R1 and 0.5-100 ng/mL for ginsenoside Re. The intra- and interday precisions (RSD%) were within 8.96% for each analyte. The absolute recoveries were greater than 93% for R1 and 96% for Re. Each analyte was stable during all sample storage, preparation, and analytic procedures. The method was successfully applied to a pharmacokinetic study of Xuesaitong dispersible tablets in eight rats.

A rapid and highly sensitive liquid chromatography/tandem mass spectrometry method for simultaneous determination of 1,3-dicaffeoylquinic acid and caffeic acid in rat plasma was developed. The analytes and internal standard (IS), tinidazole, were extracted from rat plasma via liquid/liquid extraction with ethyl acetate and separated on an Agilent Zorbax SB C18 column within 4 min. Quantitation was performed on a triple quadrupole mass spectrometer employing an electrospray ionization technique, operating in a multiple reaction monitoring (MRM) and negative ion mode. The precursor to product ion transitions monitored for 1,3-dicaffeoylquinic acid, caffeic acid and IS were m/z 515.2 → 353.0, 178.9 → 134.9, and 246.0 → 125.8, respectively. The assay was validated in the linear range of 4.00–96.0 ng mL−1 for 1,3-dicaffeoylquinic acid and 2.00–128 ng mL−1 for caffeic acid. The intra- and inter-day precisions (RSD%) were within 8.89% for each analyte. The absolution recoveries were greater than 73.52% for 1,3-dicaffeoylquinic acid and 74.32% for caffeic acid. Each analyte was proved to be stable during all sample storage, preparation and analytical procedures. The method was successfully applied to a pharmacokinetic study of Dengzhanxixin injection in 8 rats.

Forsythoside A (FTA), one of the main active ingredients in weeping forsythia extract, possesses strong antibacterial, antioxidant and antiviral effects, and its content was about 8% of totally, higher largely than that of other ingredients, but the absolute bioavailability orally was approximately 0.5%, which is significant low influencing clinical efficacies of its oral preparations. In the present study, in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo pharmacokinetics study were performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test, measurement of total amount of protein and the activity of LDH and morphology observation, respectively. The pharmacological effects such as antioxidant activity improvement by absorption enhancers were verified by PC12 cell damage inhibition rate after H₂O₂ insults. The observations from in vitro Caco-2 cell showed that the absorption of FTA in weeping forsythia extract could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/ml was safe for the Caco-2 cells, but water-soluble chitosan at different concentrations was all safe for these cells. The observations from single-pass intestinal perfusion in situ model showed that duodenum, jejunum, ileum and colon showed significantly concentration-dependent increase in P(eff)-value, and that P(eff)-value in the ileum and colon groups, where sodium caprate was added, was higher than that of duodenum and jejunum groups, but P(eff)-value in the jejunum group was higher than that of duodenum, ileum and colon groups where water-soluble chitosan was added. Intestinal mucosal toxicity studies showed no significant toxicity below 800 μg/ml sodium caprate and water-soluble chitosan at different concentrations. In pharmacokinetics study, water-soluble chitosan at dosage of 50mg/kg improved the bioavailability of FTA in weeping forsythia extract to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with weeping forsythia extract with water-soluble chitosan at dosage of 50 mg/kg prevented PC12 cell damage upon H₂O₂ stimulation better than that of control. All findings above suggested that water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antioxidant activity in vivo in weeping forsythia extract.

The samples of Huangqi injection (HI) were analyzed by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-TOF-MS), and both positive and negative ion modes were employed to obtain the LC-TOF-MS analysis information of chemical compounds in HI. Then the mass defect filtering (MDF) approach, which was developed based on the previously published articles, was utilized to rapidly screen the astragalosides from the obtained LC-TOF-MS data. Each screened astragaloside was confirmed by the presence of no less than 2 quasi-molecular ions. All the screened astragalosides were then tentatively assigned according to the parent ion and daughter ion information. Finally, a total of 62 astragalosides were screened and characterized from the HI samples, including 15 new detected ones. The identification results indicated that acetylation, hydrogenation, dehydrogenation, methoxylation and hydration might be the major conversion reactions involved in the formation of the astragalosides. The LC-TOF-MS-based MDF approach was proved to be a feasible and efficient tool to screen the chemical constituents in complex matrices such as herbal medicines.

Ethnopharmacological relevance Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Thunder God Vine (TGV). Owing to its potential anti-inflammatory and antitumor effects, celastrol has been considered as a promising candidate for drug development. Aim of the study To establish a sensitive LC–MS/MS method to investigate the pharmacokinetic properties of celastrol in rats. Key pharmacokinetic issues of celastrol including oral bioavailability, comparative pharmacokinetics between pure compound and tablet preparation, as well as gender-related pharmacokinetic difference are to be addressed for the first time. Materials and methods Sprague–Dawley rats were administrated an intravenous dose (100 μg kg−1) of pure celastrol and an oral dose (1000 μg kg−1) of pure celastrol and TGV tablets (corresponding to 534 μg kg−1 of celastrol), respectively. At different time points, the concentration of celastrol in rat plasma was determined by a sensitive and well-validated LC–MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration–time curve (AUC), maximal plasma concentration (Cmax), the time for maximal concentration (Tmax) and mean residence time (MRT) were estimated by Drug and Statistic1.0 pharmacokinetic software (Chinese Pharmacological Association, Anhui, PR China). Statistical analysis was performed using two one-side t test with p-values less than 0.05 as the level of significance. Results The standard curve of celastrol showed good linearity in the concentration range of 0.11∼54.3 ng mL−1 in our current method, with acceptable selectivity, precision, recovery, and stability. The oral absolute bioavailability of celastrol significantly increased from 17.06% for pure celastrol to 94.19% for TGV tablets containing equivalent celastrol. After oral administration of TGV tablets, the Cmax and AUC values of celastrol in female rats were (32.03±8.41) μg L−1 and (379.49±118.19) μg h L−1, which were significantly higher (p Conclusion Celastrol administered orally in the rat was poorly absorbed into the systemic circulation. However, the poor absorption of celastrol could be greatly improved when celastrol-containing TGV tablets orally administered, and thereby the oral bioavailability of celastrol was significantly increased. As for gender difference, female rats showed significantly better absorption of celastrol than males.

A highly sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the determination of limonin in beagle dog plasma using nimodipine as internal standard. The analyte and internal standard (IS) were extracted with ether followed by a rapid isocratic elution with 10 mm ammonium acetate buffer–methanol (26:74, v/v) on a C18 column (150 × 2.1 mm i.d.) and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 469.4 229.3 and m/z 417.2 122.0 were used to measure the analyte and the IS. The assay was linear over the concentration range of 0.625–100 ng/mL for limonin in dog plasma. The lower limit of quantification was 0.312 ng/mL and the extraction recovery was >90.4% for limonin. The inter- and intra-day precision of the method at three concentrations was less than 9.9%. The method was successfully applied to pharmacokinetic study of limonin in dogs. Copyright © 2012 John Wiley & Sons, Ltd.

Rationale Prenylated flavonoids and isoflavonoids are widely distributed throughout the plant kingdom, with many biological effects. Psoralea corylifolia, which contains many kinds of prenylated components, has been widely used as a medicinal plant in Asia and India for thousands of years. The goal of this study was to characterize the components in P. corylifolia using a liquid chromatography with diode-array detection and quadrupole time-of-flight mass spectrometry (LC-DAD/Q-TOF-MS) method, and to elucidate the fragmentation behavior of the different prenyl substituent groups and their appropriate characteristic pathways in positive ion mode. Methods The calculated accurate masses of the protonated molecules, the fragment ions, the retention behavior, and the data from UV spectra were used for identification of the components in P. corylifolia. Results A total of 45 compounds, including 43 prenylated components, were identified or tentatively identified in P. corylifolia. Different diagnostic fragment ions and neutral losses were observed in different prenyl substructures: neutral loss of 56 Da (C(4)H(8)) and a fragment ion at m/z 69 (C(5)H(9)(+)) were generated by a prenyl chain; neutral losses of 42 Da (C(3)H(6)), 54 Da (C(4)H(6)), 15 Da (CH(3•)) and 16 Da (CH(4)) were observed in a ring-closed prenyl group; neutral losses of 72 Da (C(4)H(8)O), 60 Da (C(2)H(4)O(2)), 58 Da (C(3)H(6)O) and 18 Da (H(2)O) were detected in a 2,2-dimethyl-3,4-dihydroxydihydropyran ring; neutral losses of 72 Da (C(4)H(8)O), 60 Da (C(3)H(8)O) and 18 Da (H(2)O) were yielded from a 2,2-dimethyl-3-hydroxydihydropyran ring, a 2-(1-hydroxy-1-methylethyl)dihydrofuran ring or a 1-hydroxy-3-methylbut-3-enyl chain. Conclusions This method can be applied for analysis of prenylated components in P. corylifolia and other herbal medicines.

In this study, a rapid and comprehensive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for simultaneous determination of nine major bioactive constituents in Dengzhanxixin injection. The chromatographic separations were obtained on an Acquity UPLC BEH C18 column (50 mm × 2.1 mm I.D., 1.7 μm) by a linear gradient elution with the mobile phase consisting of A (water and 0.6% acetic acid) and B (acetonitrile and 0.6% acetic acid). The total analytical run time was relatively short (14 min). The analytes and two internal standards (ISs) were all monitored in a selected-ion reaction (SIR) mode with a negative electrospray ionization (ESI−) interface. The calibration curves of all analytes revealed good linear regression (r2 ≥ 0.9972) within test ranges. This method provided good precision with RSD of intra- and interday variation less than 1.26% and 2.51%, respectively. The validated method was then applied to quantify the nine major constituents in six batc...

Ethnopharmacology The main components of HuangKui capsules’ are the total flavonoids extracted from the flowers of Abelmoschus manihot L medic. They have been widely used to treat chronic glomerulonephritis, diabetic nephropathy and nephrotic syndrome. The combination of HuangKui capsules and glibenclamide is a possible therapy for patients with diabetes mellitus and diabetic nephropathy. However, there is no report about effects of HuangKui capsules on the glibenclamide pharmacokinetics till now. Aim of the study This study was aimed investigating the effect of HuangKui capsules on pharmacokinetics of glibenclamide in rats. Material and methods Eight rats were administered with an oral dose of HuangKui capsules (0.75 g kg−1) once daily for 10 consecutive days. All the rats were administered orally with the glibenclamide (1 mg kg−1) before the first time and after the last time given HuangKui capsules. LC–MS/MS was utilized to determine the concentration of glibenclamide in rat plasma and to calculate the corresponding pharmacokinetic parameters. The statistical differences of the two cycles were evaluated by paired-samples t-test. Results In the rats treated with HuangKui capsules and glibenclamide, the t1/2, the time point of maximum plasma concentration (Tmax) of glibenclamide increased obviously (p

A rapid, sensitive and specific method using liquid chromatography with tandem mass spectrometric detection (LC-MS) was developed for the analysis of sauchinone in rat plasma. Di-O-methyltetrahydrofuriguaiacin B was used as internal standard (IS). Analytes were extracted from rat plasma by liquid–liquid extraction using ethyl acetate. A 2.1 mm i.d. × 150 mm, 5 µm, Agilent Zorbax SB-C18 column was used to perform the chromatographic analysis. The mobile phase was methanol–deionized water (80:20, v/v). The chromatographic run time was 7 min per injection and the flow-rate was 0.2 mL/min. The tandem mass spectrometric detection mode was achieved with electrospray ionization interface in positive-ion mode (ESI+). The m/z ratios [M + Na]+, m/z 379.4 for sauchinone and m/z 395.4 for IS were recorded simultaneously. Calibration curve were linear over the range of 0.01–5 µg/mL. The lowest limit of quantification was 0.01 µg/mL. The intra-day and inter-day precision and accuracy of the quality control samples were 2.94–9.42% and 95.79–108.05%, respectively. The matrix effect was 64.20–67.34% and the extraction recovery was 93.28–95.98%. This method was simple and sensitive enough to be used in pharmacokinetic research for determination of sauchinone in rat plasma. Copyright © 2011 John Wiley & Sons, Ltd.

A rapid and sensitive LC–MS–MS method was developed and validated for the determination of asiaticoside in rat plasma. Asiaticoside was extracted by protein precipitation with acetonitrile, and separated on a C18 column. The total analytical time was relatively short (4 min), and the limit of quantification was 38 ng mL−1 using 100 μL of rat plasma. Asiaticoside and the internal standard (felodipine) were monitored in the multi-reaction-monitoring mode as follows: m/z 957.4 → 469.3 and m/z 382.2 → 145.1, respectively. Calibration was linear over a concentration range from 38 to 7,600 ng mL−1, and the correlation coefficient was greater than 0.998. The recoveries of asiaticoside from plasma were better than 85%, and RSDs of inter-day and intra-day assays were below 10.1%. The method is sensitive and specific, and suitable for pharmacokinetic studies of asiaticoside in rats.

A rapid and sensitive liquid chromatography–electrospray ionization mass spectrometry method was developed for the determination of aesculin in rat plasma. The analyses were chromatographed on a Zorbax Extend-C18 analytical column (150 × 2.1 mm I.D., 5 µm) with 30:70 (v/v) methanol–0.1% formic acid as mobile phase. Detection was performed by triple-quadrupole tandem mass spectrometry in multi-reaction-monitoring mode with an electrospray ionization source. The method was validated for accuracy and precision, and linearity in the two matrices was good. The assay was linear in the range 12.5–1,800 ng mL−1. The lower limit of quantification of aesculin (LLOQ) was 12.5 ng mL−1. The recovery of aesculin and tinidazole (IS) were well above 85%. The within- and between-batch accuracy was 100–104% and 97–109%, respectively. There were no stability-related problems in the procedure for the analysis of aesculin. The method was successfully used in a preclinical study of the pharmacokinetics of aesculin in rats.

Novel axially chiral N-heterocyclic carbene (NHC) Pd(II) complexes were prepared from optically active 1,1′-binaphthalenyl-2,2′-diamine (BINAM) and H8-BINAM and their crystal structures were unambiguously determined by X-ray diffraction. These chiral N-heterocyclic carbene (NHC) Pd(II) complexes were applied in the oxidative kinetic resolution of secondary alcohols using molecular oxygen as a terminal oxidant or under aerobic conditions, affording the corresponding sec-alcohols in good yields with moderate to good enantioselectivities. Copyright © 2009 John Wiley & Sons, Ltd.

Liquid chromatography with quadrupole time-of-flight mass spectrometry coupled with automated data analysis by Peakview software was employed to systematically screen and characterize the astragalosides in Radix Astragali, a Chinese medical preparation. The separation was performed on a poroshell 120 SB-C18 column equipped in a conventional liquid chromatography system. After being separated using a general gradient elution, the analytes were detected by the triple quadrupole time-of-flight mass spectrometer in both positive- and negative-ion modes. The mass defect filtering function built in the Peakview software was utilized to rapidly screen the potential ions of interest, while some functions of Peakview such as Formula Finder, XIC manager, and IDA Explorer were employed to facilitate the assignment or characterization of the screened astragalosides. A total of 42 astragalosides were screened and tentatively characterized or assigned, and 20 of them were firstly detected in Radix Astragali. According to the screened astragalosides, acetylation, glycosidation, hydrogenation, oxidation, and hydration were considered to be the major secondary metabolic pathways involved in the formation of the astragalosides. The combination of liquid chromatography with quadrupole time-of-flight mass spectrometry and automated Peakview analysis is a feasible and efficient tool to screen and identify the constituents in complex matrices of herbal medicines.

To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.

The goal of Frequent Item set Mining (FIM) is to find the biggest number of frequently used subsets from a big transaction database. In previous studies, using the advantage of multicore computing, the execution time of an Apriori algorithm was sharply decreased: when the size of a data set was more than TBs and a single host had been unable to afford a large number of operations by using a number of computers connected into a super computer to speed up execution as being the obvious solution. Some parallel Apriori algorithms, based on the MapReduce framework, have been proposed. However, with these algorithms, memory would be quickly exhausted and communication cost would rise sharply. This would greatly reduce execution efficiency. In this paper, we present an improved reformative Apriori algorithm that uses the length of each transaction to determine the size of the maximum merge candidate item sets. By reducing the production of low frequency item sets in Map function, memory exhaustion is ameliorated, greatly improving execution efficiency.

To establish a LC-MS/MS method to determine caffeic acid, chlorogenic acid in rat plasma and study their pharmacokinetics in rats. Six Sprague-Dawley rats were intravenously injected with 4 mL x kg(-1) of Dengzhanxixin injection, respectively. Their drug plasma concentration was determined by LC-MS/MS, with tinidazole as an internal standard. The pharmacokinetic parameters were calculated by DAS 1.0. The linear concentration ranges of caffeic acid, and chlorogenic acid were 2-128 microg x L(-1) (r = 0.998 1) and 3-384 microg x L(-1) (r = 0.998 7), respectively. The methodological test showed conformance to the requirements. The intraday and inter-day variable coefficients were both less than 10.0%, indicating that both of legitimate precise and accuracy were in conformity with the requirements of biological sample analysis. For caffeic acid, the pharmacokinetic parameter t1/2beta AUC0-t, and CL were (130.91 +/- 38.77) min, (4.89 +/- 0.96) mg x min x L(-1) and (0.12 +/- 0.02) L x min(-1) x kg(-1), respectively. For chlorogenic acid, the pharmacokinetic parameter t1/2beta , AUC0-t, and CL were (49.38 +/- 8.85) min, (9.54 +/- 0.95) mg x min x L(-1) and (0.09 +/- 0.003) L x min(-1) x kg(-1), respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of caffeic acid and chlorogenic acid.

Transformer fluid directly affects the working state of the components and the cooling efficiency of transformer. There are three kinds of transformer fluid used for electric locomotive, EMU and suburban rail vehicles: mineral oil, silicone liquid and synthetic ester based insulating oil. In this paper, the three kinds of oil are compared from the fire safety, environmental protection, reliability and low maintenance. It provides a strong basis for the selection of transformer fluid. By comprehensive analysis, synthetic ester based insulating oil can completely replace mineral oil and silicone liquid. With rail transport safety and environmental protection standards improving, synthetic ester based insulating oil will be the best choice for transformer.

Prenylated flavonoids and isoflavonoids are widely distributed throughout the plant kingdom, with many biological effects. Psoralea corylifolia, which contains many kinds of prenylated components, has been widely used as a medicinal plant in Asia and India for thousands of years. The goal of this study was to characterize the components in P. corylifolia using a liquid chromatography with diode-array detection and quadrupole time-of-flight mass spectrometry (LC-DAD/Q-TOF-MS) method, and to elucidate the fragmentation behavior of the different prenyl substituent groups and their appropriate characteristic pathways in positive ion mode.The calculated accurate masses of the protonated molecules, the fragment ions, the retention behavior, and the data from UV spectra were used for identification of the components in P. corylifolia.A total of 45 compounds, including 43 prenylated components, were identified or tentatively identified in P. corylifolia. Different diagnostic fragment ions and neutral losses were observed in different prenyl substructures: neutral loss of 56 Da (C(4)H(8)) and a fragment ion at m/z 69 (C(5)H(9)(+)) were generated by a prenyl chain; neutral losses of 42 Da (C(3)H(6)), 54 Da (C(4)H(6)), 15 Da (CH(3•)) and 16 Da (CH(4)) were observed in a ring-closed prenyl group; neutral losses of 72 Da (C(4)H(8)O), 60 Da (C(2)H(4)O(2)), 58 Da (C(3)H(6)O) and 18 Da (H(2)O) were detected in a 2,2-dimethyl-3,4-dihydroxydihydropyran ring; neutral losses of 72 Da (C(4)H(8)O), 60 Da (C(3)H(8)O) and 18 Da (H(2)O) were yielded from a 2,2-dimethyl-3-hydroxydihydropyran ring, a 2-(1-hydroxy-1-methylethyl)dihydrofuran ring or a 1-hydroxy-3-methylbut-3-enyl chain.This method can be applied for analysis of prenylated components in P. corylifolia and other herbal medicines.

To establish an LC-MS/MS method for determination of isorhamnetin-3-O-neohesperidoside and investigate its application on pharmacokinetic study in rats.Eight rats were given 5 mg·kg(-1) isorhamnetin-3-O-neohesperidoside after intravenous administration. A highly sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of isorhamnetin-3-O-neohesperidosidein rat plasma using rutin as internal standard. The analytes and rutin (internal standard) were extracted with methanol followed by a rapid isocratic elution with 10 mmol·L(-1) ammonium acetate buffer/methanol (20 : 80, V/V) on a C18 column (150 mm × 2.1 mm, I.D., 5 μm) and subsequent analysis by mass spectrometry in the multi-eaction-monitoring mode.The assays were linear over the concentration range of 0.01-10 μg·mL(-1) for isorhamnetin-3-O-neohesperidosidein rat plasma. The lower limit of quantifications for isorhamnetin-3-O-neohesperidoside was 0.01 μg·mL(-1).The validated method is successfully applied to determine the plasma concentrations of isorhamnetin-3-O-neohesperidosidein in rats.

To investigate the mechanisms underlying the intestinal absorption of the major bioactive component forsythoside A (FTA) extracted from Forsythiae fructus.An in vitro Caco-2 cell model and a single-pass intestinal perfusion in situ model in SD rats were used.In the in vitro Caco-2 cell model, the mean apparent permeability value (P(app)-value) was 4.15×10(-7) cm/s in the apical-to-basolateral (AP-BL) direction. At the concentrations of 2.6-10.4 μg/mL, the efflux ratio of FTA in the bi-directional transport experiments was approximately 1.00. After the transport,96% of the apically loaded FTA was retained on the apical side, while97% of the basolaterally loaded FTA was retained on the basolateral side. The P(app)-values of FTA were inversely correlated with the transepithelial electrical resistance. The paracellular permeability enhancers sodium caprate and EDTA, the P-gp inhibitor verapamil and the multidrug resistance related protein (MRP) inhibitors cyclosporine and MK571 could concentration-dependently increase the Papp-values, while the uptake (OATP) transporter inhibitors diclofenac sodium and indomethacin could concentration-dependently decrease the P(app)-values. The intake transporter SGLT1 inhibitor mannitol did not cause significant change in the P(app)-values. In the in situ intestinal perfusion model, both the absorption rate constant (K(a)) and the effective permeability (P(eff)-values) following perfusion of FTA 2.6, 5.2 and 10.4 μg/mL via the duodenum, jejunum and ileum had no significant difference, although the values were slightly higher for the duodenum as compared to those in the jejunum and ileum. The low, medium and high concentrations of verapamil caused the largest increase in the P(eff)-values for duodenum, jejunum and ileum, respectively. Sodium caprate, EDTA and cyclosporine resulted in concentration-dependent increase in the P(eff)-values. Diclofenac sodium and indomethacin caused concentration-dependent decrease in the Peff-values. Mannitol did not cause significant change in the P(app)-values for the duodenum, jejunum or ileum.The results suggest that the intestinal absorption of FTA may occur through passive diffusion, and the predominant absorption site may be in the upper part of small intestine. Paracellular transport route is also involved. P-gp, MRPs and OATP may participate in the absorption of FTA in the intestine. The low permeability of FTA contributes to its low oral bioavailability.

A highly sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of limonin in beagle dog plasma using nimodipine as internal standard. The analyte and internal standard (IS) were extracted with ether followed by a rapid isocratic elution with 10 mm ammonium acetate buffer-methanol (26:74, v/v) on a C18 column (150 × 2.1 mm i.d.) and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 469.4 → 229.3 and m/z 417.2 → 122.0 were used to measure the analyte and the IS. The assay was linear over the concentration range of 0.625-100 ng/mL for limonin in dog plasma. The lower limit of quantification was 0.312 ng/mL and the extraction recovery was90.4% for limonin. The inter- and intra-day precision of the method at three concentrations was less than 9.9%. The method was successfully applied to pharmacokinetic study of limonin in dogs.

A highly sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of typhaneoside in rat plasma using rutin as internal standard. The analyte and rutin (internal standard) were extracted with methanol followed by a rapid isocratic elution with 10 mM ammonium acetate buffer/methanol (v:v, 20:80) on an C(18) column (150 mm × 2.1 mm I.D.) and subsequent analysis by mass spectrometry in the multi-reaction-monitoring mode. The precursor to product ion transitions of m/z 769.3 → 314.1 and m/z 609.2 → 300.1 were used to measure the analyte and the internal standard. The assay was linear over the concentration range of 0.01-10 μg/mL for typhaneoside in rat plasma. The lower limit of quantification was 0.01 μg/mL and the extraction recovery was larger than 90.2% for typhaneoside. The inter- and intra-day precision of the method at three concentrations was less than 6.8%. The method was firstly applied to pharmacokinetic study of typhaneoside in rats.

A liquid chromatography–mass spectrometry method has been developed and validated for the quantification of bullatacin, a bistetrahydrofuran annonaceous acetogenin, in rat plasma. Squamostatin-A was selected as the internal standard. Analytes were extracted from rat plasma by liquid/liquid extraction using ethyl acetate with high efficiency. The chromatographical separation was performed on an Agilent Zorbax SB-C18 column (150 mm × 2.1 mm, 5 μm). The mobile phase consisted of methanol and deionized water (95:5, v/v) containing 0.01% (v/v) formic acid. The chromatographic run time was 7 min per injection and flow rate was 0.2 mL/min. The retention time was 3.22 and 5.23 min for internal standard and bullatacin, respectively. The elutes were detected under positive electrospray ionization and the target analytes quantified by selected ion monitoring mode (645.9 m/z for bullatacin and 661.9 m/z for squamostatin-A). The method was sensitive with the limit of quantitation at 0.5 ng/mL in 100 μL of rat plasma. Good linearity (r2 = 0.9998) was obtained covering the concentration of 0.5–2000 ng/mL. The intra- and inter-day assay precision ranged from 3.2 to 8.7% and 2.7 to 9.2%, respectively. In addition, the stability, extraction recovery and matrix effect involved in the method were also validated. This method was applied to measure the plasma bullatacin concentrations after a single tail vein intravenous administration of bullatacin in rats.

A rapid, sensitive and specific method using liquid chromatography with tandem mass spectrometric detection (LC-MS) was developed for the analysis of sauchinone in rat plasma. Di-O-methyltetrahydrofuriguaiacin B was used as internal standard (IS). Analytes were extracted from rat plasma by liquid-liquid extraction using ethyl acetate. A 2.1 mm i.d. × 150 mm, 5 µm, Agilent Zorbax SB-C(18) column was used to perform the chromatographic analysis. The mobile phase was methanol-deionized water (80:20, v/v). The chromatographic run time was 7 min per injection and the flow-rate was 0.2 mL/min. The tandem mass spectrometric detection mode was achieved with electrospray ionization interface in positive-ion mode (ESI(+) ). The m/z ratios [M + Na](+) , m/z 379.4 for sauchinone and m/z 395.4 for IS were recorded simultaneously. Calibration curve were linear over the range of 0.01-5 µg/mL. The lowest limit of quantification was 0.01 µg/mL. The intra-day and inter-day precision and accuracy of the quality control samples were 2.94-9.42% and 95.79-108.05%, respectively. The matrix effect was 64.20-67.34% and the extraction recovery was 93.28-95.98%. This method was simple and sensitive enough to be used in pharmacokinetic research for determination of sauchinone in rat plasma.

Novel axially chiral N-heterocyclic carbene (NHC) Pd(II) complexes were prepared from optically active 1,1′-binaphthalenyl-2,2′-diamine (BINAM) and H8-BINAM and their crystal structures were unambiguously determined by X-ray diffraction. These chiral N-heterocyclic carbene (NHC) Pd(II) complexes were applied in the oxidative kinetic resolution of secondary alcohols using molecular oxygen as a terminal oxidant or under aerobic conditions, affording the corresponding sec-alcohols in good yields with moderate to good enantioselectivities. Copyright © 2009 John Wiley & Sons, Ltd.

Rice with low glutelin content is suitable as functional food for patients affected with diabetes and kidney failure. The fine mapping of the gene(s) responsible for low glutelin content will provide information regarding the distribution of glutelin related genes in rice genome and will generate markers for the selection of low glutelin rice varieties. Following an SDS-PAGE screen of rice germplasm from Taihu Valley of China, Japonica selection W3660 is identified to be a novel mutant characterized with low glutelin content. For fine mapping the mutant gene for low glutelin content, F2 and F3 populations were derived from a cross between W3660 and Jingrennuo. SDS-PAGE analysis of the total endosperm protein showed that the low glutelin content trait was controlled by a single dominant nuclear gene. Genetic mapping, using SSRs, located this gene to chromosome 2, in the region between SSR2-001/SSR2-004 and RM1358. The distances of the two markers to the target gene were 1.1 cM and 3.8 cM respectively. By semi-quantitative RT-PCR analysis, the transcripts of GluB4/GluB5 genes located within the region do not change. However, GluB5 gene located proximal to SSR2-001/SSR2-004 was specifically reduced. SSR profiles of seven Japonica varieties were compared with that of W3660 for loci in the relevant genetic region. The markers SSR2-004 and RM1358 were used for marker-assisted selection. The selection efficiencies of SSR2-004 and RM1358 were 96.8% and 92.7% respectively. This provides a standard starting point for the breeding of low glutelin content rice varieties in China.

PeiAi64S, a photoperiod and thermo-sensitive genic male sterile, has been wildly applied to hybrid rice seed production in China, but its photoperiod-sensitivity gene for heading date in this sterile line was still unknown. This definitely limited the further use of this sterile line in breeding practice and re-production of hybrid seeds. To solve this problem, using heading time nearly isogenic lines EGO - EG7, ER - LR, T65 - T65m and six heading date QTL-isogenic lines, NIL (Hd1) - NIL (Hd6) with the genes of Nipponbare but Hd1 - Hd6 genes from Kasalath respectively, we performed a genetic analysis of PeiAi64S with special reference to photoperiod-sensitivity loci, in natural long days at Nanjing (32 degrees N) where the average day-length is about 14 h and in natural short days at Linshui county, Hainan province(18 degrees 29'N), where the average day-length is about 11.6 h during the course of rice growing respectively. The F1 and F2 generations from the crosses 'PeiAi64S x heading time nearly isogenic lines' were subjected to genetic analyses. Experimental results showed that PeiAi64S carries photoperiod-sensitivity allele gene E1 and E3 and dominant earliness gene Ef-1 in E1 and E3 and Ef-1 loci, respectively, and a photoperiod insensitivity allele Se-1 degrees in Se-1 locus. Meanwhile, the photoperiod-sensitivity gene E1 and photoperiod-insensitivity gene Se-1e in PeiAi64S were also identified by crossing with the NIL(Hd1) and NIL(Hd4). In addition, a recessive inhibitor for photoperiod-sensitive gene E1 or Se-1(n) and other modified photoperiod-sensitive genes: i-Se-1, E3, Hd3 (En-Se-1), Hd5 and Hd6, were identified in PeiAi64S by crossing with QTL nearly isogenic lines: NIL(Hd2), NIL (Hd3), NIL (Hd5) and NIL( Hd6), The results indicated that the genotype of PeiAi64S's heading date was: E1E1e2e2E3E3Se-1(e)Se-1(e)Ef-1 Ef-1 i-Se-1 i-Se-1.

A set of chromosome segment substitution lines (CSSLs), derived from Asominori/IR24 with Asominori as the recurrent parent,was planted and phenotyped for grain length (GL), grain width (GW) and length-width ratio (LWR) of milled rice in two successive years and four sites. QTL for GL,GW and LWR were characterized and stability of their expression was investigated. The phenotypic values for each trait showed a continuous distribution and some transgressive lines were also observed in the CSSLs population. Additionally, a total of 13 QTL for GL, GW and LWR were identified,and six of them were consistently detected in the eight different environments. Phenotypic values were different significantly (P0. 001) between the CSSLs harboring any of the six QTL alleles and the genetic background parent, Asominori. Significant phenotypic correlations (ror = 0.75, r0.05 = 0.67) were detected among different environments for these CSSLs carrying the same target QTL. Also, the results indicated that the six QTL, namely, qGL-3 for GL, qGW-5a and qGW-5b for GW, qLWR-3, qLWR-5a and qLWR-5b for LWR, were stably expressed in different environments. Since QTL qGL-3 and qLWR-3 were mapped in the R19-C1677 interval, qGW-5a and qLWR-5a in the vicinity of RFLP marker C263, qGW-5b and qLWR-5b near R569,the four RFLP markers, R19, C1677, C263 and R569,would be useful for further marker-assisted selection (MAS) in rice quality improvement.

Rice stripe disease transmitted by small brown planthopper (Laodelphax striatellus Fall.) is one of the most serious viral diseases in East Asia. The disease is severely epidemic in most rice growing areas where the main cultivars are susceptible or moderately susceptible to rice stripe virus. In this research, a recombinant inbred lines (RILs) population of 81 lines derived from a cross of Kinmaze (japonica)/DV85(indica) by the single seed descent method was used to detect quantitative trait loci (QTL) conferring resistance to rice stripe virus(RSV). The response of the two parents and 81 RILs to RSV were investigated by inoculating seedlings with viruliferous small brown planthopper insects, and scored by the disease rate index. The quantitative trait loci for rice stripe disease resistance were analyzed by QTL Cartographer software. Three QTL controlling RSV resistance were detected on chromosomes 1, 7 and 11, respectively. Individual QTL accounted for 19.8%-30.9% of the phenotypic variance in the RILs population. The direction of the additive gene effects at two loci qStv7 and qStv11 coincided with that predicted by phenotypes of the parents. At these two loci, the DV85 alleles increased the resistance to RSV, while at qStv1, the Kinmaze alleles increased the resistance to RSV.