516 research outputs found

    Sudapyridine (WX-081) antibacterial activity against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo

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    ABSTRACT Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did not prolong QT interval in animal model studies. This study evaluated the antibacterial activity of this novel compound against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo. The minimum inhibitory concentration (MIC) of WX-081 against three kinds of non-tuberculous mycobacteria (NTM) clinical strains was determined using microplate-based alamarBlue assay (MABA), and the antibacterial activity of WX-081 against NTM in J774A.1 cells and mice was evaluated. MIC ranges of WX-081 against clinical strains of M. avium and M. abscessus were 0.05–0.94 μg/mL, 0.88–7.22 μg/mL (M. abscessus subsp. abscessus), and 0.22–8.67 μg/mL (M. abscessus subsp. massiliense), respectively, which were slightly higher than those of BDQ. For M. avium, M. abscessus, and M. chelonae, WX-081 can reduce the intracellular bacterial load by 0.13–1.18, 0.18–1.50, and 0.17–1.03 log10 colony forming units (CFU)/mL, respectively, in a concentration-dependent manner. WX-081 has bactericidal activity against three NTM species in mice. WX-081 exhibited anti-NTM activity to the same extent as BDQ both in vivo and in vitro. WX-081 is a promising clinical candidate and should be studied further in clinical trials.IMPORTANCEDue to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium chelonae during 2000–2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively

    Data_Sheet_1_Effects of Wx Genotype, Nitrogen Fertilization, and Temperature on Rice Grain Quality.xlsx

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    Quality is a complex trait that is not only the key determinant of the market value of the rice grain, but is also a major constraint in rice breeding. It is influenced by both genetic and environmental factors. However, the combined effects of genotypes and environmental factors on rice grain quality remain unclear. In this study, we used a three-factor experimental design to examine the grain quality of different Wx genotypes grown under different nitrogen fertilization and temperature conditions during grain development. We found that the three factors contributed differently to taste, appearance, and nutritional quality. Increased Wx function and nitrogen fertilization significantly reduced eating quality, whereas high temperature (HT) had almost no effect. The main effects of temperature on appearance quality and moderate Wx function at low temperatures (LTs) contributed to better appearance, and higher nitrogen fertilization promoted appearance at HTs. With regard to nutritional quality, Wx alleles promoted amylose content (AC) as well as starch-lipids content (SLC); nitrogen fertilization increased storage protein content (PC); and higher temperature increased lipid content but decreased the PC. This study helps to broaden the understanding of the major factors that affect the quality of rice and provides constructive messages for rice quality improvement and the cultivation of high-quality rice varieties.</p

    Characteristic Spectrum for Differential Systems

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    AbstractThe characteristic spectrum of the tangent map of a differential system is determined by using qualitative functions and ergodic measures over the bundle of orthonormaln-frames. The characteristic spectrum of the parallelotope cocycle of a differential system is determined by using a qualitative function and ergodic measures over the state manifold

    Image_2_Effects of Wx Genotype, Nitrogen Fertilization, and Temperature on Rice Grain Quality.JPEG

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    Quality is a complex trait that is not only the key determinant of the market value of the rice grain, but is also a major constraint in rice breeding. It is influenced by both genetic and environmental factors. However, the combined effects of genotypes and environmental factors on rice grain quality remain unclear. In this study, we used a three-factor experimental design to examine the grain quality of different Wx genotypes grown under different nitrogen fertilization and temperature conditions during grain development. We found that the three factors contributed differently to taste, appearance, and nutritional quality. Increased Wx function and nitrogen fertilization significantly reduced eating quality, whereas high temperature (HT) had almost no effect. The main effects of temperature on appearance quality and moderate Wx function at low temperatures (LTs) contributed to better appearance, and higher nitrogen fertilization promoted appearance at HTs. With regard to nutritional quality, Wx alleles promoted amylose content (AC) as well as starch-lipids content (SLC); nitrogen fertilization increased storage protein content (PC); and higher temperature increased lipid content but decreased the PC. This study helps to broaden the understanding of the major factors that affect the quality of rice and provides constructive messages for rice quality improvement and the cultivation of high-quality rice varieties.</p

    Safety evaluation and whole genome sequencing for revealing the ability of Penicillium oxalicum WX-209 to safely and effectively degrade citrus segments

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    The microbial potential of Penicillium has received critical attention. The present research aimed to elucidate the efficacy of crude enzyme secreted from Penicillium oxalicum WX-209 in degrading citrus segments and evaluate the safety of the process. Results showed that citrus segment membranes gradually dissolved after treatment with the crude enzyme solution, indicating good degradation capability. No significant differences in body weight, food ingestion rate, hematology, blood biochemistry, and weight changes of different organs were found between the enzyme intake and control groups. Serial experiments showed that the crude enzyme had high biological safety. Moreover, the whole genome of P. oxalicum WX-209 was sequenced by PacBio and Illumina platforms. Twenty-five scaffolds were assembled to generate 36 Mbp size of genome sequence comprising 11 369 predicted genes modeled with a GC content of 48.33 %. A total of 592 genes were annotated to encode enzymes related to carbohydrates, and some degradation enzyme genes were identified in strain P. oxalicum WX-209. Data availability: The whole genome sequencing data in this study can be found in GenBank database of NCBI website with the accession number PRJNA 715321. The link: http://www.ncbi.nlm.nih.gov/bioproject/715321

    Development of primary reference measurement procedures for the quantification and determination of the saturation of transferrin

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    Transferrin (Tf) als Akute-Phase-Protein ist ein wichtiger diagnostischer Marker für entzündliche Prozesse im menschlichen Körper. Deshalb wurde es auch in der „Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen“ (RiLiBÄK) in die Liste wichtiger Analyte aufgenommen. Klinisch-chemische Laboratorien sind daher dazu verpflichtet, regelmäßig in Ringversuchen nachzuweisen, dass sie die Tf- Konzentration in den von der RiLiBÄK vorgegeben Grenzen verlässlich bestimmen können. Von der Bundesärztekammer wird eine Rückführung auf das SI-System dieser Messergebnisse angestrebt, da nur auf diese Weise ein bundes- bzw. weltweiter Vergleich möglich ist. Der Physikalisch-Technischen Bundesanstalt (PTB) fällt dabei die Aufgabe zu, die Voraussetzung für die Rückführung zu schaffen, indem sie ein an das SI-System angeschlossenes Weitergabesystem aufbaut. Dafür ist es notwendig, eine Referenzmethode zu entwickeln und bereitzustellen, die es ermöglicht Tf mit einer Unsicherheit zu bestimmen, die deutlich unter der in der RiLiBÄK geforderten Unsicherheit liegt. Vor diesem Hintergrund sowie dem weiteren Ziel den Tf-Gehalt in Referenzmaterialien rückgeführt bestimmen zu können, wurden im Rahmen dieser Arbeit primäre Referenzverfahren zur Quantifizierung und Bestimmung des Fe-Beladungsgrades von Tf entwickelt. Die Quantifizierung erfolgte über eine chromatographische Trennung des Tf von der Serummatrix mit HPLC und anschließender elementspezifischer Detektion des in dem Tf gebundenen Fe mit ICP-MS. Zur Quantifizierung wurde sowohl post column (PC) als auch spezies spezifische (SS) Isotopenverdünnungsmassenspektrometrie (IDMS) eingesetzt. Beide Verfahren wurden als double IDMS unter Verwendung des Exakt Matching Prinzips angewandt. Außerdem fand zum ersten Mal in der Speziesanalytik die triple IDMS Anwendung. Alle Methoden ergaben für das humane Serum ERM-DA470k/IFCC vergleichbare Tf- Gehalte von wx = (2,36 ± 0,13) g/kg für PC-IDMS, wx = (2,317 ± 0,092) g/kg für double SS-IDMS und wx = (2,426 ± 0,086) g/kg für triple SS-IDMS, die gut mit dem zertifizierten, über herkömmliche Methoden bestimmten Wert von wx = (2,41 ± 0,08) g/kg übereinstimmen. Da der Fe-Beladungsgrad von Tf wichtige Rückschlüsse auf die Fe-Versorgung eines Patienten zulässt, wurde dieser ebenfalls mit IDMS bestimmt. Zusätzlich wurde erstmals auch eine Raman-Methode zur Bestimmung der Fe-Beladung entwickelt. Die Methoden, angewandt auf ein gefriergetrocknetes nat. Tf, ergaben auch hier vergleichbare Werte: b = (30,20 ± 1,20) % mit IDMS und b = (28,2 ± 2,0) % mit Raman. Alle Ansätze wurden, wie in der Metrologie üblich, gravimetrisch angesetzt und erweiterte Unsicherheiten (k = 2) entsprechend der Vorgabe des Bureau International des Poids et Mesures (BIPM) in “Evaluation of measurement data — Guide to the expression of uncertainty in measurement” (GUM) berechnet.Transferrin (Tf), as an acute phase protein, is an important diagnostic marker for inflammation processes in the human body. Therefore, it was included in the List of important analytes in the guidelines of the German Medical Association (RiLiBÄK). Hence, clinical chemical laboratories are bound to participate in interlaboratory comparisons periodically to guarantee their ability to determine Tf within the limits defined in the RiLiBÄK. The German Medical Association aspires the traceability to the SI of those measurement results, because this is the only reliable way to ensure comparability nationwide as well as globally. The Physikalisch-Technische Bundesanstalt (PTB) is responsible for establishing traceability. This requires a traceability chain, which is connected to the SI, and a reference method which uncertainty is significantly lower than the uncertainty required in RiLiBÄK. Considering this as well as the goal to achieve traceable results for the content of Tf in reference materials, primary reference methods were developed in this work to quantify the content and to determine the iron saturation of human Tf. For the quantification, Tf was chromatographically separated from the serum matrix with HPLC and subsequently measured with element mass spectrometry (ICP-MS) via the Fe bound to Tf. Post column (PC) and species specific (SS) isotope dilution mass spectrometry (IDMS) were used. Both, PC- and SS-IDMS, were performed as double IDMS using the exact matching principle. Furthermore, triple IDMS was used for the first time in species analysis. All methods were applied to the human serum reference material ERM-DA470k/IFCC and comparable results for the content of Tf were achieved with wx = (2.36 ± 0.13) g/kg for PC-IDMS, wx = (2.317 ± 0.092) g/kg for double SS-IDMS and wx = (2.426 ± 0.086) g/kg for triple IDMS. These results were in good agreement with the value given in the certificate of wx = (2.41 ± 0.08) g/kg which was determined with conventional methods. The iron saturation of Tf allows important conclusions on the Fe supply of patients. Therefore, it was also determined with IDMS and additionally a Raman procedure was developed the first time. The methods were adopted to a freeze dried natural Tf and also achieved comparable results: b = (30.20 ± 1.20) % for IDMS and b = (28.2 ± 2.0) % for Raman. All necessary solutions were produced gravimetrically and the expanded uncertainties (k = 2) of the results were calculated according to the recommendations of the Bureau International des Poids et Mesures (BIPM) in “Evaluation of measurement data — Guide to the expression of uncertainty in measurement” (GUM)

    Interaction of main chain cationic polyelectrolyte with sodium dodecyl sulfate

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    The interaction of x,gamma -ionene (x = 2,4,6; gamma = 4,6,12) polycations with sodium dodecyl sulfate (SDS) has been investigated in aqueous solution. It was found that there is a narrow molar ratio of SDS/cation (similar to1.0-1.35) depending on different ionenes, at which the viscosity of ionene-SDS aqueous solution rises suddenly due to the formation of water soluble inter-polymer aggregates via the SDS attached on the polymer chains. The viscosity falls sharply with further addition of excessive SDS, which forms micelle in solution and causes the de-aggregation of the inter-polymer aggregates. The x, gamma values of the ionene, the polymer concentration and the SDS/cation ratio play a key role in determining the viscosity behavior. At the higher concentration of ionene a gelation occurs suddenly from solution at a specific molar ratio of SDS/cation and was confirmed to be reversible. The viscosity increase and gel formation in ionene-SDS aqueous solution were considered to be related closely with presence of the hydrophobic domain. Using N,N-dimethylflavon as fluorescent probe, the existence of hydrophobic domain in solution has been verified, the hydrodynamic radius of the aggregates in the viscose solution was determined with laser light scattering and an explanation for the viscosity change as well as the gel formation has been proposed. (C) 2001 Elsevier Science Ltd. All rights reserved.Polymer ScienceSCI(E)EI16ARTICLE112259-22623

    Convergence of attractors

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    The system of coupled oscillators and its time-discretization (with constant stepsize h) are considered in this paper. Under some conditions, it is showed that the discrete systems have one-dimensional global attractors l(h) converging to l which is the global attractor of continuous system

    Selective electroless deposition of Cu on an ultrathin Au film pattern

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    In this report an ultrathin Au nanoparticle (AuNP) film composed of photosensitive diazoresin (DR) and mercaptophenol (MP) capped AuNPs (MP-AuNPs) was fabricated by self-assembly (SA). The DR/MP-AuNP film was than patterned through a photomask by selective exposure to UV light and instantly developed in sodium dodecyl sulfate (SDS) aqueous solution. After sintering at 550 degreesC to remove the organic components, the DR-MP-AuNPs formed AuNPs. Taking advantage of the catalytic susceptibility of AuNPs toward electroless deposition of Cu, a Cu film micropattern with fine resolution (ca. 2-3 mum) and considerable thickness (ca. 130 nm) was prepared.Polymer ScienceSCI(E)EI4ARTICLE221917-19202
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