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1.
Future Oncol ; 15(19): 2303-2317, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31237146

RESUMO

Aim: To provide clarity surrounding the association between tumor-associated macrophages (TAMs) and esophageal cancer prognosis. Materials & methods: Several databases were searched. The meta-analysis was conducted by using software Stata 12.0 and Revman. Results: Sixteen studies were included in this analysis (2292 samples). CD68+ TAM density was not associated with overall survival (OS; hazard ratio [HR]: 0.88, 95% CI: 0.67-1.15; p = 0.33) and disease-free survival (HR: 1.25, 95% CI: 0.66-2.35; p = 0.49). M2-like TAMs were associated with poor overall survival (HR: 1.47, 95% CI: 1.10-1.98; p = 0.01), Tumor, Node, Metastasis staging and vessel metastasis. Conclusion: CD68+ TAM density is not associated with esophageal cancer progression, while CD163+ M2-like TAMs is a potential risk factor.

2.
Nat Commun ; 10(1): 1217, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30872576

RESUMO

Molybdenum disulfide is naturally inert for alkaline hydrogen evolution catalysis, due to its unfavorable water adsorption and dissociation feature originated from the unsuitable orbital orientation. Herein, we successfully endow molybdenum disulfide with exceptional alkaline hydrogen evolution capability by carbon-induced orbital modulation. The prepared carbon doped molybdenum disulfide displays an unprecedented overpotential of 45 mV at 10 mA cm-2, which is substantially lower than 228 mV of the molybdenum disulfide and also represents the best alkaline hydrogen evolution catalytic activity among the ever-reported molybdenum disulfide catalysts. Fine structural analysis indicates the electronic and coordination structures of molybdenum disulfide have been significantly changed with carbon incorporation. Moreover, theoretical calculation further reveals carbon doping could create empty 2p orbitals perpendicular to the basal plane, enabling energetically favorable water adsorption and dissociation. The concept of orbital modulation could offer a unique approach for the rational design of hydrogen evolution catalysts and beyond.

3.
Adv Mater ; 31(16): e1807780, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30811711

RESUMO

Although it is commonly believed that the water-dissociation-related Volmer process is the rate-limiting step for alkaline hydrogen evolution reaction (HER) on Pt-based catalysts, the underlying essence, particularly on the atomic scale, still remains unclear. Herein, it is revealed that the sluggish water-dissociation behavior probably stems from unfavorable orbital orientation and the kinetic issue is successfully resolved via N-induced orbital tuning. Impressively, N modified Pt-Ni nanowires deliver an ultralow overpotential of 13 mV at 10 mA cm-2 , which represents a new benchmark for alkaline HER catalysis. Fine-structural characterization and density functional theory analysis illustrate that the introduced nitrogen can uniquely modulate the electron densities around the Ni sites, and further create empty dz 2 orbitals with superior orientation for water adsorption and activation. More importantly, it is demonstrated that N-induced orbital modulation can generally boost the alkaline HER activities of Pt-Co, Pt-Ni, and Pt-Cu, offering a new perspective for the design of HER catalysts and beyond.

4.
Nat Commun ; 9(1): 1425, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29651037

RESUMO

Metal sulfides for hydrogen evolution catalysis typically suffer from unfavorable hydrogen desorption properties due to the strong interaction between the adsorbed H and the intensely electronegative sulfur. Here, we demonstrate a general strategy to improve the hydrogen evolution catalysis of metal sulfides by modulating the surface electron densities. The N modulated NiCo2S4 nanowire arrays exhibit an overpotential of 41 mV at 10 mA cm-2 and a Tafel slope of 37 mV dec-1, which are very close to the performance of the benchmark Pt/C in alkaline condition. X-ray photoelectron spectroscopy, synchrotron-based X-ray absorption spectroscopy, and density functional theory studies consistently confirm the surface electron densities of NiCo2S4 have been effectively manipulated by N doping. The capability to modulate the electron densities of the catalytic sites could provide valuable insights for the rational design of highly efficient catalysts for hydrogen evolution and beyond.

5.
Mol Divers ; 19(1): 123-34, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25273562

RESUMO

Influenza is an acute respiratory infectious disease caused by influenza viruses. Its subtype can be distinguished based on the antigenicity of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). One of the main challenges in anti-influenza drug development is the quick evolution of drug resistance due to virus mutations. One solution to this problem is to develop dual-targeting anti-influenza agents. In this paper, a new rationally designed virtual screening protocol that combines structure-based approaches (molecular docking and molecular dynamic simulations) and ligand-based approaches (support vector machines and 3D shape & electrostatic similarity algorithms) is reported for the virtual screening of dual-targeting agents against HA and NA. The final hits came from the consensus of the ligand- and receptor-based knowledge of HA and NA and were tested using ADMET predictions. Evidence from the binding energy calculations and binding mode analyses suggested that several of the hits are promising as dual-targeting anti-influenza agents. The virtual screening protocol may also lead to the identification of innovative drugs in other fields.


Assuntos
Antivirais/química , Descoberta de Drogas/métodos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Virus da Influenza A Subtipo H5N1 , Simulação de Dinâmica Molecular , Neuraminidase , Proteínas Virais , Antivirais/uso terapêutico , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Neuraminidase/antagonistas & inibidores , Neuraminidase/química , Neuraminidase/metabolismo , Máquina de Vetores de Suporte , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/química , Proteínas Virais/metabolismo
6.
J Chem Inf Model ; 53(10): 2757-64, 2013 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-24001302

RESUMO

High-performance computing (HPC) has become a state strategic technology in a number of countries. One hypothesis is that HPC can accelerate biopharmaceutical innovation. Our experimental data demonstrate that HPC can significantly accelerate biopharmaceutical innovation by employing molecular dynamics-based virtual screening (MDVS). Without using HPC, MDVS for a 10K compound library with tens of nanoseconds of MD simulations requires years of computer time. In contrast, a state of the art HPC can be 600 times faster than an eight-core PC server is in screening a typical drug target (which contains about 40K atoms). Also, careful design of the GPU/CPU architecture can reduce the HPC costs. However, the communication cost of parallel computing is a bottleneck that acts as the main limit of further virtual screening improvements for drug innovations.


Assuntos
Inibidores da Protease de HIV/química , Protease de HIV/química , Simulação de Dinâmica Molecular , Neuraminidase/química , PPAR alfa/química , Bibliotecas de Moléculas Pequenas/química , Interface Usuário-Computador , Algoritmos , Inteligência Artificial , Sítios de Ligação , Bases de Dados de Compostos Químicos , Bases de Dados de Proteínas , Descoberta de Drogas , Ensaios de Triagem em Larga Escala/economia , Ensaios de Triagem em Larga Escala/instrumentação , Humanos , Ligantes , Simulação de Acoplamento Molecular , Neuraminidase/antagonistas & inibidores , PPAR alfa/antagonistas & inibidores , Ligação Proteica , Relação Estrutura-Atividade , Termodinâmica
7.
Eur J Med Genet ; 53(3): 153-8, 2010 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20346424

RESUMO

We describe a patient with multiple congenital anomalies, including hemifacial microsomia, asymmetric macrostomia, dysplastic mandible, multiple preauricular tags, atresia of the external auricular canal, and vertebral anomalies, which coincide with oculo-auriculo-vertebral spectrum. G-banding ( approximately 850 band level) showed a normal 46, XY karyotype. A genome-wide screen for copy number variations (CNVs) using single nucleotide polymorphism (SNP) arrays revealed a 1Mb and a 167 kb deletion both on chromosome 5q13.2, which were absent in the parents and in 27 controls. Sixteen genes were located in the deleted region, including BIR1C and OCLN, which are involved in apoptosis. Haploinsufficiency of these genes may be contributing to the phenotype in this patient. To our knowledge, there are no previous reports of this 5q13.2 deletion in a patient with oculo-auriculo-vertebral spectrum.


Assuntos
Cromossomos Humanos Par 5/ultraestrutura , Síndrome de Goldenhar/diagnóstico , Síndrome de Goldenhar/genética , Encéfalo/patologia , Criança , Pré-Escolar , Bandeamento Cromossômico , Cromossomos Humanos Par 5/genética , Anormalidades Congênitas/diagnóstico , Deleção de Genes , Dosagem de Genes , Humanos , Cariotipagem , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Tomografia Computadorizada por Raios X/métodos
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