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1.
J Enzyme Inhib Med Chem ; 35(1): 468-477, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31902266

RESUMO

C-Met plays a crucial role in the development and progression of neoplastic disease. Type II c-Met inhibitors recognise the inactive DFG-out conformation of the kinase, result in better anti-tumour effects due to synergistic effect against the other kinases. According to our previous works, an (E)-N'-benzylidene group was selected as the initial fragment. Two series of (E)-N'-benzylidene hydrazides were designed by fragment growth method. The inhibitory activities were in vitro investigated against c-Met and VEGFR-2. Compound 10b exhibited the most potent inhibitory activity against the c-Met inhibitor (IC50 = 0.37 nM). Compound 11b exhibited multi-target c-Met kinase inhibitory activity as a potential type II c-Met inhibitor (IC50 = 3.41 nM against c-Met; 25.34 nM against VEGFR-2). The two compounds also demonstrate the feasibility of fragment-based virtual screening method for drug discovery.


Assuntos
Compostos de Benzilideno/síntese química , Compostos de Benzilideno/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Compostos de Benzilideno/química , Descoberta de Drogas , Humanos , Inibidores de Proteínas Quinases/química , Relação Quantitativa Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
2.
Nano Lett ; 20(1): 410-417, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31860318

RESUMO

Photoluminescence (PL) from single-wall carbon nanotubes (SWCNTs) enables structural identification, but to derive the content rate of the specific chirality species it is necessary to know the quantum yield of each chirality. However, in the PL of SWCNTs, because the Stokes shift is small, the photon reabsorption effect is dominant and the apparent PL spectral shape and emission intensity are greatly modified depending on the concentration. This problem makes quantitative identification of SWCNTs by PL difficult. In this study, the concentration dependence of the PL of SWCNTs separated into a few chiralities was analyzed in detail, including the effect of reabsorption. It is clear that all changes in the PL spectrum occurring in the high concentration range can be explained simply by the reabsorption effect, and additional effects such as Coulomb interactions between SWCNTs can be negligible. Furthermore, a reliable quantum yield was derived from the emission intensity corrected for the reabsorption effect. The PL quantum yield varied with SWCNT chirality and exhibited a clear "family pattern". This is consistent with the theoretical report showing that the chirality-dependent PL quantum yield is dominated mainly by relaxation by optical phonons from E22 to E11.

3.
J Enzyme Inhib Med Chem ; 35(1): 235-244, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31760818

RESUMO

Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. A multistage virtual screening method combined by SVM, protein-ligand interaction fingerprints (PLIF) pharmacophore and docking was utilised for screening the CDK2 inhibitors. The evaluation of the validation set indicated that this method can be used to screen large chemical databases because it has a high hit-rate and enrichment factor (80.1% and 332.83 respectively). Six compounds were screened out from NCI, Enamine and Pubchem database. After molecular dynamics and binding free energy calculation, two compounds had great potential as novel CDK2 inhibitors and they also showed selective inhibition against CDK2 in the kinase activity assay.


Assuntos
Antineoplásicos/análise , Antineoplásicos/farmacologia , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/análise , Inibidores de Proteínas Quinases/farmacologia , Máquina de Vetores de Suporte , Células A549 , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade
4.
Int J Mol Sci ; 20(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795217

RESUMO

Phosphoinositide 3 kinase delta (PI3Kδ) is a lipid kinase that has been implicated in a variety of immune mediated disorders. The research on isoform selectivity was crucial for reducing side effects. In the current study, an optimized hierarchical multistage virtual screening method was utilized for screening the PI3Kδ selective inhibitors. The method sequentially applied a support vector machine (SVM), a protein ligand interaction fingerprint (PLIF) pharmacophore, and a molecular docking approach. The evaluation of the validation set showed a high hit rate and a high enrichment factor of 75.1% and 301.66, respectively. This multistage virtual screening method was then utilized to screen the NCI database. From the final hit list, Compound 10 has great potential as the PI3Kδ inhibitor with micromolar inhibition in the PI3Kδ kinase activity assay. This compound also shows selectivity against PI3Kδ kinase. The method combining SVM, pharmacophore, and docking was capable of screening out the compounds with potential PI3Kδ selective inhibitors. Moreover, structural modification of Compound 10 will contribute to investigating the novel scaffold and designing novel PI3Kδ inhibitors.

5.
Sci Adv ; 5(10): eaax6973, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31692752

RESUMO

The dynamic characterization of water multilayers on oxide surfaces is hard to achieve by currently available techniques. Despite this, there is an increasing interest in the evolution of water nanostructures on oxides to fully understand the complex dynamics of ice nucleation and growth in natural and artificial environments. Here, we report the in situ detection of the dynamic evolution of nanoscale water layers on an amorphous oxide surface probed by optical resonances. In the water nanolayer growth process, we find an initial nanocluster morphology that turns into a planar layer beyond a critical thickness. In the reverse process, the planar water film converts to nanoclusters, accompanied by a transition from a planar amorphous layer to crystalline nanoclusters. Our results are explained by a simple thermodynamic model as well as kinetic considerations. Our work represents an approach to reveal the nanostructure and dynamics at the water-oxide interface using resonant light probing.

6.
Micromachines (Basel) ; 10(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374816

RESUMO

In this paper, a liquid refractive index (LRI) measurement system based on an electrowetting lens was proposed. The system is composed of a light source, a collimating lens, a liquid measurement chamber (LMC), an electrowetting lens and an image sensor, which is integrated into a cylindrical cavity. The refractive index of the LMC changes with the addition of the measured liquid, and the incident light cannot be focused on the image plane. By adjusting the driving voltage of the electrowetting lens, the curvature of the liquid-liquid interface changes to focus the incident light onto the image plane. The refractive index of the liquid could be measured according to the voltage value. The proposed LRI measurement system has no mechanical moving parts, and the imaging surface remains stationary, which can make the measurement simply and correctly. The experiments show that the refractive index measurement range of the system can be turned from ~1.3300 to ~1.4040, and the measurement accuracy is 10-4. The system can be used to measure the optical properties of liquids and has broad potential applications in chemical reagent detection and pharmaceutical testing.

7.
Small ; 15(23): e1805477, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31026126

RESUMO

On-chip strain engineering is highly demanded in 2D materials as an effective route for tuning their extraordinary properties and integrating consistent functionalities toward various applications. Herein, rolling technique is proposed for strain engineering in monolayer graphene grown on a germanium substrate, where compressive or tensile strain could be acquired, depending on the designed layer stressors. Unusual compressive strains up to 0.30% are achieved in the rolled-up graphene tubular structures. The subsequent phonon hardening under compressive loading is observed through strain-induced Raman G band splitting, while distinct blueshifts of characteristic peaks (G+ , G- , or 2D) can be well regulated on an asymmetric tubular structure with a strain variation. In addition, due to the strong confinement of the local electromagnetic field under 3D tubular geometry, the photon-phonon interaction is highly strengthened, and thus, the Raman scattering of graphene in rolled-up tubes is enhanced. Such an on-chip rolling approach leads to a superior strain tuning method in 2D materials and could improve their light-matter interaction in a tubular configuration, which may hold great capability in 2D materials integration for on-chip applications such as in mechanics, electronics, and photonics.

8.
Light Sci Appl ; 8: 13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30701072

RESUMO

New materials that exhibit strong second-order optical nonlinearities at a desired operational frequency are of paramount importance for nonlinear optics. Giant second-order susceptibility χ (2) has been obtained in semiconductor quantum wells (QWs). Unfortunately, the limited confining potential in semiconductor QWs causes formidable challenges in scaling such a scheme to the visible/near-infrared (NIR) frequencies for more vital nonlinear-optic applications. Here, we introduce a metal/dielectric heterostructured platform, i.e., TiN/Al2O3 epitaxial multilayers, to overcome that limitation. This platform has an extremely high χ (2) of approximately 1500 pm/V at NIR frequencies. By combining the aforementioned heterostructure with the large electric field enhancement afforded by a nanostructured metasurface, the power efficiency of second harmonic generation (SHG) achieved 10-4 at an incident pulse intensity of 10 GW/cm2, which is an improvement of several orders of magnitude compared to that of previous demonstrations from nonlinear surfaces at similar frequencies. The proposed quantum-engineered heterostructures enable efficient wave mixing at visible/NIR frequencies into ultracompact nonlinear optical devices.

9.
Nano Lett ; 18(12): 8035-8040, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30427684

RESUMO

Quantum sciences are revolutionizing computing and communication technologies, in which single-photon emitters are the key components for creating strong quantum entanglement. Color centers in diamonds in coupled-cavity systems are considered great candidates for the efficient generation of quantum carriers over other solid-state emitters. Owing to the multi-mode nature of high quality factor ( Q) diamond cavities, however, it is a grand challenge to the achievement of single photon emission with high rate and indistinguishability. To this end, a single-mode high- Q diamond cavity is highly desired. Here, we report a diamond mesostructured nanomembrane microcavity of a discrete rotational symmetry that selectively produces the desired single-mode emission in a broad spectrum. The strategic rolling up of a flexible diamond nanomembrane with aligned holes effectively defines the designed symmetry while maintaining the high- Q resonance through the whispering-gallery mode supported in the central hollow microcavity. The demonstrated diamond mesostructured microcavity features a distinct and enhanced single-mode emission, a step toward efficient quantum sources with designed positions or bands for quantum information technology.

10.
PLoS One ; 13(11): e0206966, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30408083

RESUMO

Distribution centers (DCs) are an important part of the modern logistics system. The selection of a location for a DC is significant for saving costs and reducing externalities caused by distribution. In this paper, we propose a new hybrid method based on the analytic hierarchy process (AHP) and 2-tuple hybrid ordered weighted averaging (THOWA) to select the location of a DC in a megacity. First, we propose a new set of evaluation criteria integrating economic, political, social and ecological information based on the characteristics of Chinese megacities. Second, subjective criteria weights are calculated by AHP combining the evaluation of logistics experts. Third, experts from academia, enterprise and government assess the performance of alternatives. In addition, the overall evaluation values are aggregated by an improved THOWA operator to rank the alternatives. Finally, we conduct a sensitivity analysis to investigate the influence of criteria weights on the decision-making process. The proposed method is novel and addresses the uncertainty under limited quantitative information, which has the advantages of avoiding information loss and distortion problems in the integrating process and operating linguistic evaluation information effectively. The proposed method can be practically applied by municipal planning departments in deciding on the location of new DCs. A numerical application of the proposed method is provided.


Assuntos
Lógica Fuzzy , Tomada de Decisões
11.
Int J Mol Sci ; 19(3)2018 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-29562629

RESUMO

A series of imidazolium salt derivatives have demonstrated potent antitumor activity in prior research. A comprehensive in silicon method was carried out to identify the putative protein target and detailed structure-activity relationship of the compounds. The Topomer CoMFA and CoMSIA techniques were implemented during the investigation to obtain the relationship between the properties of the substituent group and the contour map of around 77 compounds; the Topomer CoMFA and CoMSIA models were reliable with the statistical data. The protein-protein interaction network was constructed by combining the Pharmmapper platform and STRING database. After generating the sub-network, the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA with protein data bank ID: 3ZIM) was selected as the putative target of imidazolium salt derivatives. A docking study was carried out to correlate interactions of amino acids in protein active pockets surrounded by the ligand with contour maps generated by the structure-activity relationship method. Then the molecular dynamics simulations demonstrated that the imidazolium salt derivatives have potent binding capacity and stability to receptor 3ZIM, and the two ligand-receptor complex was stable in the last 2 ns. Finally, the ligand-based structure-activity relationship and receptor-based docking were combined together to identify the structural requirement of the imidazolium salt derivatives, which will be used to design and synthesize the novel PIK3CA inhibitors.


Assuntos
Antineoplásicos/química , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Desenho de Drogas , Inibidores Enzimáticos/química , Imidazóis/química , Simulação de Acoplamento Molecular/métodos , Antineoplásicos/farmacologia , Sítios de Ligação , Classe I de Fosfatidilinositol 3-Quinases/química , Bases de Dados de Proteínas , Inibidores Enzimáticos/farmacologia , Imidazóis/farmacologia , Ligantes , Simulação de Dinâmica Molecular , Mapas de Interação de Proteínas , Relação Quantitativa Estrutura-Atividade
12.
ACS Appl Mater Interfaces ; 10(9): 7704-7708, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29436813

RESUMO

We demonstrate hyperbolic metamaterials (HMMs) on a curved surface for an efficient outcoupling of nonradiative modes, which lead to an enhanced spontaneous emission. Those high-wavevector plasmonic modes can propagate along the curved structure and emit into the far field, realizing a directional light emission with maximal fluorescent intensity. Detailed simulations disclose a high Purcell factor and a spatial power distribution in the curved HMM, which agrees with the experimental result. Our work presents remarkable enhancing capability in both the Purcell factor and emission intensity, which could suggest a unique structure design in metamaterials for potential application in, e.g., high-speed optical sensing and communications.

13.
Nanotechnology ; 28(43): 435203, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-28832342

RESUMO

The electrical characteristics of carbon nanotube (CNT) thin-film transistors (TFTs) strongly depend on the properties of the gate dielectric that is in direct contact with the semiconducting CNT channel materials. Here, we systematically investigated the dielectric effects on the electrical characteristics of fully printed semiconducting CNT-TFTs by introducing the organic dielectrics of poly(methyl methacrylate) (PMMA) and octadecyltrichlorosilane (OTS) to modify SiO2 dielectric. The results showed that the organic-modified SiO2 dielectric formed a favorable interface for the efficient charge transport in s-SWCNT-TFTs. Compared to single-layer SiO2 dielectric, the use of organic-inorganic hybrid bilayer dielectrics dramatically improved the performances of SWCNT-TFTs such as mobility, threshold voltage, hysteresis and on/off ratio due to the suppress of charge scattering, gate leakage current and charge trapping. The transport mechanism is related that the dielectric with few charge trapping provided efficient percolation pathways for charge carriers, while reduced the charge scattering. High density of charge traps which could directly act as physical transport barriers and significantly restrict the charge carrier transport and, thus, result in decreased mobile carriers and low device performance. Moreover, the gate leakage phenomenon is caused by conduction through charge traps. So, as a component of TFTs, the gate dielectric is of crucial importance to the manufacture of high quality TFTs from the aspects of affecting the gate leakage current and device operation voltage, as well as the charge carrier transport. Interestingly, the OTS-modified SiO2 allows to directly print horizontally aligned CNT film, and the corresponding devices exhibited a higher mobility than that of the devices with the hybrid PMMA/SiO2 dielectric although the thickness of OTS layer is only ∼2.5 nm. Our present result may provide key guidance for the further development of printed nanomaterial electronics.

14.
Sci Adv ; 2(8): e1600027, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27536723

RESUMO

Three-dimensional (3D) design and manufacturing enable flexible nanomembranes to deliver unique properties and applications in flexible electronics, photovoltaics, and photonics. We demonstrate that a quantum well (QW)-embedded nanomembrane in a rolled-up geometry facilitates a 3D QW infrared photodetector (QWIP) device with enhanced responsivity and detectivity. Circular geometry of nanomembrane rolls provides the light coupling route; thus, there are no external light coupling structures, which are normally necessary for QWIPs. This 3D QWIP device under tube-based light-trapping mode presents broadband enhancement of coupling efficiency and omnidirectional detection under a wide incident angle (±70°), offering a unique solution to high-performance focal plane array. The winding number of these rolled-up QWIPs provides well-tunable blackbody photocurrents and responsivity. 3D self-assembly of functional nanomembranes offers a new path for high conversion efficiency between light and electricity in photodetectors, solar cells, and light-emitting diodes.


Assuntos
Técnicas Biossensoriais , Raios Infravermelhos , Membranas Artificiais , Nanoestruturas , Nanotecnologia , Pontos Quânticos , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Nanotecnologia/instrumentação , Nanotecnologia/métodos
15.
Phys Rev Lett ; 116(25): 253904, 2016 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-27391725

RESUMO

Vertical gold nanogaps are created on microtubular cavities to explore the coupling between resonant light supported by the microcavities and surface plasmons localized at the nanogaps. Selective coupling of optical axial modes and localized surface plasmons critically depends on the exact location of the gold nanogap on the microcavities, which is conveniently achieved by rolling up specially designed thin dielectric films into three-dimensional microtube cavities. The coupling phenomenon is explained by a modified quasipotential model based on perturbation theory. Our work reveals the coupling of surface plasmon resonances localized at the nanoscale to optical resonances confined in microtubular cavities at the microscale, implying a promising strategy for the investigation of light-matter interactions.

16.
Zhonghua Shao Shang Za Zhi ; 32(2): 126-8, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26902280

RESUMO

After healing of burn wound, skin of scar, transplanted skin grafts, and healed donor site wound suffer from temporary or permanent loss of function of sebaceous glands and dysfunction of skin surface lipid film formation, resulting in desiccation, desquamation, and sensitiveness of the skin, making areas of newly formed skin unsatisfactory. Therefore a good rehabilitation may fail. In this paper, the composition, physiochemical properties, and reconstruction of skin surface lipid film are discussed.


Assuntos
Lipídeos/fisiologia , Transplante de Pele , Pele/patologia , Cicatrização , Cicatriz
17.
J Tissue Eng Regen Med ; 9(12): E267-75, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23509085

RESUMO

We evaluated the use of a combination of human insulin gene-modified umbilical cord mesenchymal stromal cells (hUMSCs) with silk fibroin 3D scaffolds for adipose tissue engineering. In this study hUMSCs were isolated and cultured. HUMSCs infected with Ade-insulin-EGFP were seeded in fibroin 3D scaffolds with uniform 50-60 µm pore size. Silk fibroin scaffolds with untransfected hUMSCs were used as control. They were cultured for 4 days in adipogenic medium and transplanted under the dorsal skins of female Wistar rats after the hUMSCs had been labelled with chloromethylbenzamido-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (CM-Dil). Macroscopical impression, fluorescence observation, histology and SEM were used for assessment after transplantation at 8 and 12 weeks. Macroscopically, newly formed adipose tissue was observed in the experimental group and control group after 8 and 12 weeks. Fluorescence observation supported that the formed adipose tissue originated from seeded hUMSCs rather than from possible infiltrating perivascular tissue. Oil red O staining of newly formed tissue showed that there was substantially more tissue regeneration in the experimental group than in the control group. SEM showed that experimental group cells had more fat-like cells, whose volume was larger than that of the control group, and degradation of the silk fibroin scaffold was greater under SEM observation. This study provides significant evidence that hUMSCs transfected by adenovirus vector have good compatibility with silk fibroin scaffold, and adenoviral transfection of the human insulin gene can be used for the construction of tissue-engineered adipose.


Assuntos
Tecido Adiposo/metabolismo , Fibroínas/química , Insulina , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual/métodos , Tecidos Suporte/química , Transdução Genética/métodos , Cordão Umbilical/metabolismo , Tecido Adiposo/citologia , Animais , Feminino , Humanos , Insulina/biossíntese , Insulina/genética , Masculino , Ratos , Ratos Wistar , Cordão Umbilical/citologia
18.
Opt Lett ; 39(21): 6335-8, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25361348

RESUMO

We present a detailed investigation of the resonator properties of high-quality rolled-up SiO2 optical microtubes reinforced by atomic layer deposition. The evolution of the resonant modes with increasing film thickness and the transition to a multimode regime, including higher order radial modes, is discussed. Measurements and simulations show that the higher order modes exhibit high optical quality and an increased extension of the evanescent field from the resonator into the surrounding matrix, making them a promising solution for future on-chip sensor applications with increased sensitivity.

19.
Adv Mater ; 26(47): 7973-8, 2014 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-25339523

RESUMO

A lab-on-chip device is demonstrated for probing the electrochemical kinetics, electrical properties, and structure integrity of a single Si rolled-up tube as the anode in lithium-ion batteries. Cyclic voltammetry of the tube exhibits better-resolved peaks than of the planar film due to the enhanced diffusion. The tube is wrinkled after cycling. The tube could be used as a promising ultra-microelectrode for other voltammetry research.

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