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1.
Sensors (Basel) ; 21(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34450980

RESUMO

Copper (II) ions have been shown to greatly improve the chemical stability and peroxidase-like activity of gold nanoclusters (AuNCs). Since the affinity between Cu2+ and pyrophosphate (PPi) is higher than that between Cu2+ and AuNCs, the catalytic activity of AuNCs-Cu2+ decreases with the introduction of PPi. Based on this principle, a new colorimetric detection method of PPi with high sensitivity and selectivity was developed by using AuNCs-Cu2+ as a probe. Under optimized conditions, the detection limit of PPi was 0.49 nM with a linear range of 0.51 to 30,000 nM. The sensitivity of the method was three orders of magnitude higher than that of a fluorescence method using AuNCs-Cu2+ as the probe. Finally, the AuNCs-Cu2+ system was successfully applied to directly determine the concentration of PPi in human urine samples.


Assuntos
Ouro , Nanopartículas Metálicas , Colorimetria , Cobre , Difosfatos , Corantes Fluorescentes , Humanos , Limite de Detecção , Peroxidase , Peroxidases , Espectrometria de Fluorescência
2.
BMC Cancer ; 21(1): 938, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416861

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and closely associated with poor prognosis. N6-methyladenosine (m6A), one of the most predominant modifications in mRNAs, is found to participate in tumorigenesis. However, the potential function of m6A RNA methylation in the tumor immune microenvironment is still murky. METHODS: The gene expression profile cohort and its corresponding clinical data of LUAD patients were downloaded from TCGA database and GEO database. Based on the expression of 21 m6A regulators, we identified two distinct subgroups by consensus clustering. The single-sample gene-set enrichment analysis (ssGSEA) algorithm was conducted to quantify the relative abundance of the fraction of 28 immune cell types. The prognostic model was constructed by Lasso Cox regression. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic model. RESULT: Consensus classification separated the patients into two clusters (clusters 1 and 2). Those patients in cluster 1 showed a better prognosis and were related to higher immune scores and more immune cell infiltration. Subsequently, 457 differentially expressed genes (DEGs) between the two clusters were identified, and then a seven-gene prognostic model was constricted. The survival analysis showed poor prognosis in patients with high-risk score. The ROC curve confirmed the predictive accuracy of this prognostic risk signature. Besides, further analysis indicated that there were significant differences between the high-risk and low-risk groups in stages, status, clustering subtypes, and immunoscore. Low-risk group was related to higher immune score, more immune cell infiltration, and lower clinical stages. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. Ultimately, the efficacy of this prognostic model was successfully validated in several external cohorts (GSE30219, GSE50081 and GSE72094). CONCLUSION: Our study provides a robust signature for predicting patients' prognosis, which might be helpful for therapeutic strategies discovery of LUAD.

3.
Biomed Res Int ; 2021: 6628391, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222478

RESUMO

Background: DNA methylation is an important part of epigenetic modification, and its abnormality is closely related to esophageal adenocarcinoma (EAC). This study was aimed at using bioinformatics analysis to identify methylation-driven genes (MDGs) in EAC patients and establish a risk model as a biological indicator of EAC prognosis. Method: Downloaded EAC DNA methylation, transcriptome, and related clinical data from TCGA database. MethylMix was used to identify MDGs. R package clusterProfiler and the ConsensusPathDB online database were used to analyze the rich functions and pathways of these MDGs. The prognostic risk model was established by univariate Cox regression, Lasso regression, and multivariate Cox regression analysis. Finally each MDG in the model were carried out through the survival R package. Results: A total of 273 MDGs were identified, which were enriched in transcriptional regulation and embryonic organ morphogenesis. Cox regression analysis established a risk model consisting of GPBAR1, OLFM4, FOXI2, and CASP10. In addition, further survival analysis revealed that OLFM4 and its two related sites were significantly related to the EAC patients' survival. Conclusion: In summary, this study used bioinformatics methods to identify EAC MDGs and established a reliable risk prognosis model. It provided potential biomarkers for the early treatment and prognosis evaluation of EAC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34070390

RESUMO

General land-use planning has a critical role and a guiding significance for economic and regional social development. To increase the ability of planning to cope with regional economic changes in an orderly manner and to defend the legal status of the planning guidance role, this article takes Rongchang District as a case study. This study combines GIS spatial analysis to select speed indicators, the center of gravity offset theory, and the spatial fit model and analyses the implementation process and the adjustment situation of planning from the perspectives of 'quantity', 'time', and 'space'. The main results are as follows: (1) The completion rate of cultivated land and the surplus rate of urban land show that planning can effectively guide the direction of land use, with the results of 101.9% and 15%, respectively. The difficulty of planning implementation lies in the control of rural residential land because the actual annual average withdrawal rate of rural residential land is less than one-third of the planned rate, with an actual withdrawal area of 97.22 hm2 per year on average. (2) The results of the spatial coincidence degree and the barycentric offset angle demonstrate that planning plays a prominent role in guiding the direction of land use, although deviations remain between planned and actual land-use demand, with values ranging from 0.9 to 1 and an angle of less than 30° between the implementation process and the target year. (3) From 2013 to 2015, the planning of the study area was adjusted 32 times with an area of 2301.7 hm2. This finding indicates that planning is characterized by frequent disorder and that the gap between land use and planning is alleviated at the cost of the planning authority. (4) The degree of the coincidence between the adjusted plan and the land-use change data decreased year by year, reaching 0.99 two years after implementation of the plan, which is closest to the actual land demand. Thus, general land-use planning can guide the direction of land use to some extent, and the adjustment of planning can alleviate the contradictions of land-use demand under the changes of economic development, but the disorder ignores the legal status of planning. Making regular dynamic adjustments to the plan can provide ideas for planning compilation and revision while maintaining economic benefits and guiding functions without losing legal status.


Assuntos
Conservação dos Recursos Naturais , Desenvolvimento Econômico , China , Análise Espacial
5.
Biosci Rep ; 41(5)2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33960364

RESUMO

BACKGROUND: Esophageal cancer (ESCA) is one of the most commonly diagnosed cancers in the world. Tumor immune microenvironment is closely related to tumor prognosis. The present study aimed at analyzing the competing endogenous RNA (ceRNA) network and tumor-infiltrating immune cells in ESCA. METHODS: The expression profiles of mRNAs, lncRNAs, and miRNAs were downloaded from the Cancer Genome Atlas database. A ceRNA network was established based on the differentially expressed RNAs by Cytoscape. CIBERSORT was applied to estimate the proportion of immune cells in ESCA. Prognosis-associated genes and immune cells were applied to establish prognostic models basing on Lasso and multivariate Cox analyses. The survival curves were constructed with Kaplan-Meier method. The predictive efficacy of the prognostic models was evaluated by the receiver operating characteristic (ROC) curves. RESULTS: The differentially expressed mRNAs, lncRNAs, and miRNAs were identified. We constructed the ceRNA network including 23 lncRNAs, 19 miRNAs, and 147 mRNAs. Five key molecules (HMGB3, HOXC8, HSPA1B, KLHL15, and RUNX3) were identified from the ceRNA network and five significant immune cells (plasma cells, T cells follicular helper, monocytes, dendritic cells activated, and neutrophils) were selected via CIBERSORT. The ROC curves based on key genes and significant immune cells all showed good sensitivity (AUC of 3-year survival: 0.739, AUC of 5-year survival: 0.899, AUC of 3-year survival: 0.824, AUC of 5-year survival: 0.876). There was certain correlation between five immune cells and five key molecules. CONCLUSION: The present study provides an effective bioinformatics basis for exploring the potential biomarkers of ESCA and predicting its prognosis.

6.
Sci Rep ; 11(1): 1687, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462260

RESUMO

Lung adenocarcinoma (LUAD) is characterized by high infiltration and rapid growth. The function of the stem cell population is to control and maintain cell regeneration. Therefore, it is necessary to study the prognostic value of stem cell-related genes in LUAD. Signature genes were screened out from 166 stem cell-related genes according to the least absolute shrinkage operator (LASSO) and subsequently multivariate Cox regression analysis, and then established risk model. Immune infiltration and nomogram model were used to evaluate the clinical efficacy of signature. A signature consisting of 10 genes was used to dichotomize the LUAD patients into two groups (cutoff, 1.314), and then validated in GSE20319 and GSE42127. There was a significant correlation between signature and clinical characteristics. Patients with high-risk had a shorter overall survival. Furthermore, significant differences were found in multiple immune cells between the high-risk group and low-risk group. A high correlation was also reflected between signature and immune infiltration. What's more, the signature could effectively predict the efficacy of chemotherapy in patients with LUAD, and a nomogram based on signature might accurately predict the prognosis of patients with LUAD. The signature-based of stem cell-related genes might be contributed to predicting prognosis of patients with LUAD.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/patologia , Nomogramas , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/terapia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Terapia Combinada , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Masculino , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Curva ROC , Fatores de Risco , Taxa de Sobrevida
7.
Virology ; 555: 89-101, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33308828

RESUMO

Bioinformatics and RT-PCR analysis of RNA from four Lentinula edodes samples identified 22 different virus-like contigs comprising 15 novel and 3 previously reported viruses. We further investigated the Lentinula edodes negative-stranded RNA virus 1 (LeNSRV1) isolated from a symptomatic sample, whose virion is a filamentous particle with a diameter of ~15 nm and a length of ~1200 nm. RT-PCR analysis detected LeNSRV1 in 10 of the 56 Chinese L. edodes core collection strains and 6 of the 22 monokaryotic strains from the L. edodes strain HNZMD. Genetic variation analysis showed that the sequences encoding the nucleocapsid protein (ORF2) from all the aforementioned LeNSRV1 positive strains are very conservative. The results presented here may enrich our understanding of L. edodes virus diversity and the characteristics of LeNSRV1, and will promote further research on virus-host interaction in L. edodes.

8.
Huan Jing Ke Xue ; 41(8): 3484-3491, 2020 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124320

RESUMO

The key to understanding the transport and deposition process of salt dust to Ebinur Lake involves the quantitative evaluation of the aerosol concentration and characteristics in Jinghe County. Based on the data of the CE-318 sun photometer station in Jinghe County during 2019, the characteristics of the aerosol optical depth (AOD) and Angström exponent (α) were analysed. The results showed that the daily variation of the AOD in Jinghe County was a single peak curve that increased or decreased monotonously in the early/late peak period and peaked at 12:00-14:00, which was opposite to the trend of the α. There were obvious seasonal differences in the aerosol concentration and dominant mode. The seasonal AOD was ranked as:spring (0.403±0.282) > summer (0.222±0.135) > autumn (0.218±0.112), whereas α was ranked as:summer (1.339±0.446) > autumn (1.116±0.278) > spring (0.914±0.269). During the spring, the range of the change in the AOD was more intense, the aerosol particle size was larger than that during the summer and autumn, and the range of the variation in the particle size was larger. There was a negative correlation between the AOD and α. During the spring and summer, the aerosol particle size varied over a wide range, and the composition was more complex. With the decrease of the α, the AOD tended to increase; during the autumn, the dominant aerosol mode (mainly fine particles) stabilized, and the AOD exhibited no obvious change with the α. From spring to autumn, aerosol gradually transited from a coarse to fine mode. Compared with the summer, local aerosols were more sensitive to the changes of the wind speed, wind direction, and relative humidity during the spring. The primary reason for the increase of the AOD during the spring was the main wind direction and the dust input brought by gale weather. Influenced by the soluble salt ions in the dust, the aerosol particles were able to undergo hygroscopic growth, but this was not the main reason for the high AOD. Temperature was not the internal factor for the change in the local aerosols; however, it was directly proportional to the diffusion ability of aerosol particles. Overall, the AOD of Jinghe County was primarily affected by dust aerosols. The increases in the amounts of small particles and aerosol moisture absorption were not the main reasons for the increase of the AOD in this area.

9.
Int Immunopharmacol ; 88: 106856, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32777677

RESUMO

BACKGROUND: Lung squamous cell carcinoma (LUSC) is one common type of lung cancer. Immune-related genes (IRGs) are closely associated with cancer prognosis. This study aims to screen the key genes associated with LUSC and establish an immune-related prognostic model. METHODS: Based on the Cancer Genome Atlas (TCGA) database, we screened the differentially expressed genes (DEGs) between LUSC and normal samples. Intersecting the DEGs with the immune-related genes (IRGs), we obtained the differentially expressed IRGs (DEIRGs). Univariate as well as multivariate Cox regression analyses were performed to identify the survival-associated IRGs and establish an immune-related prognostic model. The relationship between the prognostic model and tumor-infiltrating immune cells was analyzed by TIMER and CIBERSORT. RESULTS: A total of 229 DEIRGs were screened, and 14 IRGs associated with survival were identified using univariate Cox analysis. Among the 14 IRGs, six genes were selected out using Lasso and multivariate Cox analyses, and they were used to build the prognostic model. Further analysis indicated that overall survival (OS) of high-risk groups was lower than that of low-risk groups. High risk score was independently related to worse OS. Moreover, the risk score was positively correlated with several immune infiltration cells. Finally, the efficacy of the prognostic model was validated by another independent cohort GSE73403. CONCLUSION: The DEIRGs described in the study may have the potential to be the prognostic molecular markers for LUSC. In addition, the risk score model could predict the OS and provides more information for the immunotherapy of patients with LUSC.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/imunologia , Carcinoma de Células Escamosas/diagnóstico , Correlação de Dados , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Neoplasias Pulmonares/diagnóstico , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , MicroRNAs/imunologia , MicroRNAs/metabolismo , Prognóstico , Mapas de Interação de Proteínas/imunologia , RNA Longo não Codificante/imunologia , RNA Longo não Codificante/metabolismo , Fatores de Risco , Análise de Sobrevida
10.
Phys Chem Chem Phys ; 22(30): 17229-17235, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32685948

RESUMO

Compared with the conventional magnetic means (such as ferromagnetic contacts), controlling a spin current by electrical methods could largely reduce the energy consumption and dimensions of nano-devices, which has become a focus of research in spintronics. Inspired by recent progress in the synthesis of an iron-based metal-organic nanostructure, we investigate the spin-dependent electronic transport of the molecule of Fe3-terpyridine-phenyl-phenyl-terpyridine-Fe3 (Fe3-TPPT-Fe3) through first-principles calculations, and propose a three-terminal device without ferromagnetics. By applying a gate voltage, not only the spin polarization can be switched between 100% and -100% to achieve a dual-spin filter, but also its fine regulation can be realized, where the transmission with any ratio of spin-up to spin-down electron numbers is achievable. Analysis shows that the particular transmission spectra are the key mechanism, where two peaks reside discretely on both sides of the Fermi level with opposite spins. Such a feature is found to be robust to the number of Fe atoms and TPPT chain length, suggesting that it is an intrinsic feature of such systems and very conducive to practical applications. The electrical control (such as an electric field) of spin polarization is realized at the single-molecule level, showing great application potential.

11.
Microbiol Res ; 231: 126371, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734584

RESUMO

Eleven soil samples were collected from different plantations at the Forestry Model Base, Northeast Forestry University, China (45°43'10″N, 126°37'15″E), and 122 Trichoderma strains (T1-T122) were isolated. Nine Trichoderma species were identified based on morphological and molecular classification methods. The diversity of woody fungi was analyzed based on the type and quantity of Trichoderma spp. in the soil samples isolated from each plantation. Subdominant T. pseudoharzianum T17 (TpsT17) was screened and its biocontrol potential against Fusarium oxysporum CFCC86068 (Fox68) and growth promotion of Populus davidiana × P. alba var. pyramidalis (PdPap) seedlings were investigated. Compared with PdPap + Fox68 treatment, PdPap + TpsT17 + Fox68 treatment had an obvious antagonistic effect on Fox68 based on the status of roots and stomata of the poplar seedlings. In addition, pretreatment with TpsT17 increased catalase activity 14-fold and decreased hydrogen peroxide and malondialdehyde concentrations 2.57- and 7-fold, respectively, in the PdPap + TpsT17 + Fox68 treatment compared with the PdPap + Fox68 treatment. The transcription levels of PR1, JAZ6751, MYC2, MP, and JAR1 in PdPap + TpsT17+Fox68-treated plants were upregulated 5.75-, 5.63-, 14.88-, 8.24-, and 10.45-fold, respectively, at 3 d, while LAX2 exhibited little change in comparison with the level in PdPap + Fox-treated plants. TpsT17 was detected in the roots and stems of PdPap + TpsT17- and PdPap + TpsT17+Fox68-treated PdPap 28 d after inoculation, which demonstrated the endogenous capacity of TpsT17.


Assuntos
Endófitos/isolamento & purificação , Fusarium/crescimento & desenvolvimento , Populus , Trichoderma , Antibiose , Antifúngicos , Agentes de Controle Biológico , Catalase/metabolismo , DNA Espaçador Ribossômico , Endófitos/genética , Endófitos/metabolismo , Agricultura Florestal , Genes Fúngicos , Micoses/microbiologia , Filogenia , Doenças das Plantas/microbiologia , Imunidade Vegetal , Populus/enzimologia , Populus/microbiologia , Plântula/metabolismo , Microbiologia do Solo , Trichoderma/genética , Trichoderma/isolamento & purificação , Trichoderma/metabolismo
12.
Acta Biomater ; 101: 436-443, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672583

RESUMO

Protein-templated gold nanoclusters have attracted attention in fluorescence imaging due to their simple synthesis and good biocompatibility. However, limitations still exist such as poor colloid stability and undesirable fluorescence intensity. Here we describe the self-assembly of keratin-templated gold nanoclusters via a simple and mild preparation process, including keratin-templated synthesis of gold nanoclusters (AuNCs@Keratin), silver ions modification of AuNCs@Keratin (AuNCs-Ag@Keratin), and gadolinium ions-induced aggregation of AuNCs-Ag@Keratin (AuNCs-Ag@Keratin-Gd). It was demonstrated that the AuNCs-Ag@Keratin-Gd obtained an enhanced fluorescence intensity (6.5 times that of AuNCs@Keratin), high colloid stability for more than 4 months, and good biocompatibility. Moreover, the AuNCs-Ag@Keratin-Gd holds promise in multifunctional applications such as near-infrared (NIR) fluorescence imaging, magnetic resonance (MR) imaging, and redox-responsive drug delivery, extending the applicability of fluorescent gold nanoclusters, especially in biomedical fields. STATEMENT OF SIGNIFICANCE: Assembly-induced fluorescence enhancement has been rarely reported on as it relates to the protein-templated gold nanoclusters (AuNCs). In this work, self-assembly of protein-templated AuNCs was developed for enhanced fluorescence intensity and multifunctional applications, including bioimaging and responsive drug delivery. A cysteine-rich protein, keratin, was utilized as the template to synthesize AuNCs, which underwent silver ion modification and gadolinium ion-induced aggregation. The silver modification of the keratin-templated AuNCs facilitated the formation of a dense aggregate after gadolinium ion-induced assembly, thus generating an enhanced fluorescence intensity. Such a mechanism was confirmed by fluorescence correlation spectroscopy analysis. We believe that this work will extend the applicability of the fluorescent gold nanoclusters, especially in biomedical fields, and provided an effective approach for the mechanism analysis of the assembly-induced fluorescence enhancement via fluorescence correlation spectroscopy.


Assuntos
Ouro/química , Queratinas/química , Nanopartículas Metálicas/química , Espectrometria de Fluorescência , Animais , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Sobrevivência Celular , Coloides/química , Sistemas de Liberação de Medicamentos , Endocitose , Gadolínio/química , Humanos , Imageamento por Ressonância Magnética , Camundongos Endogâmicos C57BL , Prata/química
13.
Int J Mol Sci ; 20(23)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779098

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis and atherogenesis. However, there are only limited rodent models, with a functional low-density lipoprotein receptor (LDLR) pathway and cholesteryl ester transfer protein (CETP) to evaluate the drug candidates targeting the PCSK9/LDLR pathway, that are translatable to humans. Here, by using our recently generated LDLR heterozygote (Ldlr+/-) hamster model with functional LDLR pathway and CETP function, we seek to evaluate the effect of a PCSK9 antibody, evolocumab, on dyslipidemia and atherosclerosis compared with ezetimibe, an effective inhibitor of cholesterol absorption, as a positive therapeutic control. We show that the plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were significantly increased in Ldlr+/- hamsters fed a high-fat high-cholesterol (HFHC) diet; therefore, areas of atherosclerotic lesion in the aorta were obviously increased and positively correlated with plasma LDL-C and TC. Circulating free PCSK9 was downregulated by the HFHC diet and was undetectable in the evolocumab treated group, as expected. Most importantly, either evolocumab or ezetimibe treatment prevented HFHC diet-induced hyperlipidemia and subsequent atherosclerotic plaque formation. The results indicate that Ldlr+/- hamsters fed an HFHC diet represent an ideal rodent model to evaluate drug candidates that affect LDLR pathways.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Aterosclerose/tratamento farmacológico , Ezetimiba/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Receptores de LDL/deficiência , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Aterosclerose/induzido quimicamente , Aterosclerose/genética , LDL-Colesterol/sangue , Cricetinae , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ezetimiba/farmacologia , Heterozigoto , Humanos , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/genética , Masculino , Pró-Proteína Convertase 9/antagonistas & inibidores , Resultado do Tratamento , Triglicerídeos
14.
Int J Mol Sci ; 20(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323736

RESUMO

OBJECTIVE: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+/- hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+/- hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+/- hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+/- hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. CONCLUSIONS: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+/- hamsters, suggesting that the LDLR+/- hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD.


Assuntos
Aterosclerose/sangue , Aterosclerose/patologia , Colesterol na Dieta , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/patologia , Animais , Aterosclerose/metabolismo , Colesterol/sangue , Cricetinae , Feminino , Hiperlipidemias/metabolismo , Hiperlipoproteinemia Tipo II/metabolismo , Masculino , Receptores de LDL/deficiência , Receptores de LDL/metabolismo
15.
Am J Transl Res ; 11(5): 3116-3127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217881

RESUMO

Small rodents, especially mice and rats, have been widely used in atherosclerosis studies even though humans exhibit completely different lipoprotein metabolism and atherosclerotic characteristics. Until recently, various rodent models of human familial hypercholesterolemia (FH) have been created, including mice, rats, and golden Syrian hamsters. Although hamsters reportedly possess metabolic features similar to humans, there is no systematic characterization of the properties of circulating lipids and atherosclerotic lesions in these rodent models. We used three FH animal species (mice, rats, and hamsters) with low-density lipoprotein receptor (Ldlr) deficiency to fully assess lipoprotein metabolism and atherosclerotic characteristics. Compared to chow diet-fed mice and rats, Ldlr knockout (KO) hamsters showed increased cholesterols in LDL fractions similar to human FH patients. Upon 12-week high-cholesterol/high-fat diet feeding, both heterozygous and homozygous Ldlr KO hamsters displayed hyperlipidemic phenotypes, whereas only homozygous Ldlr KO mice and rats showed only moderate increases in plasma lipid levels. Moreover, rats were resistant to diet-induced atherosclerosis compared to mice, and hamsters showed more atherosclerotic lesions in the aortas and coronary arteries. Further morphological study revealed that only hamsters developed atherosclerosis in the abdominal segments, which is highly similar to FH patients. This unique animal model will provide insight into the translational study of human atherosclerosis and could be useful for developing novel treatments for FH patients.

16.
Mikrochim Acta ; 186(5): 271, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30963315

RESUMO

A method is described for the preparation of copper(II)-modified keratin-capped gold nanoclusters (AuNCs) with adjustable Au/Cu molar ratio through a two-step synthetic route. The introduction of Cu(II) is known to cause quenching of the fluorescence of such AuNCs. It is found, however, that the Cu(II) loaded AuNC (AuNC-Cu2+) display strongly enhanced peroxidase-like activity and improved chemical stability. This is assumed to be due to the synergistic effect of the gold and copper atoms and in contrast to the single components (pure AuNCs and copper ions). The kinetic parameters of the new peroxidase mimic show a higher Kcat value (12.1 × 10-4 s-1) and a lower Km value (53 µM) for H2O2 (compared to those of conventional AuNCs). The catalytic activity is stable and remains essentially unchanged after two months. The interactions of AuNCs with Cu(II) were characterized by fluorescence spectroscopy, UV-vis spectroscopy and X-ray photoelectron spectroscopy. Based on these findings, a glucose colorimetric assay at 452 nm was developed that has a detection range from 1.6 to 800 µM and a 0.26 µM detection limit. Graphical abstract Copper ion-modified keratin-capped gold nanoclusters (AuNC-Cu2+) exhibit enhanced peroxidase-like activity owing to the synergistic effect of the gold and copper atoms which is in contrast to pure AuNCs.


Assuntos
Materiais Biomiméticos/química , Colorimetria/métodos , Cobre/química , Glucose/análise , Ouro/química , Queratinas/química , Peroxidase/metabolismo , Humanos , Cinética , Limite de Detecção , Nanopartículas Metálicas/química
17.
Virus Res ; 255: 127-132, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30031846

RESUMO

Lentinula edodes partitivirus 1 (LePV1), a new mycovirus possibly responsible for serious morphological deformities during L. edodes cultivation, is widespread in the Chinese L. edodes germplasm. Here, LePV1 isolates from the Chinese genetically-diverse L. edodes core collection were identified to be highly conserved and devoid of codivergence between virus and its hosts. Phylogenetic analysis showed that the LePV1 isolates could be grouped into two distinct clades (subtype I and subtype II), without geographical bias in the composition of this population. Compared with the other LePV1 isolates, one non-synonymous variation was observed in the LePV1 isolate from the symptomatic strain SX12. Purifying selection appears to be the main evolutionary force acting on LePV1 and it may be subject to negative selection. Based on the aforementioned results, the domestication history of L. edodes in China and the high frequency of virus incidence in basidiospores, we postulate that LePV1 may exist in nature and have had relationship with L. edodes wild strains since early times. Moreover, wind-blown spores carrying LePV1 may play an important role for the transmission of LePV1 in nature, while artificial activities such as vegetative propagation and hybridization breeding may also transmit virus from wild strains to cultivated ones.


Assuntos
Micovírus/classificação , Micovírus/genética , Filogenia , Cogumelos Shiitake/virologia , Sequência de Bases , China , Variação Genética , Genoma Viral/genética , Fases de Leitura Aberta , RNA Viral/genética , Seleção Genética , Análise de Sequência de RNA , Homologia de Sequência , Esporos/virologia
18.
ACS Appl Mater Interfaces ; 10(13): 10851-10859, 2018 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-29528208

RESUMO

Polymorphous supercapacitors were constructed from flexible three-dimensional carbon network/polyaniline (PANI)/MnO2 composite textile electrodes. The flexible textile electrodes were fabricated through a layer-by-layer construction strategy: PANI, carbon nanotubes (CNTs), and MnO2 were deposited on activated carbon fiber cloth (ACFC) in turn through an electropolymerization process, "dipping and drying" method, and in situ chemical reaction, respectively. In the fabricated ACFC/PANI/CNTs/MnO2 textile electrodes, the ACFC/CNT hybrid framework serves as a porous and electrically conductive 3D network for the rapid transmission of electrons and electrolyte ions, where ACFC, PANI, and MnO2 are high-performance supercapacitor electrode materials. In the electrolyte of H2SO4 solution, the textile electrode-based symmetric supercapacitor delivers superior areal capacitance, energy density, and power density of 4615 mF cm-2 (for single electrode), 157 µW h cm-2, and 10372 µW cm-2, respectively, whereas asymmetric supercapacitor assembled with the prepared composite textile as the positive electrode and ACFC as the negative electrode exhibits an improved energy density of 413 µW h cm-2 and a power density of 16120 µW cm-2. On the basis of the ACFC/PANI/CNTs/MnO2 textile electrodes, symmetric and asymmetric solid-state textile supercapacitors with a PVA/H2SO4 gel electrolyte were also produced. These solid-state textile supercapacitors exhibit good electrochemical performance and high flexibility. Furthermore, flexible solid-state fiber-like supercapacitors were prepared with fiber bundle electrodes dismantled from the above composite textiles. Overall, this work makes a meaningful exploration of the versatile applications of textile electrodes to produce polymorphous supercapacitors.

19.
EBioMedicine ; 27: 214-224, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29289533

RESUMO

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease caused mainly by LDL receptor (Ldlr) gene mutations. Unlike FH patients, heterozygous Ldlr knockout (KO) mice do not show a dominant FH trait. Hamsters, like humans, have the cholesteryl ester transfer protein, intestine-only ApoB editing and low hepatic cholesterol synthesis. Here, we generated Ldlr-ablated hamsters using CRISPR/Cas9 technology. Homozygous Ldlr KO hamsters on a chow diet developed hypercholesterolemia with LDL as the dominant lipoprotein and spontaneous atherosclerosis. On a high-cholesterol/high-fat (HCHF) diet, these animals exhibited severe hyperlipidemia and atherosclerotic lesions in the aorta and coronary arteries. Moreover, the heterozygous Ldlr KO hamsters on a short-term HCHF diet also had overt hypercholesterolemia, which could be effectively ameliorated with several lipid-lowering drugs. Importantly, heterozygotes on 3-month HCHF diets developed accelerated lesions in the aortas and coronary arteries. Our findings demonstrate that the Ldlr KO hamster is an animal model of choice for human FH and has great potential in translational research of hyperlipidemia and coronary heart disease.


Assuntos
Aterosclerose/genética , Genes Dominantes , Hiperlipoproteinemia Tipo II/genética , Padrões de Herança/genética , Receptores de LDL/genética , Animais , Aorta/patologia , Aterosclerose/sangue , Aterosclerose/complicações , Sequência de Bases , Sistemas CRISPR-Cas/genética , Vasos Coronários/patologia , Cricetinae , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/complicações , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Mesocricetus
20.
Sci Rep ; 7(1): 12801, 2017 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-28993676

RESUMO

The transcription of TasMYB36 in the biocontrol species T. asperellum was upregulated in four different pathogenic fermentation broths, suggesting that TasMYB36 plays an important role in the response to biotic stresses. Seventy-nine MYB transcription factors that were homologous to TasMYB36 from six sequenced Trichoderma genomes were analyzed. They were distributed in fourteen clades in the phylogenetic tree. The 79 MYBs contained 113 DNA binding domains, and their amino acid sequences were conserved and were different to those in plants. The promoters of 79 MYBs contained 1374 cis-regulators related to the stress response, such as GCR1 (17.5%) and GCN4 (15.5%). Subsequently, TasMYB36 was integrated into the genome of Populus davidiana × P. alba var. pyramidalis (PdPap poplar), and after co-culture of the transformants (PdPap-TasMYB36s) with Alternaria alternate, the transcription of genes in the jasmonic acid (JA) and salicylic acid (SA) hormone signaling pathways were upregulated; the POD, SOD and CAT activities were enhanced; and the reactive oxygen content was reduced in PdPap-TasMYB36s. The disease spots area on PdPap-TasMYB36s leaves infected by A. alternate were average 0.63% (PdPap-Con: 24.7%). In summary, TasMYB36 of T. asperellum CBS433.97 is an important defense response gene that upregulates other stress response genes and could improve resistance to biotic stresses.


Assuntos
Antifúngicos/metabolismo , Proteínas Fúngicas/genética , Genes Fúngicos , Populus/fisiologia , Fatores de Transcrição/genética , Transformação Genética , Trichoderma/genética , Alternaria/fisiologia , Sequência de Aminoácidos , Sequência de Bases , Biologia Computacional , Fermentação , Proteínas Fúngicas/química , Regulação Fúngica da Expressão Gênica , Filogenia , Regiões Promotoras Genéticas , Transdução de Sinais , Estresse Fisiológico/genética , Fatores de Transcrição/química , Transcrição Genética
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