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1.
Neuroscience ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32059985

RESUMO

The application of Resting State functional MRI (RS-fMRI) in Parkinson's disease was widely performed using standard statistical tests, however, the machine learning approach has not yet been investigated in PD using RS-fMRI. In current study, we utilized the mean regional amplitude values as the features in patients with PD (n = 72) and in healthy controls (HC, n = 89). The t-test and linear support vector machine were employed to select the features and make prediction, respectively. Three frequency bins (Slow-5: 0.0107 - 0.0286 Hz; Slow-4: 0.0286 - 0.0821 Hz; Conventional: 0.01 - 0.08 Hz) were analyzed. Our results showed that the Slow-4 may provide important information than Slow-5 in PD, and it had almost identical classification performance compared with the Combined (Slow-5 and Slow-4) and Conventional frequency bands. Similar with previous neuroimaging studies in PD, the discriminative regions were mainly included the disrupted motor system, aberrant visual cortex, dysfunction of paralimbic/limbic and basal ganglia networks. The lateral parietal lobe, such as right IPL and SMG, was detected as the discriminative features exclusively in Slow-4. Our findings, at the first time, indicated that the machine learning approach is a promising choice for detecting abnormal regions in PD, and a multi-frequency scheme would provide us more specific information.

2.
Biomolecules ; 10(2)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32033407

RESUMO

Hyperlipidemia is one of the strong risk factors for ischemic heart disease. Using the Taiwan Biobank (TWB) database, we evaluated the risk of hyperlipidemia and its interaction with sex and rs688 polymorphism on the low-density lipoprotein receptor (LDLR) gene. Data collection in the biobank started in 2008 and is ongoing. Data analysis was performed on the participants' data collected between 2008 and 2015. In general, 27.92% of the 9237 female participants and 32.65% of the 8690 male participants were identified with hyperlipidemia. Compared to the C/C genotype, C/T and T/T genotypes were not significant risk factors for hyperlipidemia (OR = 1.061, CI: 0.976-1.153 for C/T and OR = 1.052, CI: 0.845-1.309 for T/T genotype) in the general model. However, there was a significant interaction between sex and rs6888 on hyperlipidemia risk (p-interaction = 0.0321). With the male sex/CC genotype being the reference group, only the female sex/CT and T/T genotypes were closely associated with hyperlipidemia, with respective ORs of 1.153 (CI: 1.014-1.311) and 1.423 (CI: 1.056-1.917). Our data indicate that rs688 C/T and T/T genotypes may be associated with increased risk of hyperlipidemia in Taiwanese women. These findings may be relevant in lipid-modification therapy.

3.
Antiviral Res ; : 104730, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014498

RESUMO

Histone positioning and modifications on viral genomes are important factors regulating virus replication. To investigate the dynamics of modified histones on the viral genome and their potential roles in antiviral response, we studied the dynamic changes of histone modifications across the HSV-1 genome in THP-1 cells. Histone modifications were detected on the HSV-1 genome soon after infection, including H3K9me3, H3K27me3, H3K4me3 and H3K27ac. These modifications emerged on the viral genome soon after infection and changed rapidly along with virus life cycle progression. The transcription repression marks, H3K9me3 and H3K27me3, decreased on the viral genome during the infection process; the transcription activation mark H3K27ac increased. Treatment with C646, an inhibitor of H3K27ac transferase p300, significantly repressed virus replication and viral gene expression. Our study reveals the relationship between histone modifications and viral gene expression and provides potential novel strategies for antiviral treatment.

6.
Org Lett ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017582

RESUMO

By using a synergistic dual directing group-assisted C-H activation strategy and simply modifying the reaction conditions, we realized a robust and general Cp*Rh(III)-catalyzed C-H cyclopropylation of N-acetoxybenzamides with cyclopropenyl alcohols, providing regio-, chemo-, and diastereoselective access to ortho trans- and cis-1,1-dimethylcyclopropane-functionalized benzamides in a redox-neutral and controllable manner. Experimental and density functional theory studies clarify the roles of the NH-OAc and OH groups and deduce two distinct Rh(III)-Rh(V)-Rh(III) pathways for presenting such selectivity.

8.
Chem Commun (Camb) ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030396

RESUMO

Both the activity and regioselectivity of Phaseolus vulgaris epoxide hydrolase were remarkably improved via reshaping two substrate tunnels based on rational design. The elegant one-step enantioconvergent hydrolysis of seven rac-epoxides was achieved by single mutants, allowing green and efficient access to valuable (R)-1,2 diols with high eep (90.1-98.3%) and yields.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31916135

RESUMO

In the original publication of the article, the deposit accession numbers of strain 15181T in the acknowledgment section were incorrectly provided as "KCTC 62172T and MCCC 1K03442T".

10.
Sci Rep ; 10(1): 866, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964941

RESUMO

Proton pump inhibitors (PPIs) are used for the long-term treatment of gastroesophageal disorders and the non-prescription medicines for acid reflux. However, there is growing concerns about PPI misuse, overuse and abuse. This study aimed to develop an animal model to examine the effects of long-term use of PPI in vivo. Twenty one Wistar rats were given omeprazole orally or intravenously for 30 days, and caerulein as a positive control. After euthanization, the serum and stool were collected to perform MS-based quantitative analysis of metabolites. We carried out 16S-based profiling of fecal microbiota, assessed the expression of bile acid metabolism regulators and examined the immunopathological characteristics of bile ducts. After long-term PPI exposure, the fecal microbial profile was altered and showed similarity to those observed in high-fat diet studies. The concentrations of several metabolites were also changed in various specimens. Surprisingly, morphological changes were observed in the bile duct, including ductal epithelial proliferation, micropapillary growth of biliary epithelium, focal bile duct stricture formation and bile duct obstruction. These are characteristics of precancerous lesions of bile duct. FXR and RXRα expressions were significantly reduced, which were similar to that observed in cholangiocarcinoma in TCGA and Oncomine databases. We established a novel animal model to examine the effects of long-term use of omeprazole. The gut microbes and metabolic change are consequences of long-term PPI exposure. And the results showed the environment in vivo tends to a high-fat diet. More importantly, we observed biliary epithelial hyperplasia, which is an indicator of a high-fat diet.

11.
J Clin Nurs ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971291

RESUMO

AIMS AND OBJECTIVES: To explore the effectiveness of nurse-led interventions to prevent urinary tract infections in older adults living in residential aged care facilities. BACKGROUND: While most empirical studies focus on the treatment of urinary tract infections, few studies have examined the effectiveness of nurse-led interventions in preventing urinary tract infections. DESIGN: Systematic review. METHODS: Eight electronic databases were searched for relevant studies published between 2008-2018. The inclusion criteria were as follows: (a) a focus on older adults, (b) evaluation of nurse-led interventions, focusing on prevention of urinary tract infection, (c) implemented in residential aged care facilities, and (d) outcomes reported as incidence or prevalence of urinary tract infection. The selected papers were critically appraised using the Mixed Methods Appraisal Tool. The data were analysed with narrative synthesis, and findings were reported following the PRISMA guidelines. RESULTS: A review of 1,614 titles and abstracts identified four studies that met the inclusion criteria. Three types of nurse-led interventions were identified: (a) the appointment of advanced practice nurses, (b) those focused on a single specific nursing intervention, and (c) implementation of a multicomponent nursing intervention. All included studies reported at least some positive outcomes. However, the included studies were highly heterogeneous and it was impossible to determine the most effective intervention approach. CONCLUSIONS: Nurses are leaders in health care and are well placed to lead prevention of urinary tract infections in residential aged care; however, evidence of the effectiveness of a nurse-led approach is limited. High-quality randomised controlled trials are warranted to address the knowledge gap and advance practice in this area. RELEVANCE TO CLINICAL PRACTICE: When developing an effective nurse-led intervention programme, the programme should be grounded in nurse-led principles and consider the complex staffing factors to ensure that nurse-led programmes are tailored to an effective level.

12.
Chemosphere ; 246: 125820, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918111

RESUMO

[Background] Melamine and phthalates have been reported to damage renal function in children. This association is scarce in general adults. [Method] A cross-sectional subsample population of 611 adults participating in the 2012 Shanghai Food Consumption Survey (SHFCS) was analyzed for urinary biomarkers of melamine, metabolites of phthalates, and renal function parameters. The correlations between renal function parameters and chemical exposure (either independently or interactively) were explored by linear regression models. To simplify the analysis, phthalate metabolites were dimensionally reduced using principal component analysis (PCA) method. [Result] Urinary melamine was positively associated with renal function parameters of both albumin-to-creatinine ratio (ACR) and ß2-microglobulin (B2M) in multivariate linear regression models (P < 0.05). A PCA pattern characterized by high-molecular-weight phthalates (HMWP) was positively associated with all three parameters of renal function (ACR, B2M, and N-acetyl-ß-d-glucosaminidase (NAG)). The co-exposure to melamine and HMWP presented an additive effect on increasing these parameters (ACR, B2M, and NAG). [Conclusion] Impaired renal function in Shanghai adults was associated with exposure to both melamine and HMWP.

13.
Clin Ther ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31937462

RESUMO

PURPOSE: Iron deficiency (ID) is one of the most commonly known nutritional deficiencies and is considered the primary cause of anemia (iron-deficiency anemia). Ferric carboxymaltose (FCM), an intravenous iron preparation, has been widely used for >10 years for iron-deficiency anemia treatment worldwide because of its many advantages. METHODS: This single-center, open-label, single dose escalation study in Chinese subjects was designed to assess the pharmacokinetic/pharmacodynamic parameters and safety of FCM in this population. The first 12 subjects received a 500-mg dose; after assessing safety data from the first 6 subjects in this cohort, another 12 subjects were assigned to the 1000-mg dose cohort. FINDINGS: After an infusion of FCM over 15 min, a rapid dose-dependent increase in total serum iron levels was observed with a median Tmax of 30 min following the start of the infusion for both cohorts. The Cmax and AUC for the 1000-mg dose were ~1.8-fold (p = 0.2929) and 2.3-fold (p = 0.0318) those associated with the 500-mg dose, respectively. Mean terminal t1/2 values were 12.3 and 10.5 h for the 2 cohorts. The renal elimination of FCM was negligible (<0.1%). Increase in mean serum iron levels and ferritin concentrations showed dose dependency. Iron-binding capacity was transiently well utilized after dosing, as indicated by transferrin saturation >88% with 500-mg FCM and >90% with 1000-mg FCM. Hemoglobin levels did not show significant changes during the 7-day observation period, whereas mean reticulocyte counts significantly increased in both cohorts, suggesting activation of the hematopoietic system. FCM was well tolerated in these Chinese subjects. No new or unexpected treatment-emergent adverse events were attributable to FCM. IMPLICATIONS: The pharmacokinetic/pharmacodynamic and safety profiles in Chinese subjects seemed comparable to those in white and Japanese populations. ChinaDrugTrials.org.cn identifier.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31967953

RESUMO

A novel, Gram-stain-positive, aerobic, non-endospore-forming, non-motile and rod-shaped bacterium designated RB2T was isolated from sap of Populus euphratica collected in Mulei county, Xinjiang province, PR China. RB2T was able to grow at 10-45 °C (optimum 35 °C), pH 6.0-12.0 (optimum 8.0) and with 0-12 % (w/v) NaCl (optimum 1 %). The genomic DNA G+C content was 63.5 % (from the genome sequence). The results of the chemotaxonomic analysis indicated that the predominant isoprenoid quinones were MK-8 and MK-9. The major fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0. The major polar lipids of RB2T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and two glycolipids. The peptidoglycan type of RB2T was A4α, l-Lys-Gly-l-Glu. The results of the phylogenetic analysis, along with the phenotypic and chemotaxonomic characteristics, indicate that strain RB2T represents a novel species of the genus Nesterenkonia, for which the name Nesterenkonia muleiensis sp. nov. is proposed. The type strain is RB2T (=MCCC 1K03528T=KCTC 49017T).

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 65-70, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948527

RESUMO

OBJECTIVE: To study the effect of epigallocatechin-3-gallate (EGCG) on liver lipid metabolism in rats with intrauterine growth restriction (IUGR) and related mechanism. METHODS: A rat model of IUGR was established by food restriction during entire pregnancy, and then the rats were randomly divided into an IUGR group and an EGCG group (n=8 each). The rats in the EGCG group were fed with water containing EGCG from after weaning to 10 weeks. Eight pup rats born from the pregnant maternal rats without food restriction were used as the control group. At the age of 13 weeks, body weight was measured. Blood and liver tissue samples were collected to measure fasting total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), and liver lipids. Homeostasis model assessment of insulin resistance (HOMA-IR) and adipose insulin resistance (adipo-IR) were calculated. Pathological sections of the liver were observed and quantitative real-time PCR was used to measure the mRNA expression of related genes in the liver. RESULTS: At the age of 13 weeks, there was no significant difference in body weight between groups (P=0.067). There were significant differences between groups in FPG, FFA, FINS, HOMA-IR, and adipo-IR (P<0.05). There were no significant differences in the serum levels of TC and TG between groups (P>0.05), while the IUGR group had significantly higher levels of TC and TG in the liver than the EGCG group (P<0.05). Oil red staining showed that the IUGR group had a significant increase in hepatic lipid accumulation, while the EGCG group had certain improvement after EGCG treatment. PCR results suggested that compared with the control group, the IUGR group had significant reductions in the mRNA expression of Ampk and Adipor1 and a significant increase in the mRNA expression of Srebf1 (P<0.05), while EGCG increased the mRNA expression of Ampk and reduced the mRNA expression of Srebf1, with no significant differences in the two indices between the EGCG and control groups (P>0.05). CONCLUSIONS: Early EGCG intervention can down-regulate the de novo synthesis of fatty acids through the Ampk/Srebf1 signaling pathway and reduce hepatic lipid accumulation in IUGR rats by improving insulin resistance of hepatocytes.


Assuntos
Resistência à Insulina , Metabolismo dos Lipídeos , Animais , Catequina/análogos & derivados , Feminino , Retardo do Crescimento Fetal , Lipídeos , Fígado , Gravidez , Ratos
17.
J Exp Bot ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990970

RESUMO

The transcription factor Woolly (Wo) and its downstream gene CycB2 have been shown to regulate trichome development in tomato (Solanum lycopersicum). It has been demonstrated that only the gain-of-function allele of Slwo (SlWoV, the Slwo woolly motif mutant allele) can increase the trichome density; however, it remains unclear why the two alleles function differently in trichome development. In this study, we used Nicotiana benthamiana as a model and cloned the homologues of Slwo and SlCycB2 (named Nbwo and NbCycB2). We also constructed a Nbwo gain-of-function allele with the same mutation site as SlWoV (named NbWoV). We found that both Nbwo and NbWoV directly regulate NbCycB2 and their own expression by binding to the promoter of NbCycB2 and their own genomic sequences. As form of a feedback regulation, NbCycB2 negatively regulates trichome formation by repressing Nbwo activity at the protein level. We also found that mutations in the Nbwo woolly motif can prevent repression of NbWoV by NbCycB2, which results in a significant increase in the amount of active Nbwo proteins and in increases in trichome density and the number of branches. Our results reveal a novel reciprocal regulation mechanism between NbCycB2 and Nbwo during trichome formation in N. benthamiana.

18.
Curr Microbiol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919672

RESUMO

Emcibacter congregatus ZYLT was isolated from a sediment sample cultured in situ in a coast located in the East China Sea. The genome of E. congregatus ZYLT was sequenced and assembled into one single circular chromosome with the size of 4,189,011 bp and G+C content of 52.6%. Genomic annotation showed that E. congregatus ZYLT had an intact Type II-C CRISPR-Cas system consists of three cas genes (cas 9, cas 1, and cas 2), 34 direct repeat sequences with the length of 36 bp, and 33 spacers. The predicted Cas 9 protein was smaller than most of existing genome editing tools. This structure might have potential in developing new gene editing system and uncovering the regulatory mechanisms of CRISPR-Cas system. Besides, the comparison between E. congregatus ZYLT and its relative species living in neritic environments unraveled some common traits of the defective strategies of these bacteria to face inshore challenges including the motility, multidrug resistance, and universal efflux pumps.

19.
Pharm Dev Technol ; : 1-10, 2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-31958240

RESUMO

Objective: A polymer-based nanoparticle was constructed to target sorafenib delivery to colorectal carcinoma cells and decrease the side effects of the drug.Methods: Sorafenib-loaded nanoparticles (S-NPs) based on PEG-PLGA were prepared using a double emulsion solvent evaporation method. The properties of S-NPs were evaluated and then their effects on the viability of colorectal cancer cells and normal human cells were assessed. The mechanism of S-NP internalization was explored using cellular uptake assays and in vitro fluorescence confocal imaging. Acute toxicity of sorafenib on its own or within S-NPs was assessed in mice.Results: S-NPs showed high drug loading and entrapment efficiencies, they did not cause extensive hemolysis, and they efficiently inhibited growth of colorectal cancer cell lines and human umbilical vein endothelial cells. S-NPs showed lower acute toxicity than the free drug.Conclusions: Loading sorafenib into nanoparticles can enhance its uptake by colorectal cancer cells and decrease its acute toxicity.

20.
Carbohydr Polym ; 230: 115578, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887880

RESUMO

The present work deals with a new type of hybrid polysaccharide-silica hydrogel fabricated by the sol-gel process in which a completely water-soluble precursor of tetrakis-(2-hydroxyethyl) orthosilicates (THEOS) and a biocompatible polysaccharide of carboxymethylated curdlan (CMCD) have been used. The kinetic gelation process, mechanical properties and morphological structures of hybrid silica hydrogels at different concentrations of CMCD and THEOS were investigated by dynamic rheology, compression testing and scanning electron microscopy. CMCD was found to be served as a catalyst and template in the sol-gel process of THEOS in water. The mechanical strength of the resulting silica gels was tunable by the modulation of either the concentration of CMCD or THEOS. Higher content of THEOS and CMCD resulted in stiffer gels. Due to the tunable mechanical property and good biocompatibility, these hybrid hydrogels are promising for the applications as drug release systems in biomedical fields.

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