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1.
Nanoscale ; 11(36): 17058-17064, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31506650

RESUMO

Two dimensional (2D) Group-VI Te, tellurene, was successfully exfoliated using a liquid phase exfoliation (LPE) method. The prepared tellurene nanosheets possessed a thickness of 4.3-4.6 nm and the lateral dimension ranged from hundreds of nanometers to several microns. The broadband nonlinear absorption properties were explored for the first time (as we know) using a z-scan method with the laser photon energy in the range of 0.73-2.76 eV, corresponding to the near-infrared-visible waveband. Tellurene nanosheets exhibited excellent broadband saturated absorption and optical limiting behaviors. The low saturable intensity and the large modulation depth for saturated absorption with low energy photon excitation highlight the superiority of the infrared band as a saturable absorber. In addition, with large energy excitation, tellurene manifested an apparent two photon absorption behavior in the visible band, thus it can be used as an optical limiting material. By adopting the mode-locking technique, this high-quality saturable absorber can be applied in all-solid-state or fiber lasers to generate ultra-short and ultra-high peak power laser pulses. Meanwhile, tellurene as an optical limiting material can protect the sensitive optical devices and human eyes. So, our work not only demonstrates that tellurene is a promising broadband nonlinear optical material, but also implies its application prospects in optics.

2.
Colloids Surf B Biointerfaces ; 183: 110394, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31398618

RESUMO

Organic solvents have been reported to exert certain influence on the structure and drug loading efficiency of albumin. It is urgent to develop organic solvent-free albumin-based paclitaxel nanoparticles for effective anticancer therapy. In this study, novel PTX liposome-albumin composite nanoparticles (Lip-PTX/BSA NPs) aimed at avoiding the direct contact of albumin with toxic organic solvents and enhancing the colloidal stability of the formulation were prepared. To methodically evaluate the impacts of multifarious factors on the critical characteristics of the nanoparticles, Box-Behnken design was applied in the formulation optimized process. Ratio of drug-phosphatidylcholine (EPC), ratio of drug-BSA and pH of the media were chosen as the independent variables, while particle size and drug-loading content (DLC) loss rate were applied as the selected response variables. A quadratic model fitted best to describe the data with maximal lack-of-fit p-value and minimum sequential p-value. Three-dimension surface figures were utilized to describe the correlation of independent variables with response variables. Optimized formulation of the nanoparticles with size of 116.2 ±â€¯2.0 nm and zeta potential of -18.4 ±â€¯1.01 mV were obtained with a high encapsulation efficiency of 99.8%. PTX was involved physical interaction with the excipient during the preparation process of the nanoparticles. The release of PTX from Lip-PTX/BSA NPs exhibited a sustained release manner compared to albumin-bound PTX (nab-PTX) and Taxol. Besides, Lip-PTX/BSA NPs presented enhanced in vitro cytotoxicity against 4T1 cells due to highly nonspecific internalization in the cytoplasm. Simultaneously, Lip-PTX/BSA NPs showed effective in vivo antitumor efficacy against 4T1 bearing BALB/c mice, while no apparent adverse effect was observed by histological section and blood biochemical analysis. In conclusion, the novel Lip-PTX/BSA NPs could be applied as a promising drug delivery system for PTX to exert efficient cancer curative effects in clinic.

3.
J Med Syst ; 43(8): 250, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31250121

RESUMO

Cervical cancer is increasingly threatening the health of women, then early screening and prevention of cervical cancer is very necessary. A traditional saliency cervical cancer detection method in Ultrasound image, assuming that there is only one salient object, is not conductive to practical application. Their effects are dependent on saliency threshold. Object detection model provides a kind of new solutions for multiple salient objects. Shot multiBox detector can accurately detect multi-objects with different scales simultaneously except for small cervical cancer regions. To overcome this drawback, this paper presents a new multi-saliency objects detection model, appending deconvolution module embedded within attention residual module. Experiments show that our proposed diagnosis algorithm achieves higher detection accuracy than comparison algorithms. Also, it improves detection performance for mult-saliency cervical cancer objects with small scales, which greatly improve the diagnosis accuracy of cervical cancer.

4.
Artif Cells Nanomed Biotechnol ; 47(1): 2179-2187, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31159591

RESUMO

Ghrelin has been widely recognized as a key peptide in the cardiovascular system. This study detected the potential of ghrelin in MI management and tried to decode one of the possible underlying mechanisms. H9c2 cells were pretreated with ghrelin and were subjected to hypoxia/reoxygenation (H/R). CCK-8, flow cytometry, Western blot and LDH analysis were conducted to assess the changes in cell survival. LY294002 and Compound C were used to treat H9c2 cells for blocking PI3K/AKT and AMPK pathways, respectively. Ghrelin expression in H9c2 cells was suppressed by siRNA-mediated silencing to see the effects of endogenous ghrelin. We found that, following H/R, H9c2 cells viability was decreased, CyclinD1 and CDK4 were down-regulated, apoptosis was induced, the release of LDH was enhanced, and the expression levels of Cox-2 and iNOS were up-regulated. Ghrelin protected H9c2 cells against H/R induced these alterations. Besides, ghrelin activated PI3K/AKT and AMPK pathways even in H/R-stimulated cells. The protective effects of ghrelin against H/R-induced cell damage were all attenuated by the addition of LY294002 or Compound C. Moreover, endogenous inhibition of ghrelin significantly induced cell death of H9c2 cells. In conclusion, this study demonstrated that ghrelin pretreatment protected H9c2 cells against H/R-induced cell damage, possibly via PI3K/AKT and AMPK pathways.

5.
Opt Lett ; 44(7): 1742-1745, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30933135

RESUMO

The temperature bandwidth of the second harmonic generation (SHG) phase-matching process was investigated for the GdCa4O(BO3)3 (GdCOB) crystal. GdCOB exhibits a much broader temperature bandwidth in comparison with many familiar nonlinear optical (NLO) crystals. For a fundamental wave of 1,064 nm, the maximum temperature bandwidth appeared at (θ=135°, ϕ=47.3°), as predicted by the theoretical calculation and demonstrated by the SHG experiments. The GdCOB crystal is a good candidate for NLO frequency conversions under extreme temperatures.

6.
J Microbiol Biotechnol ; 29(5): 731-738, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31030449

RESUMO

Endophytic fungi are an important component of plant microbiota, and have the excellent capacity for producing a broad variety of bioactive metabolites. These bioactive metabolites not only affect the survival of the host plant, but also provide valuable lead compounds for novel drug discovery. In this study, forty-two endophytic filamentous fungi were isolated from Ficus elastica leaves, and further identified as seven individual taxa by ITS-rDNA sequencing. The antimicrobial activity of these endophytic fungi was evaluated against five pathogenic microorganisms. Two strains, Fes1711 (Penicillium funiculosum) and Fes1712 (Trichoderma harzianum), displayed broad-spectrum bioactivities. Our following study emphasizes the isolation, identification and bioactivity testing of chemical metabolites produced by T. harzianum Fes1712. Two new isocoumarin derivatives (1 and 2), together with three known compounds (3-5) were isolated, and their structures were elucidated using NMR and MS. Compounds 1 and 2 exhibited inhibitory activity against Escherichia coli. Our findings reveal that endophytic fungi from the rubber tree F. elastica leaves exhibit unique characteristics and are potential producers of novel natural bioactive products.


Assuntos
Anti-Infecciosos/farmacologia , Bioprospecção/métodos , Endófitos , Ficus/microbiologia , Fungos/metabolismo , Hevea/microbiologia , Folhas de Planta/microbiologia , Anti-Infecciosos/química , DNA Ribossômico/genética , Descoberta de Drogas , Escherichia coli/efeitos dos fármacos , Fermentação , Fungos/genética , Fungos/isolamento & purificação , Isocumarinas/farmacologia , Penicillium/isolamento & purificação , Penicillium/metabolismo , Trichoderma/isolamento & purificação , Trichoderma/metabolismo
7.
Nanotechnology ; 30(26): 265703, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30889561

RESUMO

Eye-safe pulse lasers have attracted increasing attention due to their potential wide application in many fields. However, optical modulators with excellent nonlinear optical absorption properties in the range of 1.4-2.1 µm are still very scarce. In this study, tin diselenide (SnSe2), a newly-developed 2D layered semiconductor material with facile processability and low cost, was investigated. The nonlinear optical response of SnSe2 was investigated using the open aperture Z-scan method at 1500 and 1800 nm. Using SnSe2 as the saturable absorber, a passive Q-switched solid-state laser was realized at 1.3 and 1.9 µm for the first time. This study proved SnSe2 to be an effective optical modulating material for the eye-safe waveband.

8.
Opt Express ; 27(2): 590-596, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30696143

RESUMO

We report on mode-locking of an Yb:Ca3NbGa3Si2O14 laser, which is pumped by a fiber-coupled single-mode laser diode. The shortest pulse duration obtained with a semiconductor saturable absorber mirror is 52 fs, with 75 mW of average output power. Sub-60 fs operation tunable between 1055 and 1074 nm is achieved by employing semiconductor absorbers with different characteristics. We also demonstrate passive mode-locking results with transmissive graphene saturable absorber, reaching an 85 fs pulse duration with 23 mW output power. Moreover, we present the non-phase-matched self-frequency doubling properties of this non-centrosymmetric crystal in the femtosecond regime.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 206: 384-395, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30170174

RESUMO

The individual and combined interactions of bisphenol F and piceatannol with pepsin were investigated using spectroscopic methods (fluorescence, UV-vis absorption, and circular dichroism spectroscopy), combined with isothermal titration calorimetry and molecular docking. Thermodynamic data showed that hydrogen bonds and van der Waals forces might play a major role for the binding process. Site marking experiments and molecular docking confirmed the binding sites of these two ligands on pepsin. The discrepancy in the binding constant between the binary and ternary systems indicated the competitive binding of piceatannol and bisphenol F to pepsin. Circular dichroism spectra studies suggested that the binding of the two ligands led to a loosening of pepsin backbone. Enzyme activity assays indicated that the inhibition of pepsin activity by piceatannol and bisphenol F was competitive. These results will be helpful to understand the mechanism of piceatannol and bisphenol F affecting the activity of digestive proteases in the sight of the food security.


Assuntos
Compostos Benzidrílicos/química , Pepsina A/química , Fenóis/química , Estilbenos/química , Compostos Benzidrílicos/metabolismo , Sítios de Ligação , Calorimetria , Simulação de Acoplamento Molecular , Pepsina A/metabolismo , Fenóis/metabolismo , Análise Espectral , Estilbenos/metabolismo
10.
Br J Clin Pharmacol ; 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30428505

RESUMO

AIMS: Oprozomib is an oral, second-generation, irreversible proteasome inhibitor currently in clinical development for haematologic malignancies, including multiple myeloma and other malignancies. Oprozomib is a rare example of a small molecule drug that demonstrates cytochrome P450 (CYP) mRNA suppression. This unusual property elicits uncertainty regarding the optimal approach for predicting its drug-drug interaction (DDI) risk. The current study aims to understand DDI potential during early clinical development of oprozomib. METHODS: To support early development of oprozomib (e.g. inclusion/exclusion criteria, combination study design), we used human hepatocyte data and physiologically-based pharmacokinetic (PBPK) modelling to predict its CYP3A4-mediated DDI potential. Subsequently, a clinical DDI study using midazolam as the substrate was conducted in patients with advanced malignancies. RESULTS: The clinical DDI study enrolled a total of 21 patients, 18 with advanced solid tumours. No patient discontinued oprozomib due to a treatment-related adverse event. The PBPK model prospectively predicted oprozomib 300 mg would not cause a clinically relevant change in exposure to CYP3A4 substrates (≤30%), which was confirmed by the results of this clinical DDI study. CONCLUSIONS: These results indicate oprozomib has a low potential to inhibit the metabolism of CYP3A4 substrates in humans. The study shows that cultured human hepatocytes are a more reliable system for DDI prediction than human liver microsomes for studying this class of compounds. Developing a PBPK model prior to a clinical DDI study has been valuable in supporting clinical development of oprozomib.

11.
Appl Opt ; 57(28): 8236-8241, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30461773

RESUMO

Trigonal langasite-type ordered silicate crystal Yb:Ca3NbGa3Si2O14 (Yb:CNGS) is a promising material for efficient ∼1 µm lasers. We report on the first passively Q-switched Yb:CNGS laser using Cr4+:YAG and V3+:YAG saturable absorbers (SAs) with a 976 nm volume-Bragg-grating-stabilized diode as a pump source. The laser crystal was a c cut 3 at.% Yb:CNGS grown by the Czochralski method. It was placed in a compact microchip-type laser cavity. With a Cr4+:YAG SA, very stable 62.2 µJ/4.4 ns pulses were achieved at a repetition rate of 22.5 kHz. The average output power was 1.40 W at 1015.3 nm, corresponding to a Q switching conversion efficiency of 90%. With the V3+:YAG SA, the pulse characteristics were 13.3 µJ/11.1 ns at a higher repetition rate of 68.4 kHz. The performance of the Yb:CNGS/Cr4+:YAG was numerically modeled showing a good agreement with the experiment.

12.
Opt Express ; 26(20): 26179-26187, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30469708

RESUMO

The laser properties of Nd:YPO4 crystal were demonstrated for the first time. For a 1.2 at.% doped Nd:YPO4 crystal, the absorption cross-section at 803 nm, stimulated emission cross-section at 1063 nm, and fluorescence lifetime was measured to be 8.1 × 10-20 cm2, 1.6 × 10-19 cm2, 156 µs, respectively. With an as-grown 0.6 mm thin slice which was unpolished and uncoated, efficient diode-pumped continue-wave (CW) laser operations were realized at 1.06 and 1.3 µm wavebands. The 1063 nm output power reached 2.16 W when the absorbed pump power was 4.07 W, corresponding to an optical-to-optical efficiency of 53%, and a slope efficiency of 56.4%. The 1.3 µm laser output exhibited the simultaneous operations of dual-wavelengths, i.e. 1338 and 1347 nm. The maximum output power was 800 mW at an absorbed pump power of 3.08 W, giving an optical-to-optical efficiency of 26% and a slope efficiency of 28.2%.

13.
Nat Cell Biol ; 20(9): 1064-1073, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30104724

RESUMO

Oncogenic alterations in the RAS/RAF/MEK/ERK pathway drive the growth of a wide spectrum of cancers. While BRAF and MEK inhibitors are efficacious against BRAFV600E-driven cancers, effective targeted therapies are lacking for most cancers driven by other pathway alterations, including non-V600E oncogenic BRAF, RAS GTPase-activating protein (GAP) NF1 (neurofibromin 1) loss and oncogenic KRAS. Here, we show that targeting the SHP2 phosphatase (encoded by PTPN11) with RMC-4550, a small-molecule allosteric inhibitor, is effective in human cancer models bearing RAS-GTP-dependent oncogenic BRAF (for example, class 3 BRAF mutants), NF1 loss or nucleotide-cycling oncogenic RAS (for example, KRASG12C). SHP2 inhibitor treatment decreases oncogenic RAS/RAF/MEK/ERK signalling and cancer growth by disrupting SOS1-mediated RAS-GTP loading. Our findings illuminate a critical function for SHP2 in promoting oncogenic RAS/MAPK pathway activation in cancers with RAS-GTP-dependent oncogenic BRAF, NF1 loss and nucleotide-cycling oncogenic KRAS. SHP2 inhibition is a promising molecular therapeutic strategy for patients with cancers bearing these oncogenic drivers.

14.
Colloids Surf B Biointerfaces ; 172: 118-126, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30144623

RESUMO

In current study, a novel nimodipine solid dispersion (NM-SD) was prepared by hot-melt extrusion (HME) with Hypromellose methylcellulose acetate succinate (H type and fine grades, HPMCAS-HF) for its excellent recrystallization inhibition effects. NM was confirmed to exist as an amorphous state in NM-SD by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot stage microscopy (HSM) and scanning electron micrographs (SEM). FT-IR analysis illustrated hydrogen bond interaction between drugs and excipients in NM-SD. The release behavior of NM-SD tablets was investigated in the dissolution medium of pH 6.8 for the in vitro study, which showed that the release of nimodipine could be realized in vitro without recrystallization within two hours. The in vivo pharmacokinetic profiles study in Sprague-Dawley rats was also determined. It was obvious that the Cmax value of NM-SD tablets made by dry granulation was slightly higher than Nimotop®, while the area under the curve, AUC(0-t) exhibited no significant difference between them. In conclusion, the solubility of NM and dissolution rate of NM-SD tablets were greatly improved by HME due to the recrystallization inhibition characteristic of HPMCAS-HF.

15.
Nanotechnology ; 29(22): 225701, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29537386

RESUMO

As the cousins of graphene, i.e. same group IVA element, the nonlinear absorption (NLA) properties of silicene nanosheets were rarely studied. In this paper, we successfully exfoliated the two-dimensional silicene nanosheets from bulk silicon crystal using liquid phase exfoliation method. The NLA properties of silicene nanosheets were systemically investigated for the first time, as we have known. Silicene performed exciting saturable absorption and two photon absorption (2PA) behavior. The lower saturable intensity and larger 2PA coefficient at 532 nm excitation indicates that silicene has potential application in ultrafast lasers and optical limiting devices, especially in visible waveband.

16.
Opt Express ; 26(4): 4085-4095, 2018 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-29475263

RESUMO

Based on the saturable absorption feature of a two-dimensional (2D) nano-material, antimonene, the passively Q-switched operation for solid-state laser was realized for the first time. For the 946 and 1064 nm laser emissions of the Nd:YAG crystal, the Q-switched pulse widths were 209 and 129 ns, and the peak powers were 1.48, 1.77 W, respectively. For the 1342 nm laser emission of the Nd:YVO4 crystal, the Q-switched pulse width was 48 ns, giving a peak power of 28.17 W. Our research shows that antimonene can be used as a stable, broadband optical modulating device for a solid-state laser, which will be particularly effective for long wavelength operation.

17.
J Phys Condens Matter ; 30(2): 02LT01, 2018 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-29160770

RESUMO

Cascaded longitudinal stimulated Raman scattering (LSRS) and the frequency doubling process are reported for the first time. When potassium dihydrogen phosphate (KDP) crystals are used as the type I and type II frequency doublers of picosecond, focused 1064 nm laser pulses, strong LSRS effects are observed. Three new laser spectrum lines appeared successively, i.e. at 558.9, 588.9 and 622.1 nm, and were excited by the frequency doubling laser at 532 nm. Second- and third-order nonlinear optical frequency conversions were achieved in a single KDP crystal. The near-infrared light was thus converted into a new spectra laser spanning the green-to-red spectral range.

18.
Opt Express ; 25(17): 19760-19766, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-29041664

RESUMO

With Cr4+:YAG as a saturable absorber, a passively Q-switched self-frequency-doubled (SFD) laser based on a trigonal Nd:Ca3NbGa3Si2O14 (Nd:CNGS) silicate crystal was demonstrated for the first time. The maximum average output power at 532 nm was 16.2 mW, and the corresponding pulse repetition frequency, single pulse energy, pulse duration and peak power were 2.25 kHz, 7.2 µJ, 13.7 ns, 0.53 kW, respectively. We also present a rate-equation model of such a passively Q-switched SFD laser showing a good agreement with the experiment. Nd:CNGS is a promising pulse SFD material for miniature all-solid-state visible light sources.

19.
Opt Express ; 25(10): 11867-11893, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28788746

RESUMO

For the first time, the angular non-critical phase-matching (A-NCPM) second-harmonic-generation (SHG) characteristics of a family of monoclinic oxoborate crystals, RECa4O(BO3)3 (RECOB, RE = Tm, Y, Gd, Sm, Nd and La), were comprehensively investigated. For all of the realizable A-NCPM SHG styles, the feature parameters including PM wavelength, angular, wavelength and temperature acceptance bandwidths, have been derived from the theory and verified by the experiments. We discovered that the closer the ion radius between RE3+ and Ca2+, the smaller the birefringence, and the better the A-NCPM SHG properties. As a result, for the Type-I SHG on Y-axis which has the largest effective nonlinear optical coefficient (deff) among the three realizable A-NCPM styles, NdCOB crystal presents the longest PM wavelength (927 nm), the largest angular acceptance bandwidth (Δθ⋅l1/2 = 84.3 mrad·cm1/2, Δϕ⋅l1/2 = 58.8 mrad·cm1/2), and the broadest wavelength acceptance bandwidth (8.7 nm). This discovery will contribute to the design of new NCPM materials, at the same time the parameter formula will be helpful for the theoretical prediction of NCPM performance.

20.
Drug Metab Dispos ; 45(7): 712-720, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28428366

RESUMO

Oprozomib is an oral proteasome inhibitor currently under investigation in patients with hematologic malignancies or solid tumors. Oprozomib elicits potent pharmacological actions by forming a covalent bond with the active site N-terminal threonine of the 20S proteasome. Oprozomib has a short half-life across preclinical species and in patients due to systemic clearance via metabolism. Potential for drug-drug interactions (DDIs) could alter the exposure of this potent therapeutic; therefore, a thorough investigation of pathways responsible for metabolism is required. In the present study, the major drug-metabolizing enzyme responsible for oprozomib metabolism was identified in vitro. A diol of oprozomib was found to be the predominant metabolite in human hepatocytes, which formed via direct epoxide hydrolysis. Using recombinant epoxide hydrolases (EHs) and selective EH inhibitors in liver microsomes, microsomal EH (mEH) but not soluble EH (sEH) was found to be responsible for oprozomib diol formation. Coincubation with 2-nonylsulfanyl-propionamide, a selective mEH inhibitor, resulted in a significant decrease in oprozomib disappearance (>80%) with concurrent complete blockage of diol formation in human hepatocytes. On the contrary, a selective sEH inhibitor did not affect oprozomib metabolism. Pretreatment of hepatocytes with the pan-cytochrome P450 (P450) inhibitor 1-aminobenzotriazole resulted in a modest reduction (∼20%) of oprozomib metabolism. These findings indicated that mEH plays a predominant role in oprozomib metabolism. Further studies may be warranted to determine whether drugs that are mEH inhibitors cause clinically significant DDIs with oprozomib. On the other hand, pharmacokinetics of oprozomib is unlikely to be affected by coadministered P450 and sEH inhibitors and/or inducers.


Assuntos
Clorpromazina/análogos & derivados , Sistema Enzimático do Citocromo P-450/metabolismo , Epóxido Hidrolases/metabolismo , Inibidores de Proteassoma/metabolismo , Administração Oral , Adulto , Clorpromazina/metabolismo , Interações de Medicamentos/fisiologia , Feminino , Meia-Vida , Hepatócitos/metabolismo , Humanos , Masculino , Microssomos Hepáticos/metabolismo , Pessoa de Meia-Idade , Oxirredução , Proteínas Recombinantes/metabolismo , Triazóis/metabolismo , Adulto Jovem
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