Biologically guided isolation and ADMET profile of new factor Xa inhibitors fromGlycyrrhiza glabraroots usingin vitroandin silicoapproaches

Selective factor Xa inhibitors effectively block coagulation cascade with a broader therapeutic window than multitargeted anticoagulants. They have evolved as a crucial part of prevention and treatment of thromboembolic diseases and in therapeutic protocols involved in many clinical trials in coronavirus disease 2019 (COVID-19) patients. Biologically-guided isolation of specific FXa inhibitors from licorice (Glycyrrhiza glabra) root extract furnished ten flavonoids. By detailed analysis of their1H,13C NMR and MS data, the structures of these flavonoids were established as 7,4′-dihydroxyflavone (1), formononetin (2), 3-R-glabridin (3), isoliquiritigenin (4), liquiritin (5), naringenin 5-O-glucoside (6), 3,3′,4,4′-tetrahydroxy-2-methoxychalcone (7), liquiritinapioside (8) and the two isomers isoliquiritigenin-4′-O-β-d-apiosylglucoside (9) and isoliquiritigenin-4-O-β-d-apiosylglucoside (10). All the isolated compounds were assessed for their FXa inhibitory activity usingin vitrochromogenic assay for the first time. Liquirtin (5) showed the most potent inhibitory effects with an IC50of 5.15 μM. The QikProp module was implemented to perform ADMET predictions for the screened compounds

Biomass accumulation and energy conversion efficiency in aromatic rice genotypes

A field experiment was conducted to evaluate photosynthetic efficiency along with different growth parameters of aromatic rice genotypes. Forty genotypes including three non-aromatic checks exhibited enormous variations for leaf area index (LAI), crop growth rate (CGR), relative growth rate (RGR), net assimilation rate (NAR), grain yield, total dry matter, harvest index and photosynthetic efficiency or energy use efficiency (Emu) at panicle initiation and heading stages. Minimum LAI-value was 0.52 in Khazar at PI stage and maximum was 4.91 in Sakkor khora at heading stage. The CGR-value was in the range of 4.80-24.11 g m(-2) per day. The best yielder BR39 produced grain of 4.21 t ha(-1) and the worst yielder Khazar gave 1.42 t ha(-1). Total dry matter (TDM) yield varied from 4.04 to 12.26 t ha(-1) where genotypes proved their energy use efficiency a range between 0.58 to 1.65%. Emu showed a significant positive relation with TDM (r=0.80(**)), CGR (r=0.72(**)) and grain yield (r=0.66(**)). A negative correlation was established between TDM and harvest index and LAI and RGR. Path analysis result showed that NAR at heading stage exerted highest positive direct effect (0.70) on Emu

Dynamic Response of Pipelines Buried in Back-Filled Trenches

Dynamic response of pipelines buried in a back-filled rectangular trench in a semi Introduction The dynamic response of a circular shell modeling a pipeline buried in a semi-infinite elastic medium has been studied recently by Because of the complexity of the problem of dynamic response of pipes in back-filled trench

O sistema financeiro atual trava o desenvolvimento econômico

A financeirização está no centro dos debates econômicos, porque aprofunda a desigualdade e sobretudo porque trava o desenvolvimento. Este último aspecto é alvo de numerosos estudos internacionais, e aqui abordamos o mecanismo como se manifesta no Brasil. Basicamente, os crediários, cartões de crédito e juros bancários para pessoa física travam a demanda, pois tipicamente o comprador paga o dobro do valor do produto, endivida-se muito comprando pouco, o que esteriliza o impacto de dinamização da economia pela demanda. Os juros elevados para pessoa jurídica travam por sua vez o investimento, isto porque o empresário efetivamente produtivo já enfrenta a fragilidade da demanda. E a taxa Selic elevada, ao provocar a transferência de centenas de bilhões dos nosso impostos para os bancos e outros aplicadores financeiros, trava a capacidade de o Estado expandir políticas sociais e infraestruturas. Essa dinâmica no contexto de uma carga tributária que onera desproporcionalmente o consumo popular, e de um sistema de evasão dos impostos através em particular dos paraísos fiscais, gera um dreno insustentável de recursos que explica que tenhamos uma alta taxa de emprego e um PIB que estagna. As recomendações vão no sentido de uma reforma financeira, e não do ajuste fiscal atualmente proposto

Simulation of natural convective boundary layer flow of a nanofluid past a convectively heated inclined plate in the presence of magnetic field

AbstractThis paper deals with the numerical simulation of transient magnetohydrodynamics natural convective boundary layer flow of a nanofluid over an inclined plate. In the modeling of nanofluids, dynamic effects including the Brownian motion and thermophoresis are taken into account. Numerical solutions have been computed via the Galerkin-finite element method. The effects of angle of inclination, buoyancy-ratio parameter, Brownian motion, thermophoresis and magnetic field are taken into account and controlled by non-dimensional parameters. To compute the rate of convergence and error of the computed numerical solution, the double mesh principle is used. Similarity solutions are calculated and presented graphically for non-dimensional velocity, temperature, local rate of heat and mass transfer with pertinent parameters. The modified Nusselt number decreases with increasing inclination angle, buoyancy-ratio parameter, Brownian motion and thermophoresis parameter, whereas it increases with increasing Prandtl number. Validation of the results is achieved with earlier results for forced convective flow and non-magnetic studies. Such problems have several applications in engineering and petroleum industries such as electroplating, chemical processing of heavy metals and solar water heaters. External magnetic fields play an important role in electrical power generation, inclination/acceleration sensors, fine-tuning of the final materials to industrial specification because of their controlling behaviour on the flow characteristics of nanofluids

Klinische Bedeutung der Bestimmung der Bindung von Trijodthyronin an Serumproteine mittels Dextran-Gel-Filtration

Neben den bewährten älteren Verfahren zur Bestimmung des proteingebundenen127Jods und des Radiojodumsatzes hat sich die gleichzeitige Bestimmung des sog. freien und des proteingebundenen Anteils an in vitro mit Serum inkubiertem L-Trijodthyronin-131Jod mittels Dextran-Gel-Filtration klinisch zur Differentialdiagnose von Hyperthyreose und Euthyreose bewährt. Bei Ausnützung der Verdrängung von proteingebundenem L-Trijodthyronin-131Jod durch nichtmarkiertes Hormon und bei Variation der Dextran-Gel-Menge in der Säule bietet die Methode gute Differenzierungsmöglichkeiten auch für die Schilddrüsenfunktionszustände Euthyreose und Hypothyreose. Bei dem Verfahren wird der Patient nicht mit radioaktivem Jod belastet, ein für die Kinderklinik wichtiger Gesichtspunkt. Manche Störfaktoren, die den131Jodspeicherungstest und die Bestimmung des proteingebundenen Jods (PB127I) verfälschen, haben keinen Einfluß auf die mit der Dextran-Gel-Filtration untersuchten Proteinbindungsverhältnisse für L-Trijodthyronin-131Jod. So hat sich das Verfahren für die Untersuchung von Patienten mit operativ oder durch131Jodbehandlung verkleinerten Schilddrüsen, mit endokrinem Exophthalmus und in Fällen mit vorausgegangener Jodgabe, z. B. in Form von Kontrastmitteln, besonders bewährt. Mit der Bestimmung des sog. freien L-Trijodthyronin-131Jods wird ein physiologisch und pathogenetisch wichtiger Parameter der Schilddrüsenfunktion ermittelt. Die klinische Bedeutung der Bestimmung der Bindungs-und Transportverhältnisse für Trijodthyronin mittels Dextran-Gel-Filtration wird diskutiert.In addition to conventional methods of assay of protein bound iodine (PB127I) and of131iodine turnover in the thyroid, the simultaneous determination of socalled free and protein bound 1-triiodothyronine-131I, added in vitro to serum, using dextran gel filtration was found to be clinically helpful for diagnosis of euthyroidism and hyperthyroidism. Employing discharge effects of non-labelled triiodothyronine on protein bound 1-triiodothyronine-131I and varying the amount of dextran gel in the columns, the method provides reasonably good differentiation of euthyroid and hypothyroid states. No radioactive iodine is given to patients during this procedure, a fact of importance for pediatriciens. Some factors, that influence131iodine uptake or PB127I levels, do not disturb protein binding of 1-triiodothyronine-131I as determined by dextran gel filtration. The latter method was found to be especially useful for the examination of patients with surgically, or by therapy with131iodine dissected thyroid glands, with endocrine exophthalmos, and in cases of previous iodine administration (e.g. X-ray procedures). Determination of socalled free 1-triiodothyronine-131I provides information about a factor of physiological and pathogenetical significance, its clinical meaning is discussed

Expression of cytokine and chemokine mRNA and secretion of tumor necrosis factor-α by gallbladder epithelial cells: Response to bacterial lipopolysaccharides

BACKGROUND: In addition to immune cells, many other cell types are known to produce cytokines. Cultured normal mouse gallbladder epithelial cells, used as a model system for gallbladder epithelium, were examined for their ability to express the mRNA of various cytokines and chemokines in response to bacterial lipopolysaccharide. The synthesis and secretion of the tumor necrosis factor-α (TNF-α) protein by these cells was also measured. RESULTS: Untreated mouse gallbladder cells expressed mRNA for TNF-α, RANTES, and macrophage inflammatory protein-2 (MIP-2). Upon treatment with lipopolysaccharide, these cells now produced mRNA for Interleukin-1β (IL-1β), IL-6, monocyte chemoattractant protein-1 (MCP-1), and showed increased expression of TNF-α and MIP-2 mRNA. Untreated mouse gallbladder cells did not synthesize TNF-α protein; however, they did synthesize and secrete TNF-α upon treatment with lipopolysaccharide. METHODS: Cells were treated with lipopolysaccharides from 3 strains of bacteria. Qualitative and semi-quantitative RT-PCR, using cytokine or chemokine-specific primers, was used to measure mRNA levels of TNFα, IL-1β, IL-6, IL-10, KC, RANTES, MCP-1, and MIP-2. TNF-α protein was measured by immunoassays. CONCLUSION: This research demonstrates that gallbladder epithelial cells in response to lipopolysaccharide exposure can alter their cytokine and chemokine RNA expression pattern and can synthesize and secrete TNFα protein. This suggests a mechanism whereby gallbladder epithelial cells in vivo may mediate gallbladder secretory function, inflammation and diseases in an autocrine/paracrine fashion by producing and secreting cytokines and/or chemokines during sepsis