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Quinoa is a highly nutritious whole-grain crop with unique values as both a food and medicinal supplement. At present, the roles played by the intestinal microflora in human health are gaining considerable attention from the research community, and studies to date have shown that the occurrence of a range of diseases may be associated with an imbalance of the intestinal flora. The bioactive compounds of quinoa affect the production of SCFAs and the adjustment of intestinal pH. In this article, we review the mechanisms underlying the effects of different quinoa constituents on the intestinal flora, the effects of these constituents on the intestinal flora of different hosts, and progress in research on the therapeutic properties of quinoa constituents, to provide a better understanding of quinoa in terms its dual medicinal and nutritional properties. We hope this review will provide a useful reference for approaches that seek to enhance the composition and activities of the intestinal flora.
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Implant restoration is currently the most mainstream method for repairing missing teeth. With the increasing number of plantings, various planting complications begin to be paid attention to. Among them, there are many reports of disability phenomena such as loose and broken abutment screws and broken top screws, which cause the implant to fail or fail to function. In recent years, with the development of computer-aided software and its application in the field of oral treatment, digital guide plates based on 3D printing of oral CBCT scanning data are widely used in oral implants. Therefore, we explore the application prospect of post-core crown restoration after removing broken screws from the implant abutment with a digital guide plate. We reported a case of upper right first molar implant abutment screws broken, which were removed by a digital guide plate and customized turning bur. The resin-matrix ceramics crown post core was prepared, and then the occlusal force was tested by the T-ScanIII system. It provides a reference for the application of digital guide plates in special cases such as broken screws of implant abutment.
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Coronas , Impresión Tridimensional , Humanos , Cerámica , Diente Molar/cirugíaRESUMEN
Federated learning (FL) is an emerging distributed machine learning (ML) framework that operates under privacy and communication constraints. To mitigate the data heterogeneity underlying FL, clustered FL (CFL) was proposed to learn customized models for different client groups. However, due to the lack of effective client selection strategies, the CFL process is relatively slow, and the model performance is also limited in the presence of nonindependent and identically distributed (non-IID) client data. In this work, for the first time, we propose selecting participating clients for each cluster with active learning (AL) and call our method active client selection for CFL (ACFL). More specifically, in each ACFL round, each cluster filters out a small set of clients, which are the most informative clients according to some AL metrics e.g., uncertainty sampling, query-by-committee (QBC), loss, and aggregates only its model updates to update the cluster-specific model. We empirically evaluate our ACFL approach on the public MNIST, CIFAR-10, and LEAF synthetic datasets with class-imbalanced settings. Compared with several FL and CFL baselines, the results reveal that ACFL can dramatically speed up the learning process while requiring less client participation and significantly improving model accuracy with a relatively low communication overhead.
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In order to improve laser transmission efficiency at 1053 nm and 527 nm, a potassium deuterium phosphate (DKDP) crystal (a key component of high-power laser systems) needs a bi-layer antireflection coating system on its incident surface. UV-curable polysiloxane coatings with a refractive index varying from 1.500 to 1.485 were prepared through the polycondensation of a methacryloxy propyl trimethoxylsilane (MPS) monomer with a controllable degree of hydrolysis. Additionally, the influence rule of the coating structure on the refractive index was intensively studied, and the primary factors that dominate the hydrolysis process were discussed. Further refractive index adjustment was achieved using only a small amount of dopant based on the polysiloxane coating with refractive index of 1.485, allowing for high antireflection of the bi-layer coating system at desired wavelengths to be achieved. In addition, high laser damage resistance and remarkable mechanical properties of the coating were simultaneously realized through the incorporation of a minor quantity of dopants, which benefited from the successful modulation of the intrinsic refractive index of the polysiloxane coating.
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Hydrovoltaic energy technology that generates electricity directly from the interaction of materials with water has been regarded as a promising renewable energy harvesting method. With the advantages of high specific surface area, good conductivity, and easily tunable porous nanochannels, two-dimensional (2D) nanomaterials have promising potential in high-performance hydrovoltaic electricity generation applications. Herein, this review summarizes the most recent advances of 2D materials for hydrovoltaic electricity generation, including carbon nanosheets, layered double hydroxide (LDH), and layered transition metal oxides and sulfides. Some strategies were introduced to improve the energy conversion efficiency and the output power of hydrovoltaic electricity generation devices based on 2D materials. The applications of these devices in self-powered electronics, sensors, and low-consumption devices are also discussed. Finally, the challenges and perspectives on this emerging technology are outlined.
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The lytic bacteriophage JC01 was isolated using a strain of Cronobacter sakazakii previously isolated from powdered infant formula (PIF). The complete genome sequence of phage JC01 was determined. The double-stranded DNA genome of phage JC01 is composed of 61,736 bp with a G + C content of 58.9%, and it contains 76 putative open reading frames (ORFs) without any tRNA genes. The predicted ORFs were classified into functional groups, including DNA manipulation, transcription, phage packaging, phage structure, host lysis, and hypothetical proteins. Based on overall nucleotide sequence comparisons, calculation of phage intergenomic similarities, and phylogenetic analysis, JC01 appears to be a novel bacteriophage infecting C. sakazakii.
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Bacteriófagos , Cronobacter sakazakii , Humanos , Lactante , Cronobacter sakazakii/genética , Filogenia , Genoma Viral , Genómica , Sistemas de Lectura Abierta , ADNRESUMEN
This experiment was conducted to compare the antibacterial ability and to identify the antibacterial components of different fermented compound Chinese medicine feed additives in order to develop one fermented compound Chinese medicine feed additive product that can effectively alleviate metritis, vaginitis, and mastitis of sows. The Oxford cup method and double dilution method were used to compare the antibacterial ability of three fermented compound Chinese medicine feed additives (A, B, and C). UHPLC-QE-MS-based untargeted metabolomics was used to identify the antibacterial components of fermented compound Chinese medicine feed additives. Results showed that among fermented compound Chinese medicine feed additives A, B, and C, additive A had the strongest ability to inhibit the growth of Staphylococcus aureus, Salmonella cholerae suis, Escherichia coli, and Streptococcus agalactiae. The MIC and MBC of additive A were the lowest for Staphylococcus aureus compared to that for the other three pathogens. The concentrations of 23 Chinese medicine ingredients (ellagic acid, guanine, camphor, L-valine, sinapine, dipropylphthalate, 3-hydroxy-5-isopropylidene-3,8-dimethyl-2,3,3a,4,5,8a-hexahydro-6(1H)-azulenone, 7-dihydroxy-2-(4-hydroxyphenyl)-8-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-6-(3,4,5-trihydroxyoxan-2-yl)chromen-4-one, acetylcholine, farrerol, pyrogallol, ethyl gallate, demethylwedelolactone, methyl gallate, kaempferide, gallic acid, eriodictyol, threonic acid, inositol, 3',4',7-trihydroxyflavanone, taxifolin, asiatic acid, and isorhamnetin) in additive A were significantly (p < 0.05 or p < 0.01) higher than those in additive B, respectively. It is concluded that the mixture composed of 23 active components in fermented compound Chinese medicine feed additive A plays an important role in inhibiting the growth of Staphylococcus aureus, Salmonella cholerae suis, Escherichia coli, and Streptococcus agalactiae.
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BACKGROUND: To synthesize mesoporous titanium dioxide composite hydroxyapatite (TiO2-HAP) and to evaluate its effectiveness in sealing of occluding dentine tubules. METHODS: TiO2-HAP was synthesized by chemical precipitation method and characterized using infrared absorption spectrometer, X-ray diffraction, scanning electron microscope, and specific surface area detector. Forty completely extracted molars were prepared and randomly assigned into Control group, Gluma group, HAP group and TiO2-HAP group according to different treatments. The characteristics of HAP and TiO2-HAP and the sealing effectiveness of dentine tubules in these four groups, including infrared spectrum, surface contact angle, pore size distribution, and re-mineralized enamel surface profiles, were analyzed by suitable characterized techniques. The cytotoxicity of the synthesized TiO2-HAP was tested and compared using 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetry. RESULTS: Our results showed TiO2-HAP group had significantly lower contact angle, higher specific surface area, and wider range of pore size distribution than other groups. The majority of dentinal tubules in the TiO2-HAP group were blocked by white matter in a uniformed manner, and the crystals arranged in order grew along the axial direction. In addition, no significant difference in optical density (OD) value was found between control group and TiO2-HAP group (P > 0.05), and cell growth was good in TiO2-HAP group, indicating no cytotoxicity of TiO2-HAP. CONCLUSIONS: The MTT assay identified that TiO2-HAP had little effect on the L929 cell line. We showed TiO2-HAP might be used as a remineralization agent in enamel caries-like lesions.
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Dentina , Durapatita , Durapatita/química , Durapatita/farmacología , Humanos , Microscopía Electrónica de Rastreo , Titanio/química , Titanio/farmacologíaRESUMEN
In recent years, researchers have found that epigenetics plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). DNA methylation is involved in the proliferation and metastasis of HCC. However, the junctophilin 3 (JPH3) level and the potential regulatory mechanism of its DNA methylation in HCC remain uncertain. In the present study, 73 HCC samples were enrolled to analyze the expression of JPH3. Reversetranscription quantitative PCR, western blotting and immunohistochemistry were used to detect the expression of JPH3 in HCC. KaplanMeier method and Cox regression analysis were applied to evaluate the prognostic impact of JPH3 on HCC patients. DNA methylationspecific PCR and bisulfite Sanger sequencing were used to detect the degree of DNA methylation of JPH3 in HCC. The demethylation drug 5Aza2'deoxycytidine (5Aza) was used to reduce the DNA methylation of JPH3. The role of JPH3 in the malignant biological behavior of HCC by promoting epithelialmesenchymal transition (EMT) was confirmed by functional cell experiments. The results showed that JPH3 exhibited low levels in HCC tissues and cell lines. HCC patients with low expression of JPH3 had poor survival outcomes. JPH3 had higher DNA methylation levels in HCC tissues and cell lines. When the demethylation drug 5Aza was used to reduce the degree of methylation of JPH3, its protein expression level was significantly increased and it significantly inhibited the malignant biological behavior of HCC cells. Additionally, effective increase in the expression of JPH3 through gene regulation technology also inhibited the proliferation, invasion and migration of HCC cells. After altering the DNA methylation level of JPH3, the EMT of HCC cells was also affected. Therefore, our study demonstrated the inactivation of JPH3 by promoter methylation and its function as a tumor suppressor in HCC. JPH3 may serve as a biomarker for early diagnosis and as a potential therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de la Membrana , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoptosis/efectos de los fármacos , Azacitidina/farmacología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Islas de CpG , Metilación de ADN/efectos de los fármacos , Regulación hacia Abajo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Estimación de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Pronóstico , Regiones Promotoras GenéticasRESUMEN
MCM3AP-AS1 regulates the cartilage repair in osteoarthritis, but how it regulates osteogenic differentiation of dental pulp stem cells (DPSCs) remains to be determined. DPSCs were isolated and induced for osteogenic differentiation. MCM3AP-AS1 expression was increased along with the osteogenic differentiation of DPSCs, whose expression was positive correlated with those of OCN, alkaline phosphatase (ALP) and RUNX2. On contrary, miR-143-3p expression was decreased along with the osteogenic differentiation and was negatively correlated with those of OCN, ALP and RUNX2. Dual-luciferase reporter gene assay showed that miR-143-3p can be negatively regulated by MCM3AP-AS1 and can regulate IGFBP5. MCM3AP-AS1 overexpression increased the expression levels of osteogenesis-specific genes, ALP activity and mineralized nodules during DPSC osteogenic differentiation, while IGFBP5 knockdown or miR-143-3p overexpression counteracted the effect of MCM3AP-AS1 overexpression in DPSCs. Therefore, this study demonstrated the role of MCM3AP-AS1/miR-143-3p/IGFBP5 axis in regulating DPSC osteogenic differentiation.
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Acetiltransferasas/fisiología , Diferenciación Celular/genética , Pulpa Dental/citología , Regulación del Desarrollo de la Expresión Génica/genética , Expresión Génica/genética , Expresión Génica/fisiología , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Péptidos y Proteínas de Señalización Intracelular/fisiología , MicroARNs/metabolismo , Osteogénesis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/fisiología , Células Madre/fisiología , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Fosfatasa Alcalina/metabolismo , Diferenciación Celular/fisiología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Osteogénesis/fisiología , ARN Largo no Codificante/metabolismo , Células Madre/metabolismoRESUMEN
Perovskite-type transition metal oxides have emerged as promising electrocatalysts for various electrocatalytic reactions owing to their low cost, compositional tunability and high stability. However, insufficient electrocatalytic activities of pristine perovskite oxides hinder their pathway towards real-world applications. The incorporation of heteroatoms into perovskite oxide structures has been regarded as an efficient way to improve the electrocatalytic performance. This minireview summarizes the recent advances in the heteroatom doping of perovskite oxides as efficient electrocatalysts for the hydrogen evolution reaction (HER), oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). These heteroatom doping strategies are classified based on various types of doping sites. The mechanisms of improved electrocatalytic activities are discussed in detail within different doping sites and various kinds of dopants. Finally, the remaining challenges and perspectives are outlined for future developments of perovskite oxide-based catalysts.
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Indoleamine 2, 3-dioxygenase (IDO), a tryptophan-catabolizing enzyme, is essential in physiological immunoregulation. The present research was conducted to elucidate the expression and roles of IDO in decidual macrophages (dMφ) during early pregnancy. Here, we observed a remarkable decrease of IDO+ dMφ from patients with unexplained recurrent spontaneous abortion (URSA). IDO+ dMφ displayed M2 phenotype with higher CD206, CD209 and CD163, and lower CD86. Interestingly, treatment with 1-methyl-d-tryptophan (1-MT, an IDO pathway inhibitor) led to the M1 bias of dMφ. Further analysis of the cytokine array and the qPCR showed decreased levels of trophoblast proliferation or invasion-related molecules (e.g., CXCL12 and BMP2) in 1-MT-treated dMφ. The data of co-culture system showed that 1-MT-pretreated dMφ decreased the proliferation and the expression of Ki-67 and Bcl-2, and increased cell apoptosis of HTR-8/Snveo cells. Additionally, the expression of IDO in U937 cells was up-regulated by decidual stromal cells (DSC) and HTR-8/Snveo cells in vitro, as well as estradiol and medroxyprogesterone. These data suggest that endocrine environment, DSC and trophoblasts should contribute to the high level of IDO in dMφ, and IDO+ dMφ with M2 dominant phenotype promote the survival of trophoblasts during early pregnancy. The abnormal lower level of IDO should trigger the dysfunction of dMφ, further suppress the survival of trophoblasts and increase the risk of miscarriage.
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Aborto Espontáneo/inmunología , Decidua/inmunología , Macrófagos/inmunología , Embarazo/inmunología , Células Th2/inmunología , Trofoblastos/fisiología , Apoptosis , Diferenciación Celular , Proliferación Celular , Técnicas de Cocultivo , Citocinas/metabolismo , Femenino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Recurrencia , Células U937RESUMEN
Hemorrhagic fever with renal syndrome (HFRS) is an acute natural focal viral disease caused by viruses of the genus hantavirus, characterized by damage to small blood vessels, kidneys, lungs and other organs of a person. MicroRNAs (miRNAs) are 18-22 nucleotide endogenously expressed RNA molecules that inhibit gene expression at the post-transcriptional level by binding to the 3-untranslated region of the target mRNA. It has been proven that miRNAs play a significant role in various biological processes, including the cell cycle, apoptosis, cell proliferation and differentiation. It has been proven that miRNAs may be involved in the pathogenesis of infectious diseases, including HFRS. Hantavirus infection predominantly affects endothelial cells and causes dysfunction of the endothelium of capillaries and small vessels. It is known that the immune response induced by Hantavirus infection plays an important role in disrupting the endothelial barrier. In a few studies, both in vitro and in vivo, it has been shown that endothelial dysfunction and the immune response after infection with Hantavirus can be partially regulated by miRNAs by acting on certain genes. Most of the miRNAs is expressed within the cells themselves. However, in some biological fluids of the human body, for example, plasma or blood serum, numerous miRNAs, called circulating miRNAs, have been found. Circulating miRNAs can be secreted by cells into human biological fluids as part of extracellular vesicles as exosomes or be part of an RNA-bound protein complex as miRNA-Argonaute 2 (Ago2). These miRNAs are resistant to nucleases, which makes them attractive as potential biomarkers in various human diseases. There is no specific antiviral therapy for HFRS, and the determination of laboratory parameters that are used to diagnose, assess the severity, and predict the course of the disease remains a challenge due to the peculiarities of the pathophysiology and clinical course of the disease. Studying the role of miRNAs in HFRS seems to be expedient for the development of specific and effective therapy, as well as for use as diagnostic and prognostic biomarkers (in relation to circulating miRNAs).
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Fiebre Hemorrágica con Síndrome Renal , MicroARNs , Orthohantavirus , Células Endoteliales , Orthohantavirus/genética , Fiebre Hemorrágica con Síndrome Renal/genética , Humanos , Riñón , MicroARNs/genéticaRESUMEN
Tuberculosis is a chronic inflammatory disease caused by Mycobacterium tuberculosis. When tuberculosis invades the human body, innate immunity is the first line of defense. However, how the innate immune microenvironment responds remains unclear. In this research, we studied the function of each type of cell and explained the principle of an immune microenvironment. Based on the differences in the innate immune microenvironment, we modularized the analysis of the response of five immune cells and two structural cells. The results showed that in the innate immune stress response, the genes CXCL3, PTGS2 and TNFAIP6 regulated by the nuclear factor kappa B(NK-KB) pathway played a crucial role in fighting against tuberculosis. Based on the active pathway algorithm, each immune cell showed metabolic heterogeneity. Besides, after tuberculosis infection, structural cells showed a chemotactic immunity effect based on the co-expression immunoregulatory module.
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Biología Computacional/métodos , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata , Mycobacterium tuberculosis/inmunología , Tuberculosis/genética , Tuberculosis/inmunología , Algoritmos , Moléculas de Adhesión Celular/genética , Quimiocinas CXC/genética , Ciclooxigenasa 2/genética , Células Endoteliales/inmunología , Células Epiteliales/inmunología , Humanos , Linfocitos Intraepiteliales/inmunología , Células Asesinas Naturales/inmunología , Pulmón/patología , Macrófagos Alveolares/inmunología , Células T Invariantes Asociadas a Mucosa/inmunología , Células T Asesinas Naturales/inmunología , Tuberculosis/microbiología , Tuberculosis/patologíaRESUMEN
Programmed death ligand 2 (PD-L2) is the second ligand of programmed death 1 (PD-1) protein. In autoimmune myocarditis, the protective roles of PD-1 and its first ligand programmed death ligand 1 (PD-L1) have been well documented; however, the role of PD-L2 remains unknown. In this study, we report that PD-L2 deficiency exacerbates myocardial inflammation in mice with experimental autoimmune myocarditis (EAM). EAM was established in wild-type (WT) and PD-L2-deficient mice by immunization with murine cardiac myosin peptide. We found that PD-L2-deficient mice had more serious inflammatory infiltration in the heart and a significantly higher myocarditis severity score than WT mice. PD-L2-deficient dendritic cells (DCs) enhanced CD4+ T cell proliferation in the presence of T cell receptor and CD28 signaling. These data suggest that PD-L2 on DCs protects against autoreactive CD4+ T cell expansion and severe inflammation in mice with EAM.
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Enfermedades Autoinmunes/inmunología , Antígeno B7-H1/inmunología , Miocarditis/inmunología , Proteína 2 Ligando de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Animales , Enfermedades Autoinmunes/patología , Linfocitos T CD4-Positivos/inmunología , Proliferación Celular , Células Dendríticas/inmunología , Masculino , Ratones , Miocarditis/patologíaRESUMEN
Escherichia coli O157:H7 is an important foodborne pathogen that has become a major worldwide factor affecting the public safety of food. Bacteriophage has gradually attracted attention because of its ability to kill specific pathogens. In this study, a lytic phage of E. coli O157:H7, named FEC14, was isolated from hospital sewage. Transmission electron microscopy analysis showed that phage FEC14 had an isometric head 80 ± 5 nm in diameter and a contractile tail whose terminal spikes present an umbrella-like structure. Phage FEC14 revealed 158,639 bp double-stranded DNA, with the G+C content of 44.6%, 209 ORFs and four tRNAs. Genome DNA of FEC14 could not be digested by some endonucleases. Many of the features of phage FEC14 are very similar to those of the newly classified genus "Kuttervirus", including morphology, genome size and organization, etc. Phage FEC14 is proposed to be a new isolate of genus "Kuttervirus" within the family Ackermannviridae, moreover, the endonuclease resistance of phage FEC14, has priority over other genera of bacteriophages for its use in biocontrol of foodborne pathogens.
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Bacteriófagos , Escherichia coli O157 , Genoma Viral , Bacteriófagos/clasificación , Bacteriófagos/aislamiento & purificación , Composición de Base , Escherichia coli O157/virología , Genómica , Sistemas de Lectura AbiertaRESUMEN
PURPOSE: The purpose of this study was to evaluate the effect of recycling on the properties of interface between 2 dental alloys and their corresponding porcelains. MATERIALS AND METHODS: Noble alloy (Pd-Cu-Ga) and high-noble alloy (Au-Pt) were used in this study. Metal matrices (cylinders Φ4 mm × 4 mm with pedestal Φ5 mm × 1 mm) were prepared by arc melting in argon after recasting 1-3 times. Corresponding porcelain with overall dimensions of Φ4 mm × 2 mm was veneered on each metal cylinder. There were 22 specimens in each alloy group. Specifically, two specimens of each group were chosen randomly for interfacial morphology and diffusion analyses by scanning electron microscopy (SEM) equipped with energy-dispersive X-ray spectroscopy (EDS). The remaining 20 specimens were divided into 2 groups with or without thermal cycling. The bond strength was evaluated by shear test, and the data were analyzed by two-way analysis of variance (ANOVA). The failure mode of shear test specimen was observed with a stereoscopic microscopy and subjected to the exact probability test (α = 0.05). RESULTS: According to the results from SEM, no obvious difference was observed in the interfacial morphology of both Pd-Cu-Ga and Au-Pt alloys among different recasting specimens. EDS analysis revealed that no significant difference was found in the width of elemental diffusion among 2 test alloys after recycling 1-3 times. Notably, in Pd-Cu-Ga alloy groups, the peak of Ga in thrice recasting was lower than those in first and second recastings. And there was no significant difference (P > 0.05) in the metal-ceramic shear bond strength of Pd-Cu-Ga and Au-Pt alloys after recycling 1-3 times, with or without thermal cycling. The results of failure modes observed on specimens were not affected by the recycling and thermal cycling in the 2 tested alloys. CONCLUSIONS: Within the limitations of this study, the Pd-Cu-Ga and Au-Pt alloys can be recycled 2 times without significant changes on the properties of metal-ceramic interface, with or without thermal cycling.
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Cerámica/química , Aleaciones Dentales/química , Aleaciones de Cerámica y Metal/química , Reciclaje , Aleaciones de Cromo , Porcelana Dental , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Resistencia al Corte , Propiedades de SuperficieRESUMEN
Enterovirus D68 (EV-D68) is a member of the Picornavirus family and a causative agent of respiratory diseases in children. The incidence of EV-D68 infection has increased worldwide in recent years. Thus far, there are no approved antiviral agents or vaccines for EV-D68. Here, we show that methyl-ß-cyclodextrin (MßCD), a common drug that disrupts lipid rafts, specifically inhibits EV-D68 infection without producing significant cytotoxicity at virucidal concentrations. The addition of exogenous cholesterol attenuated the anti-EV-D68 activity of MßCD. MßCD treatment had a weak influence on the attachment of viral particles to the cell membrane but significantly inhibited EV-D68 entry into host cells. We demonstrated that EV-D68 facilitated the translocation of the viral receptor ICAM-5 to membrane rafts in infected cells. The colocalization of viral particles with ICAM-5 in lipid rafts was thoroughly abolished in cells after treatment with MßCD. Finally, we showed that MßCD inhibited the replication of isolated circulating EV-D68 strains. In summary, our results demonstrate that MßCD suppresses EV-D68 replication by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts. This mechanism represents a promising strategy for drug development.
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Antivirales/farmacología , Moléculas de Adhesión Celular/metabolismo , Microdominios de Membrana/efectos de los fármacos , Microdominios de Membrana/virología , Proteínas del Tejido Nervioso/metabolismo , Internalización del Virus/efectos de los fármacos , beta-Ciclodextrinas/farmacología , Células A549 , Colesterol/farmacología , Enterovirus Humano D/efectos de los fármacos , Enterovirus Humano D/fisiología , Células HeLa , Humanos , Replicación Viral/efectos de los fármacosRESUMEN
Adenosine deaminase (ADA) is an important enzyme related to purine nucleoside metabolism in human serum and various tissues. Abnormal ADA levels are related to a wide variety of diseases such as rheumatoid arthritis, AIDS, anemia, lymphoma, and leukemia and ADA is considered as a useful target for various diseases. Currently, ADA can be divided into open conformation and closed conformation according to the inhibitors of binding. As a consequence, we chose two inhibitors, namely, 6-hydroxy-1,6-dihydro purine nucleoside (PRH) and N-[4,5-bis(4-hydroxyphenyl)-1,3-thiazol-2-yl]hexanamide (FRK) to bind to ADA in the closed conformation or open conformation respectively. In this study, we performed the random acceleration molecular dynamics (RAMD) method, steered molecular dynamics (SMD) simulations and adaptive basing force (ABF) simulation to explore the unbinding tunnels and tunnel characteristics of the two inhibitors in ADA. Our results showed that PRH and FRK escaped from ADA using three main tunnels (namely, T1, T2, and T3). Inhibitors (PRH and FRK) escape through T3 more frequently and more easily. The results from ABF simulations confirm that the free energy barrier in T1 or T2 is larger than that in T3 when inhibitors dissociate from the ADA and have potential mean of force (PMF) depth. Moreover, in the complexes (ADA-PRH, ADA-FRK), we also found that the most active residue that remarkably contributed to the binding affinity is W117 in T3, and the residue played an important role in the unbinding tunnel for inhibitor leaving. Our theoretical study provided insight into the ADA inhibitor passway mechanism and may be a clue for potent ADA inhibitor design.
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Phage PA-YS35 is a novel lytic Pseudomonas aeruginosa phage belonging to the Myoviridae family and was isolated from the sewage of the First Hospital of Jilin University. The biological properties testing indicated that phage PA-YS35 is stable between - 20 and 60 °C and pH 4-9. The one-step growth curve shows that the latent period of PA-YS35 was 9 min, and the burst period was about 21 min by the size of approximately 380 progeny phages per host cell. The genome of phage PA-YS35 is linear double-stranded DNA with a size of 93,296 bp and a GC content of 49.35%. The results from RAST gene annotation analysis showed that the PA-YS35 genome contains 172 open reading frames (ORFs); the function of 41 ORFs can be predicted, whereas the product of remaining 131 ORFs are hypothetical proteins. According to phylogenetic tree of RNA ligase encoding sequence, phage PA-YS35 has a close evolutionary relationship with Pseudomonas phage PAK P1 because both of them are located on the same branch. The study of phage PA-YS35 genome will provide useful information for further research on the interaction between phages and their hosts.