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1.
Opt Express ; 26(21): 27885-27893, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30469846

RESUMO

A simple and low-cost radiative cooler based on one-dimensional photonic crystal is proposed in this work, which has an average emissivity of 96% within the atmospheric transparency window (8-13µm). The ultra-broadband emissivity property is realized by constructing the strongly overlapped optical resonances with a tandem structure composed of two lossy materials while an additional lossless material is adopted as the top layer to reduce the Fresnel reflection of the whole structure. The maximum cooling power density of the fabricated radiative cooler can reach 113.0W/m2 at night. When integrated with an excellent solar reflector that can reflect 97% incident solar power, it theoretically has the maximum cooling power of 83.0 W/m2 in the case of solar irradiance up to 1000 W/m2 at noon.

2.
Sci Technol Adv Mater ; 19(1): 174-184, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29511395

RESUMO

Series of co-sputtered silver-indium tin oxide (Ag-ITO) films are systematically fabricated. By tuning the atomic ratio of silver, composite films are manifested to have different microstructures with limited silver amount (<3 at.%). Two stages for film morphology changing are proposed to describe different status and growth mechanisms. The introduction of silver improves the preferred orientations of In2O3 component significantly. Remarkably, dielectric permittivity of Ag-ITO films is highly adjustable, allowing the cross-over wavelengths λc to be changed by more than 300 nm through rapid post-annealing, and thus resulting in tunable epsilon-near-zero and plasmonic properties in the near-infrared region. Lower imaginary permittivity compared with pure metal films, as well as larger tunability in λc than pure ITO films suggest the potentiality of Ag-ITO films as substituted near-infrared plasmonic materials. Extended Maxwell-Garnett model is applied for effective medium approximation and the red-shifting of epsilon-near-zero region with the increase of silver content is well-fitted. Angle-variable prism coupling is carried out to reveal the surface plasmon polariton features of our films at optical communication wavelength. Broad dips in reflectance curves around 52-56° correspond to the SPP in Ag-ITO films.

3.
Int J Hyperthermia ; 33(4): 459-464, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28081645

RESUMO

PURPOSE: To determine the factors affecting the recurrence of the solitary benign thyroid nodules (BTN) after microwave ablation (MWA). MATERIALS AND METHODS: Between January 2013 and January 2015, a total of 110 patients with at least one solid thyroid nodule (solid component ≥ 80%) were enrolled. MWA was performed under continuous ultrasound (US) guidance. Before and during the follow-up, the thyroid nodule volume, thyroid function and cosmetic complaints were evaluated. Recurrence is defined by the new blood flow in the total ablation area or/and > 50% increase in nodule volume. RESULTS: Almost all thyroid nodules were significantly decreased in size after MWA. After 12 months, the average volume of thyroid nodules was decreased from 12.6 ± 15.1 to 3.2 ± 5.7 ml. Of the total 110 patients, 16 cases had recurrence 12 months after MWA, and these patients had a larger initial volume than that of the non-recurrence patients (11.6 ± 14.9 vs. 23.9 ± 12.5, p < 0.01). The recurrence group also demonstrated more irregular blood vessels (1.8 8 ± 1.1 vs. 2.8 5 ± 1.3, p < 0.05), and a lower energy (1575.5 ± 674.3 J/ml vs. 1172.3 ± 454.2 J/ml, p < 0.01). In addition, 81.2% (13/16) of the patients in the recurrence group were adjacent to the vital structures, which is significantly higher than that of the non-recurrence group 28.7% (27/94) (p < 0.01). CONCLUSIONS: The US-guided MWA results in a satisfactory long-term outcome of the patients with a benign solitary thyroid nodule. We identified three risk factors for recurrence: initial volume, vascularity and the energy per 1 ml reduction in nodular volume.

4.
Int J Hyperthermia ; 32(6): 607-13, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27269816

RESUMO

PURPOSE: This study was designed to determine the safety, effectiveness and feasibility of contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma (RCC) that is inconspicuous on conventional ultrasound (US). MATERIALS AND METHODS: A total of 32 RCC nodules in 29 patients (23 men and 6 women) were treated with CEUS-guided percutaneous MWA between January 2010 and September 2014. The median maximum diameter of the nodules was 2.4 cm (interquartile range: 1.8-2.9 cm). The US contrast agent was SonoVue, a second-generation contrast agent. CEUS was applied before the needle was inserted into the tumour, and percutaneous MWA was performed under CEUS-guidance. RESULTS: In total 31 tumours were successfully visualised via CEUS using 1-2 (1.0-2.0 mL) contrast agent injections, and percutaneous MWA was performed under CEUS-guidance. The technical success rate of CEUS-guided percutaneous MWA of RCC was 96.9% (31/32). The mean number of sessions of CEUS-guided percutaneous MWA for each tumour was 1.2 ± 0.4. The mean duration of energy application for each tumour was 7.3 ± 2.7 min. All patients were followed up for 3-71 months (median 17 months) to observe the therapeutic effects and complications. The therapeutic effects were assessed at follow-up with computed tomography (CT) or magnetic resonance imaging (MRI) and CEUS. There was no local tumour progression and the technique effectiveness rate was 100% (31/31). The complications rate was 6.5% and the major complications rate was 3.2%. We observed one case of pleural effusion and one case of renal subcapsular haemorrhage after the percutaneous MWA procedures. CONCLUSION: CEUS-guided percutaneous MWA is a safe, efficient and feasible therapy for patients with RCCs inconspicuous on conventional US.


Assuntos
Técnicas de Ablação , Carcinoma de Células Renais/cirurgia , Meios de Contraste/uso terapêutico , Neoplasias Renais/cirurgia , Micro-Ondas/uso terapêutico , Fosfolipídeos/uso terapêutico , Hexafluoreto de Enxofre/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico por imagem , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Ultrassonografia de Intervenção
5.
Bioorg Med Chem Lett ; 25(16): 3129-34, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26112442

RESUMO

A series of 3,5-disubstitute-4-alkynylisoxazole derivatives were designed and synthesized through palladium(II)-copper(I) catalyzed Sonogashira cross-coupling reaction of an alkynyl moiety and an isoxazole scaffold as novel HSP90 inhibitors. The resultant compounds displayed moderate to potent binding affinity to HSP90 proteins, and also demonstrated good cell growth inhibitory activity against various cancer cell lines (A549, K562, MCF-7, DU145 and Hela). Some compounds (18d, 18e, 19a, 19d, 20c and 20q) show similar or better binding affinity towards HSP90α and HSP90ß comparing to NVP-AUY922. In addition, compounds 18e, 19a and 20q exhibited potent inhibitory activity against various human cancer cell lines.


Assuntos
Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Isoxazóis/química , Apoptose/efeitos dos fármacos , Sítios de Ligação , Catálise , Domínio Catalítico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cobre/química , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Isoxazóis/síntese química , Isoxazóis/farmacologia , Isoxazóis/toxicidade , Simulação de Acoplamento Molecular , Paládio/química , Resorcinóis/toxicidade , Relação Estrutura-Atividade
6.
Cell Death Differ ; 30(3): 716-730, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36220889

RESUMO

The hexanucleotide GGGGCC repeat expansion in the intronic region of C9orf72 is the most common cause of Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeat expansion-generated toxic RNAs and dipeptide repeats (DPRs) including poly-GR, have been extensively studied in neurodegeneration. Moreover, haploinsufficiency has been implicated as a disease mechanism but how C9orf72 deficiency contributes to neurodegeneration remains unclear. Here, we show that C9orf72 deficiency exacerbates poly-GR-induced neurodegeneration by attenuating non-homologous end joining (NHEJ) repair. We demonstrate that C9orf72 localizes to the nucleus and is rapidly recruited to sites of DNA damage. C9orf72 deficiency resulted in impaired NHEJ repair through attenuated DNA-PK complex assembly and DNA damage response (DDR) signaling. In mouse models, we found that C9orf72 deficiency exacerbated poly-GR-induced neuronal loss, glial activation, and neuromuscular deficits. Furthermore, DNA damage accumulated in C9orf72-deficient neurons that expressed poly-GR, resulting in excessive activation of PARP-1. PARP-1 inhibition rescued neuronal death in cultured neurons treated with poly-GR peptides. Together, our results support a pathological mechanism where C9orf72 haploinsufficiency synergizes with poly-GR-induced DNA double-strand breaks to exacerbate the accumulation of DNA damage and PARP-1 overactivation in C9orf72 ALS/FTD patients.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Animais , Camundongos , Esclerose Lateral Amiotrófica/patologia , Demência Frontotemporal/genética , Proteína C9orf72/genética , Inibidores de Poli(ADP-Ribose) Polimerases , Expansão das Repetições de DNA , Dipeptídeos , Dano ao DNA , DNA
7.
Artigo em Inglês | MEDLINE | ID: mdl-35206423

RESUMO

The ecological environment is important for the natural disaster prevention of human society. The monitoring of ecological environment quality has far-reaching practical significance for the functional construction of ecosystem services and policy coordination. Based on Landsat 8 operational land image (OLI)/thermal infrared sensor (TIRS) remote sensing image data, this study selected the normalized vegetation (NDVI), tasseled cap transformation humidity (WI), bare soil (SI), construction index (NDSI), and land surface temperature (LST) indexes from the aspects of greenness, humidity, dryness, and heat. Using spatial principal component analysis (SPCA) and the remote sensing ecological index (RSEI) analyzed the spatial differentiation characteristics and influencing factors of the original remote sensing ecological index (RSEI0). The results showed that: (1) the overall RSEI average value of the Qinling-Daba Mountains in 2017 was 0.61, and the ecological environment quality was at a "Good" level. Greenness contributed the most to the comprehensive index of the area, and vegetation distribution had a significant impact on the ecological environment quality of the study area. Heat is a secondary impact, and it has an inhibitory effect on habitat quality; (2) the overall distribution of regional ecological environment quality was quite different, with the ecological environment quality level showing a decreasing trend from low to high altitude; RSEI0 spatial heterogeneity at the optimal scale of 2 km was the largest, and the nugget effect was 88% which indicated a high degree of spatial variability, mainly affected by structural factors; (3) Slope, relief amplitude, elevation, the proportion of high-vegetation area, proportion of construction land area, and average population density significantly impact the spatial differentiation of RSEI0. The explanatory powers of slope and relief amplitude were 56.1% and 65.3%, respectively, which were the main factors affecting the spatial differentiation of the ecological environment quality in high undulation. The results can provide important scientific support for ecological environment construction and ecological restoration in the study area.


Assuntos
Ecossistema , Tecnologia de Sensoriamento Remoto , China , Meio Ambiente , Monitoramento Ambiental , Humanos
8.
Cell Death Dis ; 13(5): 466, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585040

RESUMO

Ischemia-induced neuronal death leads to serious lifelong neurological deficits in ischemic stroke patients. Histone deacetylase 6 (HDAC6) is a promising target for neuroprotection in many neurological disorders, including ischemic stroke. However, the mechanism by which HDAC6 inhibition protects neurons after ischemic stroke remains unclear. Here, we discovered that genetic ablation or pharmacological inhibition of HDAC6 reduced brain injury after ischemic stroke by increasing macrophage migration inhibitory factor (MIF) acetylation. Mass spectrum analysis and biochemical results revealed that HDAC6 inhibitor or aspirin treatment promoted MIF acetylation on the K78 residue. MIF K78 acetylation suppressed the interaction between MIF and AIF, which impaired MIF translocation to the nucleus in ischemic cortical neurons. Moreover, neuronal DNA fragmentation and neuronal death were impaired in the cortex after ischemia in MIF K78Q mutant mice. Our results indicate that the neuroprotective effect of HDAC6 inhibition and aspirin treatment results from MIF K78 acetylation; thus, MIF K78 acetylation may be a therapeutic target for ischemic stroke and other neurological diseases.


Assuntos
Oxirredutases Intramoleculares , AVC Isquêmico , Fatores Inibidores da Migração de Macrófagos , Doenças do Sistema Nervoso , Neurônios , Acetilação , Animais , Aspirina/farmacologia , Desacetilase 6 de Histona/metabolismo , Humanos , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , Camundongos , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Neurônios/metabolismo , Neurônios/patologia
9.
Bioorg Med Chem ; 18(14): 4897-904, 2010 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-20598554

RESUMO

The triazolopyrimidine-2-sulfonanilide, discovered from preparing bioisosteres of the sulfonylurea herbicides, is an important class of acetohydroxyacid synthase (AHAS, EC 4.1.3.18) inhibitors. At least over ten triazolopyrimidine sulfonanilides have been commercialized as herbicides for the control of broadleaf weeds and grass with cereal crop selectivity. Herein, a series of triazolopyrimidine-2-sulfonanilides were designed and synthesized with the aim of discovery of new herbicides with higher activity. The assay results of the inhibition activity of the synthesized compounds against Arabidopsis thatiana AHAS indicated that some compounds showed a little higher activity against flumetsulam (FS), the first commercial triazolopyrimidine-2-sulfonanilide-type herbicide. The ki values of two promising compounds 3d and 8h are respectively, 1.61 and 1.29 microM, while that of FS is 1.85 microM. Computational simulation results indicated the ester group of compound 3d formed hydrogen bonds with the surrounding residues Arg'198 and Ser653, which accounts for its 11.5-folds higher AHAS inhibition activity than Y6610. Further green house assay showed that compound 3d has comparable herbicidal activity as FS. Even at the concentration of 37.5g.ai/ha, 3d showed excellent herbicidal activity against Galium aparine, Cerastium arvense, Chenopodium album, Amaranthus retroflexus, and Rmumex acetasa, moderate herbicidal activity against Polygonum humifusum, Cyperus iria, and Eclipta prostrate. The combination of in vitro and in vivo assay indicated that 3d could be regarded as a new potential acetohydroxyacid synthase-inhibiting herbicide candidate for further study.


Assuntos
Acetolactato Sintase/antagonistas & inibidores , Acetolactato Sintase/metabolismo , Arabidopsis/enzimologia , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Herbicidas/síntese química , Herbicidas/farmacologia , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Acetolactato Sintase/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Herbicidas/química , Modelos Moleculares , Ligação Proteica , Sulfonamidas/química
10.
Bioorg Med Chem ; 17(8): 3011-7, 2009 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-19342247

RESUMO

Triazolopyrimidine-2-sulfonamide belongs to a herbicide group called acetohydroxyacid synthase inhibitors. With the aim to discover new triazolopyrimidine sulfonanilide compounds with high herbicidal activity and faster degradation rate in soil, the methyl group of Flumetsulam (FS) was modified into a methoxy group to produce a new herbicidal compound, N-2,6-difluorophenyl-5-methoxy-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide (experimental code: Y6610). The enzymatic kinetic results indicated that compound Y6610 and FS have k(i) values of 3.31x10(-6) M and 3.60x10(-7) M against Arabidopsis thaliana AHAS, respectively. The 10-fold lower enzyme-inhibiting activity of Y6610 was explained rationally by further computational simulations and binding free energy calculations. In addition, compound Y6610 was found to display the same level in vivo post-emergent herbicidal activity as FS against some broad-leaf weeds and good safety to rice, maize, and wheat at the dosages of 75-300 gai/ha. Further determination of the half-lives in soil revealed that the half-life in soil of Y6610 is 3.9 days shorter than that of FS. The experimental results herein showed that compound Y6610 could be regarded as a new potential acetohydroxyacid synthase-inhibiting herbicide candidate for further study.


Assuntos
Acetolactato Sintase/antagonistas & inibidores , Herbicidas/síntese química , Pirimidinas/síntese química , Sulfonamidas/síntese química , Acetolactato Sintase/metabolismo , Arabidopsis , Sítios de Ligação , Simulação por Computador , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Herbicidas/química , Humanos , Cinética , Modelos Moleculares , Plantas Geneticamente Modificadas , Pirimidinas/química , Relação Estrutura-Atividade , Sulfonamidas/química
11.
Chem Biodivers ; 6(8): 1254-65, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19697344

RESUMO

A series of new acetohydrazone-containing 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized for the purpose of searching for novel agrochemicals with higher fungicidal activity. Their in vitro fungicidal activities against Rhizoctonia solani were evaluated, and the most promising compound, 2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2'-[(2-hydroxyphenyl)methylidene]acetohydrazide (2-17), showed a lower EC(50) value (5.34 microg ml(-1)) than that of commercial carbendazim (EC(50)=7.62 microg ml(-1)). Additionally, compound 2-17 was also found to display broad-spectrum fungicidal activities, and its EC(50) value (4.56 microg ml(-1)) against Botrytis cinereapers was very similar to that of carbendazim. Qualitative structure-activity relationships (QSARs) of the synthesized compounds were also discussed.


Assuntos
Fungicidas Industriais/farmacologia , Pirimidinas/farmacologia , Triazóis/farmacologia , Agroquímicos/síntese química , Agroquímicos/farmacologia , Concentração Inibidora 50 , Pirimidinas/síntese química , Rhizoctonia/efeitos dos fármacos , Relação Estrutura-Atividade , Triazóis/síntese química
12.
Molecules ; 13(6): 1353-60, 2008 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-18596661

RESUMO

The syntheses of some diheterocyclic compounds from 2-thioacetohydrazide- 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (1) are described. Compound 1 can be converted into triazoles, 1,3,4-oxadiazoles, and 1,3,4-thiadiazoles. The structures of the intermediates and the target compounds were confirmed by (1)H-NMR, MS and elemental analyses.


Assuntos
Compostos Heterocíclicos/síntese química , Pirimidinas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Oxidiazóis/síntese química , Tiadiazóis/síntese química , Triazóis/síntese química
13.
ACS Appl Mater Interfaces ; 10(17): 14886-14893, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29644842

RESUMO

Indium tin oxide (ITO)-based sandwich structures with the insertion of ultrathin (<10 nm) titanium nitride (TiN) are investigated as near-infrared (NIR) plasmonic materials. The structural, electrical, and optical properties reveal the improvement of the sandwich structures stemmed from TiN insertion. TiN is a well-established alternative to noble metals such as gold, elevating the electron conductivity of sandwich structures as its thickness increases. Dielectric permittivities of TiN and top ITO layers show TiN-thickness-dependent properties, which lead to moderate and tunable effective permittivities for the sandwiches. The surface plasmon polaritons (SPP) of the ITO-TiN-ITO sandwich at the telecommunication window (1480-1570 nm) are activated by prism coupling using Kretschmann configuration. Compared with pure ITO films or sandwiches with metal insertion, the reflectivity dip for sandwiches with TiN is relatively deeper and wider, indicating the enhanced coupling ability in plasmonic materials for telecommunications. The SPP spatial profile, penetration depth, and degree of confinement, as well as the quality factors, demonstrate the applicability of such sandwiches for NIR plasmonic materials in various devices.

14.
RSC Adv ; 8(37): 21040-21046, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35542376

RESUMO

In this work, phase change chalcogenide Ge2Sb2Te5 (GST) thin films were fabricated by magnetron sputtering. The optical properties, especially the optical constants (refractive index and extinction coefficient), of such alloys were systematically studied by investigating their thermally and photo-thermally induced switching between different phases. The results show that GST films are highly tunable in microstructure and optical constants, either by post-annealing at 160 °C, 200 °C, 250 °C and 350 °C, respectively, or by laser irradiation of 1 mW, 3 mW, 5 mW and 10 mW power with beam diameter of 7 µm at 532 nm, respectively. From the structural analysis, we can clearly observe different crystallinities and chemical bonding in the different post-treated GST films. The optical constants of GST films under various phases were obtained from spectrophotometry, by fitting their transmittance data with the Tauc-Lorentz (TL) dispersion model. The refractive index and extinction coefficient exhibit notable change upon annealing and laser irradiation, specifically at 1550 nm, from 3.85 (amorphous) to 6.5 (crystalline) in refractive index. The optical constants have been proved capable of fine tuning via the laser irradiation method. Hence, the pronounced adjustability in optical properties due to rapid and repeatable phase change render GST suitable for tunable photonic devices.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30297620

RESUMO

Increases in the extent and level of air pollution in Chinese cities have become a major concern of the public and burden on the government. While ample literature has focused on the status, changes and causes of air pollution (particularly on PM2.5 and PM10), significantly less is known on their effects on people. In this study we used Hangzhou, China, as our testbed to assess the direct impact of PM2.5 on youth populations that are more vulnerable to pollution. We used the ground monitoring data of air quality and Aerosol optical thickness (AOT) product from the Moderate Resolution Imaging Spectroradiometer (MODIS) for the spatiotemporal changes of PM2.5 by season in 2015. We further explored these distributions with land cover, population density and schools (kindergarten, primary school and middle school) to explore the potential impacts in seeking potential mitigation solutions. We found that the seasonal variation of PM2.5 concentration was winter > spring > autumn > summer. In Hangzhou, the percentage of land area exposed to PM2.5 > 50 µg m-3 accounted for 59.86% in winter, 56.62% in spring, 40.44% in autumn and 0% in summer, whereas these figures for PM2.5 of <35 µg m-3 were 70.01%, 5.28%, 5.17%, 4.16% in summer, winter, autumn and spring, respectively. As for land cover, forest experienced PM2.5 of 35⁻50 µg m-3 (i.e., lower than those of other cover types), likely due to the potential filtering and absorption function of the forests. More importantly, a quantitative index based on population-weighted exposure level (pwel) indicated that only 9.06% of the population lived in areas that met the national air quality standards. Only 1.66% (14,055) of infants and juveniles lived in areas with PM2.5 of <35 µg m-3. Considering the legacy effects of PM2.5 over the long-term, we highly recommend improving the monitoring systems for both air quality and people (i.e., their health conditions), with special attention paid to infants and juveniles.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental/métodos , Material Particulado/análise , Adolescente , Criança , Pré-Escolar , China , Cidades/estatística & dados numéricos , Feminino , Humanos , Masculino , Estações do Ano
16.
Eng Life Sci ; 18(4): 227-235, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32624901

RESUMO

While the methylotrophic yeast Pichia pastoris enables the industrial-scale biosynthesis of many recombinant products, large amount of nutrient-rich biomass emerged along this process. Polysaccharides, especially glucans that are abundant in the cell wall of P. pastoris, are yet to be better utilized owing to their various biological activities. However, the isolation and purification of cell wall glucan from P. pastoris has not been reported. In this study, we established an environment-friendly approach, including induced autolysis, hot-water treatment, ultrasonication, isopropanol extraction, and protease treatment, to isolate and purify glucan from the cell wall of P. pastoris. We achieved a purity of 85.3% and a yield of 11.7% for the purified glucan. Proteins, nucleic acids, lipids, and ash were efficiently removed during the purification. The activities of the purified glucan were investigated in mice fed with a high-fat diet. The purified glucan decreased the level of total cholesterol and triglycerides by 30.3 and 29.7%, respectively. This result suggested that the cell wall glucan of P. pastoris could be developed to a therapeutic agent for dyslipidemia. Our study proposed an environment-friendly and effective method to isolate and purify the glucan from P. pastoris, providing solid foundation for the high-value utilization of this yeast.

17.
Int J Biol Macromol ; 112: 767-774, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29427680

RESUMO

d-Allulose 3-epimerase (DAEase) catalyzes the epimerization between d-fructose and d-allulose. We had PCR-cloned and overexpressed the gene encoding Agrobacterium sp. ATCC 31749 DAEase (AsDAEase) in Escherichia coli. A high yield of active AsDAEase, 35,300U/L or 1350U/g of wet cells, was acquired with isopropyl ß-d-1-thiogalactopyranoside induction at 20°C for 20h. Although only six residues including residue 234 located in tetrameric interface are different between AsDAEase and A. tumefaciens DAEase (AtDAEase), the specific activity of purified AsDAEase is much larger than that of AtDAEase. The optimal pHs and optimal temperatures of the purified recombinant AsDAEase are 7.5-8.0 and 55-60°C, respectively. The half-life of the enzyme is 267min at 55°C in the presence of 0.1mM Co2+, and the equilibrium ratio between d-allulose and d-fructose is 30:70 at 55°C. Besides characterizing AsDAEase, mutation N234D was constructed to assess its influence on activity. The specific activity of the purified N234D AsDAEase is only 25.5% of wild-type's activity, suggesting residue N234 is an important interfacial residue which substantially affects enzyme activity. The high specific activity and high expression yield of AsDAEase suggest its prospect to be applied in d-allulose production.


Assuntos
Agrobacterium tumefaciens/enzimologia , Aminoácidos/metabolismo , Carboidratos Epimerases/metabolismo , Proteínas Recombinantes/metabolismo , Carboidratos Epimerases/química , Carboidratos Epimerases/isolamento & purificação , Cobalto/farmacologia , Estabilidade Enzimática/efeitos dos fármacos , Frutose/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Modelos Moleculares , Peso Molecular , Mutagênese Sítio-Dirigida , Homologia Estrutural de Proteína , Especificidade por Substrato/efeitos dos fármacos , Temperatura
18.
Chem Biol Drug Des ; 89(3): 420-427, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27589335

RESUMO

Novel dasatinib analogues as DDR1 and DDR2 inhibitors were designed and synthesized. The synthesized compounds were screened for DDR1 and DDR2 kinase inhibitory and cancer cell proliferation inhibitory activities. Some of the compounds showed the potent inhibitory activities against both DDR1 and DDR2, as well as anticancer activity in low nanomolar range against K562 cell line; especially, compound 3j demonstrated significantly better inhibitory potency than the parental dasatinib against both DDRs and also demonstrated the potent inhibitory activity against K562 cell lines (IC50 values of 2.26±0.46 nm for DDR1, 7.04±2.90 nm for DDR2, and 0.125±0.017 nm for K562 cell line).


Assuntos
Dasatinibe/análogos & derivados , Receptor com Domínio Discoidina 1/antagonistas & inibidores , Receptor com Domínio Discoidina 2/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Dasatinibe/metabolismo , Receptor com Domínio Discoidina 1/metabolismo , Receptor com Domínio Discoidina 2/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligação de Hidrogênio , Células K562/efeitos dos fármacos , Simulação de Acoplamento Molecular , Piperazina , Piperazinas/química , Inibidores de Proteínas Quinases/síntese química
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