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1.
J Colloid Interface Sci ; 673: 9-18, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38870666

RESUMEN

Hydrogen peroxide (H2O2) emerges as a viable oxidant for fuel cells, necessitating the development of an efficient and cost-effective electrocatalyst for the hydrogen peroxide reduction reaction (HPRR). In this study, we synthesized a self-supporting, highly active HPRR electrocatalyst comprising two morphologically distinct components: CeO2-NiCo2O4 nanowires and CeO2-NiCo2O4 metal organic framework derivatives, via a two-step hydrothermal process followed by air calcination. X-ray diffraction and transmission electron microscopy analysis confirmed the presence of CeO2 and NiCo2O4, revealing the amalgamated interface between them. CeO2 exhibits multifunctionality in regulating the surface electronic configuration of NiCo2O4, fostering synergistic connections, and introducing oxygen deficiencies to enhance the catalytic efficacy in HPRR. Electrochemical measurements demonstrate a reduction current density of 789.9 mA·cm-2 at -0.8 V vs. Ag/AgCl. The assembly of direct borohydride-hydrogen peroxide fuel cell (DBHPFC) exhibits a peak power density of 45.2 mW·cm-2, demonstrating durable stability over a continuous operation period of 120 h. This investigation providing evidence that the fabrication of heterostructured catalysts based on CeO2 for HPRR is a viable approach for the development of high-efficiency electrocatalysts in fuel cell technology.

2.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(6): 612-616, 2023 Nov 30.
Artículo en Chino | MEDLINE | ID: mdl-38086716

RESUMEN

At present, most of the research on hip exoskeleton robots adopts the method of decoupling analysis of hip joint motion, decoupling the ball pair motion of hip joint into rotational motion on sagittal plane, coronal plane and cross section, and designing it into series mechanism. Aiming at the problems of error accumulation and man-machine coupling in series mechanism, a parallel hip rehabilitation exoskeleton structure is proposed based on the bionic analysis of human hip joint. The structure model is established and the kinematics analysis is carried out. Through the OpenSim software, the curve of hip flexion and extension, adduction and abduction angle in a gait cycle is obtained. The inverse solution of the structure is obtained by the D-H coordinate system method. The gait data points are selected and compared with the inverse solution obtained by ADAMS software simulation. The results show that the inverse solution expression is correct. The parallel hip exoskeleton structure can meet the requirements of the rotation angle of the hip joint of the human body, and can basically achieve the movement of the hip joint, which is helpful to improve the human-computer interaction performance of the exoskeleton.


Asunto(s)
Dispositivo Exoesqueleto , Humanos , Articulación de la Cadera , Marcha , Fenómenos Biomecánicos , Simulación por Computador
3.
Nanomaterials (Basel) ; 13(21)2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37947675

RESUMEN

The ball milling lining board operates in a harsh environment, and the current materials fail to meet the requirements for large-sized boards due to the lack of synergistic properties between impact toughness and wear resistance. To address this issue, a low-carbon medium-chromium steel with martensite and nano residual austenite phases have been designed for future use. However, the residual austenite network could decrease the properties. Heat treatment, which includes processes like quenching and tempering, has the potential to alter the morphology and quantity of nano-scale residual austenite in the steel. In this study, the influence of heat treatment parameters on the morphologies and properties of steel has been investigated to address the wide-ranging fluctuations in impact toughness affected by nano residual austenite. Furthermore, the effect of cooling transformation on the microstructure has also been examined. The research findings indicate that modifying the quenching temperature of the steel within the range of 950-1100 °C results in a microstructure comprising martensite and nano residual austenite. At all quenching temperatures, the hardness exceeds 45 HRC, and the impact toughness shows a consistent improvement with increasing quenching temperature, indicating a modification of the nano residual austenite phase. The failure mode is primarily dimple fracture, with quasi-dissociation fracture as a secondary mode. The optimal heat treatment parameters are annealing at 930 °C, oil quenching at 1050 °C, and tempering at 250 °C. Under this condition, the steel exhibits a hardness of 51 HRC and impact toughness of 40 J/cm2 and an approximate fourfold increase compared to the untreated sample.

4.
Nanomaterials (Basel) ; 13(16)2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37630932

RESUMEN

Railway switch plates are important components in railroads, and copper-based graphite alloys have potential as substitutes for traditional materials. Graphite as an anti-friction phase could decrease both the friction coefficient and mechanical properties, with an increasing mass fraction for their poor interface bonding strength. Chromium, a multifunctional metal plated on the graphite (Cr@graphite), has solved this problem. Results have shown that a copper-based Cr@graphite alloy is composed of copper as a base, and graphite and Cr compound transition phase as reinforcements. The transition phase is made up of nano Cr3C2 and dispersed CrC, which offers a stable combination with both graphite and copper. The tribological property of copper-based graphite alloy exhibits a steadily decreasing slope with reinforcement content increasing, and the Cr@graphite samples show lower values than the alloy without any coating treatment. Both graphite and chromic oxide play role in antifriction, and are more efficient than graphite alone. Microcutting is the dominant wear method when copper-based Cr@graphite alloy has a 1~4 wt.% reinforcements content; additionally, adhesion wear and oxidation are also generated. When the anti-friction phase increases, the wear mechanism is affected, and fatigue deformation is the dominant wear method at 4~6 wt.% content. The formation of the chromic oxide phase, as well as the graphite phase, control the formation of an anti-friction layer. In that case, the tribological properties are dramatically improved with reinforcement content enhance.

5.
Prospects (Paris) ; : 1-19, 2023 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-37360046

RESUMEN

This research is based on an approach that looks at cross-cultural research design as a "lens" for a deeper understanding of what goes on in the classroom. The research question is how a cross-cultural study like this one can lead to identifying the cultural script of teaching and help educators reflect on their practice. In this context, Chinese lessons could be described as a case-based study of pedagogical reasoning that drives a shift from focusing on "content" to "competence". This article draws on qualitative data collected by the researchers and a cross-cultural analysis of a science lesson in an elementary school in Beijing, China. Using the Japanese educators' critiques and Chinese reviews, the article determines the cultural script of teaching science (the first research question) and the way Chinese teachers reflect on their practice through the Japanese lens (the second research question). This study exposes the importance of teachers' understanding and reflecting on their practice, technically, practically, and critically. The analysis results show how teachers learn to change their lenses, to reflect on their teaching and reconstruct their understanding about teacher professionalism through at least four basic elements: didactics, praxis, pedagogy, and theory.

6.
Cell Death Dis ; 13(2): 100, 2022 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-35110525

RESUMEN

Acetaminophen (APAP)-induced liver injury (AILI) is the most frequent cause of acute liver failure; but the underlying mechanisms still remain obscure. Macrophages and endoplasmic reticulum (ER) stress play an important role in the pathogenesis of AILI. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a newly identified 18-kDa soluble protein, whose expression and secretion are stimulated by ER stress. To investigate the role of myeloid cell MANF in the pathogenesis of AILI, we assayed serum and liver samples from AILI model mice and patients with drug-induced liver injury (DILI). We demonstrated that the levels of MANF were elevated in patients with DILI and in mice with AILI. Moreover, myeloid-specific MANF knockout mice were generated and used. It was observed that a delayed liver recovery from myeloid-specific MANF gene knockout mice following APAP overdose compared to that from wild-type mice. MANF deficiency in myeloid cells resulted in increased infiltrating monocyte-derived macrophages (MoMFs) but reduced restorative Ly6Clow macrophages after APAP treatment. MANF supplementation increased restorative Ly6Clow macrophages and subsequently alleviated liver injury. Moreover, MANF could enhance IL-10 expression and phagocytosis in macrophages via p38 MAPK pathway. Altogether, MANF seems to be a critical immune modulator in promoting liver repair via reducing and reprogramming MoMFs. MANF perhaps promoted the phenotype conversion of pro-inflammatory MoMFs to pro-restorative Ly6Clow MoMFs via p38 MAPK pathway, particularly through enhancing IL-10 and phagocytosis.


Asunto(s)
Acetaminofén/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Macrófagos/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Interleucina-10/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Ratones Noqueados , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Células Mieloides/metabolismo , Factores de Crecimiento Nervioso/uso terapéutico , Fagocitosis , Transducción de Señal
7.
Materials (Basel) ; 13(8)2020 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-32316102

RESUMEN

Atmospheric plasma spraying (APS) was taken to fabricate the NiCrAlY coating. The corrosion-wear properties of NiCrAlY coating was measured respectively under deionized water, artificial seawater, NaOH solution and HCl solution. Experimental results presented that the as-sprayed NiCrAlY coating consisted of Ni3Al, nickel-based solid solution, NiAl and Y2O3. In deionized water, the coating with the lowest corrosion current density (icorr) of 7.865 × 10-8 A/cm2 was hard to erode. Meanwhile, it presented a lower friction coefficient and the lowest wear rate. In HCl solution, NiCrAlY coating gave the highest corrosion current density (icorr) of 3.356 × 10-6 A/cm2 and a higher wear rate of 6.36 × 10-6 mm3/Nm. Meanwhile, the emergence of Al(OH)3 on the coating surface could reduce the direct contact between the counter ball and sample effectively, which was conducive to the lowest friction coefficient of 0.24.

8.
Nanomicro Lett ; 12(1): 13, 2019 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-34138087

RESUMEN

WC-Co alloys have enjoyed great practical significance owing to their excellent properties during the past decades. Despite the advantages, however, recently there have been concerns about the challenges associated with the use of Co, i.e. price instability, toxicity and properties degeneration, which necessitates the fabrication of binderless tungsten carbide (BTC). On the other hand, BTC or BTC composites, none of them, to date has been commercialized and produced on an industrial scale, but only used to a limited extent for specialized applications, such as mechanical seals undergoing high burthen as well as high temperature electrical contacts. There are two challenges in developing BTC: fully densifying the sintered body together with achieving a high toughness. Thus, this review applies towards comprehensively summarize the current knowledge of sintering behavior, microstructure, and mechanical properties of BTC, highlighting the densification improving strategies as well as toughening methods, so as to provide reference for those who would like to enhance the performance of BTC with better reliability advancing them to further wide applications and prepare the material in a way that is environment friendly, harmless to human health and low in production cost. This paper shows that the fabrication of highly dense and high-performance BTC is economically and technically feasible. The properties of BTC can be tailored by judiciously selecting the chemical composition coupled with taking into careful account the effects of processing techniques and parameters.

9.
J Reprod Immunol ; 123: 48-57, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28915450

RESUMEN

In addition to natural killer cells, other innate lymphoid cells have recently been identified in the mouse and human uterus, but their roles in successful pregnancy remain poorly defined. In this study, we examined the dynamic changes of uterine innate lymphoid cells throughout pregnancy in mice. We found that the total number of uterine innate lymphoid cells markedly increased at early-gestation. Among the three groups of uterine innate lymphoid cells, the number of the group 2 uterine innate lymphoid cells increased the most during pregnancy. We also determined that the depletion of uterine innate lymphoid cells in Rag1-/- mice resulted in impaired uterine spiral artery remodeling. These results suggest that uterine innate lymphoid cells may play an important role in mouse reproduction.


Asunto(s)
Endometrio/irrigación sanguínea , Proteínas de Homeodominio/genética , Linfocitos/inmunología , Embarazo/inmunología , Útero/patología , Animales , Células Cultivadas , Citocinas/metabolismo , Femenino , Viabilidad Fetal/genética , Proteínas de Homeodominio/metabolismo , Humanos , Inmunidad Innata , Depleción Linfocítica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células TH1/inmunología , Remodelación Vascular/genética
10.
Sci Rep ; 7: 46765, 2017 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-28436459

RESUMEN

Hepatic macrophages play a central role in disease pathogenesis during hepatitis B virus (HBV) infection. Our previous study found that CD205+ macrophages in the liver of hepatitis B surface antigen transgenic (HBs-Tg) mice increased significantly compared with those in wild-type mice, and these increased CD205+ macrophages were involved in CpG-oligodeoxynucleotide-induced liver injury in HBs-Tg mice. Here, we analysed the phenotype and function of CD205+ macrophages derived from the liver of HBs-Tg mice and patients with chronic hepatitis B (CHB). We found that HBs-Tg mice-derived hepatic macrophages produced larger amounts of pro-inflammatory cytokines, including IL-6, IL-12, TNF-α, and of the anti-inflammatory cytokine IL-10 after stimulation with CpG-oligodeoxynucleotides or commensal bacteria DNA than B6 mice-derived hepatic macrophages. Furthermore, hepatic CD205+ macrophages from HBs-Tg mice showed an activated phenotype and expressed higher levels of inflammatory cytokine genes, chemokine genes, and phagocytosis-related genes than hepatic CD205- macrophages. In addition, CD205+ macrophages displayed an inflammatory phenotype and were increased in the liver of patients with CHB compared with those in healthy controls. Our data suggest that hepatic CD205+ macrophages are a unique pro-inflammatory subset observed during HBV infection. Thus, development of intervention targeting these cells is warranted for immunotherapy of HBV-induced liver diseases.


Asunto(s)
Antígenos CD/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Lectinas Tipo C/inmunología , Hígado/inmunología , Macrófagos/inmunología , Antígenos de Histocompatibilidad Menor/inmunología , Receptores de Superficie Celular/inmunología , Animales , Antígenos CD/metabolismo , Citocinas/genética , Citocinas/inmunología , Citocinas/metabolismo , Femenino , Expresión Génica/genética , Expresión Génica/inmunología , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/metabolismo , Hepatitis B Crónica/virología , Humanos , Mediadores de Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Lectinas Tipo C/metabolismo , Hígado/metabolismo , Hígado/virología , Macrófagos/metabolismo , Macrófagos/virología , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor/metabolismo , Oligodesoxirribonucleótidos/inmunología , Receptores de Superficie Celular/metabolismo
11.
Microsc Microanal ; 22(1): 122-30, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26914997

RESUMEN

A novel type of alumina (Al2O3)-doped molybdenum (Mo) alloy sheet was prepared by a hydrothermal method and a subsequent powder metallurgy process. Then the characterization of α-Al2O3 was investigated using high-resolution transmission electron microscopy as the research focus. The tensile strength of the Al2O3-doped Mo sheet is 43-85% higher than that of the pure Mo sheet, a very obvious reinforcement effect. The sub-micron and nanometer-scale Al2O3 particles can increase the recrystallization temperature by hindering grain boundary migration and improve the tensile strength by effectively blocking the motion of the dislocations. The Al2O3 particles have a good bond with the Mo matrix and there exists an amorphous transition layer at the interface between Al2O3 particles and the Mo matrix in the as-rolled sheet. The sub-structure of α-Al2O3 is characterized by a number of nanograins in the $\left[ {2\bar{2}1} \right]$ direction. Lastly, a new computer-based method for indexing diffraction patterns of the hexagonal system is introduced, with 16 types of diffraction patterns of α-Al2O3 indexed.

12.
PLoS One ; 9(11): e112273, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25380401

RESUMEN

Increased fertilizer input in agricultural systems during the last few decades has resulted in large yield increases, but also in environmental problems. We used data from published papers and a soil testing and fertilization project in Shaanxi province during the years 2005 to 2009 to analyze chemical fertilizer inputs and yields of wheat (Triticum aestivum L.) and maize (Zea mays L.) on the farmers' level, and soil fertility change from the 1970s to the 2000s in the Loess Plateau in China. The results showed that in different regions of the province, chemical fertilizer NPK inputs and yields of wheat and maize increased. With regard to soil nutrient balance, N and P gradually changed from deficit to surplus levels, while K deficiency became more severe. In addition, soil organic matter, total nitrogen, alkali-hydrolysis nitrogen, available phosphorus and available potassium increased during the same period. The PFP of N, NP and NPK on wheat and maize all decreased from the 1970s to the 2000s as a whole. With the increase in N fertilizer inputs, both soil total nitrogen and alkali-hydrolysis nitrogen increased; P fertilizer increased soil available phosphorus and K fertilizer increased soil available potassium. At the same time, soil organic matter, total nitrogen, alkali-hydrolysis nitrogen, available phosphorus and available potassium all had positive impacts on crop yields. In order to promote food safety and environmental protection, fertilizer requirements should be assessed at the farmers' level. In many cases, farmers should be encouraged to reduce nitrogen and phosphate fertilizer inputs significantly, but increase potassium fertilizer and organic manure on cereal crops as a whole.


Asunto(s)
Productos Agrícolas/crecimiento & desarrollo , Fertilizantes/análisis , Suelo/química , Triticum/crecimiento & desarrollo , Zea mays/crecimiento & desarrollo , Agricultura/métodos , China , Conservación de los Recursos Naturales , Nitrógeno/análisis , Fósforo/análisis , Potasio/análisis
14.
Antiviral Res ; 106: 116-24, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24713119

RESUMEN

To increase efficacy of hepatitis C treatment, future regiments will incorporate multiple direct-acting antiviral drugs. HCV NS5A protein was expressed and purified. Aptamers against NS5A were screened and obtained by the selective evolution of ligands by exponential enrichment approach and the antiviral actions of the aptamers were tested. The mechanisms through which the aptamers exert their antiviral activity were explored. The aptamers NS5A-4 and NS5A-5 inhibit HCV RNA replication and infectious virus production without causing cytotoxicity in human hepatocytes. The aptamers do not affect hepatitis B virus replication in HepG2.2.15 cells. Interferon beta (IFN-ß) and interferon-stimulated genes (ISGs) are not induced by the aptamers in HCV-infected hepatocytes. Further study shows that domain I and domain III of NS5A protein are involved in the suppression of HCV RNA replication and infectious virus production by NS5A-4. Y2105H within NS5A is the major resistance mutation identified. NS5A aptamer disrupts the interaction of NS5A with core protein. The data suggest that the aptamers against NS5A protein may exert antiviral effects through inhibiting viral RNA replication, preventing the interaction of NS5A with core protein. Aptamers for NS5A may be used to understand the mechanisms of virus replication and assembly and served as potential therapeutic agents for hepatitis C.


Asunto(s)
Antivirales/farmacología , Aptámeros de Nucleótidos/farmacología , Hepacivirus/efectos de los fármacos , Proteínas no Estructurales Virales/antagonistas & inhibidores , Replicación Viral/efectos de los fármacos , Antivirales/aislamiento & purificación , Aptámeros de Nucleótidos/aislamiento & purificación , Línea Celular , Hepacivirus/fisiología , Hepatocitos/virología , Humanos , Técnica SELEX de Producción de Aptámeros
15.
Proc Natl Acad Sci U S A ; 111(13): E1264-73, 2014 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-24616513

RESUMEN

The absence of a robust cell culture system for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection has limited the analysis of the virus lifecycle and drug discovery. We have established a hepatoma cell line, HLCZ01, the first cell line, to the authors' knowledge, supporting the entire lifecycle of both HBV and HCV. HBV surface antigen (HBsAg)-positive particles can be observed in the supernatant and the lumen of the endoplasmic reticulum of the cells via electron microscopy. Interestingly, HBV and HCV clinical isolates propagate in HLCZ01 cells. Both viruses replicate in the cells without evidence of overt interference. HBV and HCV entry are blocked by antibodies against HBsAg and human CD81, respectively, and the replication of HBV and HCV is inhibited by antivirals. HLCZ01 cells mount an innate immune response to virus infection. The cell line provides a powerful tool for exploring the mechanisms of virus entry and replication and the interaction between host and virus, facilitating the development of novel antiviral agents and vaccines.


Asunto(s)
Carcinoma Hepatocelular/virología , Hepacivirus/fisiología , Virus de la Hepatitis B/fisiología , Neoplasias Hepáticas/virología , Replicación Viral/fisiología , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Coinfección/tratamiento farmacológico , Coinfección/patología , Coinfección/virología , Hepacivirus/efectos de los fármacos , Hepacivirus/crecimiento & desarrollo , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/crecimiento & desarrollo , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos NOD , Replicación Viral/efectos de los fármacos
16.
PLoS One ; 9(2): e90333, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24587329

RESUMEN

NS2 protein is essential for hepatitis C virus (HCV) replication. NS2 protein was expressed and purified. Aptamers against NS2 protein were raised and antiviral effects of the aptamers were examined. The molecular mechanism through which the aptamers exert their anti-HCV activity was investigated. The data showed that aptamer NS2-3 inhibited HCV RNA replication in replicon cell line and infectious HCV cell culture system. NS2-3 and another aptamer NS2-2 were demonstrated to inhibit infectious virus production without cytotoxicity in vitro. They did not affect hepatitis B virus replication. Interferon beta (IFN-ß) and interferon-stimulated genes (ISGs) were not induced by the aptamers in HCV-infected hepatocytes. Furthermore, our study showed that N-terminal region of NS2 protein is involved in the inhibition of HCV infection by NS2-2. I861T within NS2 is the major resistance mutation identified. Aptamer NS2-2 disrupts the interaction of NS2 with NS5A protein. The data suggest that NS2-2 aptamer against NS2 protein exerts its antiviral effects through binding to the N-terminal of NS2 and disrupting the interaction of NS2 with NS5A protein. NS2-specific aptamer is the first NS2 inhibitor and can be used to understand the mechanisms of virus replication and assembly. It may be served as attractive candidates for inclusion in the future HCV direct-acting antiviral combination therapies.


Asunto(s)
Antivirales/farmacología , Aptámeros de Nucleótidos/farmacología , Regulación Viral de la Expresión Génica , Hepacivirus/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Proteínas no Estructurales Virales/genética , Aptámeros de Nucleótidos/biosíntesis , Aptámeros de Nucleótidos/genética , Secuencia de Bases , Sitios de Unión , Línea Celular Tumoral , Escherichia coli/genética , Escherichia coli/metabolismo , Hepacivirus/fisiología , Hepatocitos/inmunología , Hepatocitos/virología , Interacciones Huésped-Patógeno , Humanos , Interferón beta , Datos de Secuencia Molecular , Unión Proteica , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/metabolismo , Replicación Viral
17.
J Virol ; 88(4): 1990-9, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24307579

RESUMEN

Hepatitis C virus (HCV) core protein is essential for virus assembly. HCV core protein was expressed and purified. Aptamers against core protein were raised through the selective evolution of ligands by the exponential enrichment approach. Detection of HCV infection by core aptamers and the antiviral activities of aptamers were characterized. The mechanism of their anti-HCV activity was determined. The data showed that selected aptamers against core specifically recognize the recombinant core protein but also can detect serum samples from hepatitis C patients. Aptamers have no effect on HCV RNA replication in the infectious cell culture system. However, the aptamers inhibit the production of infectious virus particles. Beta interferon (IFN-ß) and interferon-stimulated genes (ISGs) are not induced in virally infected hepatocytes by aptamers. Domains I and II of core protein are involved in the inhibition of infectious virus production by the aptamers. V31A within core is the major resistance mutation identified. Further study shows that the aptamers disrupt the localization of core with lipid droplets and NS5A and perturb the association of core protein with viral RNA. The data suggest that aptamers against HCV core protein inhibit infectious virus production by disrupting the localization of core with lipid droplets and NS5A and preventing the association of core protein with viral RNA. The aptamers for core protein may be used to understand the mechanisms of virus assembly. Core-specific aptamers may hold promise for development as early diagnostic reagents and potential therapeutic agents for chronic hepatitis C.


Asunto(s)
Anticuerpos Monoclonales/metabolismo , Aptámeros de Nucleótidos/farmacología , Hepacivirus/genética , Hepacivirus/metabolismo , Proteínas del Núcleo Viral/metabolismo , Virión/efectos de los fármacos , Animales , Aptámeros de Nucleótidos/genética , Aptámeros de Nucleótidos/metabolismo , Western Blotting , Línea Celular , Cartilla de ADN/genética , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Biblioteca de Genes , Hepacivirus/efectos de los fármacos , Humanos , Inmunoprecipitación , Ratones , Plásmidos/genética , Unión Proteica/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Técnica SELEX de Producción de Aptámeros , Proteínas del Núcleo Viral/genética
18.
PLoS One ; 8(5): e64932, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23741428

RESUMEN

Many chronic hepatitis C virus (HCV)-infected patients with current therapy do not clear the virus. It is necessary to find novel treatments. The effect of 2-octynoic acid (2-OA) on HCV infection in human hepatocytes was examined. The mechanism of 2-OA antiviral activity was explored. Our data showed that 2-OA abrogated lipid accumulation in HCV replicon cells and virus-infected hepatocytes. It suppressed HCV RNA replication and infectious virus production with no cytotoxicity to the host cells. 2-OA did not affect hepatitis B virus replication in HepG2.2.15 cells derived from HepG2 cells transfected with full genome of HBV. Further study demonstrated that 2-OA activated AMP-activated protein kinase (AMPK) and inhibited acetyl-CoA carboxylase in viral-infected cells. Compound C, a specific inhibitor of AMPK, inhibited AMPK activity and reversed the reduction of intracellular lipid accumulation and the antiviral effect of 2-OA. Knockdown of AMPK expression by RNA interference abolished the activation of AMPK by 2-OA and blocked 2-OA antiviral activity. Interestingly, 2-OA induced interferon-stimulated genes (ISGs) and inhibited microRNA-122 (miR-122) expression in virus-infected hepatocytes. MiR-122 overexpression reversed the antiviral effect of 2-OA. Furthermore, knockdown of AMPK expression reversed both the induction of ISGs and suppression of miR-122 by 2-OA, implying that activated AMPK induces the intracellular innate response through the induction of ISGs and inhibiting miR-122 expression. 2-OA inhibits HCV infection through regulation of innate immune response by activated AMPK. These findings reveal a novel mechanism by which active AMPK inhibits HCV infection. 2-OA and its derivatives hold promise for novel drug development for chronic hepatitis C.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Antivirales/farmacología , Ácidos Grasos Monoinsaturados/farmacología , Hepacivirus/efectos de los fármacos , Hepatitis C/metabolismo , Línea Celular , Activación Enzimática/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Hepatitis C/genética , Humanos , Factores Reguladores del Interferón/genética , Metabolismo de los Lípidos/efectos de los fármacos , MicroARNs/genética , Replicación Viral/efectos de los fármacos
19.
Ying Yong Sheng Tai Xue Bao ; 16(3): 496-500, 2005 Mar.
Artículo en Chino | MEDLINE | ID: mdl-15943364

RESUMEN

In a pot experiment with allium as test plant and NH4HCO3 as nitrogen source, this paper studied the effects of element sulphur (S0) and dicyandiamide (DCD) on mitigating the NO3- -N leaching loss from soil and on soil inorganic nitrogen (NO3- -N and NH4+ -N) content. The results showed that within the 12 weeks of the experiment, the cumulative leaching loss of soil NO3- -N in treatments S0 + DCD and S0 was 83%-86% and 83% lower, while that of soil NH4+ -N was 16.8-21.0 mg x pot(-1) and 20.4-25.0 mg x pot(-1) higher than CK, respectively, and the cumulative loss of soil (NH4+ + NO3-)-N was 60% lower. By the end of the experiment, soil inorganic nitrogen content in treatments S0 + DCD and S0 was 79.9%-85.4% and 74.9-82.6% higher than CK, respectively. The cumulative leaching loss of inorganic N in treatment S0 + DCD was 4.6%-14.4% and 15.4%-30.1% lower, and the soil inorganic nitrogen content by the end of the experiment was 6.1% and 16.8%-36.0% higher than that of treatments S0 and DCD, respectively. Similar results were obtained when S0 was replaced by Na2S2O3, but not by Na2SO4. The fact that the application of S0 could obviously decrease the NO3- -N leaching loss from soil could be contributed to the inhibitory effects of S2O3(2-) and S4O6(2-) originated from S0 oxidation in soil on the nitrification of NH4+ -N. S0 could retard the decomposition of DCD due to the effect of its oxidized products S2O3(2-) and S4O6(2-), and thus, extend the inhibitory effect of DCD on NH4+ -N nitrification. It is suggested that S0 combined with DCD could be used as an effective nitrification inhibitor to control the NO3- -N leaching loss from vegetable soils.


Asunto(s)
Guanidinas/análisis , Suelo/análisis , Azufre/análisis , Verduras/crecimiento & desarrollo , Fertilizantes/análisis , Nitratos/análisis , Nitrógeno/análisis
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