Orthogonal printing of uniform nanocomposite monolayer and oriented organic semiconductor crystals for high-performance nano-crystal floating gate memory.

Inkjet printing is of great interest in the preparation of optoelectronic and microelectronic devices due to its low cost, low process temperature, versatile material compatibility, and ability to precisely manufacture multi-layer devices on demand. However, interlayer solvent erosion is a typical problem that limits the printing of organic semiconductor devices with multi-layer structures. In this study, we proposed a solution to address this erosion problem by designing polystyrene-block-poly(4-vinyl pyridine)-grafted Au nanoparticles (Au@PS-b-P4VP NPs). With a colloidal ink containing the Au@PS-b-P4VP NPs, we obtained a uniform monolayer of Au nano-crystal floating gates (NCFGs) embedded in the PS-b-P4VP tunneling dielectric (TD) layer using direct-ink-writing (DIW). Significantly, PS-b-P4VP has high erosion resistance against the semiconductor ink solvent, which enables multi-layer printing. An active layer of semiconductor crystals with high crystallinity and well-orientation was obtained by DIW. Moreover, we developed a strategy to improve the quality of the TD/semiconductor interface by introducing a polystyrene intermediate layer. We show that the NCFG memory devices exhibit a low threshold voltage (<3 V), large memory window (66 V), stable endurance (>100 cycles), and long-term retention (>10 years). This study provides universal guidance for printing functional coatings and multi-layer devices.

A Versatile 3D-Confined Self-Assembly Strategy for Anisotropic and Ordered Mesoporous Carbon Microparticles.

Mesoporous carbon microparticles (MCMPs) with anisotropic shapes and ordered structures are attractive materials that remain challenging to access. In this study, a facile yet versatile route is developed to prepare anisotropic MCMPs by combining neutral interface-guided 3D confined self-assembly (3D-CSA) of block copolymer (BCP) with a self-templated direct carbonization strategy. This route enables pre-engineering BCP into microparticles with oblate shape and hexagonal packing cylindrical mesostructures, followed by selective crosslinking and decorating of their continuous phase with functional species (such as platinum nanoparticles, Pt NPs) via in situ growth. To realize uniform in situ growth, a "guest exchange" strategy is proposed to make room for functional species and a pre-crosslinking strategy is developed to preserve the structural stability of preformed BCP microparticles during infiltration. Finally, Pt NP-loaded MCMPs are derived from the continuous phase of BCP microparticles through selective self-templated direct carbonization without using any external carbon source. This study introduces an effective concept to obtain functional species-loaded and N-doped MCMPs with oblate shape and almost hexagonal structure (p6mm), which would find important applications in fuel cells, separation, and heterogeneous catalysis.

Advances in rapid drug detection technology.

Spurious/Falsely-labeled/Falsified/Counterfeit (SFFC)drugs have become a major threat to public health, especially in rural areas of developing countries.The goal of this review is to provide an overview of rapid detection technologies for counterfeits recently reported, such as Near Infrared Spectroscopy, Near Infrared Chemical Imaging, Raman Spectroscopy, X-Ray Fluorescence, X-RayPowder Diffraction, Ion Mobility Spectrometry, Ion MobilityMass Spectrometry,Isotope Ratio Mass Spectrometry and visual analytical methods The advantages of each of these detection methods are introduced. Examples of characterization of SFFC drugs using the detection technology mentioned are presented. In addition, new characteristics and trends of SFFC drugs are listed and the solution is discussed.

Analysis of micronomicin by liquid chromatography with pulsed electrochemical detection.

This paper describes the separation of the main component micronomicin from its related substances using a new established liquid chromatographic method with pulsed electrochemical detection (LC-PED). The mobile phase consists of 1 volume of acetonitrile and 99 volumes of an aqueous solution containing 1.25% (v/v) trifluoroacetic acid, 0.025% (v/v) pentafluoropropionic acid and 0.85% (v/v) of 50% sodium hydroxide. The pH of the aqueous solution is adjusted to 2.6 with 0.5 M NaOH. The influence of the different chromatographic parameters on the separation was investigated. A quadruple-potential waveform was used as detection waveform. 0.5 M NaOH was added post column at a flow rate of 0.3 mL/min to raise the pH of detection to at least 12. The LOD and LOQ of micronomicin are 0.08 µg/mL (1.6 ng injected) and 0.25 µg/mL (5 ng injected), respectively. The linearity of micronomicin ranges from 0.25 to 60 µg/mL with a correlation coefficient of 0.9978. Intra-day RSD and inter-day RSD of micronomicin are 0.89% and 0.55%, respectively. This method proved to be robust and is also applicable to a wider number of C18 columns. A number of commercial samples of micronomicin sulfate were analyzed using this method and 18 peaks can be separated from the main component and from each other in one sample. Seven peaks could be identified using reference substances. The chemical structure of two unknown impurities could be characterized by LC-MS based on comparison of their fragmentation patterns with those of available reference substances.

Simultaneous determination of ten biogenic amines in a thymopolypeptides injection using ultra-performance liquid chromatography coupled with electrospray ionization tandem quadrupole mass spectrometry.

A selective and sensitive ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-MS) method was developed for the simultaneous determination of ten biogenic amines (tryptamine, 2-phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, adrenaline, dopamine and spermine) in a thymopolypeptides injection from the Chinese market for the first time. Biogenic amines (BAs) were pre-column derivatised by dansyl chloride after direct sample dilution. Dansylated amines were separated on an ACQUITY UPLC BEH Shield RP18 column (2.1mm×150mm I.D., 1.7µm) using a gradient elution. Quantification was done by monitoring fragment ions of each derivative under the MS mode of multiple reaction monitoring (MRM). A satisfactory result of method validation was obtained. The linearity ranged from 0.32 to 1182.9µg/L and the correlation coefficients (r) for all amines were above 0.99. The LOD ranged from 0.08µg/L for 2-phenylethylamine and tyramine to 8.00µg/L for adrenaline; the LOQ ranged from 0.32µg/L for 2-phenylethylamine to 12.12µg/L for dopamine. The recovery ranged from 75.8 to 110.3% after spiking standard solutions of BAs to a sample at three levels. The intra and inter-day precision RSD were 0.78-8.85% and 1.39-9.93% respectively. Eighty-four injections were analyzed by this method. Nine biogenic amines were found in them except adrenaline. Moreover, the relationship between the result of test for depressor substances and the content of BAs was statistically analyzed.

Analysis of impurities in vertilmicin sulfate by liquid chromatography ion-trap mass spectrometry.

The characterization of impurities present in vertilmicin by liquid chromatography (LC) coupled with mass spectrometry (MS) is described. A reversed phase (RP)-LC method using a C18 column resistant to basic pH with an alkaline (pH 11) aqueous mobile phase was developed and coupled to MS with an electrospray ionization (ESI) source in the positive ion mode which provides MS(n) capability. In total, 18 impurities were detected in a commercial sample. Eleven impurities described in this work were newly identified.

Impurity profiling of micronomicin sulfate injection by liquid chromatography-ion trap mass spectrometry.

The characterization of impurities present in micronomicin sulfate injection by liquid chromatography (LC) coupled with mass spectrometry (MS) is described. A reversed phase (RP)-LC method using a C18 column resistant to an alkaline (pH 11) aqueous mobile phase was developed and coupled to MS with an electrospray ionization (ESI) source in the positive ion mode which provides MS(n) capability. A total of thirty six impurities were detected in commercial samples: five impurities were identified by comparison of their fragmentation patterns with those of available related substances, eleven of them were identified in accordance with relevant literature, while the other twenty impurities were newly identified using the MS/MS spectra of the available related reference substances as interpretative templates combined with knowledge of the nature of functional group fragmentation behaviors. This work was applied to evaluate the quality of micronomicin sulfate injection from different manufacturers.

Impurity profiling of etimicin sulfate by liquid chromatography ion-trap mass spectrometry.

A reversed phase (RP)-LC method using a C(18) column resistant to basic pH and an alkaline (pH 10) aqueous mobile phase was developed and coupled to MS with an electrospray ionization (ESI) source in the positive ion mode which provides MS(n) capability. In total, 26 impurities were detected in a commercial sample. The structures of the impurities were proposed based on comparison of their fragmentation patterns with those of the available reference substances, the synthetic route and literature data. Starting material and its residual impurities, intermediates, synthetic by-products and degradation products were the main sources of those impurities. 14 impurities described in this work were newly identified.

Gambogic acid deactivates cytosolic and mitochondrial thioredoxins by covalent binding to the functional domain.

Gambogic acid (1) is a cytotoxic caged xanthone derived from the resin of Garcinia hanburyi. Compound 1 selectively induces apoptosis in cancer cells, at least partially, by targeting the stress response to reactive oxygen species (ROS). However, the molecular mechanism of ROS toxicity stimulated by 1 remains poorly understood. In this study, mass spectrometric and biochemical pharmacological approaches were used that resulted in the identification of both cytosolic thioredoxin (TRX-1) and mitochondrial thioredoxin (TRX-2) as the molecular targets of 1. The results obtained showed that 1 deactivates TRX-1/2 proteins by covalent binding to the active cysteine residues in the functional domain via Michael addition reactions. Since both TRX-1 and TRX-2 play key roles in regulating the redox signaling of cancer cells, the present findings may shed light on the relationship between protein binding and cellular ROS accumulation induced by 1. This provides support for the current clinical trials of gambogic acid (1) being conducted alone or in combination with other agents that appear to increase ROS generation in order to selectively kill cancer cells.

Rapid characterization of caged xanthones in the resin of Garcinia hanburyi using multiple mass spectrometric scanning modes: the importance of biosynthetic knowledge based prediction.

Although the anticancer activities of the resin of Garcinia hanburyi have been well demonstrated, the chemical composition of this medicinal plant is still not fully understood. In this study, a highly effective qualitative method was developed for rapidly profiling the target and non-target caged xanthones in the resin of G. hanburyi. This method mainly involves three steps as follows: (1) prediction of the possible unknown caged xanthones in the resin of G. hanburyi according to the structure characters of the known ones and some well established biosynthetic knowledge; (2) structure classification according to the diagnostic fragment ions (DFIs) of the known caged Garcinia xanthones; (3) detection and characterization of the target and non-target caged xanthones in the resin of G. hanburyi using multiple mass spectrometric (MS) scanning modes. By use of such procedures, mass spectrometric data can be used for confirming the rationally predicted chemical structure rather than sophisticated and time-consumed de novo structure elucidation of a completely unknown component. Finally, a total of 34 caged xanthones including 18 likely new ones from the resin of G. hanburyi were rapidly detected and characterized within one working day.

Screening adulteration of polypropylene bottles with postconsumer recycled plastics for oral drug package by near-infrared spectroscopy.

Adulteration of pharmaceutical packaging containers with postconsumer recycled plastic materials was considerably difficult to identify due to the similar chemical compositions of virgin and recycled plastics. In the present study, near-infrared (NIR) spectroscopy coupled with conformity test was proposed to screen the adulteration of pharmaceutical packaging containers. Two kinds of representative screening models were investigated on polypropylene (PP) bottles for oral drug package. The reliability of the screening models was validated through studying the identification reliability, specificity, and robustness of the methods. The minimum spiking level of two modeled adulterants at the proportion of 20% could be detected, and the unqualified sample from a domestic manufacturer was rejected by this developed method. This strategy represents a rapid and promising analytical method for screening the adulteration of pharmaceutical plastic packaging containers with postconsumer recycled plastics.

Wide dissemination of multidrug-resistant Shigella isolates in China.

OBJECTIVES: To evaluate the prevalence of antimicrobial resistance and selected antimicrobial resistance mechanisms in Shigella isolates recovered in outpatients from 1997 to 2009 in China. METHODS: The isolates were subjected to serotyping and antimicrobial susceptibility testing. Shigella isolates producing extended-spectrum ß-lactamases (ESBLs) or resistance to ciprofloxacin were further characterized by PFGE to determine the genetic relatedness. These isolates were also screened for ß-lactamase genes and mutations in the quinolone resistance-determining regions (QRDRs) by PCR. DNA sequence analysis was also performed. RESULTS: After serotyping, 301 Shigella isolates were grouped into three subgroups and 13 distinct serotypes. The antimicrobial resistance profiles differed among subgroups and serotypes. Ciprofloxacin-resistant isolates were mainly Shigella flexneri serotypes f2a and f4a, which were resistant to at least four additional non-quinolone antimicrobials. Three point mutations in the QRDRs of gyrA and parC were identified in all 30 ciprofloxacin-resistant S. flexneri isolates. Plasmid-mediated bla(CMY-2), bla(CTX-M-14), bla(CTX-M-15) and bla(CTX-M-55)-like genes were found in 29 ESBL-producing isolates and three clavulanic-acid-resistant isolates, and six isolates also exhibited resistance to ciprofloxacin. Distinct genetic differences in both serotypes and PFGE profiles were observed for these ciprofloxacin- or extended-spectrum-cephalosporin-resistant isolates. CONCLUSIONS: ESBL-producing or fluoroquinolone-resistant Shigella is no longer an unusual phenomenon in the local community. The monitoring programme in China should stay vigilant to the dissemination of these isolates and the health agencies must take appropriate measures to restrict the abuse of antimicrobials, especially in the community.

Characterization of Escherichia coli isolates from healthy food handlers in hospital.

Recent studies have reported that Escherichia coli in fecal samples of healthy humans could also serve as important reservoirs of drug-resistant bacteria. Limited data are available for E. coli-resistant profiles of healthy food handlers in hospitals who provide food service to inpatients and hospital staffs. E. coli isolates were recovered from hospital healthy food handlers, and one random selected isolate from each food handler was subjected to antimicrobial susceptibility testing, phylogenetic typing, and screening for antimicrobial-resistant mechanisms by polymerase chain reaction amplification. Ciprofloxacin-resistant isolates were further characterized by mutation analysis in the quinolone resistance determining regions (QRDRs) of GyrA and ParC. And extended-spectrum ß-lactamase (ESBL) producing isolates were screened for bla(CTX-M) by polymerase chain reaction amplification and DNA sequence analysis. In total, more than 50% (47/92) of E. coli isolates from healthy food handlers showed multidrug-resistant profiles and 50% (46/92) isolates carried intI. Resistance prevalence of the B2 phylogenetic group was significantly lower than that of the non-B2 groups for all tested antimicrobials (p < 0.05) except chloramphenicol and tetracycline. Seven isolates of phylogenetic group A (n = 3) and D (n = 4) produced ESBL, and 12 isolates of phylogenetic group A (n = 5), B2 (n = 2), and D (n = 5) were resistant to ciprofloxacin. Transferable quinolone resistance determinants were identified in four isolates. Point mutations in QRDRs of GyrA or ParC were identified among 59 out of 62 E. coli isolates showing decreased susceptibility or resistance to ciprofloxacin. Genes encoding CTX-M enzyme were identified in seven ESBL-producing isolates. The preponderance in hospital food handlers of multidrug-resistant E. coli makes it important to introduce control measures such as improved biosecurity to ensure that they do not pass through the food service and limit inpatient therapeutic options.

Joint effects of topoisomerase alterations and plasmid-mediated quinolone-resistant determinants in Salmonella enterica Typhimurium.

Alterations in topoisomerases and plasmid-mediated quinolone-resistant (PMQR) determinants have been identified as main quinolone-resistant mechanisms in Salmonella enterica Typhimurium. But the joint effects of these mechanisms have not been thoroughly characterized in homologous Salmonella Typhimurium strains. In this study, isogenic topoisomerase mutants were constructed using phage λ Red recombinase system and phage transduction. And the joint effects of topoisomerase mutations (gyrA [S83F], gyrA [S83F, D87N] and parC [S80I]) and PMQR determinants (including qnrB4, qnrS1, aac(6')-Ib-cr, and qepA) were studied in homologous genetic constitutions. Our data showed that mutations in gyrA played a dominant role in fluoroquinolone resistance in Salmonella Typhimurium and have a synergistic effect with other resistant mechanisms. The mutation (S80I) in parC would have no effect in quinolone resistance without gyrA mutations. The joint effect of aac(6')-Ib-cr and topoisomerase mutations were only observed for ciprofloxacin among tested quinolones. Different joint effects between topoisomerase mutations and qepA, qnrB4, or qnrS1 were observed for tested quinolones. Importantly, the acquirement of the PMQR determinants could improve 0- to 32-fold of the host mutant prevention concentration to ciprofloxacin. Our data showed that the acquirement of PMQR determinants could not only improve the host minimal inhibitory concentrations to quinolones but also accelerate the generation of high-level fluoroquinolone-resistant mutants.

Metabolism of gambogic acid in rats: a rare intestinal metabolic pathway responsible for its final disposition.

Gambogic acid (GA) is a promising natural anticancer candidate. Although the anticancer activity of GA has been well demonstrated, information regarding the metabolic fate of GA is limited. Previous studies suggested that GA is mainly excreted into intestinal tract in rats through bile after intravenous administration, whereas only traces appeared in the feces, suggesting that GA is metabolized extensively in the intestine. However, there has been no report about the intestinal metabolism of GA either in animals or humans. In this study, large amounts of two sulfonic acid metabolites of GA were found in the feces samples of rats after intravenous administration, and their structures were identified as 10-α sulfonic acid GA and 10-ß sulfonic acid GA by comparison of the retention times and spectral data with those of synthesized reference substances using liquid chromatography-diode array detector-tandem mass spectrometry. This rare intestinal metabolic pathway mainly involves Michael addition of the sulfite ion to the 9,10 carbon-carbon double bond of α,ß-unsaturated ketone. In addition, a more detailed metabolic profile in rats is proposed, according to the results of in vitro and in vivo studies. It was found that GA can be metabolized by a variety of routes, including monooxidation, hydration, glutathionylation, glucuronidation, and glucosidation in the liver of rats. These findings provide information on the major metabolic soft spot of GA in the intestine and liver of rats, which is not only useful in the future human metabolic study of this compound but also of value in the metabolic studies of GA analogs.

Impurity profiling of acetylspiramycin by liquid chromatography-ion trap mass spectrometry.

Investigation of acetylspiramycin (ASPM) and its related substances was carried out using a reversed-phase liquid chromatography/tandem mass spectrometry method. The identification of impurities in the ASPM complex was performed with a quadrupole ion trap mass spectrometer, with an electrospray ionization (ESI) source in the positive ion mode which provides MS(n) capability. A total of 83 compounds were characterized in commercial samples, among which 31 impurities that had never been reported and 31 partially characterized impurities were deduced using the collision-induced dissociation (CID) spectra of major ASPM components as templates. Most of the major impurities arise from the starting materials and the synthesis process. This work provides very useful information for quality control of ASPM and evaluation of its synthesis process.

Comparison of electron capture-atmospheric pressure chemical ionization and electrospray ionization for the analysis of gambogic acid and its main circulating metabolite in dog plasma.

Gambogic acid (GA), a promising anticancer candidate, is a polyprenylated xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi. Electron capture-atmospheric pressure chemical ionization (EC- APCI) and electrospray ionization (ESI) techniques, both in the negative ion mode, were evaluated regarding ionization, fragmentation patterns and sensitivity for simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of GA and its main circulating metabolite, 10-hydroxygambogic acid (10-OHGA) in dog plasma. Both analytes underwent extensive in-source fragmentation in EC-APCI, which was not desirable for reliable quantification of these analytes, whereas the substitution of ESI for EC-APCI almost eliminated the source instability of both analytes. Negative ion ESI was, therefore, chosen for the development of an LC-MS/MS method for simultaneous determination of these analytes. After protein precipitation by acetonitrile, all analytes were separated on a Luna C18 HST column (50 x 2.0 mm i.d., 2.5 microm) with a mobile phase of 20 mmol L(-1) ammonium acetate water solution containing 0.2% acetic acid:acetonitrile (18:82, v/v). The detection was performed on a tandem mass spectrometer using selective reaction monitoring mode. Calibration curves were linear over the range of 10-6000 ng mL(-1) for GA and 3-2000 ng mL(-1) for 10-OHGA. The method was successfully applied to the pharmacokinetics study of GA injection in six beagle dogs.

Dissemination of cefotaxime-M-producing Escherichia coli isolates in poultry farms, but not swine farms, in China.

The objective of this study was to investigate the distribution of extended spectrum ß-lactamase (ESBL)-producing Escherichia coli isolates in swine and poultry farms in China. Rectal or cloaca swabs of swine and chicken were collected from four province-level regions of China, and E. coli isolates were recovered and tested for antimicrobial susceptibility. The isolates producing ESBLs were further characterized by pulsed-field gel electrophoresis (PFGE) and sequence analysis of genes encoding ß -lactamases and class I integrons. In total, 156 and 224 E. coli isolates were recovered from rectal swabs of four swine farms and cloaca swabs of six chicken farms, respectively. Prevalence of resistant isolates was higher in chicken than in swine. Fifty-six isolates producing ESBLs were identified from chicken samples, but no ESBL-producing isolates were identified from swine samples. Of 56 ESBL-producing isolates, 54 isolates contained cefotaxime (CTX)-M type ß-lactamases, including bla(CTX-M-14) (n = 24), bla(CTX-M-65) (n = 13), bla(CTX-M-55) (n = 10), bla(CTX-M-24) (n = 3), bla(CTX-M-3) (n = 2), bla(CTX-M-15) (n = 1), and bla(CTX-M-64) (n = 1). Among 54 E. coli isolates containing bla(CTX-M), 11 PFGE clusters and 42 PFGE patterns were identified. More importantly, more than three-fourth of the ESBL-producing isolates in chicken were also resistant to ciprofloxacin. Our data demonstrated that chicken had become an important reservoir of bla(CTX-M) in China. Detailed molecular comparison of plasmids and genomes of isolates from various sources will help to better define the transmission dynamics of bla(CTX-M) between humans and food-producing animals.

Identification and quantitative determination of a major circulating metabolite of gambogic acid in human.

Gambogic acid (GA), a promising anticancer candidate, is a polyprenylated xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi. The major circulating metabolite of GA in human, 10-hydroxygambogic acid (10-OHGA), was identified by comparison of the retention time and mass spectra with those of reference standard using liquid chromatography-tandem mass spectrometry. The reference standard of 10-OHGA was isolated from bile samples of rats after intravenous injection of GA injection, and its structure was confirmed by NMR. Then, a selective and sensitive method was developed for the quantitative determination of this metabolite in human plasma. After liquid-liquid extraction by ethyl acetate, the analyte and the internal standard were separated on a Sepax HPC18 column (100 mm x 2.1 mm i.d., 3.0 microm) with a mobile phase of 10mM ammonium acetate water solution containing 0.1% formic acid-acetonitrile (20:80, v/v). The detection was performed on a single quadrupole mass spectrometer equipped with electrospray ionization (ESI) source. The calibration curve was linear over the range of 3-2000 ng/mL for 10-OHGA. The developed quantification method can now be used for the pharmacokinetic and pharmacological studies of 10-OHGA after intravenous infusion of GA injection in human.