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BACKGROUND: Acyl-CoA-binding domain-containing 3 (ACBD3) is a multifunctional protein, that plays essential roles in cellular signaling and membrane domain organization. Although the precise roles of ACBD3 in various cancers remain unclear. Thus, we aimed to determine the diverse roles of ACBD3 in pan-cancers. METHODS: Relevant clinical and RNA-sequencing data for normal tissues and 33 tumors from The Cancer Genome Atlas (TCGA) database, the Human Protein Atlas, and other databases were applied to investigate ACBD3 expression in various cancers. ACBD3-binding and ACBD3-related target genes were obtained from the STRING and GEPIA2 databases. The possible functions of ACBD3-binding genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also applied the diagnostic value and survival prognosis analysis of ACBD3 in pan-cancers using R language. The mutational features of ACBD3 in various TCGA cancers were obtained from the cBioPortal database. RESULTS: When compared with normal tissues, ACBD3 expression was statistically upregulated in eleven cancers and downregulated in three cancers. ACBD3 expression was remarkably different among various pathological stages of tumors, immune and molecular subtypes of cancers, cancer phosphorylation levels, and immune cell infiltration. The survival of four tumors was correlated with the expression level of ACBD3, including pancreatic adenocarcinoma, adrenocortical carcinoma, sarcoma, and glioma. The high accuracy in diagnosing multiple tumors and its correlation with prognosis indicated that ACBD3 may be a potential biomarker of pan-cancers. CONCLUSION: According to our pan-cancer analysis, ACBD3 may serve as a remarkable prognostic and diagnostic biomarker of pan-cancers as well as contribute to tumor development. ACBD3 may also provide new directions for cancer treatment targets in the future.
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Adenocarcinoma , Neoplasias Pancreáticas , Neoplasias de los Tejidos Blandos , Humanos , Biomarcadores , Biología Computacional , Pronóstico , Proteínas de la Membrana/genética , Proteínas Adaptadoras Transductoras de SeñalesRESUMEN
BACKGROUND: Mucinous adenocarcinoma (MC) has attracted much attention as a distinct histologic subtype of colorectal cancer in recent years. However, data about its epidemiologic and prognostic characteristics are limited. Therefore, patient data extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program were collected to analyze the epidemiologic and clinicopathological characteristics of MC. AIM: To determine the epidemiologic and clinicopathological characteristics of MC. METHODS: The incidence trend of MC was calculated through the Joinpoint Regression Program. Cox regression analyses were performed to identify prognostic factors associated with overall survival (OS). A nomogram was established to predict the survival probability of individual patients with MC. RESULTS: We found that rates of MC decreased from 4.50/100000 in 2000 to 1.54/100000 in 2018. Rates of MCs in patients aged ≤ 50 years decreased 2.27%/year during 2000-2018. The incidence of appendiceal MCs increased from 0.14/100000 in 2000 to 0.24/100000 in 2018, while the incidence in other anatomic subsites continued to decrease. On multivariable Cox analyses, age, race, tumor site, T stage, N stage, M stage, surgery, and chemotherapy were associated with OS. A nomogram was developed based on these factors, and the area under the curve for 1-year, 3-year, and 5-year OS in the training cohort was 0.778, 0.778, and 0.768, respectively. CONCLUSION: Our results demonstrated that MC incidence decreased in almost all anatomic subgroups except for the appendix. A nomogram predicting the survival probability of patients with MCs showed good performance.
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Moringa oleifera Lam. leaf is not only a new food resource in China, but also a traditional medicinal plant. It is commonly used in the folk to alleviate constipation, but its laxative mechanism is not fully understood. Hence we investigated it in loperamide-induced functional constipation (FC) mice. The results showed that MOAE significantly regulated not only gastrointestinal hormones and neurotransmitters in serum but also important gastrointestinal motility factors in the enteric nervous system (ENS)-interstitial cells of Cajal (ICCs)-smooth muscle cell (SMC) network. Meanwhile, MOAE attenuated intestinal inflammation, increased cecal short-chain fatty acid levels and colonic antimicrobial peptide expression, and improved the impaired intestinal barrier function in loperamide-induced FC mice. In addition, MOAE also increased fecal water content by inhibiting the mRNA expression of colonic aquaporins (Aqp3 and Aqp4) in FC mice. Interestingly and importantly, MOAE affected the intestinal microbiota by inhibiting some key "constipation-causing" microbiota, such as Bacteroidaceae, Clostridiaceae, Bacteroides, and Ruminococcus, and promoting the growth of other important "constipation-curing" microbiota, such as Butyricoccus, Tyzzerella, and Desulfovibrio. These important taxa are significantly associated with a variety of indicators of constipation. These findings suggest that MOAE can promote defecation through its rich chemical composition to modulate the ENS-ICCs-SMCs network and the gut microecosystem.
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Pu-erh tea is very popular in Southwestern China and South Asian countries and is now becoming increasingly popular in Europe due to its well-documented beneficial effects on human health. Pu-erh tea aqueous extracts can maintain intestinal homeostasis. However, the mechanism of its beneficial effects on intestinal flora disorder is not clear. In this study, we focused on the effects of ripe Pu-erh tea aqueous extracts on the intestinal microbiota in an intestinal flora disorder mouse model. Physiological indexes and the tissue section staining results showed that feeding Pu-erh tea extract could help mice regain weight and alleviate intestinal inflammation. Further assessment of the intestinal microflora found that Pu-erh tea extract could promote the growth of intestinal probiotics and inhibit pathogenic bacteria, thereby achieving a treatment effect for enteritis. This study provides new evidence for the therapeutic effect of Pu-erh tea.
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Synthetic aperture radar (SAR) is a widely used remote sensing observation technique. However, SAR raw echo data may be lost during the process of data acquisition by radar platform. In this paper, the imaging problem of SAR echo signal with periodically missing data along the azimuth is analyzed and a novel imaging method is proposed. Firstly, the problem of artificial artifact targets caused by periodically missing data is explained in detail, and the corresponding mathematical model is established. Then, the recovery method based on the RELAX algorithm with periodic notches data is proposed. In addition, when the size of two-dimensional (2D) echo data are large, block restoration along the azimuth is proposed to reduce the amount of calculation. Finally, the advantages of the algorithm proposed in this paper is demonstrated by the points target simulated SAR echo data processing and the real raw SAR echo data processing. When the azimuth periodically missing data rate is 50%, the SAR echo data can be recovered and the well-focused image can be obtained. Comparing the image entropy value and structural similarity index (SSIM) of the focused image, it proves the superiority of the proposed algorithm in solving the imaging problem of SAR azimuth periodically missing data.
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As a global phenomenon, the theme of math anxiety has received increasing attention. The present study aimed to investigate the relationship between math anxiety and performance and determine the role of arithmetic skill in two different tasks. Fifty-seven college freshmen were recruited to perform a comparison task and a calculation task. Only main effect of arithmetic skill was found on the behavioral level. In the comparison task, participants with high math anxiety (HMA) showed faster latencies and greater amplitudes of N1 and longer P3b latency relative to their counterparts with low math anxiety (LMA). Number, as a negative stimulus, occupied attentional resources and delayed the speed of cognitive processing for individuals with HMA. Furthermore, among those with HMA, individuals with high arithmetic skill showed larger amplitudes and shorter latencies of P2 compared with those with low airthmetic skill in the calculation task. Thus, arithmetic skill could refine the performance efficiency of individuals with HMA, especially in the calculation task. These results suggest that educational interventions emphasizing control of negative emotional responses to math stimuli will be more effective when considering different populations of mathematically competent individuals.
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Rendimiento Académico/psicología , Matemática , Ansiedad de Desempeño/psicología , Adolescente , Ansiedad/psicología , Atención/fisiología , Ondas Encefálicas/fisiología , Electroencefalografía , Femenino , Humanos , MasculinoRESUMEN
In this work, super strong all-cellulose multifilaments were obtained from cellulose dissolved in LiOH/urea system by inducing nanofiber formation, and were simultaneously reinforced by the introduction of TEMPO-oxidized nanofibrillated cellulose (NFC) with mean diameter of 20 nm. The all-cellulose composite filaments (CF) containing only 3 wt % NFC exhibits a high orientation that Herman's parameter is 0.89. Importantly, the NFC can simultaneously reinforce and toughen the CF, with a tensile strength and elongation at break of 3.92 cN/dT and 14.6%, respectively, which make the obtained CF to become super strong. The strengthened mechanism of CF is considered as the nanofibril-induced crystallization and orientation, which makes up for the deficits and constructs a flawless structure in the regenerated cellulose filaments. Of note, the stability of spinning dope was also effectively improved by adding small amount of NFC, which is very important for fiber spinning on industry. This finding contributes to the preparation of high performance regenerated cellulose multifilaments by a simple, energy-efficient, and eco-friendly route.
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Celulosa/química , Nanofibras/química , Cristalización , Temperatura , Resistencia a la Tracción , AguaRESUMEN
Autonomously self-healing hydrogels have received considerable attentions due to their capacity for repairing themselves spontaneously after suffering damage, which can provide a better stability and a longer life span. In this work, a robust and mechanically and electrically self-healing hydrogel with an efficient electromagnetic interference (EMI) shielding performance was successfully fabricated via the incorporation of multiwalled carbon nanotubes (MWCNTs) into the hydrophobically associated polyacrylamide (PAM) hydrogels by using cellulose nanofiber (CNF) as the dispersant. It was been found that CNF could not only assist the homogeneous dispersion of MWCNTs but also effectively enhance the mechanical property of the resultant hydrogels. As a result, the optimal tensile strength (≈0.24 MPa), electrical conductivity (≈0.85 S m-1), and EMI shielding effectiveness (≈28.5 dB) were achieved for the PAM/CNF/MWCNT composite hydrogels with 1 wt % MWCNTs and 0.3 wt % CNF, which showed 458, 844, and 90% increase over (≈0.043 MPa, ≈0.09 S m-1, and ≈15 dB, respectively) the PAM hydrogel. More encouragingly, these composite hydrogels could rapidly restore their electrical conductivity and EMI shielding effectiveness after mechanical damage at room temperature without any external stimulus. With outstanding mechanical and self-healing properties, the prepared composite hydrogels were similar to human skin, but beyond human skin owing to their additional satisfactory electrical and EMI shielding performances. They may offer promising and broad prospects in the field of simulate skin and protection of precision electronics.
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It is still a challenge to fabricate polymer-based composites with excellent thermal conductive property because of the well-known difficulties such as insufficient conductive pathways and inefficient filler-filler contact. To address this issue, a synergistic segregated double network by using two fillers with different dimensions has been designed and prepared by taking graphene nanoplates (GNPs) and multiwalled carbon nanotubes (MWCNT) in polystyrene for example. In this structure, GNPs form the segregated network to largely increase the filler-filler contact areas while MWCNT are embedded within the network to improve the network-density. The segregated network and the randomly dispersed hybrid network by using GNPs and MWCNT together were also prepared for comparison. It was found that the thermal conductivity of segregated double network can achieve almost 1.8-fold as high as that of the randomly dispersed hybrid network, and 2.2-fold as that of the segregated network. Meanwhile, much higher synergistic efficiency (f) of 2 can be obtained, even greater than that of other synergistic systems reported previously. The excellent thermal conductive property and higher f are ascribed to the unique effect of segregated double network: (1) extensive GNPs-GNPs contact areas via overlapped interconnections within segregated GNPs network; (2) efficient synergistic effect between MWCNT network and GNPs network based on bridge effect as well as increasing the network-density.
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Phosphodiesterase 4 (PDE4) has four isoforms (PDE4A-D) with at least 25 splice variants. PDE4 subtype nonselective inhibitors produce potent antidepressant-like and cognition-enhancing effects via increased intracellular cyclic AMP (cAMP) signaling in the brain. Our previous data have demonstrated that long-form PDE4Ds appear to be involved in these pharmacological properties of PDE4 inhibitors in the normal animals. However, it is not clear whether long-form PDE4Ds are critical for the behaviors and related cellular signaling/neuronal plasticity/neuroendocrine alterations in the depressed animals. In the present study, animals exposed to the chronic unpredictable stress (CUS), a rodent model of depression, exhibited elevated corticosterone, depressive-like behavior, memory deficits, accompanied with decreased cAMP-PKA-CREB and cAMP-ERK1/2-CREB signaling and neuroplasticity. These alterations induced by CUS were reversed by RNA interference (RNAi)-mediated prefrontal cortex long-form PDE4Ds (especially PDE4D4 and PDE4D5) knock-down, similar to the effects of the PDE4 subtype nonselective inhibitor rolipram. Furthermore, these effects of RNAi were not enhanced by rolipram. These data indicate a predominant role of long-form PDE4Ds in the pharmacotherapies of PDE4 inhibitors for depression and concomitant memory deficits. Long-form PDE4Ds, especially PDE4D4 and PDE4D5, appear to be the promising targets for the development of antidepressants with high therapeutic indices.
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Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/genética , Depresión/etiología , Trastornos de la Memoria/etiología , Corteza Prefrontal/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Corticosterona/sangre , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/química , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Dendritas/efectos de los fármacos , Dendritas/fisiología , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Inhibidores de Fosfodiesterasa 4/farmacología , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Rolipram/farmacología , Rolipram/uso terapéutico , Transducción de Señal/efectos de los fármacos , Estrés FisiológicoRESUMEN
OBJECTIVE: To study the effect of exogenous Ca2+ on photosynthetic parameters of Pinellia ternate and accumulations of active components under high temperature stress. METHOD: The pigment contents of P. ternata leaves, photosynthesis parameters and chlorophyll fluorescence parameters of P. ternata leaves, the contents of guanosine, adenosine and polysaccharide in P. ternata tubers were measured based on different concentrations of exogenous Ca2+ in heat stress when the plant height of P. ternata was around 10 cm. RESULT: The contents of total chlorophyll and ratio of chlorophyll a/b were relatively higher by spaying Ca2+. Compared with the control, spaying 6 mmol x L(-1) Ca2+ significantly enhanced the net photosynthetic rate (Pn), transpiration (Tr) and stomatal limitation (L8), but reduced intercellular CO2 concentration (C) in P. ternata leaves. With the increase of Ca2+ concentration, maximal PS II efficiency (Fv/Fm), actual photosynthetic efficiency (Yield) and photochemical quenching coefficient (qP) initially increased and then decreased, however, minimal fluorescence (Fo) and non-photochemical quenching coefficient (NPQ) went down first and then went up. The contents of guanosine and polysaccharide and dry weight of P. ternata tubers showed a tendency of increase after decrease, and the content of adenosine increased with the increase of Ca2+ concentration. The content of guanosine and polysaccharide in P. ternata tubers and its dry weight reached maximum when spaying 6 mmol x L(-1) Ca2+. CONCLUSION: With the treatment of calcium ion, the inhibition of photosynthesis and the damage of PS II system were relieved in heat stress, which increased the production of P. ternata tubers.
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Calcio/farmacología , Respuesta al Choque Térmico/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Pinellia/efectos de los fármacos , Pinellia/metabolismo , Cruzamiento , Clorofila/metabolismo , Clorofila A , Relación Dosis-Respuesta a Droga , Tamaño de los Órganos/efectos de los fármacos , Pinellia/crecimiento & desarrollo , Pinellia/fisiología , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismoRESUMEN
Tyro3, a member of the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases, has emerged as a potential oncogene in melanoma. Here, we confirm that Tyro3 is specifically overexpressed in primary melanoma samples and show that Tyro3 is expressed at varying levels in numerous melanoma cell lines. Short hairpin RNA-mediated knockdown of Tyro3 led to significant cell death via apoptotic mechanisms in nearly all melanoma cell lines tested, regardless of the BRAF or NRAS mutation status or co-expression of Axl and/or Mer. We generated soluble and monomeric versions of the human Tyro3 extracellular domain and human Gas6 for affinity measurements and correlated these values with the level of Gas6 required to induce Tyro3 signaling in cellular assays. Calcium was critical for the correct folding of Gas6 and its binding to Tyro3. In melanoma cell lines, Gas6 induced Tyro3 phosphorylation and downstream Akt phosphorylation without apparent effects on Erk. We generated monoclonal antibodies (mAbs) against Tyro3 to examine their effect on survival signaling in melanoma cell lines. The mAbs generated against Tyro3 included nonligand blockers, partial blockers, and competitive ligand blockers. A number of weak and partial ligand blockers (all recognizing the Tyro3 Ig domains) were the most effective at blocking ligand-mediated downstream signaling of Tyro3. Overall, these data indicate that Tyro3 may confer increased survival signals in melanoma cells and can be stymied using inhibitory mAbs. These mAbs may be useful for further investigations of the role of Tyro3 in melanoma.
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Anticuerpos Monoclonales/inmunología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Melanoma/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Western Blotting , Rastreo Diferencial de Calorimetría , División Celular , Línea Celular Tumoral , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Dicroismo Circular , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoprecipitación , Melanoma/inmunología , Melanoma/patología , Fosforilación , ARN Mensajero/análisis , Proteínas Tirosina Quinasas Receptoras/inmunologíaRESUMEN
We consider chemical plume tracing (CPT) in time-varying airflow environments using multiple mobile robots. The purpose of CPT is to approach a gas source with a previously unknown location in a given area. Therefore, the CPT could be considered as a dynamic optimization problem in continuous domains. The traditional ant colony optimization (ACO) algorithm has been successfully used for combinatorial optimization problems in discrete domains. To adapt the ant colony metaphor to the multi-robot CPT problem, the two-dimension continuous search area is discretized into grids and the virtual pheromone is updated according to both the gas concentration and wind information. To prevent the adapted ACO algorithm from being prematurely trapped in a local optimum, the upwind surge behavior is adopted by the robots with relatively higher gas concentration in order to explore more areas. The spiral surge (SS) algorithm is also examined for comparison. Experimental results using multiple real robots in two indoor natural ventilated airflow environments show that the proposed CPT method performs better than the SS algorithm. The simulation results for large-scale advection-diffusion plume environments show that the proposed method could also work in outdoor meandering plume environments.
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Survival and differentiation of oligodendrocytes are important for the myelination of central nervous system (CNS) axons during development and crucial for myelin repair in CNS demyelinating diseases such as multiple sclerosis. Here we show that death receptor 6 (DR6) is a negative regulator of oligodendrocyte maturation. DR6 is expressed strongly in immature oligodendrocytes and weakly in mature myelin basic protein (MBP)-positive oligodendrocytes. Overexpression of DR6 in oligodendrocytes leads to caspase 3 (casp3) activation and cell death. Attenuation of DR6 function leads to enhanced oligodendrocyte maturation, myelination and downregulation of casp3. Treatment with a DR6 antagonist antibody promotes remyelination in both lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis (EAE) models. Consistent with the DR6 antagoinst antibody studies, DR6-null mice show enhanced remyelination in both demyelination models. These studies reveal a pivotal role for DR6 signaling in immature oligodendrocyte maturation and myelination that may provide new therapeutic avenues for the treatment of demyelination disorders such as multiple sclerosis.
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Vaina de Mielina/metabolismo , Oligodendroglía/metabolismo , Receptores del Factor de Necrosis Tumoral/fisiología , Animales , Western Blotting , Caspasa 3/metabolismo , Caspasa 3/fisiología , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Supervivencia Celular/fisiología , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/fisiopatología , Encefalomielitis Autoinmune Experimental/terapia , Activación Enzimática , Regulación de la Expresión Génica , Ratones , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/terapia , Vaina de Mielina/fisiología , Oligodendroglía/fisiología , Ratas , Receptores del Factor de Necrosis Tumoral/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
This paper addresses the collective odor source localization (OSL) problem in a time-varying airflow environment using mobile robots. A novel OSL methodology which combines odor-source probability estimation and multiple robots' search is proposed. The estimation phase consists of two steps: firstly, the separate probability-distribution map of odor source is estimated via Bayesian rules and fuzzy inference based on a single robot's detection events; secondly, the separate maps estimated by different robots at different times are fused into a combined map by way of distance based superposition. The multi-robot search behaviors are coordinated via a particle swarm optimization algorithm, where the estimated odor-source probability distribution is used to express the fitness functions. In the process of OSL, the estimation phase provides the prior knowledge for the searching while the searching verifies the estimation results, and both phases are implemented iteratively. The results of simulations for large-scale advection-diffusion plume environments and experiments using real robots in an indoor airflow environment validate the feasibility and robustness of the proposed OSL method.
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Movimientos del Aire , Algoritmos , Odorantes/análisis , Robótica/métodos , Contaminantes Atmosféricos/análisis , Teorema de Bayes , Simulación por Computador , Difusión , Lógica Difusa , Gases/análisis , Gases/química , Modelos Estadísticos , Fenómenos Físicos , Reología , Robótica/instrumentación , Tecnología InalámbricaRESUMEN
OBJECTIVE: A strain of highly pathogenic duck hepatitis virus was isolated in south China from a Pekin duck flock in 1999. No cross reaction with type 1 and 3 duck hepatitis virus was found by serum neutralization. We suggested the strain should be classified as a new serotype of duck hepatitis virus and named it as DHV-N G strain in our previous study. We wanted to reveal the evolution of this virus in molecular level and gene sequence differences between it and DHV-1 strains. METHODS: We used RT-PCR and 5'-/3'-RACE to amplify the complete genome sequence of DHV-N G strain and compared it with other picornaviruses. RESULTS: The genome of DHV-N G consists of 7774 nucleotides excluding a poly (A) tail of 12 nucleotides. It contains a single large open reading frame encoding a polypeptide of 2251 amino acid residues. The length of 3' UTR of DHV-N G is 366 nucleotides, which is 52 nucleotides longer than that of DHV-1 C80 strain. Significant amino acid variation was found in the protein VP1, especially at the position of 140 - 221 comparing with DHV-1. The DHV-N G genome shares 72.8% - 73.4%, 96.3% - 96.5% and 78.3% similarity with DHV-1 strains, Korea's and Taiwanese DHV-N strains, respectively. CONCLUSION: The genome structure of DHV-N G strain is obviously different with that of DHV-1 strains. The homologies of genome among the DHV-N group are variable, therein DHV-N G strain is more homologous with Korea's strains than with Taiwanese.
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Enfermedades de las Aves/virología , Genoma Viral/genética , Virus de la Hepatitis del Pato/genética , Hepatitis Viral Animal/virología , Infecciones por Picornaviridae/virología , Regiones no Traducidas 3'/genética , Regiones no Traducidas 5'/genética , Secuencia de Aminoácidos , Animales , Patos/virología , Virus de la Hepatitis del Pato/clasificación , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genética , Proteínas Estructurales Virales/química , Proteínas Estructurales Virales/genéticaRESUMEN
OBJECTIVE: To study the chemical constituents in the total saponin from Trigonellf foenum-graecum. METHOD: The compounds were isolated by column chromatography on macroporous resin and silica gel and elucidated by physical and chemical evidences and spectroscopic analysis. RESULT: Two compounds were obtained and identifiedas methyl-protodioscin and methyl-protodeltonin. CONCLUSION: Methyl-protodioscin and methyl-protodeltonin were isolated from this plant for the first time.
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Diosgenina/análogos & derivados , Plantas Medicinales/química , Saponinas/aislamiento & purificación , Trigonella/química , Diosgenina/química , Diosgenina/aislamiento & purificación , Saponinas/análisis , Saponinas/química , Semillas/químicaRESUMEN
The Nogo66 receptor (NgR1) is a neuronal, leucine-rich repeat (LRR) protein that binds three central nervous system (CNS) myelin proteins, Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein, and mediates their inhibitory effects on neurite growth. Although the LRR domains on NgR1 are necessary for binding to the myelin proteins, the exact epitope(s) involved in ligand binding is unclear. Here we report the generation and detailed characterization of an anti-NgR1 monoclonal antibody, 7E11. The 7E11 monoclonal antibody blocks Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein binding to NgR1 with IC50 values of 120, 14, and 4.5 nm, respectively, and effectively promotes neurite outgrowth of P3 rat dorsal root ganglia neurons cultured on a CNS myelin substrate. Further, we have defined the molecular epitope of 7E11 to be DNAQLR located in the third LRR domain of rat NgR1. Our data demonstrate that anti-NgR1 antibodies recognizing this epitope, such as 7E11, can neutralize CNS myelin-dependent inhibition of neurite outgrowth. Thus, specific anti-NgR1 antibodies may represent a useful therapeutic approach for promoting CNS repair after injury.
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Anticuerpos Monoclonales/farmacología , Proteínas de la Mielina/inmunología , Vaina de Mielina/fisiología , Neuritas/fisiología , Secuencia de Aminoácidos , Animales , Especificidad de Anticuerpos , Química Encefálica , Bovinos , Epítopos/análisis , Epítopos/química , Epítopos/inmunología , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/fisiología , Humanos , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Vaina de Mielina/efectos de los fármacos , Neuritas/efectos de los fármacos , Proteínas Nogo , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Conformación Proteica , Ratas , Proteínas Recombinantes/inmunologíaRESUMEN
Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis.