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1.
J Ethnopharmacol ; 246: 112243, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31541722

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba leaves and Panax ginseng are Chinese medicine commonly used in combination for cerebral disease. AIM OF THE STUDY: To investigate the effect of standard extract of Ginkgo biloba leaves (EGb) on facilitating brain uptake of ginsenoside and its underlying mechanisms. MATERIALS AND METHODS: The increasing uptake of ginsenosides in the brain of rats by EGb were detected by LC-MS/MS analysis. Evans blue and FITC-dextran leakage were determined to evaluate blood-brain barrier (BBB) permeability in vivo. Transendothelial electrical resistance (TEER) and Na-F penetration rate were measured with a co-culture of the human cerebral microvascular endothelial cell line (hCMEC/D3) and human normal glial cell line (HEB) in vitro BBB model. WB were used to analyzed the expression of BBB tight junctions (TJs) related protein (ZO-1, Occludin, Claudin-3, p-ERM, and p-MLC), ultrastructure of TJs was determined by transmission electron microscope. RESULTS: LC-MS/MS analysis demonstrated that EGb could improve brain uptake of ginsenoside Rg1, Re, Rd and Rb1. In vivo study showed that, BBB permeability was significantly increased after EGb administration, evidenced by the markedly increased penetration of FITC-dextran and Evans Blue into the mice brain parenchyma. In the in vitro BBB model, reduced TEER and increased Na-F penetration rate was observed in EGb group, which was associated with alteration of TJs ultrastructure. Furthermore, the expression of p-ERM and p-MLC in hCMEC/D3 as well as mice brain microvessels were significantly upregulated, but no significant change on the expression of TJs proteins (ZO-1, Occludin and Claudin-3). Moreover, the effect of EGb on in vitro BBB permeability and ERM, MLC phosphorylation was counteracted by DPCPX, an A1 adenosine receptor (A1R) antagonist. CONCLUSIONS: EGb might induce ERM/MLC phosphorylation and increase the cell-cell junction gaps to cause a reversible increase of the BBB permeability via A1R signaling pathway. Our results may contribute to better use of EGb in the treatment of brain diseases.

2.
Chemosphere ; 241: 125075, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31683435

RESUMO

Carbon black nanoparticle (CBNP) is a core constituent of air pollutants like fine particulate matter (PM2.5) as well as a common manufactural material. It was proved to pose adverse effects on lung function and even provoke pulmonary fibrosis. However, the underlying mechanisms of CBNPs-induced pulmonary fibrosis remain unclear. The present study aimed to investigate the mechanism of fibrotic effects caused by CBNPs in rat lung and human bronchial epithelial (16HBE) cells. Forty-nine male rats were randomly subjected to 7 groups, means the 14-day exposure group (30 mg/m3), the 28-day exposure groups (5 mg/m3 and 30 mg/m3), the 90-day exposure group (30 mg/m3) and their respective controls. Rats were nose-only-inhaled CBNPs. 16HBE cells were treated with 0, 50, 100 and 200 µg/mL CBNPs respectively for 24 h. Besides, Forkhead transcription factor class O (FOXO)3a and miR-96 overexpression or suppression 16HBE cells were established to reveal relative mechanisms. Our results suggested CBNPs induced pulmonary fibrosis in time- and dose-dependent manners. CBNPs induced persisting inflammation in rat lung as observed by histopathology and cytology analyses in whole lung lavage fluid (WLL). Both in vivo and in vitro, CBNPs exposure significantly increased the expression of NLRP3 inflammasome, accompanied by the increased reactive oxygen species (ROS), decreased miR-96 and increased FOXO3a expressions dose -and time-dependently. MiR-96 overexpression or FOXO3a suppression could partially rescue the fibrotic effects through inhibiting NLRP3 inflammasome. Conclusively, our research show that CBNPs-induced pulmonary fibrosis was at least partially depended on activation of NLRP3 inflammasome which modulated by miR-96 targeting FOXO3a.

3.
Nanoscale ; 11(44): 21137-21146, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686059

RESUMO

Green-emissive Cs4PbBr6 shows promise for light-emitting diode devices superior to that of CsPbBr3 NCs owing to their stability and high photoluminescence efficiency. Nevertheless, there is still no consensus regarding the basis of their green emission, which decelerates their advance in light-emitting applications. Herein, a systematic investigation on the concentration of capping ligands (oleylamine and oleic acid), which determines the predominant phase between CsPbBr3 and Cs4PbBr6 for a given Cs to Pb feed ratio, is conducted. This study deduces that oleylamine to oleic acid ratio plays a crucial role in obtaining either green-emissive or non-emissive Cs4PbBr6 NCs. Scrutiny of Cs4PbBr6 microscopic and optical data in addition to their emission quenching study with a hole-withdrawing molecule reveals that the green emission originates from the CsPbBr3 impurity phase. Furthermore, stable green emission is observed for CsPbBr3/Cs4PbBr6 nanocrystals when CsPbBr3 particles are well protected by the Cs4PbBr6 matrix. These CsPbBr3/Cs4PbBr6 films remained highly luminescent even after UV exposure for hours or annealing at ∼150 °C for days in addition to their long-term stability under an ambient atmosphere, which are the desirable properties for various practical applications.

4.
Nat Commun ; 10(1): 5099, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704930

RESUMO

High strength and high ductility are often mutually exclusive properties for structural metallic materials. This is particularly important for aluminum (Al)-based alloys which are widely commercially employed. Here, we introduce a hierarchical nanostructured Al alloy with a structure of Al nanograins surrounded by nano-sized metallic glass (MG) shells. It achieves an ultrahigh yield strength of 1.2 GPa in tension (1.7 GPa in compression) along with 15% plasticity in tension (over 70% in compression). The nano-sized MG phase facilitates such ultrahigh strength by impeding dislocation gliding from one nanograin to another, while continuous generation-movement-annihilation of dislocations in the Al nanograins and the flow behavior of the nano-sized MG phase result in increased plasticity. This plastic deformation mechanism is also an efficient way to decrease grain size to sub-10 nm size for low melting temperature metals like Al, making this structural design one solution to the strength-plasticity trade-off.

5.
Mar Pollut Bull ; : 110690, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31708108

RESUMO

To master the distribution patterns and environmental risk of 16 USEPA preferential polycyclic aromatic hydrocarbons (PAHs) in surface sediments from Laizhou Bay, 20 samples were collected and investigated in this survey. The average PAH concentration in these sediments ranged from 268.97 ng/g to 895.37 ng/g with an average of 612.52 ng/g, thereby suggesting a relatively low PAH pollution in Laizhou Bay compared with other bays in the world. Tricyclic PAHs account for 79% of the total PAH content and were eventually identified as the most crucial component of these sediments. The PCA-MLR results identify fossil fuel combustion, biomass burning, and coke oven as the main sources of PAHs that account for 26.69%, 67.16%, and 6.15% of the total PAH concentration in the collected sediments, respectively. The effect range low/effect range median (ERL/ERM) reveal the low toxicity of PAHs in these sediments. However, the concentration of Fle at each survey site exceeds the ERL level. Meanwhile, the mean effects range-median quotient (M-ERM-Q) indicates the low level of ecological risk of PAHs in the surface sediments from Laizhou Bay. However, the contingency risk of Fle and Phe cannot be ruled out.

6.
Cell Biochem Funct ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31702057

RESUMO

It is well known that the sine oculis homeobox 4 (SIX4) expression is very relevant to the progression of multiple cancers. Moreover, we found that miR-802 could directly target the SIX4. However, the precise mechanism of miR-802 in glioblastoma multiforme (GBM) is still unknown. The aim of this study is to investigate the roles of miR-802/SIX4 axis in GBM. Here, our results showed that the SIX4 expression was obviously increased in GBM tissues and cell lines, and the miR-802 level was distinctly decreased. What is more, the SIX4 expression was negatively related to the miR-802 level in GBM tissues. Furthermore, increased miR-802 level evidently restrained the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of GBM cells. Next, we confirmed that miR-802 could directly target SIX4 by using luciferase reporter assay. Besides, the knockdown of SIX4 had the similar effects with miR-802 overexpression on GBM cells. The inhibitory effects of miR-802 mimic were partially blocked by SIX4 overexpression. Altogether, the overexpression of miR-802 restrained cell proliferation, invasion, and EMT of GBM cells via the regulation of SIX4. SIGNIFICANCE OF THE STUDY: An elevated expression of SIX4 has been observed in colorectal cancer and nonsmall cell lung cancer. However, the precise roles of SIX4 in GBM have not been elucidated. Our study for the first time demonstrated that SIX4 level was significantly upregulated in GBM. Additionally, the knockdown of SIX4 inhibited cell growth, invasion, and the EMT of GBM. Moreover, our data suggested a significant negative correlation between miR-802 and SIX4 expression in GBM. MiR-802 suppressed GBM cell proliferation, invasion, and EMT by directly targeting SIX4, which suggested important roles for miR-802/SIX4 axis in the GBM pathogenesis and its potential application in cancer therapy.

7.
FASEB J ; : fj201901149RR, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31718280

RESUMO

Reactive oxygen species (ROS) generation and mitochondrial dysfunction are related to neuron loss in multiple sclerosis (MS). Although peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) appears to play a key role in modulating levels of mitochondrial ROS, antioxidants, and uncoupling proteins (UCPs), and PGC-1α expression is reduced in the neocortex of patients with MS, it is unclear what its role is in neurons and in the manifestation of clinical symptoms of MS. Here, we show in wild-type (WT) experimental autoimmune encephalomyelitis (EAE) mice that PGC-1α is decreased 13 d after EAE induction followed by a steady decline up to 20 d. These changes were accompanied by parallel alterations in levels of superoxide dismutase 2, peroxiredoxin 3, thioredoxin 2, UCP4, and UCP5. In transgenic (TG) mice with neuron-specific overexpression of PGC-1α (PGC-1αf/fEno2-Cre), clinical symptoms after EAE induction were delayed and less severe than in WT mice. The degrees of apoptotic neuron loss and demyelination were also less severe in PGC-1α-TG mice. Overexpression of PGC-1α in neuronal neuroblastoma spinal cord 34 cells subjected to EAE inflammatory conditions showed similar results to those obtained in vivo. RNA sequencing analysis showed that apoptotic processes were significantly enriched in the top 10 significant gene ontology (GO) terms of differentially expressed genes, and the apoptotic pathway was significantly enriched in Kyoto Encyclopedia of Genes and Genomes pathway analysis. Our findings indicate that up-regulation of neuronal PGC-1α protected neurons from apoptosis in EAE. Manipulating PGC-1α levels in MS may help stave off this devastating disease.-Dang, C., Han, B., Li, Q., Han, R., Hao, J. Up-regulation of PGC-1α in neurons protects against experimental autoimmune encephalomyelitis.

8.
Theor Appl Genet ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31720701

RESUMO

Genome-wide association studies (GWAS), genetic surveys of the whole genome to detect variants associated with a trait in natural populations, are a powerful approach for dissecting complex traits. This genetic mapping approach has been applied in rice over the last 10 years. During the last decade, GWAS was used to identify the loci underlying tens of rice traits, and several important genes were detected in GWAS and further confirmed in follow-up functional experiments. In this review, we present an overview of the whole process in a typical GWAS, including population design, genotyping, phenotyping and analysis methods. Recent advances in rice GWAS are also provided, including several examples of the functional characterization of candidate genes. The possible breakthroughs of rice GWAS in the next decade are discussed with regard to their application in breeding, the consideration of epistatic interactions and in-depth functional annotations of DNA elements and genetic variants throughout the rice genome.

9.
BMC Neurol ; 19(1): 236, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615442

RESUMO

BACKGROUND: Brain ischemia activates the parasympathetic cholinergic pathway in animal models of human disease. However, it remains unknown whether activation of the cholinergic pathway impacts immune defenses and disease outcomes in patients with ischemic stroke. This study investigated a possible association between peripheral cholinergic activity, post-stroke infection, and mortality. METHODS: In this study, we enrolled 458 patients with acute ischemic stroke (< 24 h after onset), 320 patients with ischemic stroke on day 10, and 216 healthy subjects. Peripheral cholinergic activity, reflected by intracellular acetylcholine (ACh) content in human peripheral blood mononuclear cells (PBMCs), was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Expression of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) was measured by quantitative real-time PCR and western blot. Regression analyses were used to assess associations between peripheral cholinergic function and clinical outcomes. RESULTS: Within 24 h after the onset of acute ischemic stroke, there was a rapid increase in peripheral cholinergic activity that correlated with brain infarction volume (r = 0.67, P < 0.01). Specifically, lymphocyte-derived ACh levels were significantly higher in stroke patients with pneumonia (0.21 ± 0.02 ng/106 PBMC versus 0.15 ± 0.01 ng/106 PBMC, P = 0.03). Of note, lymphocytic AChE catalytic activity was significantly lower in these patients. One-year mortality was significantly greater in patients with higher intracellular ACh levels within the first 24 h after acute stroke. CONCLUSIONS: Lymphocytes produced increased amounts of ACh in patients with acute stroke, and pneumonia was a likely result. The association between this enhanced cholinergic activity and increased risk of pneumonia/mortality suggests that increased cholinergic activity may contribute to fatal post-stroke infection.

10.
Mar Pollut Bull ; 145: 42-46, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31590806

RESUMO

Sediment samples were collected from Caofeidian Long Island, China to investigate the contamination level and distribution pattern of 16 polycyclic aromatic hydrocarbons (PAHs). Source identification and risk assessment were also performed on these PAHs. The distribution patterns and source identification results indicated that the PAHs in the survey area originated from coal, biomass, and petroleum combustion as well as the combination of these three processes. Although the concentration of fluorene in the sediment exceeded the ERL level in some sampling sites, the effect range low-effect range median ratio implied a relatively low level of toxicity in these sediments. Meanwhile, the mean effects range-median quotient indicated that the 16 PAHs in sediments from Caofeidian Long Island pose a low ecological risk.

11.
Sensors (Basel) ; 19(20)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623259

RESUMO

The multi-hop cognitive radio network (CRN) has attracted much attention in industry and academia because of its seamless wireless coverage by forming multi-hop links and high spectrum utilization of cognitive radio (CR) technology. Using multi-slot statistical spectrum status information (SSI), this work investigates the average spectrum efficiency (SE) of a multi-radio multi-hop (MRMH) CRN where each hop is permitted to use different spectra and long-distance hops can reuse the same idle primary user (PU) spectrum. Faced with the modeled SE problem, which is a complex non-convex fractional mixed integer nonlinear programming (MINLP) problem, the optimal spectrum and power allocation for multi-hop links in multi-slot and multi-channel scenarios can be obtained with the proposed successive multi-step convex approximation scheme (SMCA). As shown through computational complexity and simulation analysis, SMCA can obtain an approximate lower bound of the optimal solution for the modeled SE problem with a lower computational cost. Furthermore, some potential relationships between network performance and spectrum idle rate can be easily discussed with SMCA, which can provide some sensible deployment strategies for the MRMH CRN in future multi-slot scenarios.

12.
Environ Pollut ; 255(Pt 2): 113320, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610505

RESUMO

Smoky coal burning is a predominant manner for heating and cooking in most rural areas, China. Air pollution is associated with the risk of atherosclerosis, however, the link between indoor air pollution induced by smoky coal burning and atherosclerosis is not very clear. Therefore, we designed a cross-sectional study to evaluate the association of long-term exposure to smoky coal burning pollutants with the risk of atherosclerosis. 426 and 326 participants were recruited from Nangong, China and assigned as the coal exposure and control group according to their heating and cooking way, respectively. The indoor air quality (PM2.5, CO, SO2) was monitored. The association between coal burning exposure and the prevalence of atherosclerosis was evaluated by unconditional logistic regression analysis, adjusted for confounding factors. The inflammatory cytokines mRNAs (IL-8, SAA1, TNF-α, CRP) expression in whole blood were examined by qPCR. People in the coal exposure group had a higher risk of carotid atherosclerosis compared with the control (risk ratio [RR], 1.434; 95% confidence interval [95%CI], 1.063 to 1.934; P = 0.018). The association was stronger in smokers, drinkers and younger (<45 years old) individuals. The elevation of IL-8 (0.24, 95%CI, 0.06-0.58; P < 0.05), CRP (0.37, 95%CI, 0.05-0.70; P < 0.05), TNF-α (0.41, 95%CI, 0.14-0.67; P < 0.01) mRNAs expression in whole blood were positively related to coal exposure. Our results suggested long-term exposure to smoky coal burning emissions could increase the risk of carotid atherosclerosis. The potential mechanism might relate that coal burning emissions exposure induced inflammatory cytokines elevation which had adverse effects on atherosclerotic plaque, and then promoted the development of atherosclerosis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31494851

RESUMO

The different part powders of rape straw as adsorbents were performed to remove zinc ions from aqueous solution in this work. The various factors on influencing removal efficiency of Zn(II) were investigated, and the operational conditions were optimized using the Box-Behnken design of response surface methodology (RSM). Under the optimum conditions obtained, the removal rates of Zn(II) were attained to 100.00%, 78.02%, and 17.00% by straw pith core, seedpods, and shell of rape straw, respectively. Equilibrium and kinetic models were applied to evaluate the adsorption behaviors of Zn(II) on the adsorbents. The equilibrium data were best described by the Langmuir isotherm model, which indicated that the adsorption behaviors were favorably monolayer adsorption processes. The biosorption capacities of Zn(II) were 34.66 mg g-1, 36.41 mg g-1, and 36.74 mg g-1 of rape straw pith core; 23.33 mg g-1, 23.85 mg g-1, and 24.30 mg g-1 of seedpods; and 11.19 mg g-1, 11.23 mg g-1, and 11.27 mg g-1 of shell, respectively, at the various temperatures of 20 °C, 30 °C, and 40 °C based on Langmuir isotherm equation. The pseudo-second-order kinetic model was well to determine the adsorption kinetics, which suggested that ion exchange were occurred during adsorption processes of Zn(II). The characteristics of adsorbents before and after adsorption of Zn(II) were measured using the methods of scanning electron microscope (SEM), zeta potential classes, energy dispersive spectrometer (EDS), and Fourier transform infrared spectroscopy (FT-IR), respectively. The results provided evidences for the adsorption mechanisms of Zn(II) including electrostatic attraction, ion exchange, and functional group involvement on the three part powders of rape straw in aqueous water.

14.
Nanotoxicology ; : 1-20, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502903

RESUMO

The pulmonary fibrosis could be caused by long-term inhalation of carbon black (CB) particles. Studies on the mechanisms of pulmonary fibrosis induced by CB are required to develop the stratagem of prevention and treatment on fibrosis. The RNA-binding protein DiGeorge syndrome critical region gene 8 (DGCR8)-dependent pri-miRNAs processing is regulated by N6-methyladenosine (m6A) modification, which targets the downstream signal pathway. However, its role in pulmonary fibrosis has not been known clearly. In the present study, rats inhaled CB at dose of 0, 5 or 30 mg/m3 for 28 days, 6 h/day, respectively. The rats inhaled CB at dose of 0 or 30 mg/m3 for 14 days, 28 days and 90 days, respectively. In vitro experiments, the normal human bronchial epithelial cell line (16HBE) was treated with CB (0, 50, 100 and 200 µg/mL) for 24 h. In vitro and vivo study, the levels of fibrosis indicators including α-SMA, vimentin, collagen-I and hydroxyproline in CB treatment groups statistically increased in dose- or time- dependent manners compared with the control. After CB treatment, PI3K-AKT-mTOR pathway was activated and regulated by miRNA-126. We found that both of m6A modifications of pri-miRNA-126 and its binding with DGCR8 were decreased after CB treatment, which resulted in the reduction of mature miRNA-126 accompanied by accumulation of unprocessed pri-miRNA-126. This work demonstrated that m6A modification of pri-miRNA-126 and its binding with DGCR8 decreases blocked miRNA-126 maturation, and then activated the PI3K/AKT/mTOR pathway, which drove the fibro genesis in the lung after CB exposure.

15.
Aging (Albany NY) ; 11(18): 7537-7552, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31525733

RESUMO

Glucocorticoids contribute to the increased incidence of secondary osteoporosis. Hydrogen sulfide (H2S) is a gasotransmitter and plays an essential role in bone metabolism. In this study, we investigated the therapeutic effects of H2S on glucocorticoid-induced osteoporosis (GIO). We found that dexamethasone (Dex) decreased serum H2S and two key H2S-generating enzymes in the bone marrow in vivo, cystathione b-synthase and cystathione g-lyase. Treatment of H2S-donor GYY4137 in rat significantly relieved the inhibitory effect of Dex on bone formation. Dex inhibited osteoblasts proliferation and osteogenic differentiation and decreased the expressions of the two H2S-generating enzymes. Further investigation showed that H2S was involved in Dex-mediated osteoblasts proliferation, differentiation, and apoptosis. Mechanistically, GYY4137 promoted osteoblastogenesis by activating Wnt signaling through increased production of the Wnt ligands. In comparison, the blockage of Wnt/ß-catenin signaling pathway significantly alleviated the effect of H2S on osteoblasts. In conclusion, the restoration of H2S levels is a potential novel therapeutic approach for GIO.

16.
Int J Biol Macromol ; 141: 553-563, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31499112

RESUMO

Honeybees communicate with members of their intra-species via pheromones. The volatile pheromones, ß-ocimene and allo-ocimene, are the primary signals of larvae to beg for the care from the nurses. Of the odorant binding proteins (OBPs)/chemosensory proteins (CSPs), CSP4 has the best affinity with ß-ocimene and allo-ocimene. To reveal the binding mechanism of CPS4 with them, fluorescent quenching, UV absorption spectra, circular dichroism (CD) spectra, isothermal titration calorimetry (ITC), molecular docking, molecular dynamic (MD) simulation, and site-directed mutagenesis were applied. The quenching constant Ksv decreased with temperature increase, and the interaction distance was 2.73 nm and 2.43 nm (<10 nm), indicating that ß-ocimene and allo-ocimene could form stable complexes with CSP4. The observed △H < 0 and △S > 0 of thermodynamics suggest the main driving forces are electrostatic or hydrophobic force. All above thermodynamics findings are in line with the results of ITC experiments. Furthermore, molecular docking, MD simulation and site-directed mutagenesis indicate the binding cavities are located at cavity 1 in C-terminal of CSP4, where Tyr98 and Asp67 are vital amino acids in maintaining the stable form of protein and larval pheromones, and electrostatic energies are the main driving forces. Our findings gain novel insight into the binding mechanism of chemosensory protein with volatile larval pheromones and are important for understanding olfactory interaction of honeybees.

17.
Environ Pollut ; 254(Pt A): 112875, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377334

RESUMO

Ambient fine particulate matter (PM2.5) as an environmental pollution has been associated with the lung cancer. However, the mechanism of epigenetics such as miRNAs deregulation between PM2.5-exposure and lung cancer has not been elucidated clearly. Twenty C57BL/6 mice were divided randomly into 2 groups and exposed to the filtered air (FA) and the concentrated air (CA), respectively. The FA mice were exposed to filtered air in chambers with a high-efficient particulate air filter (HEPA-filter), and the CA mice were exposed to concentration ambient PM2.5. The total duration of exposure was performed 6 h per day from December 1st, 2017 to January 27th, 2018. The mice exposed 900.21 µg/m3 PM2.5 for 6 h per day in CA chamber, which was nearly equaled to 225.05 µg/m3 for 24-h calculatingly. After exposure, the serum miRNAs levels were detected by microarray. Genetic and pathological alterations in lung of mice with/without PM2.5 exposure were detected. 38 differential miRNAs in serum of mice were found after PM2.5 exposure for 8 weeks. Among of them, 13 miRNAs related with lung cancer were consistent in serum and lung of mice. The target genes of 13 deregulated miRNAs including CRK, NR2F2, VIM, RASSF1, CCND2, PRKCA, SIRT1, CDK6, MAP3K7, HIF1A, UBE2V2, ATG10, BAX, E2F1, RASSF5 and CTNNB1, could involve in the pathway of lung cancer developing. Compared with the FA group, the significantly increases of histopathological changes, ROS and DNA damage were observed in lung of mice in CA group. Our study suggested that miRNAs in serum could be identified as candidate biomarkers to predict the lung cancer development during early PM2.5 exposure.

18.
Antiviral Res ; 170: 104574, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31394118

RESUMO

High sequence diversity of HCV may lead to variation in susceptibility to antiviral agents amongst different genotypes and subtypes of the virus. We assessed the susceptibility to sofosbuvir of chimeric replicons carrying the full length NS5B coding region from 479 HCV infected, treatment-naïve patients, including 15 subtypes in 6 genotypes. NS5B replicon vectors with subtype 1b, subtype 4a and subtype 6a backbone were modified to support testing of patient samples. We also evaluated sofosbuvir susceptibility in a panel of 331 replicons containing engineered NS5B inhibitor resistance-associated substitutions. The mean 50% effective sofosbuvir concentration (EC50) amongst different genotypes ranged from 32 (subtype 2a) to 130 nM (genotype 4); while some variation in susceptibility amongst patient isolates was observed, the 95th percentile for any genotype did not exceed 189 nM. Levels of resistance to sofosbuvir in replicons containing S282T were between 2.4 and 18 fold-change in EC50; no other single NS5B resistance-associated substitution demonstrated reduced sofosbuvir susceptibility. These data suggest that S282T is the only known substitution that confers detectable resistance to sofosbuvir in vitro. Sofosbuvir displayed potent antiviral activity across a diverse range of NS5B mutants and HCV clinical isolates in multiple subtypes of genotypes 1 to 6.

19.
Proc Natl Acad Sci U S A ; 116(37): 18717-18722, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31451662

RESUMO

The contradiction between "high yielding" and "early maturing" hampers further improvement of annual rice yield. Here we report the positional cloning of a major maturity duration regulatory gene, Early flowering-completely dominant (Ef-cd), and demonstrate that natural variation in Ef-cd could be used to overcome the above contradictory. The Ef-cd locus gives rise to a long noncoding RNA (lncRNA) antisense transcript overlapping the OsSOC1 gene. Ef-cd lncRNA expression positively correlates with the expression of OsSOC1 and H3K36me3 deposition. Field test comparisons of early maturing Ef-cd near-isogenic lines with their wild types as well as of the derivative early maturing hybrids with their wild-type hybrids conducted under different latitudes determined that the early maturing Ef-cd allele shortens maturity duration (ranging from 7 to 20 d) without a concomitant yield penalty. Ef-cd facilitates nitrogen utilization and also improves the photosynthesis rate. Analysis of 1,439 elite hybrid rice varieties revealed that the 16 homozygotes and 299 heterozygotes possessing Ef-cd matured significantly earlier. Therefore, Ef-cd could be a vital contributor of elite early maturing hybrid varieties in balancing grain yield with maturity duration.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31430886

RESUMO

Studies related to air pollution exposure and neurocognitive disorders, specifically cognitive impairment, among older adults are limited. We investigated the association between short-term and long-term exposure to ambient air pollution (i.e., particulate matter with an aerodynamic diameter of <10 µm and ozone) and the effects of their interaction on cognitive function in a community-dwelling, free-living elderly population. Study participants were in a multiple-wave representative sample, namely the Taiwan Longitudinal Study on Aging (n = 2241). In four surveys between 1996 and 2007, their cognitive function was assessed using the Short Portable Mental Status Questionnaire (SPMSQ). We estimated air pollution from 1993 to 2007, including daily concentrations of PM10 and O3 from air quality monitoring stations, based on the administrative zone of each participant's residence. Generalized linear mixed models were used to examine these associations after adjusting for covariates. We found that long-term exposure to PM10 and O3 was significantly associated with cognitive impairment (OR = 1.094, 95% CI: 1.020, 1.174 for PM10; OR = 1.878, 95% CI: 1.363, 2.560 for O3). The joint effect of exposure to PM10 and O3 was associated with cognitive impairment (p < 0.001). Co-exposure to ambient PM10 and O3 may deteriorate cognitive function in older adults.

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