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1.
Chaos ; 30(1): 013104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32013467

RESUMO

Complex networks have found many applications in various fields. An important problem in theories of complex networks is to find factors that aid link prediction, which is needed for network reconstruction and to study network evolution mechanisms. Though current similarity-based algorithms study factors of common neighbors and local paths connecting a target node pair, they ignore factor information on paths between a node and its neighbors. Therefore, this paper first supposes that paths between nodes and neighbors provide basic similarity features. Accordingly, we propose a so-called relative-path-based method. This method utilizes factor information on paths between nodes and neighbors, besides paths between node pairs, in similarity calculation for link prediction. Furthermore, we solve the problem of determining the parameters in our algorithm as well as in other algorithms after a series of discoveries and validations. Experimental results on six disparate real networks demonstrate that the relative-path-based method can obtain greater prediction accuracy than other methods, as well as performance robustness.

3.
Environ Microbiol ; 22(1): 286-296, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31667998

RESUMO

The (R)- and (S)-enantiomers of the chiral herbicide napropamide (NAP) show different biological activities and ecotoxicities. These two enantiomers behave differently in the environment due to enantioselective catabolism by microorganisms. However, the molecular mechanisms underlying this enantioselective catabolism remain largely unknown. In this study, the genes (snaH and snpd) involved in the catabolism of NAP were cloned from Sphingobium sp. B2, which was capable of catabolizing both NAP enantiomers. Compared with (R)-NAP, (S)-NAP was much more rapidly transformed by the amidase SnaH, which initially cleaved the amide bonds of (S)/(R)-NAP to form (S)/(R)-2-(1-naphthalenyloxy)-propanoic acid [(S)/(R)-NP] and diethylamine. The α-ketoglutarate-dependent dioxygenase Snpd, showing strict stereoselectivity for (S)-NP, further transformed (S)-NP to 1-naphthol and pyruvate. Molecular docking and site-directed mutagenesis analyses revealed that when the (S)-enantiomers of NAP and NP occupied the active sites, the distance between the ligand molecule and the coordination atom was shorter than that when the (R)-enantiomers occupied the active sites, which facilitated formation of the transition state complex. This study enhances our understanding of the preferential catabolism of the (S)-enantiomer of NAP on the molecular level.

4.
Comput Math Methods Med ; 2019: 1926156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814842

RESUMO

The analysis and prediction of small molecule binding sites is very important for drug discovery and drug design. The traditional experimental methods for detecting small molecule binding sites are usually expensive and time consuming, and the tools for single species small molecule research are equally inefficient. In recent years, some algorithms for predicting binding sites of protein-small molecules have been developed based on the geometric and sequence characteristics of proteins. In this paper, we have proposed SmoPSI, a classification model based on the XGBoost algorithm for predicting the binding sites of small molecules, using protein sequence information. The model achieved better results with an AUC of 0.918 and an ACC of 0.913. The experimental results demonstrate that our method achieves high performances and outperforms many existing predictors. In addition, we also analyzed the binding residues and nonbinding residues and finally found the PSSM; hydrophilicity, hydrophobicity, charge, and hydrogen bonding have obviously different effects on the binding-site predictions.

5.
Microbiol Resour Announc ; 8(50)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831608

RESUMO

Escherichia coli sequence type 410 (ST410) is now an international high-risk clone and is responsible for a large number of clinical infections. Here, we report the draft genome sequence of an ST410 clinical isolate harboring multiple bla NDM-5 genes that was obtained from urine culture in China.

6.
J Glob Antimicrob Resist ; 19: 354-355, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31698110

RESUMO

OBJECTIVES: Mortality associated with carbapenemase-producing Enterobacteriaceae is high as there are few therapeutic options. Escherichia coli sequence type 410 (ST410) is currently an international high-risk clone and is responsible for a large number of clinical infections. Here we report the draft genome sequence of a ST410 clinical E. coli isolate (ECS9) co-harbouring blaNDM-5, blaOXA-1, blaCTX-M-15, blaCMY-2, aac(3)-IIa and aac(6')-Ib-cr genes, obtained from a patient with bloodstream infection in China. METHODS: The genome of E. coli ECS9 was sequenced using an Illumina HiSeqTM 4000 instrument with a 150-bp paired-end approach. Generated sequence reads were assembled using Velvet 1.2.10. Contigs were annotated using Rapid Annotation using Subsystem Technology (RAST), and further whole-genome sequence data analyses were performed. RESULTS: Escherichia coli ECS9 belongs to multilocus sequence typing (MLST) ST410. The total number of assembled bases was 4 935 145 bp, with 5077 protein-coding sequences. The presence of the blaNDM-5, blaOXA-1, blaCTX-M-15 and blaCMY-2 genes was detected in addition to other antimicrobial resistance genes conferring resistance to fluoroquinolones, aminoglycosides, trimethoprim, sulfonamides and tetracyclines. CONCLUSION: To our knowledge, this is the first report of anE. coli ST410 strain co-harbouring blaNDM-5, blaOXA-1, blaCTX-M-15, blaCMY-2, aac(3)-IIa and aac(6')-Ib-cr, obtained from a bloodstream infection in China. The presented genome sequence of carbapenemase-producing E. coli strain ST410 could provide further insight into the acquisition of multiple resistance genes by this successful lineage.

7.
Cell ; 179(6): 1342-1356.e23, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31759698

RESUMO

Mammalian switch/sucrose non-fermentable (mSWI/SNF) complexes are multi-component machines that remodel chromatin architecture. Dissection of the subunit- and domain-specific contributions to complex activities is needed to advance mechanistic understanding. Here, we examine the molecular, structural, and genome-wide regulatory consequences of recurrent, single-residue mutations in the putative coiled-coil C-terminal domain (CTD) of the SMARCB1 (BAF47) subunit, which cause the intellectual disability disorder Coffin-Siris syndrome (CSS), and are recurrently found in cancers. We find that the SMARCB1 CTD contains a basic α helix that binds directly to the nucleosome acidic patch and that all CSS-associated mutations disrupt this binding. Furthermore, these mutations abrogate mSWI/SNF-mediated nucleosome remodeling activity and enhancer DNA accessibility without changes in genome-wide complex localization. Finally, heterozygous CSS-associated SMARCB1 mutations result in dominant gene regulatory and morphologic changes during iPSC-neuronal differentiation. These studies unmask an evolutionarily conserved structural role for the SMARCB1 CTD that is perturbed in human disease.

8.
Sensors (Basel) ; 19(19)2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557972

RESUMO

environmental perception technology based onWiFi, and some state-of-the-art techniques haveemerged. The wide application of small-scale motion recognition has aroused people's concern.Handwritten letter is a kind of small scale motion, and the recognition for small-scale motion basedon WiFi has two characteristics. Small-scale action has little impact on WiFi signals changes inthe environment. The writing trajectories of certain uppercase letters are the same as the writingtrajectories of their corresponding lowercase letters, but they are different in size. These characteristicsbring challenges to small-scale motion recognition. The system for recognizing small-scale motion inmultiple classes with high accuracy urgently needs to be studied. Therefore, we propose MCSM-Wri,a device-free handwritten letter recognition system using WiFi, which leverages channel stateinformation (CSI) values extracted from WiFi packets to recognize handwritten letters, includinguppercase letters and lowercase letters. Firstly, we conducted data preproccessing to provide moreabundant information for recognition. Secondly, we proposed a ten-layers convolutional neuralnetwork (CNN) to solve the problem of the poor recognition due to small impact of small-scaleactions on environmental changes, and it also can solve the problem of identifying actions with thesame trajectory and different sizes by virtue of its multi-scale characteristics. Finally, we collected6240 instances for 52 kinds of handwritten letters from 6 volunteers. There are 3120 instances fromthe lab and 3120 instances are from the utility room. Using 10-fold cross-validation, the accuracyof MCSM-Wri is 95.31%, 96.68%, and 97.70% for the lab, the utility room, and the lab+utility room,respectively. Compared with Wi-Wri and SignFi, we increased the accuracy from 8.96% to 18.13% forrecognizing handwritten letters.

9.
Phys Rev Lett ; 123(4): 047203, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31491273

RESUMO

The recent discovery of intrinsic ferromagnetic order in the atomically thin van der Waals crystal CrXTe_{3} (X=Si, Ge) stimulates intensive studies on the nature of low-dimensional magnetism because the presence of long-range magnetic order in two-dimensional systems with continuous symmetry is strictly prohibited by thermal fluctuations. By combining advanced many-body calculations with angle-resolved photoemission spectroscopy we investigate CrSiTe_{3} single crystals and unveil the pivotal role played by the strong electronic correlations at both high- and low-temperature regimes. Above the Curie temperature (T_{c}), Coulomb repulsion (U) drives the system into a charge transfer insulating phase. In contrast, below T_{c} the crystal field arranges the Cr-3d orbitals such that the ferromagnetic superexchange profits, giving rise to the bulk ferromagnetic ground state with which the electronic correlations compete. The excellent agreement between theory and experiment establishes CrSiTe_{3} as a prototype low-dimensional crystal with the cooperation and interplay of electronic correlation and ferromagnetism.

10.
Int J Syst Evol Microbiol ; 69(12): 3806-3811, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31464658

RESUMO

A strictly aerobic, Gram-stain-negative, rod-shaped, yellow, non-spore-forming bacterial strain, designated P-25T, was isolated from soil collected in Yantai, Shandong Province, PR China. The temperature, pH and NaCl concentration ranges for the growth of strain P-25T were 10-37 °C (optimum, 28-30 °C), pH 6.0-9.0 (optimum, pH 7.5-8.0) and 0-4 % (w/v) (optimum, 1 % w/v), respectively. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain P-25T was most closely related to Pedobacter xixiisoli S27T (98.1 % 16S rRNA gene sequence similarity), followed by Pedobacter chitinilyticus CM134L-2T (97.2 %) and Pedobacter ureilyticus THG-T11T (97.1 %). The genomic DNA G+C content of strain P-25T based on its draft genome sequence was 38.1 %. MK-7 was the major respiratory quinone, and iso-C15 : 0, C16 : 1ω7c and/or C16 : 1ω6c (summed feature 3) and iso-C17 : 0 3-OH were the major fatty acids. The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid, one unidentified phospholipid, two unidentified lipids, five unidentified aminolipids and two unidentified glycolipids. Average nucleotide identity values for the draft genomes between strain P-25T and strains S27T, CM134L-2T and THG-T11T were 81.8, 77.6 and 81.2 %, respectively, and the digital DNA-DNA hybridization (dDDH) values were 30.0, 19.2 and 27.6 %, respectively. Based on their phylogenetic and phenotypic characteristics, chemotaxonomic data, and dDDH results, strain P-25T is considered to represent a novel species of the genus Pedobacter, for which the name Pedobacter helvus sp. nov. is proposed; the type strain is strain P-25T (KCTC 62821T=CCTCC AB 2018185T).


Assuntos
Fazendas , Pedobacter/classificação , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Glicolipídeos/química , Hibridização de Ácido Nucleico , Pedobacter/isolamento & purificação , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/química
11.
Int J Syst Evol Microbiol ; 69(11): 3443-3447, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31436521

RESUMO

A Gram-stain-negative bacterial strain, designated JW-3T, was isolated from a soil sample collected from farmland in Yantai, Shandong Province, PR China. Cells of strain JW-3T are motile rods and strictly aerobic, showing catalase- and oxidase-positive reactions. Strain JW-3T could grow at 16-37 °C (optimum, 30 °C), at pH 6.0-9.0 (pH 7.0) and in the presence of 0-1 % (w/v) NaCl (0.5 %, in Luria-Bertani broth). The major fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 35.5 %), iso-C16 : 0 (16.7 %) and C12 : 0 (10.8 %). The major respiratory quinone was ubiquinone-8 (Q8). The polar lipids of strain JW-3T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, four unidentified phospholipids, two unidentified lipids, two unidentified glycolipids and a partial unidentified aminophospholipid. Strain JW-3T was most closely related to Steroidobacter agariperforans KA5-BT with 97.67 % 16S rRNA gene sequence similarity. Results of phylogenetic analyses, based on 16S rRNA gene sequencing, showed that strain JW-3T forms a distinct phylogenic lineage within the genus Steroidobacter of the family Sinobacteraceae. The DNA G+C content of strain JW-3T was 62.57 mol%, based on its draft genome sequence. Average nucleotide identity values and digital DNA-DNA hybridization values for draft genomes, between strain JW-3T and strain KA5-BT, were 84.54 and 30.80 %, respectively. Based on its phenotypic, chemotaxonomic and molecular features, and DNA-DNA hybridization results, strain JW-3T represents a novel species of the genus Steroidobacter, for which the name Steroidobactersoli sp. nov. is proposed. The type strain is JW-3T (=CCTCC AB 2018184T=KCTC 62820T).


Assuntos
Fazendas , Gammaproteobacteria/classificação , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Gammaproteobacteria/isolamento & purificação , Glicolipídeos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
12.
Artif Cells Nanomed Biotechnol ; 47(1): 2830-2837, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31298047

RESUMO

Abnormal expression of microRNAs (miRNAs) contributes to tumour growth and invasion. MiR-326 expression often down-regulates in several kinds of cancer and low expression of miR-326 is linked with poor prognosis in cancer patients. In the present study, we aimed to explore the modulatory mechanism of miR-326 in hepatocellular carcinoma (HCC). miR-326 expression was significantly decreased in HCC cell lines and tissues. miR-326 decreased HCC cell growth by affecting cell-cycle progression and by promoting apoptosis. In addition, miR-326 inhibited HCC cell invasion by decreasing the EMT phenotype. We found that miR-326 functioned as a tumour suppressor by repressing its down-stream target PDK1. C-myc contributed to miR-326 down-regulation through binding at its promoter and inhibited its expression. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying miR-326. Restoration of miR-326 reduced tumour growth in vivo. Our findings suggest that miR-326 may be a candidate prognostic biomarker and a target for new therapies in HCC patients.


Assuntos
Carcinoma Hepatocelular/patologia , Ouro/química , Nanopartículas Metálicas/química , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , /metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Portadores de Fármacos/química , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias Hepáticas/patologia , MicroRNAs/química , Terapia de Alvo Molecular
13.
J Agric Food Chem ; 67(24): 6819-6827, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31135148

RESUMO

Napropamide [ N, N-diethyl-2-(1-naphthalenyloxy)propenamide, NAP] is a highly efficient and broad-spectrum amide herbicide. Little is known about the bacterial catabolism of its different enantiomers. Here, we report the isolation of two NAP-degrading strains of Sphingobium sp., A1 and B2, and the different catabolic pathways of different enantiomers in these two strains. Strain A1 dioxygenated NAP at different positions of the naphthalene ring of different enantiomers, leading to the complete degradation of R-NAP while producing a dead-end product from S-NAP. Strain B2 cleaved the amido bonds of both enantiomers, but only the product from S-NAP could be further transformed to form α-naphthol and mineralize in strain B2. The degradation rates of R-NAP and S-NAP in the combination degradation by strains A1 and B2 were 24.8 and 7.5 times that in the single-strain degradation by strain B2 or A1, respectively, showing enhanced synergistic catabolism between strains A1 and B2. This study provides new insights into the enantioselective catabolic network of the chiral herbicide NAP in microorganisms.


Assuntos
Herbicidas/química , Herbicidas/metabolismo , Naftalenos/química , Naftalenos/metabolismo , Sphingomonadaceae/metabolismo , Biodegradação Ambiental , Sphingomonadaceae/química , Estereoisomerismo
14.
J Int Med Res ; 47(6): 2371-2380, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30991875

RESUMO

OBJECTIVE: To compare genome-wide DNA methylation between samples of sinonasal inverted papilloma (SNIP) and squamous cell carcinoma (SCC) samples in order to identify aberrantly methylated genes that might be involved in malignant transformation. METHODS: Tissue samples were collected from patients. DNA methylation in C-phosphate-G islands and gene promoters was analysed using a DNA methylation microarray kit. The levels of mRNA or protein from aberrantly methylated genes were measured using real-time polymerase chain reaction or Western blot analysis. RESULTS: A total of 27 tissue samples were included in this study; 15 SNIP samples and 12 SCCs arising in SNIPs. A total of 11 201 nominally differentially methylated sites were observed between SNIP and SCC arising in SNIPs. Six sites were significantly different at P < 0.01 and contained three genes ( MIR661, PLEC and OPA3). These three genes were hypermethylated. In addition, the levels of mature miR-661 mRNA and PLEC protein were significantly upregulated in SCC tissues compared with SNIP samples. The levels of OPA3 protein were downregulated in SCC tissues compared with SNIP samples. CONCLUSIONS: This study demonstrated hypermethylation and abnormal expression of the MIR661, PLEC and OPA3 genes, suggesting a role for their involvement in the malignant transformation of SNIP.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Transformação Celular Neoplásica/patologia , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Papiloma Invertido/diagnóstico , Neoplasias dos Seios Paranasais/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Papiloma Invertido/genética , Papiloma Invertido/metabolismo , Neoplasias dos Seios Paranasais/genética , Neoplasias dos Seios Paranasais/metabolismo , Plectina/genética , Plectina/metabolismo , Prognóstico , Proteínas/genética , Proteínas/metabolismo , Estudos Retrospectivos
15.
Int J Syst Evol Microbiol ; 69(6): 1783-1788, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30973320

RESUMO

An aerobic bacterial strain, designated XJ-2T, was isolated from a soil sample collected from Gurbantunggut Sandy Desert in PR China. Cells of strain XJ-2T were Gram-stain-negative, non-motile, rod-shaped and non-spore-forming. The new isolate grew well at 10-37 °C (optimum, 28-30 °C), pH 6.0-11.0 (pH 7.0) and 0-1 % (w/v) NaCl (0 %). The 16S rRNA gene sequence of strain XJ-2T showed the highest similarity to that of Chitinophaga rhizosphaerae T16R-86T (99.0 %), followed by Chitinophaga barathri YLT18T (97.0 %), Chitinophagahumicola Ktm-2T (96.7 %) and Chitinophaga niabensis JS13-10T (96.4 %). The major menaquinone of strain XJ-2T was menaquinone 7 and the predominant fatty acids (>5 %) were iso-C15 : 0, C16 : 1ω5c and iso-C17 : 0 3-OH. The polar lipids consisted of phosphatidylethanolamine, an unidentified glycolipid, three unidentified aminolipids and five unidentified lipids. The genome size was 6.33 Mb, comprising 5268 predicted genes with a G+C content of 41.5 mol%. The DNA G+C content was 50.5 mol% based on total genome calculations. The average nucleotide identity and the digital DNA-DNA hybridization values between strain XJ-2T and strain T16R-86T were 79.6 and 22.3 %, respectively. DNA-DNA relatedness between strain XJ-2T and strain YLT18T was 17.0 %. Based on the physiological, biochemical and chemotaxonomic characteristics, strain XJ-2T represents a novel species of the genus Chitinophaga, for which the name Chitinophagadeserti sp. nov. is proposed. The type strain is XJ-2T (KCTC 62443T=CCTCC AB 2018019T).


Assuntos
Bacteroidetes/classificação , Clima Desértico , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
16.
J Exp Clin Cancer Res ; 38(1): 138, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922366

RESUMO

BACKGROUND: SOX11 is a transcription factor that plays an important role in mantle cell lymphoma development. However, its functional role in head and neck squamous cell carcinoma (HNSCC) remains unknown. METHODS: Protein expression was measured with Western blotting, immunohistochemistry or quantitative proteomics, and gene expression was measured with quantitative RT-PCR. Functional role of SOX11 in HNSCC was evaluated with MTS/apoptosis, migration, invasion assays and a xenograft model. A SOX11-targeting gene, SDCCAG8, was confirmed with chromatin immunoprecipitation (ChIP), luciferase reporter and rescue assays. RESULTS: SOX11 was up-regulated in recurrent versus primary HNSCC and in highly invasive versus low invasive HNSCC cell lines. Silencing SOX11 in HNSCC cell lines significantly inhibited the cell proliferation, migration, invasion and resistance to Cisplatin, and vice versa. Quantitative proteomic analysis of SOX11-silencing HNSCC cells revealed a number of differentially expressed proteins, including a down-regulated tumor antigen SDCCAG8. Silencing of SDCCAG8 in HNSCC cells also significantly inhibited the cell proliferation, migration and invasion, and vice versa. ChIP assays demonstrated that endogenous SOX11 strongly bound to Sdccag8 gene promoter in highly invasive HNSCC cells. When over-expressed in low invasive HNSCC cells, wild type SOX11 but not mutant SOX11 induced the promoter activity of Sdccag8 and significantly induced the expression of SDCCAG8. However, exogenous mutant SOX11 abolished the expression of SDCCAG8 in highly invasive HNSCC cells. In addition, the inhibitory effects of SOX11 knockdown were partially rescued by over-expression of SDCCAG8 in HNSCC cells. CONCLUSION: Collectively, our findings indicate SOX11 promotes HNSCC progression via the regulation of SDCCAG8.


Assuntos
Autoantígenos/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição SOXC/metabolismo , Regulação para Cima , Animais , Autoantígenos/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Camundongos , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Fatores de Transcrição SOXC/genética
17.
Am J Respir Cell Mol Biol ; 60(6): 705-716, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30742493

RESUMO

Bicarbonate facilitates mucin unpacking and bacterial killing; however, its transport mechanisms in the airways are not well understood. cAMP stimulates anion efflux through the cystic fibrosis (CF) transmembrane conductance regulator (CFTR; ABCC7) anion channel, and this is defective in CF. The anion exchanger pendrin (SLC26A4) also mediates HCO3- efflux and is upregulated by proinflammatory cytokines. Here, we examined pendrin and CFTR expression and their contributions to HCO3- secretion by human nasal and bronchial epithelia. In native tissue, both proteins were most abundant at the apical pole of ciliated surface cells with little expression in submucosal glands. In well-differentiated primary nasal and bronchial cell cultures, IL-4 dramatically increased pendrin mRNA levels and apical immunostaining. Exposure to low-Cl- apical solution caused intracellular alkalinization (ΔpHi) that was enhanced fourfold by IL-4 pretreatment. ΔpHi was unaffected by 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) or CFTR inhibitor CFTRinh-172, but was reduced by adenoviral shRNA targeting pendrin. Forskolin increased ΔpHi, and this stimulation was prevented by CFTRinh-172, implicating CFTR, yet forskolin only increased ΔpHi after pendrin expression had been induced by IL-4. The dependence of ΔpHi on pendrin suggests there is minimal electrical coupling between Cl- and HCO3- fluxes and that CFTR activation increases anion exchange-mediated HCO3- influx. Conversely, inducing pendrin expression increased forskolin-stimulated, CFTRinh-172-sensitive current by approximately twofold in epithelial and nonepithelial cells. We conclude that pendrin mediates most HCO3- secretion across airway surface epithelium during inflammation and enhances electrogenic Cl- secretion via CFTR, as described for other SLC26A transporters.


Assuntos
Bicarbonatos/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Pulmão/metabolismo , Mucosa Respiratória/metabolismo , Transportadores de Sulfato/metabolismo , Animais , Antiporters/metabolismo , Linhagem Celular , Antiportadores de Cloreto-Bicarbonato/metabolismo , Colforsina/farmacologia , AMP Cíclico/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Interleucina-4/genética , Interleucina-4/metabolismo , Transporte de Íons/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Transportadores de Sulfato/genética
18.
Adv Mater ; 31(7): e1806341, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30589119

RESUMO

Manipulation of light below the diffraction limit forms the basis of nanophotonics. Metals can confine light at the subwavelength scale but suffer from high loss of energy. Recent reports have theoretically demonstrated the possibility of light confinement below the diffraction limit using transparent dielectric metamaterials. Here, nanoscale light confinement (<λ/20) in transparent dielectric materials is shown experimentally through a luminescent nanosystem with rationally designed dielectric claddings. Theoretically, green light with a wavelength of 540 nm has a transmission of 98.8% when passing through an ultrathin NaYF4 /NaGdF4 superlattice cladding (thickness: 6.9 nm). Unexpectedly, the complete confinement of green emission (540 nm) by such an ultrathin dielectric cladding is directly observed. FDTD calculations are used to confirm that the ultrathin dielectric cladding has negligible influence on the transmission of propagating light, but extraordinary confinement of evanescent waves. This will provide new opportunities for nanophotonics by completely averting the use of metals.

19.
Sci Rep ; 8(1): 17014, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30451945

RESUMO

Link prediction aims to predict the existence of unknown links via the network information. However, most similarity-based algorithms only utilize the current common neighbor information and cannot get high enough prediction accuracy in evolving networks. So this paper firstly defines the future common neighbors that can turn into the common neighbors in the future. To analyse whether the future common neighbors contribute to the current link prediction, we propose the similarity-based future common neighbors (SFCN) model for link prediction, which accurately locate all the future common neighbors besides the current common neighbors in networks and effectively measure their contributions. We also design and observe three MATLAB simulation experiments. The first experiment, which adjusts two parameter weights in the SFCN model, reveals that the future common neighbors make more contributions than the current common neighbors in complex networks. And two more experiments, which compares the SFCN model with eight algorithms in five networks, demonstrate that the SFCN model has higher accuracy and better performance robustness.

20.
Onco Targets Ther ; 11: 7053-7059, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410362

RESUMO

Background: The aim of this study was to validate the antitumor function of EGFR-chimeric antigen T-cells (CART) targeted to FaDu cells, a hypopharyngeal squamous cell carcinoma cell line, and to provide a preclinical basis for the application of CART cell technology in hypopharyngeal squamous cell carcinoma. Methods: Detection of cytokine secretions of EGFR-CAR T and CART-controls in the presence of target cells and nontarget cells as an indicator of CART cell activation. Detection of the cytotoxic effects of EGFR-CAR T on specific tumors in the presence of target cells was evaluated by LDH release and CART cell proliferation. Results: The results showed that cytokine secretion increased significantly after EGFR-CAR T-cells were incubated with target cells, and EGFR-CAR T-cells has higher cytotoxic effect on target cells than the CART-control group. The target cell lysis rate was 52.66%. The proliferation of EGFR-CAR T-cells in the presence of target cells was not distinctly observed. Conclusion: In this study, we validated the antitumor function of EGFR-CAR T-cells targeted to the FaDu cell line and provided the foundation for application of the CART technique in the treatment of hypopharyngeal carcinoma.

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