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1.
Proc Natl Acad Sci U S A ; 121(9): e2313464121, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38346211

RESUMO

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth surface on the order of microns, which can effectively overcome the layered morphology in conventional extrusion-based three-dimensional bioprinting methods. Since the support bath is sensitive to temperature change, it can be easily removed after printing by tuning the ambient temperature, which facilitates the fabrication of human eyeballs with optic nerves and aortic heart valves with overhanging leaflets on the order of a few millimeters. The thermosensitivity of the support bath also enables the reconstruction of the full-scale human heart on the order of tens of centimeters by on-demand adding support bath materials during printing. The proposed MSEP demonstrates broader printable functional feature sizes ranging from microns to centimeters, providing a viable and reliable technical solution for tissue and organ printing in the future.


Assuntos
Bioimpressão , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Córnea , Bioimpressão/métodos , Impressão Tridimensional , Alicerces Teciduais/química , Hidrogéis/química
2.
Proc Natl Acad Sci U S A ; 119(39): e2202157119, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36122209

RESUMO

CTNNB1, encoding ß-catenin protein, is the most frequently altered proto-oncogene in hepatic neoplasms. In this study, we studied the significance and pathological mechanism of CTNNB1 gain-of-function mutations in hepatocarcinogenesis. Activated ß-catenin not only triggered hepatic tumorigenesis but also exacerbated Tp53 deletion or hepatitis B virus infection-mediated liver cancer development in mouse models. Using untargeted metabolomic profiling, we identified boosted de novo pyrimidine synthesis as the major metabolic aberration in ß-catenin mutant cell lines and livers. Oncogenic ß-catenin transcriptionally stimulated AKT2, which then phosphorylated the rate-limiting de novo pyrimidine synthesis enzyme CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase) on S1406 and S1859 to potentiate nucleotide synthesis. Moreover, inhibition of ß-catenin/AKT2-stimulated pyrimidine synthesis axis preferentially repressed ß-catenin mutant cell proliferation and tumor formation. Therefore, ß-catenin active mutations are oncogenic in various preclinical liver cancer models. Stimulation of ß-catenin/AKT2/CAD signaling cascade on pyrimidine synthesis is an essential and druggable vulnerability for ß-catenin mutant liver cancer.


Assuntos
Neoplasias Hepáticas , Pirimidinas , beta Catenina , Animais , Ácido Aspártico , Carcinogênese , Di-Hidro-Orotase/genética , Di-Hidro-Orotase/metabolismo , Sistemas de Liberação de Medicamentos , Ligases , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , Camundongos , Nucleotídeos , Fosfatos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/biossíntese , beta Catenina/metabolismo
3.
J Biol Chem ; 299(11): 105315, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37797700

RESUMO

A high-fat diet (HFD) plays a critical role in hepatocyte insulin resistance. Numerous models and factors have been proposed to elucidate the mechanism of palmitic acid (PA)-induced insulin resistance. However, proteomic studies of insulin resistance by HFD stimulation are usually performed under insulin conditions, leading to an unclear understanding of how a HFD alone affects hepatocytes. Here, we mapped the phosphorylation rewiring events in PA-stimulated HepG2 cells and found PA decreased the phosphorylation level of the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2) at S65/T70. Further experiments identified 4EBP2 as a key node of insulin resistance in either HFD mice or PA-treated cells. Reduced 4EBP2 levels increased glucose uptake and insulin sensitivity, whereas the 4EBP2_S65A/T70A mutation exacerbated PA-induced insulin resistance. Additionally, the nascent proteome revealed many glycolysis-related proteins translationally regulated by 4EBP2 such as hexokinase-2, pyruvate kinase PKM, TBC1 domain family member 4, and glucose-6-phosphate 1-dehydrogenase. In summary, we report the critical role of 4EBP2 in regulating HFD-stimulated insulin resistance in hepatocytes.


Assuntos
Resistência à Insulina , Animais , Masculino , Camundongos , Proteínas de Transporte/metabolismo , Linhagem Celular , Dieta Hiperlipídica/efeitos adversos , Hepatócitos/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Camundongos Endogâmicos C57BL , Ácido Palmítico/metabolismo , Biossíntese de Proteínas , Proteômica
4.
J Am Chem Soc ; 146(15): 10716-10722, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38579164

RESUMO

Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination. In this reaction, the flavin-dependent ene-reductase photocatalytically generates the aminium radical cation from the corresponding hydroxylamine and catalyzes the asymmetric intermolecular hydroamination to furnish the enantioenriched tertiary amine, whereby enantioinduction occurs through enzyme-mediated hydrogen atom transfer. This work highlights the use of photoenzymatic catalysis to generate and control highly reactive radical intermediates for asymmetric synthesis, addressing a long-standing challenge in chemical synthesis.

5.
J Am Chem Soc ; 146(10): 6449-6455, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38316013

RESUMO

By virtue of noninvasive regulations by light, photocontrolled polymerizations have attracted considerable attention for the precision synthesis of macromolecules. However, a cationic polymerization with simultaneous photocontrol and tacticity-regulation remains elusive so far. Herein, we introduce an asymmetric ion-pairing photoredox catalysis strategy that allows for the development of a stereoselective cationic polymerization with concurrent light regulation for the first time. By employing an ion pair catalyst (PC+/*A-) consisting of a photoredox active cation (PC+) and a sterically confined chiral anion (*A-) to deliver the stereochemical control, the cationic polymerization of vinyl ethers can be achieved with photocontrol and high isotactic selectivity (up to 91% m) at a remarkable low catalyst loading (50 ppm).

6.
J Magn Reson Imaging ; 59(3): 837-848, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37431848

RESUMO

BACKGROUND: Native T1 and radiomics were used for hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) differentiation previously. The current problem is that global native T1 remains modest discrimination performance and radiomics requires feature extraction beforehand. Deep learning (DL) is a promising technique in differential diagnosis. However, its feasibility for discriminating HCM and HHD has not been investigated. PURPOSE: To examine the feasibility of DL in differentiating HCM and HHD based on T1 images and compare its diagnostic performance with other methods. STUDY TYPE: Retrospective. POPULATION: 128 HCM patients (men, 75; age, 50 years ± 16) and 59 HHD patients (men, 40; age, 45 years ± 17). FIELD STRENGTH/SEQUENCE: 3.0T; Balanced steady-state free precession, phase-sensitive inversion recovery (PSIR) and multislice native T1 mapping. ASSESSMENT: Compare HCM and HHD patients baseline data. Myocardial T1 values were extracted from native T1 images. Radiomics was implemented through feature extraction and Extra Trees Classifier. The DL network is ResNet32. Different input including myocardial ring (DL-myo), myocardial ring bounding box (DL-box) and the surrounding tissue without myocardial ring (DL-nomyo) were tested. We evaluate diagnostic performance through AUC of ROC curve. STATISTICAL TESTS: Accuracy, sensitivity, specificity, ROC, and AUC were calculated. Independent t test, Mann-Whitney U-test and Chi-square test were adopted for HCM and HHD comparison. P < 0.05 was considered statistically significant. RESULTS: DL-myo, DL-box, and DL-nomyo models showed an AUC (95% confidential interval) of 0.830 (0.702-0.959), 0.766 (0.617-0.915), 0.795 (0.654-0.936) in the testing set. AUC of native T1 and radiomics were 0.545 (0.352-0.738) and 0.800 (0.655-0.944) in the testing set. DATA CONCLUSION: The DL method based on T1 mapping seems capable of discriminating HCM and HHD. Considering diagnostic performance, the DL network outperformed the native T1 method. Compared with radiomics, DL won an advantage for its high specificity and automated working mode. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.


Assuntos
Cardiomiopatia Hipertrófica , Aprendizado Profundo , Cardiopatias , Hipertensão , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos
7.
Clin Oral Investig ; 28(7): 368, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38862733

RESUMO

OBJECTIVES: The aims of this clinical study were to investigate success rate, vital pulp survival rate, tooth survival rate and patient-reported masticatory ability by evaluating the pain symptoms and signs of the cracked teeth as well as Index of Eating Difficulty (IED) and Oral Health Impact Profile-14 (OHIP-14) questionnaire after cracked teeth were restored with occlusal veneers. MATERIALS AND METHODS: 27 cracked teeth of 24 patients with cold and/or biting pains without spontaneous/nocturnal pains were recruited in this study. The cracked teeth were restored with occlusal veneers fabricated by lithium disilicate ceramic. Cold test and biting test were used to evaluate pain signs. IED and OHIP-14 questionnaire were used to evaluate masticatory ability. FDI criteria was used to evaluate restorations. The paired Wilcoxon test was used to analyze significant differences of detection rate of pain signs, OHIP scores and IED grade before and after restorations. Kaplan-Meier survival curve was used to describe the success rate, vital pulp survival rate, and tooth survival rate. RESULTS: 27 cracked teeth were restored with occlusal veneers with average of 22.4-month follow-up. Two cracked teeth had pulpitis and pain signs of the other cracked teeth completely disappeared. OHIP total scores were significantly reduced after treatment. Scores of 'pain', 'occlusal discomfort', 'uncomfortable to eat', 'diet unsatisfactory' and 'interrupted meals' reduced significantly after treatment. After treatment, IED grades of 25 vital teeth were significantly lower than those before treatment. FDI scores of 25 restorations except for 2 teeth with pulpitis were no greater than 2. The 12 months accumulated pulp survival rate of the cracked teeth was 92.6%. The 12 months accumulated tooth survival rate was 100%. The success rate at the latest recall was 92.6%. CONCLUSION: Occlusal veneer restorations with success rate of 92.6% and the same pulp survival rate might be an effective restoration for treating the cracked teeth. CLINICAL RELEVANCE: The occlusal veneer restorations might be an option for treating the cracked teeth when cracks only involve enamel and dentin, not dental pulp.


Assuntos
Síndrome de Dente Quebrado , Facetas Dentárias , Humanos , Feminino , Masculino , Adulto , Seguimentos , Síndrome de Dente Quebrado/terapia , Resultado do Tratamento , Inquéritos e Questionários , Pessoa de Meia-Idade , Medição da Dor , Porcelana Dentária , Restauração Dentária Permanente/métodos , Mastigação/fisiologia
8.
New Phytol ; 240(6): 2404-2418, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37845836

RESUMO

Rice panicles, a major component of yield, are regulated by phytohormones and nutrients. How mineral nutrients promote panicle architecture remains largely unknown. Here, we report that NIN-LIKE PROTEIN3 and 4 (OsNLP3/4) are crucial positive regulators of rice panicle architecture in response to nitrogen (N). Loss-of-function mutants of either OsNLP3 or OsNLP4 produced smaller panicles with reduced primary and secondary branches and fewer grains than wild-type, whereas their overexpression plants showed the opposite phenotypes. The OsNLP3/4-regulated panicle architecture was positively correlated with N availability. OsNLP3/4 directly bind to the promoter of OsRFL and activate its expression to promote inflorescence meristem development. Furthermore, OsRFL activates OsMOC1 expression by binding to its promoter. Our findings reveal the novel N-responsive OsNLP3/4-OsRFL-OsMOC1 module that integrates N availability to regulate panicle architecture, shedding light on how N nutrient signals regulate panicle architecture and providing candidate targets for the improvement of crop yield.


Assuntos
Oryza , Oryza/metabolismo , Inflorescência/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Int J Mol Sci ; 24(20)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37895088

RESUMO

The fat body has important functions in energy, fertility, and immunity. In female insects, mating stimulates physiological, behavioral, and gene expression changes. However, it remains unclear whether the metabolites in the fat body are affected after the bumblebee (Bombus terrestris) queen mates. Here, the ultrastructure and lipid metabolites in fat body of mated queens were compared with those of virgins. The fat body weight of mated bumblebee queens was significantly increased, and the adipocytes were filled with lipid droplets. Using LC-MS/MS-based untargeted lipidomics, 949 and 748 differential metabolites were identified in the fat body of virgin and mated bumblebee queens, respectively, in positive and negative ion modes. Most lipid metabolites were decreased, especially some biomembrane components. In order to explore the relationship between the structures of lipid droplets and metabolite accumulation, transmission electron microscopy and fluorescence microscopy were used to observe the fat body ultrastructure. The size/area of lipid droplets was larger, and the fusion of lipid droplets was increased in the mated queen's fat body. These enlarged lipid droplets may store more energy and nutrients. The observed differences in lipid metabolites in the fat body of queens contribute to understanding the regulatory network of bumblebees post mating.


Assuntos
Corpo Adiposo , Lipidômica , Abelhas , Feminino , Animais , Cromatografia Líquida , Espectrometria de Massas em Tandem , Lipídeos
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(8): 1234-1242, 2023 Aug 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-37875364

RESUMO

OBJECTIVES: Many studies have shown that the quality of life for patients with atrial fibrillation (AF) is significantly impaired, but the impact on family function is still unclear. This study aims to evaluate the family function and quality of life in patients with AF using scales, to analyze the correlation between family function and quality of life, and to predict the influencing factors of quality of life. METHODS: A total of 223 patients with AF who were admitted to the Department of Cardiology and General Medicine of the Lanzhou University Second Hospital from January 1, 2021 to May 1, 2022, were selected as research subjects, the general information of patients with AF were collected via a questionnaire, the family function and quality of life were assessed by the Family Assessment Device (FAD) and Atrial Fibrillation Effect on Quality-of-Life (AFEQT) scale. The patients were divided into a non-family functional disorder group and a family functional disorder group on the basis of their FAD scores. The above data were analyzed using SPSS 26.0 statistical software. RESULTS: Among the 223 patients, 64 (28.70%) were in the non-family functional disorder group, and 159 (71.30%) were in the family functional disorder group. The total score of FAD and scores of all dimensions in the family functional disorder group were higher than those in the non-family functional disorder group (all P<0.01). AFEQT total score and symptoms, treatment concerns and daily activities in the non-family functional disorder group were significantly higher than those in the family functional disorder group (all P<0.01). The Pearson linear analysis showed that there was a linear negative correlation between the total score and each dimension of FAD with the total score and each dimension of AFEQT (all P<0.01). The variables with statistical significance in the univariate analysis were included in the multiple linear regression analysis, and the result showed that female, and the problem solving, role, affective involvement, and general functioning dimensions of family function had an impact on the quality of life (all P<0.01). CONCLUSIONS: Most patients with AF have different degrees of family dysfunction. The quality of life in patients with family functional disorder group is generally low. Female, and the problem solving, role, affective involvement, and general functioning of family function have a significant impact on the quality of life in patients with AF. In clinical treatment of AF, attention should be paid to the family function of patients, and family members can be involved in clinical intervention to improve family function and improve the quality of life.


Assuntos
Fibrilação Atrial , Humanos , Feminino , Qualidade de Vida , Pacientes , Inquéritos e Questionários
11.
Inorg Chem ; 60(11): 8111-8122, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34019764

RESUMO

To push forward the structural development and fully explore the potential utility, it is highly desired but challenging to regulate in a controllable manner the structures and properties of MOFs. In this work, we reported the structural and functional modulation of Cu(II)-tricarboxylate frameworks by employing a strategy of engineering the functionalities and their positions. Two pairs of unsymmetrical biaryl tricarboxylate ligands modified with a methyl group and a pyridinic-N atom at distinct positions were logically designed and synthesized, and their corresponding Cu(II)-based MOFs were solvothermally constructed. Diffraction analyses revealed that the variation of functionalities and their positions furnished three different types of topological structures, which we ascribed to the steric effect exerted by the methyl group and the chelating effect involving the pyridinic-N atom. Furthermore, gas adsorption studies showed that three of them are potential candidates as solid separation media for acetylene (C2H2) purification, with the separation potential tailorable by altering functionalities and their locations. At 106.7 kPa and 298 K, the C2H2 uptake capacity varies from 64.1 to 132.4 cm3 (STP) g-1, while the adsorption selectivities of C2H2 over its coexisting components of CO2 and CH4 fall in the ranges of 3.28-4.60 and 14.1-21.9, respectively.

12.
J Nanobiotechnology ; 19(1): 385, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809623

RESUMO

Demineralization of hard tooth tissues leads to dental caries, which cause health problems and economic burdens throughout the world. A biomimetic mineralization strategy is expected to reverse early dental caries. Commercially available anti-carious mineralizing products lead to inconclusive clinical results because they cannot continuously replenish the required calcium and phosphate resources. Herein, we prepared a mineralizing film consisting of hydroxypropylmethylcellulose (HPMC) and polyaspartic acid-stabilized amorphous calcium phosphate (PAsp-ACP) nanoparticles. HPMC which contains multiple hydroxyl groups is a film-forming material that can be desiccated to form a dry film. In a moist environment, this film gradually changes into a gel. HPMC was used as the carrier of PAsp-ACP nanoparticles to deliver biomimetic mineralization. Our results indicated that the hydroxyl and methoxyl groups of HPMC could assist the stability of PAsp-ACP nanoparticles and maintain their biomimetic mineralization activity. The results further demonstrated that the bioinspired mineralizing film induced the early mineralization of demineralized dentin after 24 h with increasing mineralization of the whole demineralized dentin (3-4 µm) after 72-96 h. Furthermore, these results were achieved without any cytotoxicity or mucosa irritation. Therefore, this mineralizing film shows promise for use in preventive dentistry due to its efficient mineralization capability.


Assuntos
Materiais Biomiméticos , Fosfatos de Cálcio , Cárie Dentária/metabolismo , Derivados da Hipromelose , Calcificação de Dente/efeitos dos fármacos , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacocinética , Materiais Biomiméticos/farmacologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacocinética , Fosfatos de Cálcio/farmacologia , Células Cultivadas , Dentina/efeitos dos fármacos , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Derivados da Hipromelose/química , Derivados da Hipromelose/farmacologia , Masculino , Camundongos , Sistemas de Liberação de Fármacos por Nanopartículas , Nanopartículas , Coelhos
13.
Ecotoxicol Environ Saf ; 208: 111709, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396040

RESUMO

A novel phenol-degrading strain was isolated and identified as Rhodococcus ruber C1. The degradation analysis shows that 1806 mg/L of phenol can be completely degraded by strain C1 within 38 h, and the maximum specific growth rate (µmax=1.527 h-1) and maximum specific phenol degradation rate (qmax=3.674 h-1) indicate its excellent phenol metabolism capability. More importantly, phenol can be degraded by strain C1 in the temperature range of 20-45 °C within 72 h, and with longer degradation time, phenol can be completely degraded even at 10, 15 and 50 °C. The whole genome of strain C1 was sequenced, and a comparative genome analysis of strain C1 with 36 other genomes of Rhodococcus was performed. A remarkable gene family expansion occurred during the evolution of Rhodococcus, and a comprehensive evolutionary picture of Rhodococcus at genomic level was presented. Moreover, the copy number of genes involved in phenol metabolism was compared among genus Rhodococcus, and the results demonstrate high phenol degradation capability of strain C1 at genomic level. These findings suggest that Rhodococcus ruber C1 is a bacterium capable of degrading phenol efficiently in the temperature range of 10-50 °C.


Assuntos
Genoma Bacteriano/genética , Fenol/metabolismo , Rhodococcus/genética , Rhodococcus/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biodegradação Ambiental , Dosagem de Genes , Genômica , Fenóis/metabolismo , Rhodococcus/classificação , Temperatura
14.
J Am Chem Soc ; 142(1): 495-501, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31820964

RESUMO

This Article describes the design of a colloidal quantum dot (QD) photosensitizer for the Pd-photocatalyzed Heck coupling of styrene and iodocyclohexane to form 2-cyclohexylstyrene. In the presence of 0.05 mol % CdS QDs, which have an emission spectrum that overlaps the absorption spectrum of a key Pd(II)alkyl iodide intermediate, the reaction proceeds with 82% yield for the Heck product at 0.5 mol % loading of Pd catalyst; no product forms at this loading without a sensitizer. A radical trapping experiment and steady-state and transient optical spectroscopies indicate that the QDs transfer energy to a Pd(II)alkyl iodide intermediate, pushing the reaction toward a Pd(I) alkyl radical species that leads to the Heck coupled product, and suppressing undesired ß-hydride elimination directly from the Pd(II)alkyl iodide. Functionalization of the surfaces of the QDs with isonicotinic acid increases the rate constant of this reaction by a factor of 2.4 by colocalizing the QD and the Pd-complex. The modularity and tunability of the QD core and surface make it a convenient and effective chromophore for this alternative mode of cooperative photocatalysis.


Assuntos
Transferência de Energia , Paládio/química , Processos Fotoquímicos , Compostos de Cádmio/química , Catálise , Fármacos Fotossensibilizantes/química , Pontos Quânticos/química , Sulfetos/química
15.
Biol Pharm Bull ; 42(7): 1102-1111, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30867344

RESUMO

This study aimed to evaluate the effects of combined use of tetrahydrobiopterin (BH4) and nebivolol on cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs were treated with BH4, nebivolol, or a combination of both. Left ventricle function was evaluated, and reactive oxygen species (ROS) production (including dihydroethidium (DHE) and 3-nitrotyrosine (3-NT)), nitric oxide synthase (NOS) activity and the level of NO in myocardial tissue were determined. The expression levels of endothelial NOS (eNOS), phospholamban (PLN), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ß3-adrenoceptor, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) were assayed. Treatment with BH4, nebivolol, or both reversed the noninvasive indexes of diastolic function, including E/E' and E'/A', and the invasive indexes, including time constant of isovolumic left ventricle (LV) relaxation (tau), -dP/dtmin, -dP/dtmin/LV systolic pressure (LVSP), and LV end-diastolic pressure (LVEDP) in SHRs. mRNA and protein expression levels of eNOS dimer, phosphorylated PLN, SERCA2a, cGMP, and PKG in the myocardium of treated SHRs were significantly up-regulated compared with those in control rats (p < 0.05 or p < 0.01). The expression levels of 3-NT and DHE were reduced in all treated groups (p < 0.05 or p < 0.01). Notably, combined use of BH4 and nebivolol had better cardioprotective effects than monotherapies. BH4 or nebivolol has a protective effect on diastolic dysfunction in SHRs, and BH4 combined with nebivolol may exert a synergistically cardioprotective effect through activation of ß3-adrenoceptor and the NO/cGMP/PKG signaling pathway.


Assuntos
Anti-Hipertensivos/farmacologia , Biopterinas/análogos & derivados , Cardiotônicos/farmacologia , Diástole/efeitos dos fármacos , Nebivolol/farmacologia , Animais , Biopterinas/farmacologia , GMP Cíclico/metabolismo , Sinergismo Farmacológico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos
16.
J Chem Phys ; 151(21): 210901, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31822081

RESUMO

Quantum electrodynamics is rapidly finding a set of new applications in thresholdless lasing, photochemistry, and quantum entanglement due to the development of sophisticated patterning techniques to couple nanoscale photonic emitters with photonic and plasmonic cavities. Colloidal and epitaxial semiconductor nanocrystals or quantum dots (QDs) are promising candidates for emitters within these architectures but are dramatically less explored in this role than are molecular emitters. This perspective reviews the basic physics of emitter-cavity coupling in the weak-to-strong coupling regimes, describes common architectures for these systems, and lists possible applications (in particular, photochemistry), with a focus on the advantages and issues associated with using QDs as the emitters.


Assuntos
Dispositivos Ópticos , Pontos Quânticos/química , Processos Fotoquímicos
17.
J Nanobiotechnology ; 17(1): 88, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426815

RESUMO

BACKGROUND: Gold nanoparticles (AuNPs) have been proposed for many applications in medicine and bioanalysis. For use in all these applications, maintaining the stability of AuNPs in solution by suppressing aggregation is paramount. Herein, the effects of amino acids were investigated in stabilizing AuNPs by rationally designed peptide scaffolds. RESULTS: Compared to other tested amino acids, phosphotyrosine (pY) significantly stabilized AuNPs. Our results indicated that pY modified AuNPs presented a high level of stability in various solutions, and had good biocompatibility. When a pY-peptide was used in stabilizing AuNPs, the phosphate group could be removed by phosphatases, which subsequently caused the aggregation and the cargo release of AuNPs. In vitro study showed that AuNPs formed aggregation in a phosphatase concentration depending manner. The aggregation of AuNPs was well correlated with the enzymatic activity (R2 = 0.994). In many types of cancer, a significant increase in phosphatases has been observed. Herein, we demonstrated that cancer cells treated with pY modified AuNPs in conjunction with doxorubicin killed SGC-7901 cells with high efficiency, indicating that the pY peptide stabilized AuNPs could be used as carriers for targeted drug delivery. CONCLUSION: In summary, pY peptides can act to stabilize AuNPs in various solutions. In addition, the aggregation of pY-AuNPs could be tuned by phosphatase. These results provide a basis for pY-AuNPs acting as potential drug carriers and anticancer efficacy.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Peptídeos/química , Monoéster Fosfórico Hidrolases/química , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos
18.
Lipids Health Dis ; 18(1): 227, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870374

RESUMO

BACKGROUND: Conflicting results on the prognostic value of blood adiponectin level in patients with coronary artery disease (CAD) have been reported. This meta-analysis aimed to investigate the prognostic value of elevated adiponectin level in CAD patients. METHODS: A comprehensive literature search was conducted in PubMed and Embase databases up to May 10, 2019. Studies evaluating the association between adiponectin level and major adverse cardiovascular events (death, stroke, acute coronary syndrome or coronary revascularisation), cardiovascular mortality, and all-cause mortality in CAD patients were included. Pooled multivariable adjusted risk ratios (RR) and 95% confidence intervals (CI) was calculated for the highest vs the lowest category of adiponectin level. RESULTS: Twelve studies including 10,974 CAD patients were included. Elevated adiponectin level was independently associated with higher risk of cardiovascular (RR 1.93; 95% CI 1.55-2.42; p < 0.001) and all-cause mortality (RR 1.96; 95% CI 1.64-2.34; p < 0.001) in CAD patients. However, CAD patients with higher adiponectin level did not significantly increase major cardiovascular events risk (RR 1.12; 95% CI 0.86-1.45; p = 0.407) after adjustment for potential confounders. CONCLUSIONS: This meta-analysis indicates that elevated adiponectin level is an independent predictor of cardiovascular and all-cause mortality in CAD patients. Measurement of blood adiponectin level has potential to identify CAD patients who have high risk of death.


Assuntos
Adiponectina/sangue , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Prognóstico , Doença da Artéria Coronariana/mortalidade , Humanos , Fatores de Risco
19.
J Mater Sci Mater Med ; 30(3): 36, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30840155

RESUMO

It has been widely recognized that one of the critical limitations in biofabrication of functional tissues/organs is lack of vascular networks which provide tissues and organs with oxygen and nutrients. Biofabrication of 3D vascular-like constructs is a reasonable first step towards successful printing of functional tissues and organs. In this paper, a dynamic optical projection stereolithography system has been implemented to successfully fabricate 3D Y-shaped tubular constructs with living cells encapsulated. The effects of operating conditions on the cure depth of a single layer have been investigated, such as UV intensity, exposure time, and cell density. A phase diagram has been constructed to identify optimal operating conditions. Cell viability immediately after printing has been measured to be around 75%. Post-printing mechanical properties, swelling properties, and microstructures of the gelatin methacrylate hydrogels have been characterized. The resulting fabrication knowledge helps to effectively and efficiently print tissue-engineered vascular networks with complex geometries.


Assuntos
Impressão Tridimensional/instrumentação , Medicina Regenerativa/métodos , Estereolitografia/instrumentação , Engenharia Tecidual/métodos , Animais , Sobrevivência Celular , Células Cultivadas , Desenho de Equipamento , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Gelatina/química , Humanos , Hidrogéis/química , Metacrilatos/química , Camundongos , Células NIH 3T3 , Estresse Mecânico , Alicerces Teciduais/química
20.
Ecotoxicol Environ Saf ; 183: 109581, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446172

RESUMO

Chlorimuron-ethyl is a sulfonylurea herbicide with a long residual period in the field and is toxic to rotational crops. Klebsiella jilinsis 2N3 is a gram-negative bacterium that can rapidly degrade Chlorimuron-ethyl. In this study, the gene expression changes in strain 2N3 during degradation of Chlorimuron-ethyl was analyzed by RNA-Seq. Results showed that 386 genes were up-regulated and 453 genes were down-regulated. KEGG pathway enrichment analysis revealed the highest enrichment ratio in the pathway of sulfur metabolism. On the basis of the functional annotation and gene expression, we predicted that carboxylesterase, monooxygenase, glycosyltransferase, and cytochrome P450 were involved in the metabolism of Chlorimuron-ethyl biodegradation. Results of qRT-PCR showed that the relative mRNA expression levels of these genes were higher in treatment group than those in control group. The cytochrome P450 encoded by Kj-CysJ and the alkanesulfonate monooxygenase encoded by Kj-SsuD were predicted and further experimentally confirmed by gene knockout as the key enzymes in the biodegradation process. Cultured in basal medium containing Chlorimuron-ethyl (5  mg L-1) in 36 h, the strains of ΔKj-CysJ, ΔKj-SsuD, and WT reached the highest OD600 values of 0.308, 0.873, and 1.085, and the highest degradation rates of Chlorimuron-ethyl of 11.83%, 96.21%, and 95.62%, respectively.


Assuntos
Herbicidas/metabolismo , Klebsiella/genética , Pirimidinas/metabolismo , Poluentes do Solo/metabolismo , Compostos de Sulfonilureia/metabolismo , Transcriptoma , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biodegradação Ambiental , Regulação Bacteriana da Expressão Gênica , Klebsiella/crescimento & desenvolvimento , Klebsiella/metabolismo , Enxofre/metabolismo
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