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1.
Analyst ; 147(12): 2843-2850, 2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35621375

RESUMEN

Raman spectroscopy is a powerful method for estimating the molecular structure of a target that can be adapted for biomedical analysis given its non-destructive nature. Inflammatory skin diseases impair the skin's barrier function and interfere with the patient's quality of life. There are limited methods for non-invasive and objective assessment of skin inflammation. We examined whether Raman spectroscopy can be used to predict skin inflammation with high sensitivity and specificity when combined with artificial intelligence (AI) analysis. Inflammation was chemically induced in mouse ears, and Raman spectra induced by a 785 nm laser were recorded. A principal component (PC) analysis of the Raman spectra was performed to extract PCs with the highest percentage of variance and to estimate the statistical score. The accuracy in predicting inflammation based on the Raman spectra with or without AI analysis was assessed using receiver operating characteristic (ROC) curves. We observed some typical changes in the Raman spectra upon skin inflammation, which may have resulted from vasodilation and interstitial oedema. The estimated statistical scores based on spectral changes correlated with the histopathological changes in the skin. The ROC curve based on PC2, which appeared to include some spectral features, revealed a maximum accuracy rate of 80.0% with an area under the curve (AUC) of 0.864. The AI analysis improved the accuracy rate to 93.1% with an AUC of 0.972. The current findings demonstrate that the combination of Raman spectroscopy with near-infrared excitation and AI analysis can provide highly accurate information on the pathology of skin inflammation.


Asunto(s)
Inteligencia Artificial , Espectrometría Raman , Animales , Modelos Animales de Enfermedad , Inflamación/inducido químicamente , Inflamación/diagnóstico , Ratones , Análisis de Componente Principal , Calidad de Vida , Espectrometría Raman/métodos
2.
Blood Purif ; 51(10): 831-839, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35021168

RESUMEN

INTRODUCTION: Ultrapurification of dialysis fluid has enabled highly efficient dialysis treatments. Online hemodiafiltration is one such treatment that uses a purified dialysis fluid as a supplemental fluid. In this method, an endotoxin retentive filter (ETRF) is used in the final step of dialysis fluid purification, with the aim of preventing leakage of endotoxins. Sodium hypochlorite and peracetic acid are used as disinfecting agents for the dialysis fluid pipes containing the ETRF; however, the effects of these agents on ETRF membrane pores have not been fully clarified. METHODS: Water permeability (flux) and endotoxin permeability were assessed in 3 types of ETRFs made with different membrane materials: polyester polymer alloy (PEPA), polyether sulfone (PES), and polysulfone (PS). High-concentration sodium hypochlorite and 2 types of peracetic acid were used as disinfecting agents, and the changes in flux and the endotoxin sieving coefficient (SC) were measured. RESULTS: After repeated use of high concentrations of sodium hypochlorite and peracetic acid, the PEPA and PES ETRFs did not permit passage of endotoxins, regardless of their flux. However, in the PS ETRF, the flux and endotoxin SC increased with the number of cleaning cycles. No differences were observed according to the concentration of peracetic acid disinfecting agents. CONCLUSION: PEPA and PES ETRFs completely prevent endotoxin leakage and can be disinfected at concentrations higher than the conventionally recommended concentration without affecting pore expansion. Even new PS ETRFs have low levels of endotoxin leakage, which increase after disinfection cycles using sodium hypochlorite and peracetic acid.


Asunto(s)
Endotoxinas , Hipoclorito de Sodio , Aleaciones , Soluciones para Diálisis , Humanos , Membranas Artificiales , Ácido Peracético , Poliésteres , Polímeros , Diálisis Renal , Sulfonas , Agua
3.
Phys Rev Lett ; 121(8): 087202, 2018 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-30192624

RESUMEN

Using an intense negative muon (µ^{-}) source, we have studied the internal magnetic fields in a powder sample of magnesium hydride (MgH_{2}). By extracting the signal from the µ^{-} captured on Mg nuclei, we found that the negative muon spin rotation and relaxation (µ^{-}SR) spectra clearly showed a Kubo-Toyabe-type relaxation, which indicates a random magnetic field at the Mg site. The field distribution width obtained is very consistent with the predicted value at the Mg site estimated by dipole field calculations, supporting our claim to have observed the nuclear magnetic fields of hydrogens in MgH_{2}. As is the case with µ^{+}SR, µ^{-}SR promises to soon be an indispensable tool for materials analyses.

4.
Phys Chem Chem Phys ; 19(29): 19058-19066, 2017 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-28702527

RESUMEN

In order to study a diffusive behavior of Li+ in Li intercalated graphites, we have measured muon spin relaxation (µ+SR) spectra for C6Li and C12Li synthesized with an electrochemical reaction between Li and graphite in a Li-ion battery. For both compounds, it was found that Li+ ions start to diffuse above 230 K and the diffusive behavior obeys a thermal activation process. The activation energy (Ea) for C6Li is obtained as 270(5) meV, while Ea = 170(20) meV for C12Li. Assuming a jump diffusion of Li+ in the Li layer of C6Li and C12Li, a self-diffusion coefficient DLi at 310 K was estimated as 7.6(3) × 10-11 (cm2 s-1) in C6Li and 14.6(4) × 10-11 (cm2 s-1) in C12Li.

5.
Proc Natl Acad Sci U S A ; 111(31): 11557-62, 2014 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-25049419

RESUMEN

The plant hormone auxin is a key morphogenetic signal that controls many aspects of plant growth and development. Cellular auxin levels are coordinately regulated by multiple processes, including auxin biosynthesis and the polar transport and metabolic pathways. The auxin concentration gradient determines plant organ positioning and growth responses to environmental cues. Auxin transport systems play crucial roles in the spatiotemporal regulation of the auxin gradient. This auxin gradient has been analyzed using SCF-type E3 ubiquitin-ligase complex-based auxin biosensors in synthetic auxin-responsive reporter lines. However, the contributions of auxin biosynthesis and metabolism to the auxin gradient have been largely elusive. Additionally, the available information on subcellular auxin localization is still limited. Here we designed fluorescently labeled auxin analogs that remain active for auxin transport but are inactive for auxin signaling and metabolism. Fluorescent auxin analogs enable the selective visualization of the distribution of auxin by the auxin transport system. Together with auxin biosynthesis inhibitors and an auxin biosensor, these analogs indicated a substantial contribution of local auxin biosynthesis to the formation of auxin maxima at the root apex. Moreover, fluorescent auxin analogs mainly localized to the endoplasmic reticulum in cultured cells and roots, implying the presence of a subcellular auxin gradient in the cells. Our work not only provides a useful tool for the plant chemical biology field but also demonstrates a new strategy for imaging the distribution of small-molecule hormones.


Asunto(s)
Colorantes Fluorescentes/metabolismo , Ácidos Indolacéticos/metabolismo , Arabidopsis/citología , Arabidopsis/metabolismo , Transporte Biológico , Fluorescencia , Ácidos Indolacéticos/química , Meristema/citología , Meristema/metabolismo , Raíces de Plantas/metabolismo , Transducción de Señal , Fracciones Subcelulares/metabolismo
6.
Bioorg Med Chem Lett ; 25(20): 4464-71, 2015 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-26364943

RESUMEN

Phytohormone auxin is a master regulator in plant growth and development. Regulation of cellular auxin level plays a central role in plant development. Auxin polar transport system modulates an auxin gradient that determines plant developmental process in response to environmental conditions and developmental programs. Photolabile caged auxins allow optical control of artificial auxin gradients at cellular resolution. Especially, two-photon uncaging system achieves high spatiotemporal control of photolysis reaction at two-photon cross-section. However, the development of caged versions of auxin has been limited by the instability of the caged auxins to higher plant metabolic activities. Here, we describe the synthesis and application of highly stable caged auxins, 4-methoxy-7-nitroindolinyl (MNI)-caged auxins. Natural auxin, indole 3-acetic acid, and two synthetic auxins, 1-NAA and 2,4-D were caged by MNI caging group. MNI-caged auxins showed a high stability in planta and a rapid release the original auxin when photolyzed. We demonstrated that optical control of auxin-responsive gene expression and auxin-related physiological responses by using MNI-caged auxins. We anticipate that MNI-caged auxins will be an effective tool for high-resolution control of endogenous auxin level.


Asunto(s)
Arabidopsis/química , Ácidos Indolacéticos/química , Indoles/química , Reguladores del Crecimiento de las Plantas/química , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Fotólisis , Reguladores del Crecimiento de las Plantas/metabolismo
7.
Biochem J ; 462(3): 539-46, 2014 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-24983886

RESUMEN

ent-Kaurene is a key intermediate in the biosynthesis of the plant hormone gibberellin. In ent-kaurene biosynthesis in flowering plants, two diterpene cyclases (DTCs), ent-copalyl diphosphate (ent-CDP) synthase (ent-CPS) and ent-kaurene synthase (KS), catalyse the cyclization of geranylgeranyl diphosphate to ent-CDP and ent-CDP to ent-kaurene, respectively. In contrast, the moss Physcomitrella patens has a bifunctional ent-CPS/KS (PpCPS/KS) that catalyses both cyclization reactions. To gain more insight into the functional diversity of ent-kaurene biosynthetic enzymes in land plants, we focused on DTCs in the lycophyte Selaginella moellendorffii. The present paper describes the characterization of two S. moellendorffii DTCs (SmKS and SmDTC3) in vitro. SmDTC3 converted ent-CDP into ent-16α-hydroxykaurane and also used other CDP stereoisomers as substrate. Remarkably, SmKS, which produces ent-kaurene from ent-CDP, showed similar substrate selectivity: both SmKS and SmDTC3 synthesized sandaracopimaradiene from normal CDP. Therefore, the diversity of substrate recognition among KSs from other plants was investigated. PpCPS/KS could use normal CDP and syn-CDP as well as ent-CDP as substrate. In contrast, lettuce KS showed high specificity for ent-CDP, and rice KS recognized only ent-CDP. Our studies imply that ancient KS having low substrate specificity has evolved to be specific for ent-CDP to the biosynthesis of gibberellin.


Asunto(s)
Transferasas Alquil y Aril/metabolismo , Giberelinas/biosíntesis , Proteínas de Plantas/metabolismo , Transferasas Alquil y Aril/genética , Clonación Molecular , Embryophyta/enzimología , Evolución Molecular , Resonancia Magnética Nuclear Biomolecular , Organofosfatos/metabolismo , Proteínas de Plantas/genética , Selaginellaceae/enzimología , Selaginellaceae/genética , Estereoisomerismo , Especificidad por Sustrato
8.
Chem Pharm Bull (Tokyo) ; 62(3): 267-73, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24583781

RESUMEN

Seven new cassane-type diterpenoids, echinalides A-G (1-7), were isolated from the stem of Caesalpinia echinata LAM. (Leguminosae). The structures were established on the basis of their chemical properties and spectroscopic evidence, including two dimensional (2D)-NMR analysis. These compounds were assessed for inhibitory activity against nuclear factor κB (NF-κB). Echinalides C and D, in particular, significantly inhibited NF-κB-responsive reporter gene expression at 5.0 µM, an effect almost equivalent to that of parthenolide, a known potent inhibitor of NF-κB.


Asunto(s)
Caesalpinia/química , Diterpenos/farmacología , Genes Reporteros/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Extractos Vegetales/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Expresión Génica/efectos de los fármacos , Células HeLa , Humanos , Estructura Molecular , FN-kappa B/metabolismo , Extractos Vegetales/química , Tallos de la Planta/química , Sesquiterpenos/farmacología , Relación Estructura-Actividad
9.
Phys Chem Chem Phys ; 15(25): 10402-12, 2013 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-23681365

RESUMEN

The self-diffusion coefficient of Li(+) ions (D(Li)) in the positive electrode material Li(x)(Co(1/3)Ni(1/3)Mn(1/3))O2 has been estimated by muon-spin relaxation (µ(+)SR) using powder samples with x = 1-0.49, which were prepared by an electrochemical reaction in a Li-ion battery. Here, since the implanted muons sense a slight change in the internal magnetic field due to Li-diffusion, µ(+)SR provides an intrinsic D(Li) through the temperature dependence of the nuclear field fluctuation rate (ν) [Sugiyama et al., Phys. Rev. Lett., 2009, 103, 147601]. Both D(Li) at 300 K and activation energy (E(a)) were estimated to be ∼2.9 × 10(-12) cm(2) s(-1) and 0.074 eV for the x = 1 sample, ∼11.0 × 10(-12) cm(2) s(-1) and 0.097 eV for x = 0.70, and ∼8.9 × 10(-12) cm(2) s(-1) and 0.062 eV for x = 0.49, assuming that the diffusing Li(+) ions mainly jump from a regular occupied site to a regular vacant site. The estimated D(Li) was smaller by roughly one order of magnitude than those for Li(x)CoO2 in the whole x range measured. Furthermore, by making comparison with D(Li) obtained by electrochemical measurements, the reactive surface area of the Li(x)(Co(1/3)Ni(1/3)Mn(1/3))O2 electrode in a liquid electrolyte was found to strongly depend on x particularly at x > 0.8.

10.
Chem Pharm Bull (Tokyo) ; 61(8): 816-22, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23902864

RESUMEN

Culcitiolides E-J (1-6), six new eremophilane-type sesquiterpenes, were isolated from the stem of Senecio culcitioides SCH. BIP. (Asteraceae). The structures were determined by detailed NMR spectral analysis. The inhibitory activities of these compounds against nuclear factor κB (NF-κB)-dependent gene expression were assessed. Culcitiolides E, H, and I potently inhibited NF-κB-induced gene expression at 20 µM.


Asunto(s)
FN-kappa B/antagonistas & inhibidores , Naftalenos/química , Naftalenos/farmacología , Senecio/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Células HeLa , Humanos , FN-kappa B/metabolismo , Naftalenos/aislamiento & purificación , Tallos de la Planta/química , Sesquiterpenos Policíclicos , Sesquiterpenos/aislamiento & purificación
11.
Sci Rep ; 13(1): 22082, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38086907

RESUMEN

Lithium-ion batteries (LIBs) have become essential components that power most current technologies, such as smartphones and electric vehicles, thus making various safety evaluations necessary to ensure their safe use. Among these evaluations, heating tests remain the most prominent source of safety issues. However, information on the phenomena occurring inside batteries during heating has remained inaccessible. In this study, we demonstrate the first in situ neutron imaging method to observe the internal structural deformation of LIBs during heating. We developed an airtight aluminium chamber specially designed to prevent radioactive contamination during in situ neutron imaging. We successfully observed the liquid electrolyte fluctuation inside a battery sample and the deformation of the protective plastic film upon heating up to thermal runaway. Hence, this work provides the foundation for future investigations of the internal changes induced in batteries during heating tests and experiments.

12.
J Biol Chem ; 286(50): 42840-7, 2011 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-22027823

RESUMEN

Diterpenes show diverse chemical structures and various physiological roles. The diversity of diterpene is primarily established by diterpene cyclases that catalyze a cyclization reaction to form the carbon skeleton of cyclic diterpene. Diterpene cyclases are divided into two types, monofunctional and bifunctional cyclases. Bifunctional diterpene cyclases (BDTCs) are involved in hormone and defense compound biosyntheses in bryophytes and gymnosperms, respectively. The BDTCs catalyze the successive two-step type-B (protonation-initiated cyclization) and type-A (ionization-initiated cyclization) reactions of geranylgeranyl diphosphate (GGDP). We found that the genome of a lycophyte, Selaginella moellendorffii, contains six BDTC genes with the majority being uncharacterized. The cDNA from S. moellendorffii encoding a BDTC-like enzyme, miltiradiene synthase (SmMDS), was cloned. The recombinant SmMDS converted GGDP to a diterpene hydrocarbon product with a molecular mass of 272 Da. Mutation in the type-B active motif of SmMDS abolished the cyclase activity, whereas (+)-copalyl diphosphate, the reaction intermediate from the conversion of GGDP to the hydrocarbon product, rescued the cyclase activity of the mutant to form a diterpene hydrocarbon. Another mutant lacking type-A activity accumulated copalyl diphosphate as the reaction intermediate. When the diterpene hydrocarbon was enzymatically synthesized from [U-(13)C(6)]mevalonate, all carbons were labeled with (13)C stable isotope (>99%). The fully (13)C-labeled product was subjected to (13)C-(13)C COSY NMR spectroscopic analyses. The direct carbon-carbon connectivities observed in the multidimensional NMR spectra demonstrated that the hydrocarbon product by SmMDS is miltiradiene, a putative biosynthetic precursor of tanshinone identified from the Chinese medicinal herb Salvia miltiorrhiza. Hence, SmMDS functions as a bifunctional miltiradiene synthase in S. moellendorffii. In this study, we demonstrate that one-dimensional and multidimensional (13)C NMR analyses of completely (13)C-labeled compound are powerful methods for biosynthetic studies.


Asunto(s)
Isótopos de Carbono/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Proteínas de Plantas/metabolismo , Selaginellaceae/metabolismo , Terpenos/química , Terpenos/metabolismo , Isótopos de Carbono/química , Proteínas de Plantas/genética , Fosfatos de Poliisoprenilo/metabolismo , Selaginellaceae/genética
13.
J Biol Chem ; 286(3): 2354-64, 2011 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-21084292

RESUMEN

Polar auxin movement is a primary regulator of programmed and plastic plant development. Auxin transport is highly regulated at the cellular level and is mediated by coordinated transport activity of plasma membrane-localized PIN, ABCB, and AUX1/LAX transporters. The activity of these transporters has been extensively analyzed using a combination of pharmacological inhibitors, synthetic auxins, and knock-out mutants in Arabidopsis. However, efforts to analyze auxin-dependent growth in other species that are less tractable to genetic manipulation require more selective inhibitors than are currently available. In this report, we characterize the inhibitory activity of 5-alkoxy derivatives of indole 3-acetic acid and 7-alkoxy derivatives of naphthalene 1-acetic acid, finding that the hexyloxy and benzyloxy derivatives act as potent inhibitors of auxin action in plants. These alkoxy-auxin analogs inhibit polar auxin transport and tropic responses associated with asymmetric auxin distribution in Arabidopsis and maize. The alkoxy-auxin analogs inhibit auxin transport mediated by AUX1, PIN, and ABCB proteins expressed in yeast. However, these analogs did not inhibit or activate SCF(TIR1) auxin signaling and had no effect on the subcellular trafficking of PIN proteins. Together these results indicate that alkoxy-auxins are inactive auxin analogs for auxin signaling, but are recognized by PIN, ABCB, and AUX1 auxin transport proteins. Alkoxy-auxins are powerful new tools for analyses of auxin-dependent development.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/antagonistas & inhibidores , Ácidos Indolacéticos/metabolismo , Naftalenos/farmacología , Zea mays/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Ácidos Indolacéticos/farmacología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Saccharomyces cerevisiae/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Zea mays/genética
14.
Bioorg Med Chem Lett ; 22(17): 5663-7, 2012 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-22832308

RESUMEN

Cytokinins are phytohormones that regulate diverse developmental processes throughout the life of a plant. trans-Zeatin, kinetin, benzyladenine and dihydrozeatin are adenine-type cytokinins that are perceived by the AHK cytokinin receptors. Endogenous cytokinin levels are critical for regulating plant development. To manipulate intracellular cytokinin levels, caged cytokinins were designed on the basis of the crystal structure of the AHK4 cytokinin receptor. The caged cytokinin was photolyzed to release the cytokinin molecule inside the cells and induce cytokinin-responsive gene expression. The uncaging of intracellular caged cytokinins demonstrated that cytokinin-induced root growth inhibition can be manipulated with photo-irradiation. This caged cytokinin system could be a powerful tool for cytokinin biology.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Citocininas/química , Citocininas/metabolismo , Reguladores del Crecimiento de las Plantas/química , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Proteínas Quinasas/metabolismo , Receptores de Superficie Celular/metabolismo , Arabidopsis/metabolismo , Citocininas/síntesis química , Modelos Moleculares , Fotólisis , Reguladores del Crecimiento de las Plantas/síntesis química , Raíces de Plantas/metabolismo
15.
Plant Physiol ; 153(3): 1085-97, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20488896

RESUMEN

Gibberellins (GAs) are a group of diterpene-type plant hormones biosynthesized from ent-kaurene via ent-kaurenoic acid. GAs are ubiquitously present in seed plants. The GA signal is perceived and transduced by the GID1 GA receptor/DELLA repressor pathway. The lycopod Selaginella moellendorffii biosynthesizes GA and has functional GID1-DELLA signaling components. In contrast, no GAs or functionally orthologous GID1-DELLA components have been found in the moss Physcomitrella patens. However, P. patens produces ent-kaurene, a common precursor for GAs, and possesses a functional ent-kaurene synthase, PpCPS/KS. To assess the biological role of ent-kaurene in P. patens, we generated a PpCPS/KS disruption mutant that does not accumulate ent-kaurene. Phenotypic analysis demonstrates that the mutant has a defect in the protonemal differentiation of the chloronemata to caulonemata. Gas chromatography-mass spectrometry analysis shows that P. patens produces ent-kaurenoic acid, an ent-kaurene metabolite in the GA biosynthesis pathway. The phenotypic defect of the disruptant was recovered by the application of ent-kaurene or ent-kaurenoic acid, suggesting that ent-kaurenoic acid, or a downstream metabolite, is involved in protonemal differentiation. Treatment with uniconazole, an inhibitor of ent-kaurene oxidase in GA biosynthesis, mimics the protonemal phenotypes of the PpCPS/KS mutant, which were also restored by ent-kaurenoic acid treatment. Interestingly, the GA(9) methyl ester, a fern antheridiogen, rescued the protonemal defect of the disruption mutant, while GA(3) and GA(4), both of which are active GAs in angiosperms, did not. Our results suggest that the moss P. patens utilizes a diterpene metabolite from ent-kaurene as an endogenous developmental regulator and provide insights into the evolution of GA functions in land plants.


Asunto(s)
Bryopsida/citología , Bryopsida/metabolismo , Diferenciación Celular , Giberelinas/metabolismo , Transferasas Alquil y Aril/metabolismo , Vías Biosintéticas/efectos de los fármacos , Bryopsida/enzimología , Bryopsida/genética , Diferenciación Celular/efectos de los fármacos , Ésteres/farmacología , Técnicas de Inactivación de Genes , Genes de Plantas/genética , Germinación/efectos de los fármacos , Giberelinas/química , Giberelinas/farmacología , Ácidos Indolacéticos/farmacología , Modelos Biológicos , Mutación/genética , Fenotipo , Esporas/efectos de los fármacos , Esporas/metabolismo
16.
J Nat Prod ; 74(8): 1698-706, 2011 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-21800859

RESUMEN

Arabidopsis thaliana pER8:GUS, a low-cost, highly efficient, and convenient transgenic plant system, was used to assay the estrogen-like activity of 30 traditional Chinese medicines. The MeOH extract of Caesalpinia sappan exhibited significant bioactivity in this assay, and subsequent bioactivity-guided fractionation of the extract led to the isolation of one new compound, (S)-3,7-dihydroxychroman-4-one (1), and 10 known compounds. Both the plant pER8:GUS and in vitro estrogen response element reporter assays were used to evaluate the estrogenic activity of the isolated compounds, and these two systems produced comparable results. Compounds 6, 8, and 11 showed significant estrogenic activity comparable to genistein. These active compounds were determined to be nontoxic new sources of phytoestrogens. In addition, compounds 2 and 3 inhibited ERE transcription induced by 17ß-estradiol. A docking model revealed that compounds 6, 8, and 11 showed high affinity to the estrogen receptor. The pER8:GUS reporter system was demonstrated to be a useful and effective technique in phytoestrogen discovery.


Asunto(s)
Caesalpinia/metabolismo , Cromonas/análisis , Medicamentos Herbarios Chinos/farmacología , Estrógenos/análisis , Fitoestrógenos/análisis , Arabidopsis/genética , Arabidopsis/metabolismo , Cromonas/química , Cromonas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Estradiol/farmacología , Estrógenos/farmacología , Femenino , Genisteína/farmacología , Células Hep G2 , Humanos , Modelos Moleculares , Estructura Molecular , Fitoestrógenos/química , Fitoestrógenos/farmacología , Plantas Modificadas Genéticamente/genética , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Taiwán , Madera/química
17.
Proc Natl Acad Sci U S A ; 105(14): 5632-7, 2008 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-18391211

RESUMEN

The regulation of gene expression by the hormone auxin is a crucial mechanism in plant development. We have shown that the Arabidopsis F-box protein TIR1 is a receptor for auxin, and our recent structural work has revealed the molecular mechanism of auxin perception. TIR1 is the substrate receptor of the ubiquitin-ligase complex SCF(TIR1). Auxin binding enhances the interaction between TIR1 and its substrates, the Aux/IAA repressors, thereby promoting the ubiquitination and degradation of Aux/IAAs, altering the expression of hundreds of genes. TIR1 is the prototype of a new class of hormone receptor and the first example of an SCF ubiquitin-ligase modulated by a small molecule. Here, we describe the design, synthesis, and characterization of a series of auxin agonists and antagonists. We show these molecules are specific to TIR1-mediated events in Arabidopsis, and their mode of action in binding to TIR1 is confirmed by x-ray crystallographic analysis. Further, we demonstrate the utility of these probes for the analysis of TIR1-mediated auxin signaling in the moss Physcomitrella patens. Our work not only provides a useful tool for plant chemical biology but also demonstrates an example of a specific small-molecule inhibitor of F-box protein-substrate recruitment. Substrate recognition and subsequent ubiquitination by SCF-type ubiquitin ligases are central to many cellular processes in eukaryotes, and ubiquitin-ligase function is affected in several human diseases. Our work supports the idea that it may be possible to design small-molecule agents to modulate ubiquitin-ligase function therapeutically.


Asunto(s)
Proteínas de Arabidopsis , Proteínas F-Box/metabolismo , Ácidos Indolacéticos/metabolismo , Transducción de Señal , Proteínas de Arabidopsis/agonistas , Proteínas de Arabidopsis/antagonistas & inhibidores , Proteínas de Arabidopsis/metabolismo , Bryopsida , Cristalografía por Rayos X , Proteínas F-Box/agonistas , Proteínas F-Box/antagonistas & inhibidores , Unión Proteica , Receptores de Superficie Celular/agonistas , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores de Superficie Celular/metabolismo , Especificidad por Sustrato , Ubiquitinación
18.
RSC Adv ; 11(11): 6361-6366, 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-35423138

RESUMEN

Li plating/stripping on Cu and Y2O3 (Cu + Y2O3) electrodes was examined in a super-concentrated electrolyte of lithium bis(fluorosulfonyl)amide and methylphenylamino-di(trifluoroethyl) phosphate. In principle, Li+ ions cannot intercalate into a Y2O3 crystal because its intercalation potential obtained from first-principles calculations is -1.02 V vs. Li+/Li. However, a drastic decrease in the electrode potential and a subsequent constant-potential region were observed during Li plating onto a Cu + Y2O3 electrode, suggesting that Li+ interacted with Y2O3. X-ray diffraction (XRD) patterns and X-ray absorption fine structure (XAFS) spectra of the Cu + Y2O3 electrodes after the Li plating were recorded to verify this phenomenon. The XRD and XAFS results indicated that the crystallinity of Y2O3 crystals was lowered because of attack by Li+ ions or that the Y2O3 crystal structure was broken while the +3 valence state of Y was maintained.

19.
RSC Adv ; 11(22): 13359-13365, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-35423877

RESUMEN

Lithium plating/stripping was investigated under constant current mode using a copper powder electrode in a super-concentrated electrolyte of lithium bis(fluorosulfonyl)amide (LiFSA) with methylphenylamino-di(trifluoroethyl) phosphate (PNMePh) and vinylene carbonate (VC) as additives. Typical Li plating/stripping for Cu electrodes in organic electrolytes of conventional lithium batteries proceeds at potentials of several millivolts versus a Li counter electrode. In contrast, a large overpotential of hundreds of millivolts was observed for Li plating/stripping with the super-concentrated electrolyte. When Li stripping started immediately after Li plating and with no rest time between plating and stripping, two potential plateaus, i.e., two-step Li stripping, was observed. The potential plateau for the 1st stripping step appeared at -0.2 V versus a Li metal counter electrode. The electrical capacity for the 1st stripping step was 0.04 mA h cm-2, which indicates irregular Li stripping. Two-step Li stripping was also recorded using cyclic voltammetry. The electrochemical impedance spectroscopy (EIS) studies indicated that the two-step Li stripping behaviour reflected two different solid electrolyte interphases (SEIs) on electrodeposited Li in a Cu electrode. The SEI for the 1st-step stripping was in a transition period of the SEI formation. The open circuit voltage (OCV) relaxation with an order of tens of hours was detected after Li plating and before Li stripping. The in operando EIS study suggested a decrease of the charge transfer resistance in the Cu powder electrode during the OCV relaxation. Since the capacitance for the voltage relaxation was a dozen microfarads, it had a slight contribution to the 1st-step Li stripping behaviour. The voltage relaxation indicated the possibility that it is difficult for Li ions to be electrodeposited or that the Li plating is in a quasi-stable state.

20.
ACS Nano ; 15(2): 2719-2729, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33525874

RESUMEN

Low resistance of Li-intercalated negative electrodes is important for the safe and fast charging required for large-scale batteries. Here, we demonstrated that nanosized two-dimensional crystalline aromatic dicarboxylate negative electrode materials synthesized via spray drying exhibit low internal resistances at approximately 0.7 V vs Li/Li+, while retaining flat potential profiles. The spray-dried sample with a hollow structure is crushed into nanoflakes during ink preparation for electrode coating and forms a uniform and highly dispersed electrode structure. The charge-discharge evaluation indicates that the nanoflake sample showed smaller charge-discharge polarization than the bulk sample with stable cycling characteristics, resulting in significant high-rate property enhancement. Charge-transfer resistance of the nanoflake sample exhibits the lowest value (ca. 2.2 Ω cm2) among those reported for existing intercalation electrodes (5.2 to 235 Ω cm2). In comparison of the negative electrodes, the estimated maximum current density without Li deposition (ca. 316 mA cm-2) is more than 1 order of magnitude higher than that for currently used graphite (ca. 11 mA cm-2) and is also higher than those for high-rate oxides (137-298 mA cm-2). The resistance-crystal correlation using multiple regression analysis predictions and its verification reveal that this low resistance is owing to an improved Li acceptability associated with selective structural defects induced by the loss of incorporated crystallized water during drying. The crystal plane exposed by the selective structural defects is perpendicular to electronic and ionic conduction directions inside the solid, resulting in improved kinetics. Therefore, the proposed negative electrode allows safe and fast charging, with easy scale-up and sustainable resources.

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