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1.
Sensors (Basel) ; 24(1)2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-38202949

RESUMEN

With the flourishing development of the Internet of Things (IoT), federated learning has garnered significant attention as a distributed learning method aimed at preserving the privacy of participant data. However, certain IoT devices, such as sensors, face challenges in effectively employing conventional federated learning approaches due to limited computational and storage resources, which hinder their ability to train complex local models. Additionally, in IoT environments, devices often face problems of data heterogeneity and uneven benefit distribution between them. To address these challenges, a personalized and fair split learning framework is proposed for resource-constrained clients. This framework first adopts a U-shaped structure, dividing the model to enable resource-constrained clients to offload subsets of the foundational model to a central server while retaining personalized model subsets locally to meet the specific personalized requirements of different clients. Furthermore, to ensure fair benefit distribution, a model-aggregation method with optimized aggregation weights is used. This method reasonably allocates model-aggregation weights based on the contributions of clients, thereby achieving collaborative fairness. Experimental results demonstrate that, in three distinct data heterogeneity scenarios, employing personalized training through this framework exhibits higher accuracy compared to existing baseline methods. Simultaneously, the framework ensures collaborative fairness, fostering a more balanced and sustainable cooperation among IoT devices.

2.
Sensors (Basel) ; 21(19)2021 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-34640995

RESUMEN

Stepped-frequency waveform may be used to synthesize a wideband signal with several narrow-band pulses and achieve a high-resolution range profile without increasing the instantaneous bandwidth. Nevertheless, the conventional stepped-frequency waveform is Doppler sensitive, which greatly limits its application to moving targets. For this reason, this paper proposes a waveform design method using a staggered pulse repetition frequency to improve the Doppler tolerance effectively. First, a generalized echo model of the stepped-frequency waveform is constructed in order to analyze the Doppler sensitivity. Then, waveform design is carried out in the stepped-frequency waveform by using a staggered pulse repetition frequency so as to eliminate the high-order phase component that is caused by the target's velocity. Further, the waveform design method is extended to the sparse stepped-frequency waveform, and we also propose corresponding methods for high-resolution range profile synthesis and motion compensation. Finally, experiments with electromagnetic data verify the high Doppler tolerance of the proposed waveform.

3.
Environ Sci Technol ; 49(18): 10945-50, 2015 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-26301518

RESUMEN

The concentrations and formation pathways of mono- to octa-chlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) were investigated in main organochemical industries. High levels of PCDDs and PCDFs were detected. The total concentrations of 27 PCDD/F congeners in chloranil, 2,4-D, and 1,4-dichlorobenzene were 5302397 ± 8944449, 20963 ± 15908, and 242 ± 67 pg g(-1), respectively, and the less-chlorinated PCDD/F levels were 12006 ± 20155, 9536 ± 5594, and 195 ± 94 pg g(-1), respectively. The distribution trends of less and more chlorinated PCDD/Fs were similar in different chemical plants because of their similar formation pathways, which may also be related to the degree of chlorination of chemical products and purification processes. 1,2,3,4-TeCDF and 2,4,8-TrCDF were selected as model molecules to calculate the bond dissociation energy, showing that 2-MCDF, 3-MCDF, and 2,8-DCDF are more easily formatted as shown by the analytical results. The formation pathways of less to more chlorinated PCDFs are proposed to explain why 2-MoCDF, 2,8-DiCDF, 2,4,8-TrCDF, and 2,3,4,7,8-PeCDF are the dominant congeners and to explain why 2,3,4,7,8-PeCDF is the largest contributor of I-TEQs in most studies.


Asunto(s)
Benzofuranos/síntesis química , Industrias , Dibenzodioxinas Policloradas/análogos & derivados , Halogenación , Dibenzodioxinas Policloradas/síntesis química , Termodinámica
4.
PLoS One ; 19(4): e0302176, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635601

RESUMEN

As one of the key materials used in the civil engineering industry, concrete has a global annual consumption of approximately 10 billion tons. Cement and fine aggregate are the main raw materials of concrete, and their production causes certain harm to the environment. As one of the countries with the largest production of industrial solid waste, China needs to handle solid waste properly. Researchers have proposed to use them as raw materials for concrete. In this paper, the effects of different lithium slag (LS) contents (0%, 10%, 20%, 40%) and different substitution rates of recycled fine aggregates (RFA) (0%, 10%, 20%, 30%) on the axial compressive strength and stress-strain curve of concrete are discussed. The results show that the axial compressive strength, elastic modulus, and peak strain of concrete can increase first and then decrease when LS is added, and the optimal is reached when the LS content is 20%. With the increase of the substitution rate of RFA, the axial compressive strength and elastic modulus of concrete decrease, but the peak strain increases. The appropriate amount of LS can make up for the mechanical defects caused by the addition of RFA to concrete. Based on the test data, the stress-strain curve relationship of lithium slag recycled fine aggregate concrete is proposed, which has a high degree of agreement compared with the test results, which can provide a reference for practical engineering applications. In this study, LS and RFA are innovatively applied to concrete, which provides a new way for the harmless utilization of solid waste and is of great significance for the control of environmental pollution and resource reuse.


Asunto(s)
Administración de Residuos , Administración de Residuos/métodos , Litio , Residuos Sólidos , Materiales de Construcción , Reciclaje/métodos , Residuos Industriales/análisis
5.
Artículo en Inglés | MEDLINE | ID: mdl-24427038

RESUMEN

In the title compound, C18H28O8, the five-membered ring with one O atom attached to the ethyl substituent has a twisted conformation about the C-O bond. The adjacent cis-fused ring with two O atoms also has a twisted conformation about one of the C-O bonds. The dihedral angle between these rings (all atoms) is 59.05 (12)°. The five-membered ring linked to the ethynyl susbtituent is twisted about a C-C bond; the cis-fused adjacent ring is twisted about a C-O bond [dihedral angle between the rings (all atoms) = 71.78 (12)°]. Two intra-molecular O-H⋯O hydrogen bonds occur. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, generating [001] chains.

6.
Ann Hepatol ; 11(3): 311-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22481448

RESUMEN

BACKGROUND AND AIMS: Effective assessing the prognosis of patients with end-stage liver disease is always challenging. This study aimed to investigate the accuracy of different models in predicting short-term prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). MATERIAL AND METHODS: We retrospectively evaluated survival of a cohort of patients with at least 3-month follow up. The receiver-operating-characteristic curves (ROC) were drawn for Child-Turcotte-Pugh (CTP) classification, King's College Hospital (KCH) criteria, model for end-stage liver disease (MELD), MELD combined with serum sodium (Na) concentration (MELDNa), integrated MELD (iMELD) and logistic regression model (LRM). RESULTS: Of the 273 eligible patients, 152 patients (55.7%) died within 3-month follow up. In cirrhotic patients (n = 101), the AUCs of LRM (0.851), MELDNa (0.849), iMELD (0.845) and MELD (0.840) were all significantly higher than those of KCH criteria (0.642) and CTP (0.625) (all p < 0.05), while the differences among LRM, MELD, MELDNa and iMELD were not significant, and the most predictive cutoff value was 0.5176 for LRM, 30 for MELDNa, 47.87 for iMELD and 29 for MELD, respectively. In non-cirrhotic patients (n = 172), the AUC of LRM (0.897) was significantly higher than that of MELDNa (0.776), iMELD (0.768), MELD (0.758), KCH criteria (0.647) and CTP (0.629), respectively (all p < 0.05), and the most predictive cutoff value for LRM was -0.3264. CONCLUSIONS: LRM, MELD, MELDNa and iMELD are with similar accuracy in predicting the shortterm prognosis of HBV-ACLF patients with liver cirrhosis, while LRM is superior to MELD, MELDNa and iMELD in predicting the short-term prognosis of HBV-ACLF patients without liver cirrhosis.


Asunto(s)
Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/virología , Virus de la Hepatitis B , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/virología , Modelos Logísticos , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hepatitis B/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Análisis de Regresión , Estudios Retrospectivos , Sodio/sangre , Adulto Joven
7.
Materials (Basel) ; 15(4)2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-35207815

RESUMEN

The present work demonstrated the first-ever preparation of block specimens by the microwave sintering of H13 alloy powder. Varying proportions of vanadium powder (1.5%, 2.5%, 3.5%, 4.5%, and 5.5% on a mass basis) were added to H13 mold steel and these mixtures were sintered using microwaves. X-ray fluorescence spectroscopy was employed to determine the compositions of the resulting specimens and vanadium percentages of 1.56%, 2.04%, 3.10%, 4.06%, and 4.20% were determined. These results demonstrate a clear trend, with significantly lower vanadium amounts than expected based on the nominal values at higher vanadium loadings. Different samples were also found to exhibit different degrees of ablation, and this effect was related to the presence of voids in the materials. The surface compositions of these specimens were examined by laser-induced breakdown spectroscopy and were found to be relatively uniform. The microstructures as well as the hardness properties of the materials were assessed. Microwave sintering of 100 g specimens at 1300 °C for 10-min generated samples with hardness values ranging from 205 HV (at the lowest vanadium content) to 175.2 HV (at the highest vanadium content). The wear behavior of samples prepared by microwave sintering H13 die steel with different vanadium contents at room temperature has been studied. The results showed that 1.5% vanadium content is the best mass ratio.

8.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 7): o1673, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21837072

RESUMEN

The title compound, C(10)H(15)NO(7), consists of one methyl-enedi-oxy ring and two fused tetra-hydro-furan rings. The three fused rings exhibit cis arrangements at the ring junctions. One O atom of a tetra-hydro-furan ring and the H atoms bound to the neighboring C atoms are disordered over two orientations with site-occupancy factors of 0.69 (1) and 0.31 (1). intra-molecular O-H⋯O and C-H⋯O inter-actions stabilize the mol-ecular conformation. In the crystal structure, inter-molecular O-H⋯O and C-H⋯O inter-actions link the mol-ecules into a three-dimensional network.

9.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 7): o1800, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21837173

RESUMEN

The title compound, C(23)H(22)O(8), is a binary benzoyl ester whose nucleus consists of a fused system made up of a methyl-enedi-oxy ring and two tetra-hydro-furan rings. One of the benzoyl ester groups is attached at the junction of the two tetra-hydro-furan rings. The other is attached to the outer tetra-furan ring. Both the benzoyl ester groups are in an axial conformation with respect to the outer tetrhydro-furan ring. In the crystal, mol-ecules are linked by two weak C-H⋯O hydrogen bonds, forming a chain running parallel to the a axis.

10.
Materials (Basel) ; 14(17)2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34500989

RESUMEN

This study investigated the effects of microwave sintering on the microstructures and properties of copper-rGO composites. Graphene oxide was coated onto copper particles by wet ball milling, and copper-rGO composites were formed upon microwave sintering in an argon atmosphere. Scanning electron microscopy was then used to observe the mixing in the ball-milled composite powder, and the morphology of the bulk composite after microwave sintering. Raman spectra revealed how graphene oxide changed with ball milling and with microwave sintering. The microhardness, electrical conductivity, and thermal conductivity of the composite were also measured. The results showed that graphene oxide and copper particles were well combined and uniformly distributed after wet ball milling. The overall microhardness of microwave-sintered samples was 81.1 HV, which was 14.2% greater than that of pure copper (71 HV). After microwave sintering, the microhardness of the samples in areas showing copper oxide precipitates with eutectic structures was 89.5 HV, whereas the microhardness of the precipitate-free areas was 70.6 HV. The electrical conductivity of the samples was 87.10 IACS%, and their thermal conductivity was 391.62 W·m-1·K-1.

11.
Peptides ; 144: 170613, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34314760

RESUMEN

To evaluate the role of ghrelin in cardiac fibrosis after myocardial infarction (MI) and to investigate the underlying mechanisms of ghrelin-regulated Nrf2/NADPH/ROS pathway-mediated cardioprotection, the profile of Nrf2, fibrosis markers, and oxidative stress markers were characterized in a rat model of MI and Angiotensin II (Ang II)-stimulated cardiac fibroblasts (CFs). The effects of ghrelin on cardiac function, fibrosis and oxidative stress were investigated after MI in vivo. The role of ghrelin in CF migration and proliferation was evaluated in Ang II-stimulated CFs in vitro. Inhibition of ghrelin receptors using the antagonist, d-Lys3-GHRP-6, in addition to ghrelin was employed in MI and CFs to investigate the direct effect of ghrelin on cardiac fibrosis. Loss function of Nrf2 in CFs was performed to investigate the effect of ghrelin-regulated Nrf2 on oxidative stress and cardiac fibrosis. Ghrelin improved the post-MI cardiac function and reduced cardiac fibrosis. This phenotype is associated with the upregulation of Nrf2 and downregulation of fibrotic proteins, NADPH oxidase and ROS production. In line with in vivo findings, ghrelin attenuated Ang II-stimulated CF migration, proliferation, and oxidative stress in vitro. Inhibition of the ghrelin receptor or knockdown of Nrf2 abolished the beneficial effects of ghrelin on MI or Ang II-stimulated cardiac fibroblasts. In conclusion, ghrelin ameliorates post-MI and Ang II-induced cardiac fibrosis by activating Nrf2, which in turn inhibits the NADPH/ROS pathway.


Asunto(s)
Ghrelina/farmacología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Animales , Cardiotónicos/farmacología , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Colágeno/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibrosis , Masculino , Malondialdehído/sangre , Miocardio/metabolismo , Miocardio/patología , NADP/metabolismo , NADPH Oxidasas/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Péptido Natriurético Encefálico/sangre , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo
12.
Front Med (Lausanne) ; 8: 717125, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34527683

RESUMEN

ALT is one of the most sensitive biochemical indexes to reflect liver injury. It is generally believed that hepatitis B virus (HBV) infected patients with normal ALT levels are in either immune tolerance or low replication stage of the natural history of hepatitis B, and there is no or only mild inflammation in liver tissue, so antiviral therapy is not recommended. However, chronic HBV-infected patients with normal ALT levels are not always in a stable state. A considerable number of patients will develop active hepatitis or occult progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, whether antiviral therapy should be recommended for chronic HBV infection with normal ALT level has been a hot topic in clinical practice. In this paper, the definition of immune tolerance, the relationship between ALT and liver inflammation, and the benefits of antiviral therapy were reviewed, and we hope it will be helpful for clinicians to have a deeper understanding of whether antiviral therapy should be considered for chronic HBV infection with normal ALT.

13.
Mol Membr Biol ; 26(5): 321-32, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19626554

RESUMEN

To date there are few compounds known to pharmacologically discriminate between alpha1 and alpha3 subunit-containing glycine receptors (GlyRs). The present study stemmed from an observation that the glycinergic agonists, taurine and beta-alanine, act with much lower agonist efficacy at alpha3 GlyRs than at alpha1 GlyRs. We sought to understand the structural basis of this difference to provide insights relevant to the development of alpha3-specific modulators as leads for the development of new anti-inflammatory analgesics. Using chimeras of alpha1 and alpha3 subunits, we identified the structurally divergent M4 transmembrane segment and C-terminal tail as a specific determinant of the efficacy difference. Because mutation of individual non-conserved M4 residues had little influence on agonist efficacies, the reduced agonist efficacy at alpha3 GlyRs is most likely a distributed effect of all non-conserved M4 residues. Given the lack of contact between M4 and other transmembrane segments, the efficacy differences are probably mediated by differential interactions with the surrounding lipid environment. This may explain why GlyR agonist efficacies differ among expression systems where membrane lipid composition is not conserved. It may also explain why GlyR agonist efficacy increases at high expression densities, as this would increase the propensity of receptors to cluster thereby inducing M4 segments of neighboring receptors to interact. This strong influence of M4 primary structure on partial agonist efficacy suggests that the relatively poorly conserved alpha3 GlyR M4 segment may be a promising domain to target in the search for alpha3 GlyR-specific modulators.


Asunto(s)
Receptores de Glicina/agonistas , Secuencia de Aminoácidos , Animales , Humanos , Datos de Secuencia Molecular , Mutación , Oocitos/metabolismo , Estructura Terciaria de Proteína , Subunidades de Proteína , Ratas , Receptores de Glicina/química , Receptores de Glicina/genética , Receptores de Glicina/metabolismo , Alineación de Secuencia , Relación Estructura-Actividad , Taurina/metabolismo , Xenopus , beta-Alanina/metabolismo
14.
Sci Rep ; 10(1): 18836, 2020 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-33139739

RESUMEN

Based on Navier-Stokes equations, a numerical model for studying the dynamic responses and mooring forces of the moored Submerged Floating Tunnel (SFT) driven by surface waves is presented in this paper. The mechanics models of the vertically and inclinedly moored floating body under wave forces are built, and the overset meshing method is employed to dynamically configure the computational meshes. Two laboratory experiments are used for validating the numerical model in terms of motion responses and mooring forces of the SFT, indicating the proposed model is capable of accurately simulating the instantaneous position of the body under the wave action. This hydrodynamic model is then utilized to simulate the wave-structure interaction of the prototype SFT designed for Qiongzhou Strait located between Mainland China and Hainan Island. The effects of the fundamental structure parameter, or the inclined mooring angle (IMA), on the dynamic responses of SFT are analyzed. The numerical experiments not only shed light on the mooring forces, as well as pitch, sway and heave responses of the SFT with various values of IMA, but also provide guidance for the choice of IMA in engineering design. The range of IMA is separated into five zones, and Zone 2 is regarded as the best choice for the design of IMA for both motion displacements and mooring forces are relatively small in this zone. Zone 3 is considered to be the worst choice as not only are motion responses of SFT severe in this zone, but also the mooring chains are at the risk of going slack under severe wave conditions.

15.
Medicine (Baltimore) ; 99(43): e22726, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33120769

RESUMEN

Several new, pangenotypic direct-acting antiviral agents (DAAs) have been approved, may reduce the need for genotyping to guide therapy decisions for patients with chronic hepatitis C (CHC).This study aimed to investigate the efficacy and safety of Sofosbuvir (SOF)-based pangenotypic DAAs therapy for CHC patients without genotype (GT determination in the real-world practice.This retrospective cohort study included treatment-naïve CHC patients without GT determination, who received SOF-based DAAs therapy, including 400 mg SOF plus 60 mg daclatasvir (DCV) daily or 400 mg SOF plus 100 mg velpatasvir (VEL) daily for 12 or 24 weeks. Clinical and laboratory data, including sustained virologic response (SVR), were obtained at baseline, end of treatment (EOT), 12 weeks after EOT, and 48 weeks after EOT.A total of 95 CHC patients, including 30 (31.58%) had liver cirrhosis were enrolled. SVR rates after 12 weeks of treatment (SVR12) was 96.84% (92/95), including 96.20% (76/79) of patients receiving SOF plus DCV and 100% (16/16) of patients receiving SOF plus VEL. For 92 patients achieving an SVR12, no virological relapse was observed at 48 weeks after EOT. Furthermore, serum evaluation of liver fibrosis aspartate aminotransferase-to-platelet ratio index and Fibrosis-4 score were decreased significantly at EOT and 12 weeks after EOT, compared to pre-treatment values (both P < .05). Treatment was well-tolerated by our patients.SOF-based pangenotypic DAAs including SOF plus DCV and SOF plus VEL, were effective and safe for CHC patients without GT determination in this study. This may provide a potential simple strategy for CHC treatment without GT determination.


Asunto(s)
Antivirales/uso terapéutico , Carbamatos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Imidazoles/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Anciano , Estudios de Cohortes , Femenino , Genotipo , Hepacivirus/genética , Humanos , Masculino , Persona de Mediana Edad , Pirrolidinas , Estudios Retrospectivos , Resultado del Tratamiento , Valina/análogos & derivados , Adulto Joven
16.
Adv Mater ; 32(32): e1906129, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32583916

RESUMEN

With developments in materials, thin-film processing, fine-tuning of morphology, and optimization of device fabrication, the performance of organic solar cells (OSCs) has improved markedly in recent years. Designing low-bandgap materials has been a focus in order to maximize solar energy conversion. However, there are only a few successful low-bandgap donor materials developed with near-infrared (NIR) absorption that are well matched to the existing efficient acceptors. Porphyrin has shown great potential as a useful building block for constructing low-bandgap donor materials due to its large conjugated plane and strong absorption. Porphyrin-based donor materials have been shown to contribute to many record-high device efficiencies in small molecule, tandem, ternary, flexible, and OSC/perovskite hybrid solar cells. Specifically, non-fullerene small-molecule solar cells have recently shown a high power conversion efficiency of 12% using low-bandgap porphyrin. All these have validated the great potential of porphyrin derivatives as effective donor materials and made DPPEZnP-TRs a family of best low-bandgap donor materials in the OSC field so far. Here, recent progress in the rational design, morphology, dynamics, and multi-functional applications starting from 2015 will be highlighted to deepen understanding of the structure-property relationship. Finally, some future directions of porphyrin-based OSCs are presented.

17.
J Neurochem ; 110(5): 1685-94, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19619142

RESUMEN

beta-Carbolines are potent modulators of GABA type A receptors and they have recently been shown to inhibit glycine receptors in a subunit-specific manner. The present study screened four structurally similar beta-carbolines, 1,2,3,4-tetrahydronorharmane, norharmane, harmane and 6-methoxyharmalan, at recombinantly expressed alpha1, alpha1beta, alpha2 and alpha3 glycine receptors with the aims of identifying structural elements of both the receptor and the compounds that are important for binding and subunit specificity. The four compounds exhibited only weak subunit specificity, rendering them unsuitable as pharmacological probes. Because they displayed competitive antagonist activity, we investigated the roles of known glycine binding residues in coordinating the four compounds. The structural similarity of the compounds, coupled with the differential effects of C-loop mutations (T204A, F207Y) on compound potency, implied direct interactions between variable beta-carboline groups and mutated residues. Mutant cycle analysis employing harmane and norharmane revealed a strong pairwise interaction between the harmane methyl group and the C-loop in the region T204 and F207. These results which define the orientation of the bound beta-carbolines were supported by molecular docking simulations. The information may also be relevant to understanding the mechanism beta-carboline of binding to GABA type A receptors where they are potent pharmacological probes.


Asunto(s)
Carbolinas/metabolismo , Carbolinas/farmacología , Receptores de Glicina/antagonistas & inhibidores , Receptores de Glicina/metabolismo , Sitios de Unión , Carbolinas/química , Línea Celular , Harmina/análogos & derivados , Harmina/química , Harmina/metabolismo , Humanos , Mutagénesis Sitio-Dirigida , Mutación , Estructura Secundaria de Proteína , Subunidades de Proteína/antagonistas & inhibidores , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Receptores de Glicina/genética , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
18.
Neuropharmacology ; 56(1): 318-27, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18657556

RESUMEN

The dihydropyridines (DHPs), nifedipine and nicardipine, modulate native glycine receptors (GlyRs) at micromolar concentrations. Nicardipine has a biphasic potentiating and inhibitory effect, whereas nifedipine causes inhibition only. The present study sought to investigate (1) the molecular mechanism by which these compounds inhibit recombinant GlyRs, and (2) their potential utility as subunit-selective inhibitors of alpha1, alpha1beta, alpha3 and alpha3beta GlyRs. The rate of onset of inhibition in the open state was accelerated by pre-application of DHP in the closed state, with the degree of acceleration proportional to the concentration of pre-applied DHP. This implies a non-inhibitory binding site close to the DHP inhibitory site. DHP inhibition was use-dependent and independent of glycine concentration, consistent with a pore-blocking mode of action. DHP sensitivity was abolished by the G2'A mutation, providing a strong case for a DHP binding site in the pore. Nifedipine exhibited an approximately 10-fold higher inhibitory potency at alpha1-containing relative to alpha3-containing receptors, whereas nicardipine was only weakly selective for alpha1-containing GlyRs. The differential sensitivities of nifedipine and nicardipine for different GlyR isoforms suggest that DHPs may be a useful resource to screen as pharmacological tools for selectively inhibiting different synaptic GlyR isoforms.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Dihidropiridinas/farmacología , Subunidades de Proteína/química , Subunidades de Proteína/fisiología , Receptores de Glicina/química , Receptores de Glicina/fisiología , Secuencia de Aminoácidos , Análisis de Varianza , Sitios de Unión/efectos de los fármacos , Sitios de Unión/genética , Fenómenos Biofísicos , Línea Celular Transformada , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Antagonistas del GABA/farmacología , Humanos , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/genética , Modelos Moleculares , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida/métodos , Técnicas de Placa-Clamp , Picrotoxina/análogos & derivados , Picrotoxina/farmacología , Subunidades de Proteína/genética , Receptores de Glicina/genética , Sesterterpenos , Relación Estructura-Actividad
19.
Neurosci Lett ; 435(2): 147-51, 2008 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-18329806

RESUMEN

Bilobalide, a major bioactive component of Ginkgo biloba herbal extracts, exhibits neuroprotective and anti-ischaemic activity. However, its therapeutic potential is limited because of its instability. Attempts to synthesise a more stable analogue culminated in the development of NV-31. This compound recapitulates some aspects of bilobalide pharmacology. However, although bilobalide inhibits recombinant glycine receptor Cl channels (GlyRs), NV-31 potentiates hippocampal neuron GlyRs. Because of the possible therapeutic relevance of this effect, the present study investigated the molecular mechanism and subunit specificity of NV-31 actions at recombinantly expressed alpha1, alpha1beta, alpha2 and alpha3 GlyRs. NV-31 potentiated alpha1 GlyRs by approximately 135% with an EC50 near 170 nM. Its potentiating effect was observed only at low (EC10) glycine concentrations. The magnitude of its potentiating effect was reduced at alpha1beta GlyRs and it had no effect at all at alpha2 and alpha3 GlyRs. NV-31 was unlikely to bind at the bilobalide pore-binding site as its efficacy was not affected by the alpha1 subunit G2'A and T6'S mutations. However, the S15'C mutation to the alcohol-binding site abolished its effects, suggesting that NV-31 modulates the GlyR via a specific (steric or allosteric) interaction with S15'. GlyRs are potential therapeutic targets for chronic anti-inflammatory pain and movement disorders. NV-31, as a positive modulator of these receptors, thus remains viable as a therapeutic candidate for these disorders.


Asunto(s)
Bilobálidos/farmacología , Ginkgo biloba/química , Subunidades de Proteína/metabolismo , Piranos/farmacología , Receptores de Glicina/agonistas , Bilobálidos/química , Línea Celular Transformada , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Estimulación Eléctrica/métodos , Antagonistas del GABA/farmacología , Glicina/farmacología , Humanos , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Potenciales de la Membrana/efectos de la radiación , Mutación/fisiología , Técnicas de Placa-Clamp , Picrotoxina/farmacología , Subunidades de Proteína/genética , Receptores de Glicina/genética , Transfección/métodos
20.
ACS Appl Mater Interfaces ; 10(1): 668-675, 2018 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-29241328

RESUMEN

Small molecules (SMs) with elongated backbones are promising for achieving a higher photovoltaic performance. Herein, a dimeric porphyrin small molecule, ZnP2-DPP, consisting of two porphyrin units linked with an ethynylene as the core and two diketopyrrolopyrrole (DPP) units as the arms is designed and synthesized as an electron donor for solution-processed bulk-heterojunction (BHJ) organic solar cells (OSCs). A significantly enhanced power conversion efficiency of 8.45% with an impressive short-circuit current density (Jsc) up to 19.65 mA cm-2 is achieved for the BHJ OSCs based on ZnP2-DPP under AM 1.5G irradiation (100 mW cm-2) compared to that for the OSCs based on the dimeric porphyrin linked with bis-ethynylenes reported previously. Furthermore, the devices show broad photoelectron responses up to 1000 nm with high near-infrared external quantum efficiency up to 66% at 780 nm. This is the first study reporting SM OSCs displaying such a large Jsc of about 20 mA cm-2 simultaneously with a considerably high and deep photoelectron response of up to 1000 nm.

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