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1.
Virol Sin ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32236817

RESUMO

Porcine adenoviruses (PAdVs) are classified into three species, PAdV-A, PAdV-B, and PAdV-C. The genomes of PAdV-A and PAdV-C have been well characterized. However, the genome of PAdV-B has never been completely sequenced, and the epidemiology of PAdV-B remains unclear. In our study, we have identified a novel strain of PAdV-B, named PAdV-B-HNU1, in porcine samples collected in China by viral metagenomic assay and general PCR. The genome of PAdV-B-HNU1 is 31,743 bp in length and highly similar to that of California sea lion adenovirus 1 (C. sea lion AdV-1), which contains typical mastadenoviral structures and some unique regions at the carboxy-terminal end. Especially, PAdV-B-HNU1 harbors a dUTPase coding region not clustering with other mastadenoviruses except for C. sea lion AdV-1 and a fiber coding region homologous with galectin 4 and 9 of animals. However, the variance of GC contents between PAdV-B-HNU1 (55%) and C. sea lion AdV-1 (36%) indicates their differential evolutionary paths. Further epidemiologic study revealed a high positive rate (51.7%) of PAdV-B-HNU1 in porcine lymph samples, but low positive rates of 10.2% and 16.1% in oral swabs and rectal swabs, respectively. In conclusion, this study characterized a novel representative genome of a lymphotropic PAdV-B with unique evolutionary origin, which contributes to the taxonomical and pathogenic studies of PAdVs.

3.
Microbes Infect ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32199943

RESUMO

SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia pandemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2. As a result, we predicted that SARS-CoV-2 tends to utilize ACE2s of various mammals, except murines, and some birds, such as pigeon. This prediction may help to screen the intermediate hosts of SARS-CoV-2.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32070993

RESUMO

Breast cancer is a heterogeneous disease with many clinically distinguishable molecular subtypes each corresponding to a cluster of patients. Identification of prognostic and heterogeneous biomarkers for breast cancer is to detect cluster-specific gene biomarkers which can be used for accurate survival prediction of breast cancer outcomes. In this study, we proposed a FUsion Network-based method (FUNMarker) to identify prognostic and heterogeneous breast cancer biomarkers by considering the heterogeneity of patient samples and biological information from multiple sources. To reduce the affect of heterogeneity of patients, samples were first clustered using the K-means algorithm based on the principal components of gene expression. For each cluster, to comprehensively evaluate the influence of genes on breast cancer, genes were weighted from three aspects: biological function, prognostic ability and correlation with known disease genes. Then they were ranked via a label propagation model on a fusion network that combined physical protein interactions from seven types of networks and thus could reduce the impact of incompleteness of interactome. We compared FUNMarker with three state-of-the-art methods and the results showed that biomarkers identified by FUNMarker were biological interpretable and had stronger discriminative power than the existing methods in differentiating patients with different prognostic outcomes.

5.
Microbes Infect ; 22(2): 80-85, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32087334

RESUMO

At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.


Assuntos
Betacoronavirus/patogenicidade , Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Antivirais/uso terapêutico , Betacoronavirus/genética , China/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Epidemias , Genoma Viral , Humanos , Filogenia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Receptores Virais , Tropismo Viral
6.
Nanotechnology ; 31(23): 235705, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935691

RESUMO

We report a heavily Yb3+/Al3+/B3+/F- co-doped high silica rod with a negative refractive index relative to pure silica. The high silica rod was fabricated from nanoporous silica rod using glass phase-separation technology. To lower the refractive index, B3+ and F- were simultaneously introduced into the silica rod and the optical properties of the silica rod were investigated. The fiber preform was prepared with the rod-in-tube method by which the Yb3+ doped high silica rod was only used as an active core. The fiber has a core diameter of 80 µm and a cladding diameter of 400 µm. The measurements show that the Yb3+ in the high silica fiber core is 15856 ppm by weight, while the refractive index is 0.0024 lower than that of the inner cladding. The amplification performance of the fiber was investigated. The results indicate that nanoporous silica glass based on the glass phase-separation technology has great potential for gain-guided index anti-guided high silica fiber.

7.
Bioorg Med Chem ; 28(1): 115178, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31753798

RESUMO

A series of ß2-adrenoceptor agonists with an 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one moiety is presented. The stimulatory effects of the compounds on human ß2-adrenoceptor and ß1-adrenoceptor were characterized by a cell-based assay. Their smooth muscle relaxant activities were tested on isolated guinea pig trachea. Most of the compounds were found to be potent and selective agonists of the ß2-adrenoceptor. One of the compounds, (R)-18c, possessed a strong ß2-adrenoceptor agonistic effect with an EC50 value of 24 pM. It produced a full and potent airway smooth muscle relaxant effect same as olodaterol. Its onset of action was 3.5 min and its duration of action was more than 12 h in an in vitro guinea pig trachea model of bronchodilation. These results suggest that (R)-18c is a potential candidate for long-acting ß2-AR agonists.

8.
Luminescence ; 35(3): 373-378, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31858706

RESUMO

A new pH-dependent fluorescence probe 2,8-bis((E)-4-([2,2':6',2″-terpyridin]-4'-yl)styryl)-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (TBPTP) based on Tröger's base (TB) bound to terpyridine was designed and synthesized. Photophysical properties and titration experiments of TBPTP were investigated by absorption and fluorescence spectroscopy. TBPTP exhibited high sensitivity in an acidic environment with the working pH range 7.2-2.5, especially having a good liner response to pH changes in the range 2.5-4.3, which suggested that TBPTP is a good candidate for pH monitoring.

9.
BMC Med Genomics ; 12(Suppl 8): 183, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31856830

RESUMO

BACKGROUND: The early diagnosis of lung cancer has been a critical problem in clinical practice for a long time and identifying differentially expressed gene as disease marker is a promising solution. However, the most existing gene differential expression analysis (DEA) methods have two main drawbacks: First, these methods are based on fixed statistical hypotheses and not always effective; Second, these methods can not identify a certain expression level boundary when there is no obvious expression level gap between control and experiment groups. METHODS: This paper proposed a novel approach to identify marker genes and gene expression level boundary for lung cancer. By calculating a kernel maximum mean discrepancy, our method can evaluate the expression differences between normal, normal adjacent to tumor (NAT) and tumor samples. For the potential marker genes, the expression level boundaries among different groups are defined with the information entropy method. RESULTS: Compared with two conventional methods t-test and fold change, the top average ranked genes selected by our method can achieve better performance under all metrics in the 10-fold cross-validation. Then GO and KEGG enrichment analysis are conducted to explore the biological function of the top 100 ranked genes. At last, we choose the top 10 average ranked genes as lung cancer markers and their expression boundaries are calculated and reported. CONCLUSION: The proposed approach is effective to identify gene markers for lung cancer diagnosis. It is not only more accurate than conventional DEA methods but also provides a reliable method to identify the gene expression level boundaries.

10.
Opt Express ; 27(23): 33135-33142, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31878387

RESUMO

With the research of hollow-core fiber with large core diameter, the coupling efficiency from hollow-core fiber with large core diameter to single-mode fiber is difficult to increase through the traditional technology, we proposed a novel coupling method to improve the coupling efficiency by attaching a pure silica small ball at the front end of single-mode fiber, the coupling efficiency of 50% from hollow-core fiber with a large core diameter of 110 µm to single-mode fiber can be achieved.

11.
Opt Express ; 27(26): 37522-37531, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31878531

RESUMO

As the heat load within the central core of chirally-coupled-core (CCC) fibers will change the pre-designed refractive index profile through the thermo-optic effect, its impact on the laser performance of CCC fibers is investigated. Analysis and simulation results on two typical CCC fibers show that the effects of the heat load include the modal loss reduction and the transmission spectrum drift. The former comes from the thermal lensing effect in the central core, and the latter is caused by the change in the refractive index difference between the central core and the side core. Considering the non-uniform axial heat distribution in the actual laser operation, the overall laser performance of CCC fibers with different pump power is simulated. It is found that, because of the high pre-designed high-order mode loss, the single-mode operation of CCC fibers will be maintained but the slope efficiency may reduce dramatically if the fundamental mode loss is strongly dependent on the heat load.

12.
Opt Express ; 27(24): 35065-35078, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31878682

RESUMO

Mode instabilities (MI) threshold in the Yb:YAG crystalline fiber amplifier is simulated by a full numerical model. The propagation of signal fields is simulated by the finite-difference beam-propagation method combined with the rate equations, and the time-dependent heat equation is solved by the alternating-direction-implicit method. Considering the strong temperature-dependent laser performance of Yb:YAG, an iterative method is applied to reach the steady state of Yb:YAG, the crystalline fiber amplifier, before the simulation of MI behavior. The simulated MI thresholds in Yb:YAG crystalline fiber amplifiers are found to be at least 28 times of those in Yb-doped silica-glass fiber amplifiers, up to tens of kilowatts. Simulation results show that, in addition to the expected higher thermal conductivity and lower thermo-optic coefficient, strong gain saturation also plays an important role in the high MI threshold of the Yb:YAG crystalline fiber.

13.
BMC Bioinformatics ; 20(Suppl 19): 661, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31870276

RESUMO

BACKGROUND: Drug-drug interactions (DDIs) are a major concern in patients' medication. It's unfeasible to identify all potential DDIs using experimental methods which are time-consuming and expensive. Computational methods provide an effective strategy, however, facing challenges due to the lack of experimentally verified negative samples. RESULTS: To address this problem, we propose a novel positive-unlabeled learning method named DDI-PULearn for large-scale drug-drug-interaction predictions. DDI-PULearn first generates seeds of reliable negatives via OCSVM (one-class support vector machine) under a high-recall constraint and via the cosine-similarity based KNN (k-nearest neighbors) as well. Then trained with all the labeled positives (i.e., the validated DDIs) and the generated seed negatives, DDI-PULearn employs an iterative SVM to identify a set of entire reliable negatives from the unlabeled samples (i.e., the unobserved DDIs). Following that, DDI-PULearn represents all the labeled positives and the identified negatives as vectors of abundant drug properties by a similarity-based method. Finally, DDI-PULearn transforms these vectors into a lower-dimensional space via PCA (principal component analysis) and utilizes the compressed vectors as input for binary classifications. The performance of DDI-PULearn is evaluated on simulative prediction for 149,878 possible interactions between 548 drugs, comparing with two baseline methods and five state-of-the-art methods. Related experiment results show that the proposed method for the representation of DDIs characterizes them accurately. DDI-PULearn achieves superior performance owing to the identified reliable negatives, outperforming all other methods significantly. In addition, the predicted novel DDIs suggest that DDI-PULearn is capable to identify novel DDIs. CONCLUSIONS: The results demonstrate that positive-unlabeled learning paves a new way to tackle the problem caused by the lack of experimentally verified negatives in the computational prediction of DDIs.


Assuntos
Interações de Medicamentos , Análise por Conglomerados , Humanos , Máquina de Vetores de Suporte
14.
BMC Genomics ; 20(Suppl 9): 943, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874629

RESUMO

BACKGROUND: A long noncoding RNA (lncRNA) can act as a competing endogenous RNA (ceRNA) to compete with an mRNA for binding to the same miRNA. Such an interplay between the lncRNA, miRNA, and mRNA is called a ceRNA crosstalk. As an miRNA may have multiple lncRNA targets and multiple mRNA targets, connecting all the ceRNA crosstalks mediated by the same miRNA forms a ceRNA network. Methods have been developed to construct ceRNA networks in the literature. However, these methods have limits because they have not explored the expression characteristics of total RNAs. RESULTS: We proposed a novel method for constructing ceRNA networks and applied it to a paired RNA-seq data set. The first step of the method takes a competition regulation mechanism to derive candidate ceRNA crosstalks. Second, the method combines a competition rule and pointwise mutual information to compute a competition score for each candidate ceRNA crosstalk. Then, ceRNA crosstalks which have significant competition scores are selected to construct the ceRNA network. The key idea, pointwise mutual information, is ideally suitable for measuring the complex point-to-point relationships embedded in the ceRNA networks. CONCLUSION: Computational experiments and results demonstrate that the ceRNA networks can capture important regulatory mechanism of breast cancer, and have also revealed new insights into the treatment of breast cancer. The proposed method can be directly applied to other RNA-seq data sets for deeper disease understanding.

15.
Medicine (Baltimore) ; 98(52): e18564, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876758

RESUMO

BACKGROUND: This study was designed to systematically evaluate the clinical efficacy and safety of ultrasound-guided intrathyroidal injection of glucocorticoids (GCs) versus routine oral administration of GCs for subacute thyroiditis (SAT) and to help seek evidence of evidence-based medicine (EBM) for ultrasound-guided intrathyroidal injection of GCs in the treatment of SAT. METHODS: Seven Chinese and English databases, including Chinese National Knowledge Infrastructure, Wanfang Data, VIP Information China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Embase, were searched to collect randomized control trials on ultrasound-guided intrathyroidal injection of GCs in the treatment of SAT, which were published up to July 1, 2019. According to the method as described in Cochrane Reviewers' Handbook 5.1.0, the Cochrane Collaboration's tool for assessing risk of bias was employed to evaluate the quality of the literatures included. Statistical analysis was made by using Stata 12.0. The "metanif" command was used for sensitivity analysis to assess the stability of the results. Funnel diagram method, Egger linear regression method, and clipping complement method were used to evaluate publication bias. RESULTS: This study was carried out in strict accordance with the standard procedures for meta-analysis in the Cochrane Reviewers' Handbook 5.1.0. Critical data about the primary and secondary outcome measures were obtained by statistical analysis. CONCLUSION: This study would draw a definite conclusion about whether ultrasound-guided intrathyroidal injection of GCs is effective and safe in the treatment of SAT on the basis of EBM. This conclusion would provide scientific evidence for the clinical treatment of SAT.


Assuntos
Glucocorticoides/administração & dosagem , Tireoidite Subaguda/tratamento farmacológico , Ultrassonografia de Intervenção , Administração Oral , Glucocorticoides/uso terapêutico , Humanos , Injeções/efeitos adversos , Injeções/métodos , Glândula Tireoide/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia de Intervenção/efeitos adversos , Ultrassonografia de Intervenção/métodos
16.
BMC Bioinformatics ; 20(Suppl 23): 605, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881829

RESUMO

BACKGROUND: Detection of new drug-target interactions by computational algorithms is of crucial value to both old drug repositioning and new drug discovery. Existing machine-learning methods rely only on experimentally validated drug-target interactions (i.e., positive samples) for the predictions. Their performance is severely impeded by the lack of reliable negative samples. RESULTS: We propose a method to construct highly-reliable negative samples for drug target prediction by a pairwise drug-target similarity measurement and OCSVM with a high-recall constraint. On one hand, we measure the pairwise similarity between every two drug-target interactions by combining the chemical similarity between their drugs and the Gene Ontology-based similarity between their targets. Then we calculate the accumulative similarity with all known drug-target interactions for each unobserved drug-target interaction. On the other hand, we obtain the signed distance from OCSVM learned from the known interactions with high recall (≥0.95) for each unobserved drug-target interaction. After normalizing all accumulative similarities and signed distances to the range [0,1], we compute the score for each unobserved drug-target interaction via averaging its accumulative similarity and signed distance. Unobserved interactions with lower scores are preferentially served as reliable negative samples for the classification algorithms. The performance of the proposed method is evaluated on the interaction data between 1094 drugs and 1556 target proteins. Extensive comparison experiments using four classical classifiers and one domain predictive method demonstrate the superior performance of the proposed method. A better decision boundary has been learned from the constructed reliable negative samples. CONCLUSIONS: Proper construction of highly-reliable negative samples can help the classification models learn a clear decision boundary which contributes to the performance improvement.


Assuntos
Algoritmos , Descoberta de Drogas , Reposicionamento de Medicamentos , Aprendizado de Máquina , Área Sob a Curva , Interações de Medicamentos , Humanos
17.
Opt Express ; 27(19): 26523-26531, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674532

RESUMO

A novel method for mitigating photo-darkening and the effective photo-bleaching phenomenon by 532 nm cladding pump in Yb-doped fiber were herein reported. Compared with the pristine fiber, beyond 30% of photo-darkening induced excess loss was suppressed by 532 nm pretreatment. Moreover, the excess loss in the photo-darkened fiber was completely bleached with 532 nm pump. Additionally, the bleached fiber exhibited better photo-darkening resistance. Therefore, for high power application, a 20/400 gamma irradiated fiber was bleached in situ by 532 nm pump and the laser properties were explored. The output power restored to 421W accounting for 82% of the pristine fiber, with the mode instability threshold rising to over 2.6 times and the efficiency increasing from 37% to 63%. The results indicate 532 nm pump has bright prospects for the stable operation of high power fiber lasers.

18.
Nat Commun ; 10(1): 5026, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690716

RESUMO

The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most over-expressed in MYCN-amplified, compared with MYCN-non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription. The GTPase-activating protein DEPDC1B induces ERK protein phosphorylation and N-Myc protein stabilization. Importantly, lncNB1 knockdown abolishes neuroblastoma cell clonogenic capacity in vitro and leads to neuroblastoma tumor regression in mice, while high levels of lncNB1 and RPL35 in human neuroblastoma tissues predict poor patient prognosis. This study therefore identifies lncNB1 and its binding protein RPL35 as key factors for promoting E2F1 protein synthesis, N-Myc protein stability and N-Myc-driven oncogenesis, and as therapeutic targets.


Assuntos
Carcinogênese/genética , RNA Longo não Codificante/metabolismo , Proteínas Ribossômicas/metabolismo , Animais , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Fator de Transcrição E2F1/metabolismo , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/genética , Neuroblastoma/patologia , Prognóstico , Biossíntese de Proteínas , Estabilidade Proteica , RNA Longo não Codificante/genética , Transcrição Genética , Regulação para Cima/genética
19.
Opt Express ; 27(14): 19548-19554, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31503712

RESUMO

We report on a double negative curvature anti-resonance hollow core fiber, in which, the cladding is constituted of 6 large tubes and 6 small tubes arranged in a staggered pattern. The simulation shows that the loss of the fiber can reach or even exceed the loss of double-clad negative curvature anti-resonance hollow core fibers in short wavelength band, due to the staggered arrangement of two kind of tubes and the double negative curvature on the core boundary. The best single mode performance with a loss ratio as high as 100,000 between LP11 mode and LP01 mode is obtained due to simultaneously inhibited LP11 modes and LP21 modes in the fiber structure. The reason for loss oscillations in long wavelength band and the fabrication feasibility of proposed fiber are also discussed.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31514149

RESUMO

Biological targets are most commonly proteins such as enzymes, ion channels, and receptors. They are anything within a living organism to bind with some other entities (like an endogenous ligand or a drug), resulting in change in their behaviors or functions. Exploring potential drug-target interactions (DTIs) are crucial for drug discovery and effective drug development. Computational methods were widely applied in drug-target interactions, since experimental methods are extremely time-consuming and resource-intensive. In this paper, we proposed a novel deep learning-based prediction system, with a new negative instance generation, to identify DTIs. As a result, our method achieved an accuracy of 0.9800 on our created dataset. Another dataset derived from DrugBank was used to further assess the generalization of the model, which yielded a good performance with accuracy of 0.8814 and AUC value of 0.9527 on the dataset. The outcome of our experimental results indicated that the proposed method, involving the credible negative generation, can be employed to discriminate the interactions between drugs and targets.

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