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1.
Environ Pollut ; 259: 113923, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31935612

RESUMO

The emerging flame retardants pentabromobenzene (PBB) has been frequently detected in recent years and may pose exposure risks to wild animals and human beings. In this study, the inflation of posterior swim bladder of zebrafish larvae was used as an endpoint to study the developmental toxicity and putative mechanisms associated with PBB toxicity. Our results showed that embryonic exposure to PBB could significantly inhibit the inflation of posterior swim bladders. Reduced T3 levels and transcriptional changes of crh and pomc were observed in PBB treated zebrafish larvae at 120 hpf. However, key regulators of thyroid and adrenocortical system involved in the synthesis (tsh), biological conversion (ugt1ab, dio2) and functional regulation (trα, trß, gr) showed no significant changes. Further data revealed that prlra was the only gene that was altered among the detected genes at 96 h post fertilization (hpf). At 120 hpf, the morphology of swim bladder indicated deflation in treatments at 0.25 µM and higher. In addition, the mRNA levels of anxa5, prlra, prlrb, atp1b2 and slc12a10 were all significantly changed at 120 hpf. Taken together, we suppose that embryonic exposure to PBB inhibited the inflation of swim bladder in zebrafish probably via prlra mediated pathways. The observed changes of thyroid and adrenocortical parameters might be indirect effects evoked by PBB exposure. Overall, our results provide important data and indications for future toxicological study and risk assessment of the emerging flame retardants PBB.

2.
Onco Targets Ther ; 12: 9827-9848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819482

RESUMO

Introduction: MIR22HG has a reported involvement in the tumorigenesis of a variety of cancers, including hepatocellular carcinoma (HCC). However, the exact molecular mechanism of MIR22HG in HCC has not been clarified. Methods: In the present study, we integrated data from in-house RT-qPCR, RNA-sequencing, microarray, and literature studies to conduct a comprehensive evaluation of the clinico-pathological and prognostic significance of MIR22HG in an extremely large group of HCC samples. We also explored the potential mechanism of MIR22HG in HCC by analyzing the alteration profiles of MIR22HG in HCC to predict transcription factors (TFs) that may interact with MIR22HG and to annotate the biological functions of genes co-expressed with MIR22HG. MIR22HG expression was also compared in HCC nude mice xenografts before and after a treatment with nitidine chloride. Results: We found that MIR22HG was downregulated in HCC and that this downregulation correlated with the malignant phenotype of HCC. Comprehensive analysis of the prognostic impact of MIR22HG in HCC revealed a beneficial effect of MIR22HG on the survival outcome of HCC patients. Seven cases of MIR22HG deep deletion occurred in 360 of the cancer genome atlas (TCGA) provisional HCC samples. A total of 22 MIR22HG-TF-mRNA triplets in HCC were predicted by the lncRNAmap. Co-expressed genes of MIR22HG, identified by weighted correlation network analysis (WGCNA), mainly participated in the pathways involving osteoclast differentiation, chemokine signaling pathways, and hematopoietic cell lineage. In vivo experiments demonstrated that nitidine chloride could stimulate MIR22HG expression in HCC xenografts. Conclusion: In summary, MIR22HG may play a tumor-suppressive role in HCC by coordinating with predicted TFs and co-expressed genes, such as NLRP3, CSF1R, SIGLEC10, and ZEB2, or by being controlled by nitidine chloride.

3.
Appl Plant Sci ; 7(11): e11304, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31832286

RESUMO

Premise: We developed single-copy nuclear DNA markers for a perennial herb, Oreocharis auricula (Gesneriaceae), to help infer the evolutionary history of the genus Oreocharis in subtropical China. Methods and Results: We screened 834 putative single-copy nuclear genes from transcriptomes of 11 species of Primulina using the Illumina HiSeq 2000 platform. Based on the screening results, we developed 16 primer sets for accessions of O. auricula representing three wild populations. The number of alleles per locus ranged from three to 34. The levels of expected and observed heterozygosity varied from 0.000 to 0.372 and 0.000 to 0.650, respectively. The markers were successfully cross-amplified in the related species O. magnidens, O. speciosa, O. maximowiczii, and O. henryana. Conclusions: The newly developed markers will facilitate further studies on genetic diversity and phylogeographic structure throughout the distributional range of O. auricula. Additionally, these markers may be useful for other related species in Gesneriaceae.

4.
Environ Monit Assess ; 192(1): 62, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31865452

RESUMO

Butralin is widely used to control single-leaf weeds and some dicotyledons. The application of butralin in the environment may cause residue beyond regulation criteria and residual toxicity. Therefore, it is important to detect and supervise the dissipation behavior of butralin in edible raw food and in the environment. The aim of this study was to monitor butralin in peanuts and soil under farmland conditions and examine the likely dietary risk assessment of butralin for Chinese people on the basis of residual concentrations. A method for the analysis of butralin residue and its dissipation in peanut plants and soil under field conditions was investigated. The results show that an analytical method for the quantization of butralin in peanuts and soil utilizing gas chromatography with electron capture detection (GC-ECD) was developed. Standard recovery experiments using three different butralin spiking levels of 0.01, 0.1, and 1.0 mg kg-1 in different samples (i.e., peanut kernels, shell, seedling, stalk, and soil) were conducted. The recoveries of butralin from all matrices ranged from 86 to 108% with relative standard deviations from 3 to 6% (n = 5). The limit of quantification (LOQ) of the method was 0.01 mg kg-1. After storage at - 20 °C for 365 days, the degradation rate of residues of butralin in peanut kernels was less than 30%, which met the storage stability test criteria for pesticide residues in stored commodities of plant origin. The dissipation half-lives of butralin ranged from 4.2 to 6.6 days and 4.6 to 6.6 days in peanut seedlings and soil, respectively, in farmland ecosystems. At the normal harvest time, the final residue concentrations of butralin in peanuts and soil were all below the LOQ. The final total risk quotient (RQ) values were much lower than RQ = 100%, which indicated that the long-run fitness risk associated with butralin residue in different groups of registered crops is correspondingly low for people in China. The current research results could offer guidance for the rational use of butralin and provide data support for the building of maximum residue limits (MRLs) in China.

5.
J Colloid Interface Sci ; 563: 197-206, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31874307

RESUMO

A cobalt(0/II)-incorporated N-doped porous carbon (Co/NC) catalyst was prepared via one-step thermal decomposition of ethylene-diamine tetra-acetic acid and a Co salt. Fine Co nanoparticles composed of metallic and oxidized Co species were formed and well dispersed in the graphene-like film-type N-doped carbon support. The Co species played a dominant role in peroxymonosulfate (PMS) activation to generate sulfate and hydroxyl radicals. The N-doped porous carbon synergistically affected the catalytic performance by enhancing electronic transfer. The resulting Co/NC was a highly efficient heterogeneous catalyst for PMS activation and enabled considerably enhanced quinclorac (QNC) degradation. Typically, 93% QNC (50 mg L-1) removal was achieved with 0.08 g L-1 Co/NC and 20 mmol L-1 PMS. The QNC degradation kinetic data fitted a pseudo-first-order kinetic model well, with a correlation coefficient (R2) higher than 0.99. Investigation of the reaction mechanism suggested that hydroxyl (HO) and sulfate (SO4-) radicals were the predominant active species in the Co/NCPMS system and QNC degradation mainly involved dehydroxylation and substitution of OH for COOH. This Co/NC catalyst is promising for use in advanced oxidation processes for the removal of persistent organic pollutants.

6.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691337

RESUMO

Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed cancer in children and single-nucleotide polymorphisms (SNPs) in certain genes influence risk of ALL. Although FOXO3 had been demonstrated to be involved leukemia, the role of FOXO3 polymorphisms was still not clear. In the present study, we explored the association of FOXO3 SNPs with ALL risk in Chinese children. We genotyped four polymorphisms (rs17069665 A>G, rs4945816 T>C, rs4946936 C>T, and rs9400241 A>C) of FOXO3 in 425 ALL cases and 1339 health controls. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Further analyses were performed to explore associations of rs17069665 and rs9400241 with ALL susceptibility in terms of age, gender, immunophenotype, minimal residual disease (MRD), and other clinical characteristics. We found rs17069665 related to the increased ALL risk (OR = 1.76; 95% CI = 1.02-3.04), rs9400241 related to decreased ALL risk (OR = 0.80; 95% CI = 0.64-0.99). The effects of rs17069665 on ALL risk were more predominant in males and children < 10 years, and patients with lower rates of platelet or neutrophil. As for rs9400241, the effects were more predominant in children < 10 years, and in patients with pre B ALL, positive MRD, anemia, or hepatomegaly. In conclusion, FOXO3 gene polymorphisms influence the risk of ALL in children and might be a potential biomarker for ALL susceptibility.

7.
Med Image Anal ; 60: 101600, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31739280

RESUMO

A novel method based on multiset canonical correlation analysis (mCCA) and linear discriminant analysis (LDA) is presented to identify the major depressive disorder (MDD). The new method comprises two parts, namely, the mCCA-rreg and sparse LDA models. The mCCA-rreg model extends the classical canonical correlation model to calculate functional connections by restricting the references to a reference space and adding a spatial regularization term. The reference space is used to ensure that the model extracts important components first from several datasets simultaneously by decreasing the importance of the components in which we are uninterested. The spatial regularization term helps in avoiding the multicollinearity and overfitting problems under the low signal-to-noise ratio circumstance. The sparse LDA model extends the classical LDA model to extract a small subset of discriminative classification features by fusing clinical scores. In the real data experiment, we extract two functional connection modes from 45 subjects by the mCCA-rreg model. Then, we construct classifiers to identify the patients with MDD based on the connections selected by the sparse LDA model. The best accuracy is higher than 95%. The results show that the mCCA-rreg model can retrieve the important components characterized by a preassigned reference space and exclude the noise or components of no interest. The sparse LDA model can extract discriminative classification features related to clinical scores.

8.
Eur J Clin Invest ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675435

RESUMO

BACKGROUND: Recent studies indicated that fragmented QRS (fQRS) is associated with malignant cardiac arrhythmias in patients with acute myocardial infarction (AMI). However, a systematic review and meta-analysis on this issue still has not been conducted. Thus, we performed a systematic review and meta-analysis to access the predictive value of fQRS for ventricular tachyarrhythmias (VTAs) in patients with AMI. MATERIALS AND METHODS: We searched the databases of PubMed, Embase and Cochrane Library for relevant studies until Jun 08, 2019. We included studies which compared VTAs in AMI patients with fQRS versus without fQRS. RESULTS: Six studies enrolling 2,218 ST-segment elevation myocardial infarction (STEMI) patients were included in this meta-analysis. The fQRS was significantly associated with greater risk of VTAs in STEMI patients (Odd ratio (OR) 2.81, 95% confidence interval (CI) 1.99-3.95, p< 0.00001; I2= 30%). This association was still significant both in prospective (OR 3.25, 95% CI 1.94-5.46, p< 0.00001; I2= 0%) and retrospective (OR 2.40, 95% CI 1.22-4.74, p=0.01; I2= 54%) studies. In particularly, fQRS in patients with low left ventricular ejection fraction (≤50%) (OR 2.97, 95% CI 1.88-4.70, p< 0.00001; I2= 21%) or <60 years old (OR 3.07, 95% CI 2.02-4.66, p< 0.00001; I2= 0%) tripled the risk of VTAs during AMI. CONCLUSION: Our meta-analysis demonstrated that fQRS increases the risk of developing VTAs in patients with STEMI.

9.
Micromachines (Basel) ; 10(10)2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31569544

RESUMO

Elastic deformation and gaseous rarefaction effects are of great importance to the static and dynamic characteristics of gas microbearings. Based on the effective viscosity model of Veijola, the governing equations can be solved by the partial derivative method, finite element procedure, and relaxed iterative algorithm. The numerical results showed that the maximum gas pressure is relatively lower compared to a microbearing with a rigid liner at a local pressure peak region, owing to the film thickness of two converging-diverging profiles and the existence of bimodal pressure inside the elastic microbearing liner. However, the effect of bearing flexibility provides a marginal increase in the load capacity on account of the integral area of pressure distribution is larger than the rigid bearing liner. The friction coefficient and direct stiffness coefficients increase as the elastic modulus decreases while the direct damping coefficients become smaller at high eccentricity ratios and bearing numbers. Since the Poiseuille flow rate increases in connection with an increasing Knudsen number, the effective viscosity of the lubricant leads to a decreased load carrying capacity, friction coefficient, and direct stiffness coefficient, which produces an increase in the direct damping coefficients.

10.
Sci Rep ; 9(1): 12626, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477775

RESUMO

miR-146a, an anti-inflammatory microRNA, is shown to be a negative regulator of adipocyte inflammation. However, the functional contribution of miR-146a in the development of obesity is not defined. In order to determine whether miR-146a influences diet-induced obesity, mice that were either wild type (WT) or miR-146a deficient (KO) were fed with high (60% kcal) fat diet (HFD) for 16 weeks. Deficiency of miR-146a did not influence obesity measured as HFD-induced body weight and fat mass gain, or metabolism of glucose and insulin tolerance. In addition, adipocyte apoptosis, adipose tissue collagen and macrophage accumulation as detected by TUNEL, Picro Sirius and F4/80 immunostaining, respectively, were comparable between the two groups of mice. Although, miR-146a deficiency had no influence on HFD-induced hepatic lipid accumulation, interestingly, it significantly increased obesity-induced inflammatory responses in liver tissue. The present study demonstrates that miR-146a deficiency had no influence on the development of HFD-induced obesity and adipose tissue remodeling, whereas it significantly increased hepatic inflammation in obese mice. This result suggests that miR-146a regulates hepatic inflammation during development of obesity.

11.
Mol Immunol ; 114: 629-642, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31542608

RESUMO

Neutrophils are essential to the pathogenesis of many inflammatory diseases. In the autoantibody-mediated K/BxN model of inflammatory arthritis, the alternative pathway (AP) of complement and Fc gamma receptors (FcγRs) are required for disease development while the classical pathway is dispensable. The reason for this differential requirement is unknown. We show that within minutes of K/BxN serum injection complement activation (CA) is detected on circulating neutrophils, as evidenced by cell surface C3 fragment deposition. CA requires the AP factor B and FcγRs but not C4, implying that engagement of FcγRs by autoantibody or immune complexes directly triggers AP C3 convertase assembly. The absence of C5 does not prevent CA on neutrophils but diminishes the upregulation of adhesion molecules. In vivo two-photon microscopy reveals that CA on neutrophils is critical for neutrophil extravasation and generation of C5a at the site of inflammation. C5a stimulates the release of neutrophil proteases, which contribute to the degradation of VE-cadherin, an adherens junction protein that regulates endothelial barrier integrity. C5a receptor antagonism blocks the extracellular release of neutrophil proteases, suppressing VE-cadherin degradation and neutrophil transendothelial migration in vivo. These results elucidate the AP-dependent intravascular neutrophil-endothelial interactions that initiate the inflammatory cascade in this disease model but may be generalizable to neutrophil extravasation in other inflammatory processes.

12.
Cardiology ; 144(3-4): 69-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434097

RESUMO

Several studies have indicated that early repolarization (ER) is a risk factor for ventricular tachyarrhythmias (VTAs) in acute myocardial infarction (AMI) patients. The prognostic values of ER detail characteristics except J-point morphology, and inferior leads ER location for VTAs are still unclear. We searched PubMed, Embase, and the Cochrane Library for eligible studies up to March 4, 2019. Studies to investigate the relationship between ER and the incidence of VTAs in AMI patients were extracted. A total of 10 studies with 2,672 participants were included in the analysis. ER significantly predicted the incidence of VTAs (odds ratio [OR] 3.62, 95% confidence intervals [CI] 2.77-4.73), regardless of the type of AMI. The presence of ER before AMI (OR 5.58, 95% CI 3.41 to 9.12) and after AMI (OR 3.02, 95% CI 2.19-4.15) increased the risk of VTAs. The prognostic value of ER for VTAs in the long follow-up (≥30 days) (OR 2.39, 95% CI 1.59-3.59) fell by half compared to the short follow-up duration (<30 days) (OR 4.97, 95% CI 3.48-7.09). Patients with ER displayed a higher risk of developing ventricular fibrillation (VF) (OR 6.94, 95% CI 3.87-12.43) than those without ER. However, neither J-point elevation with OR = 2.48 nor lateral leads' ER location with OR = 3.83 remarkably increased the risk of VTAs in patients with AMI. ER is significantly associated with increasing risk of VTAs, particularly VF, in AMI patients. This relationship is weaker in the 30-day follow-up and is not reinforced by J-point elevation and lateral leads' ER location.

13.
Cell Death Discov ; 5: 120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341646

RESUMO

Sorafenib resistance is one of the main obstacles to the treatment of advanced/recurrent hepatocellular carcinoma (HCC). Here, sorafenib-resistant HCC cells and xenografts in nude mice were used as experimental models. A cohort of patients with advanced recurrent HCC who were receiving sorafenib therapy was used to assess the clinical significance of this therapy. Our data showed that 14-3-3η maintained sorafenib resistance in HCC. An analysis of the underlying molecular mechanisms revealed that 14-3-3η stabilizes hypoxia-inducible factor 1α (HIF-1α) through the inhibition of ubiquitin-dependent proteasome protein degradation, which leads to the maintenance of cancer stem cell (CSC) properties. We further found that microRNA-16 (miR-16) is a competent miRNA that reverses sorafenib resistance by targeting the 3'-UTR of 14-3-3η and thereby inhibits 14-3-3η/HIF-1α/CSC properties. In HCC patients, significant negative correlations were found between the expression of miR-16 and 14-3-3η, HIF-1α, or CSC properties. Further analysis showed that low miR-16 expression but high 14-3-3η expression can prognosticate sorafenib resistance and poor survival. Collectively, our present study indicated that miR-16/14-3-3η is involved in sorafenib resistance in HCC and that these two factors could be potential therapeutic targets and biomarkers for predicting the response to sorafenib treatment.

14.
Aquat Toxicol ; 214: 105257, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31336221

RESUMO

The interactions between nanoparticles (NPs) and metals in aquatic environments may modify the bioavailability and toxicity of metals to organisms. In this study, we investigated the effects of titanium dioxide NPs (n-TiO2) on the bioconcentration, depuration, and neurotoxic effects of lead (Pb) in zebrafish larvae. Transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy showed that Pb2+ was adsorbed by n-TiO2 to form NP-Pb complexes in suspension, and these complexes were observed in larval tissues. The bioconcentration of Pb in larvae along with the depuration rates of Pb were higher in the presence of n-TiO2 compared to when n-TiO2 was absent. Exposure to Pb alone induced the expression of the biomarker metallothionein, downregulated neurodevelopment-related genes, and reduced swimming activity of larvae. However, the addition of n-TiO2 to the exposure solution alleviated these effects. The results suggest that n-TiO2 can act as a carrier of Pb to increase its bioconcentration; however, the formation of NP-Pb complexes likely reduces the amount of free Pb2+, thereby reducing toxicity to larvae.


Assuntos
Chumbo/toxicidade , Nanopartículas/toxicidade , Titânio/toxicidade , Peixe-Zebra/metabolismo , Adsorção , Animais , Comportamento Animal/efeitos dos fármacos , Disponibilidade Biológica , Larva/efeitos dos fármacos , Larva/genética , Larva/ultraestrutura , Locomoção/efeitos dos fármacos , Metalotioneína/metabolismo , Nanopartículas/ultraestrutura , Suspensões , Transcrição Genética/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética
15.
Curr Med Sci ; 39(3): 455-462, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209819

RESUMO

Myopia is the leading cause of visual impairments worldwide. Some studies revealed that visual experience in early life affected the final myopia, indicating that environmental factors play an impellent role in the development of myopia. However, risk factors of myopia are still not identified among adolescents in China. A total of 4104 cases of myopia symptom and 3306 emmetropia controls were selected from students in primary and middle schools in Wuhan in 2008. We identified the risk factors associated with myopia symptom by multivariate logistic regression in this cross-sectional study and constructed a risk score system for myopia symptom. The value of the area under the receiver operating characteristic curve (ROC) was 0.735. Furthermore, we followed up 93 students aged 7-9 years for one year and calculated the total points using the score system. We found no significant difference between the final myopia symptom and the results predicted by the total points by pair chi-square test (P>0.05). The score system had a modest ability to estimate the risk factors of myopia symptom. Using this score system, we could identify the students who are at risk of myopia symptom in the future according to their behaviors and environmental factors, and take measures to slow the progress of myopia symptom.

16.
Oncol Rep ; 42(1): 115-130, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180554

RESUMO

Borax is a boron compound that is becoming widely recognized for its biological effects, including lipid peroxidation, cytotoxicity, genotoxicity, antioxidant activity and potential therapeutic benefits. However, it remains unknown whether exposure of human liver cancer (HepG2) cells to borax affects the gene expression of these cells. HepG2 cells were treated with 4 mM borax for either 2 or 24 h. Gene expression analysis was performed using Affymetrix GeneChip Human Gene 2.0 ST Arrays, which was followed by gene ontology analysis and pathway analysis. The clustering result was validated using reverse transcription­quantitative polymerase chain reaction. A cell proliferation assay was performed using Celigo Image Cytometer Instrumentation. Following this, 2­ or 24­h exposure to borax significantly altered the expression level of a number of genes in HepG2 cells, specifically 530 genes (384 upregulated and 146 downregulated) or 1,763 genes (1,044 upregulated and 719 downregulated) compared with the control group, respectively (≥2­fold; P<0.05). Twenty downregulated genes were abundantly expressed in HepG2 cells under normal conditions. Furthermore, the growth of HepG2 cells was inhibited through the downregulation of PRUNE1, NBPF1, PPcaspase­1, UPF2 and MBTPS1 (≥1.5­fold, P<0.05). The dysregulated genes potentially serve important roles in various biological processes, including the inflammation response, stress response, cellular growth, proliferation, apoptosis and tumorigenesis/oncolysis.

17.
Chemosphere ; 233: 579-589, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195263

RESUMO

Complex interactions have been established between nanoparticles (NPs) and heavy metals in real environments. Herein we used zebrafish embryos to investigate the influence of titanium dioxide NPs (n-TiO2) on the uptake, bioconcentration, and depuration, and toxicity of Pb. The formation of n-TiO2-Pb complexes was confirmed in an exposure suspension. An increase in Pb bioconcentration was observed in zebrafish embryos upon co-exposure to n-TiO2 and Pb; moreover, n-TiO2-Pb complexes could be found in the embryos, indicating the bioavailability of NPs. However, there was no difference in the depuration rates of Pb in the presence of n-TiO2. Metallothionein (MT) content was significantly increased upon exposure to Pb alone, and the content significantly increased even further upon co-exposure. A downregulation in the expression levels of the neurodevelopment-related genes gfap, syn2α, and elavl3 was observed in the embryos, and we also noted a reduction in the swimming speed of and the total distance traveled by the larvae. To summarize, our results indicate that n-TiO2 can act as an effective carrier of Pb to enhance its uptake, bioavailability, and toxicity in zebrafish embryos.


Assuntos
Embrião não Mamífero/fisiologia , Chumbo/toxicidade , Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Disponibilidade Biológica , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Larva/metabolismo , Metalotioneína/metabolismo , Nanopartículas/toxicidade , Peixe-Zebra/metabolismo
18.
J Phys Chem Lett ; 10(11): 3006-3012, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31117694

RESUMO

Under compression, "'simple'" alkali metals and their alloys exhibit complex structural and electronic properties, leading to fundamental interest in their high-pressure behaviors. Here, the swarm-intelligence structure-searching method was employed to identify the high-pressure phases of binary interalkali Na2K, which has long been known to possess a MgZn2-Laves phase at ambient pressure, but the high-pressure behavior remains elusive. We uncovered four new structures over a pressure range of 10-500 GPa, although the compound was found to become unstable upon decomposition into Na and K from 37 to 273 GPa. In phases before decomposition, the electrons were gradually delocalized with an increase in pressure and there was charge transfer from K to Na, whereas in phases after recombination, the electrons were gradually localized into the interstitials of the crystals, showing the unexpected opposite trend of charge transfer from Na to K, remarkably, where K was found to exhibit an oxidation state beyond the -1 valence state. The results can improve our understanding of the interaction and evolution of s electrons under compression.

19.
Eur J Med Chem ; 176: 41-49, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31091479

RESUMO

Hepatitis B virus (HBV) infection is a worldwide public health issue. Search for novel non-nucleoside anti-HBV agents is of great importance. In the present study, a series of quinazolinones derivatives (4a-t and 5a-f) were synthesized and evaluated as novel anti-HBV agents. Among them, compounds 5e and 5f could significantly inhibit HBV DNA replication with IC50 values of 1.54 µM and 0.71 µM, respectively. Interestingly, the selective index values of 5f was higher than that of lead compound K284-1405, suggesting 5f possessed relatively safety profile than K284-1405. Notably, 5e and 5f exhibited remarkably anti-HBV activities against lamivudine and entecavir resistant HBV strain with IC50 values of 1.90 and 0.84 µM, confirming their effectiveness against resistant HBV strain. In addition, molecular docking studies indicated that compounds 5e and 5f could well fit into the dimer-dimer interface of HBV core protein dominated by hydrophobic interactions. Notably, their binding modes were different from the lead compound K284-1405, which may be attributed to the additional substituent groups in the quinazolinone scaffold. Taken together, 5e and 5f possessed novel chemical structure and potent anti-HBV activity against both drug sensitive and resistant HBV strains, thus warranting further research as potential non-nucleoside anti-HBV candidates.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Quinazolinonas/farmacologia , Antivirais/síntese química , Antivirais/química , Antivirais/toxicidade , Sítios de Ligação , Replicação do DNA/efeitos dos fármacos , Células Hep G2 , Antígenos do Núcleo do Vírus da Hepatite B/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Quinazolinonas/síntese química , Quinazolinonas/química , Quinazolinonas/toxicidade , Relação Estrutura-Atividade
20.
Am J Infect Control ; 47(9): 1140-1145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31003750

RESUMO

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) tops the list of threats to human health. Studies exploring predictors of mortality in patients with CRAB infection produced conflicting results. METHODS: A systematic search of the PubMed, Embase, and the Cochrane Library databases was performed from inception to June 2018 to identify studies reporting mortality predictors in patients infected with CRAB. Two authors independently assessed trials for inclusion and data extraction. RESULTS: A total of 19 observational studies were enrolled in this study. Factors associated with mortality of patients infected with CRAB were inappropriate empirical antimicrobial treatment (odds ratio [OR], 5.04; 95% confidence interval [CI], 2.56-9.94), septic shock (OR, 5.65; 95% CI, 2.35-13.57), chronic liver disease (OR, 2.36; 95% CI, 1.33-4.16), chronic renal disease (OR, 2.02; 95% CI, 1.37-2.99), hypertension (OR, 1.74; 95% CI, 1.08-2.80), neutropenia (OR, 3.31; 95% CI, 1.25-8.77), immunosuppressant use (OR, 3.15; 95% CI, 1.94-5.11), total parenteral nutrition (OR, 1.66; 95% CI, 1.08-2.56), and intubation (OR, 5.03; 95% CI, 2.33-10.87). Acute Physiology and Chronic Health Evaluation II score at admission and Pitt bacteremia score at the onset of CRAB bacteremia were higher in nonsurvivors. CONCLUSIONS: Our study suggests that severity of baseline condition and receiving inappropriate experience antibiotic therapy are major risk factors for higher mortality in patients with CRAB infections. These findings may help clinicians to take appropriate preventive measures and decrease mortality in such patients.

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