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1.
Bioresour Technol ; 295: 122225, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31629283

RESUMO

Recently, upflow microaerobic sludge blanket (UMSB) system has been developed to remove ammonium and organic matter simultaneously. This study aims to establish influent and operational conditions promoting anammox-based nitrogen removal process in the UMSB reactor by using a modified Activated Sludge Model. Experiments were performed on a laboratory-scale UMSB reactor treated piggery wastewater for over two years. With the experimentally determined model parameters, the established model well simulated the UMSB reactor performance. The maximum anammox growth rate was calibrated to be 0.41 d-1 at 35 °C. Further simulations showed that UMSB reactor operated with high influent organics or nitrogen loading rates at temperature above 15 °C can achieve efficient nitrogen removal (>70%). The nitrogen loading over 0.6 kg N/(m3·d)) significantly favors anammox activity. UMSB could also be a promising system for nitrogen removal from low-strength ammonium wastewater with fluctuated COD influence. These results provide support to UMSB design and operational optimization.


Assuntos
Nitrogênio , Esgotos , Reatores Biológicos , Desnitrificação , Eliminação de Resíduos Líquidos , Águas Residuárias
2.
Toxicol Lett ; 318: 57-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31585160

RESUMO

3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few studies showing the toxicity of rotenone and 3-BrPA in the myocardium. To support further medical exploration, it is necessary to clarify the side effects of these compounds on the heart. This study was designed to examine the cardiotoxicity of 3-BrPA and rotenone by investigating electrical and structural cardiac remodeling in rats. Forty male rats were divided into 4 groups (n = 10 in each group) and injected intraperitoneally with 3-BrPA, rotenone or a combination of 3-BrPA and rotenone. The ventricular effective refractory period (VERP), corrected QT interval (QTc), and ventricular tachycardia/ventricular fibrillation (VT/VF) inducibility were measured. The expression of Cx43, Kir2.1, Kir6.2, DHPRα1, KCNH2, caspase3, caspase9, Bax, Bcl2, and P53 was detected. Masson's trichrome, TUNEL, HE, and PAS staining and transmission electron microscopy were used to detect pathological and ultrastructural changes. Our results showed that rotenone alone and rotenone combined with 3-BrPA significantly increased the risk of ventricular arrhythmias. Rotenone combined with 3-BrPA caused myocardial apoptosis, and rotenone alone and rotenone combined with 3-BrPA caused electrical and structural cardiac remodeling in rats.


Assuntos
Antineoplásicos/toxicidade , Ventrículos do Coração/efeitos dos fármacos , Inseticidas/toxicidade , Piruvatos/toxicidade , Rotenona/toxicidade , Taquicardia Ventricular/induzido quimicamente , Fibrilação Ventricular/induzido quimicamente , Remodelação Ventricular/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade , Conexina 43/genética , Conexina 43/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/ultraestrutura , Masculino , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Ratos Wistar , Período Refratário Eletrofisiológico/efeitos dos fármacos , Medição de Risco , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/patologia , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/patologia , Fibrilação Ventricular/fisiopatologia
3.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692047

RESUMO

Lung cancer is the dominating cause of cancer-induced death and can be classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the most common histological subtype of NSCLC and its pathology remains unclear. Mounting reports have revealed that lncRNAs could regulate cellular activities in cancers. Yet the role of ZFPM2 antisense RNA 1 (ZFPM2-AS1) in LUAD has not been elucidated. Using GEPIA online dataset, we identified the amplification of ZFPM2-AS1 in LUAD tissues. Through quantitative real-time reverse transcription-polymerase chain reaction analysis, we observed an upregulation of ZFPM2-AS1 in LUAD cell lines. Conducting loss-of-function assays, we found that ZFPM2-AS1 depletion impaired cell viability, suppressed cell migration, and reversed epithelial-mesenchymal transition progress in LUAD cells. Mechanism investigation manifested that ZFPM2-AS1 was distributed in the cytoplasm of LUAD cells. Moreover, ZFPM2-AS1 functioned as a molecular sponge of miR-511-3p, which was a suppressor in LUAD. Moreover, ZFPM2-AS1 sponged miR-511-3p and thereby deregulated AF4/FMR2 family member 4 (AFF4), a target of miR-511-3p. At length, rescue assays indicated that AFF4 overexpression revived the inhibiting effects of ZFPM2-AS1 knockdown on the biological processes in LUAD. All in all, this study uncovered the function and the mechanism of ZFPM2-AS1 in LUAD.

4.
Sci Total Environ ; 702: 134997, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31726340

RESUMO

Rapid urbanization and human disturbance of land often results in serious soil erosion and releases of fine sediments and soil-bound toxic metals/metalloids. Yet, technologies for simultaneously controlling soil erosion and metals/metalloids leaching have been lacking. This study developed a new class of polyacrylamide-dispersed magnetite (PAM-MAG) nanoparticles and tested the effectiveness for simultaneous control of soil erosion and arsenic leaching from a model soil. Two parallel box test setups (L × W × H: 91.4 × 30.5 × 7.6 cm) were constructed to test the releases of sediments and soluble pollutants from the surface soil under simulated rainfall conditions (intensity = 11.15 cm/hr). A sandy loam soil from a local quarry mining site was used as the model soil, and arsenate As(V) as a prototype leachable metalloid. A stable dispersion of PAM-MAG was prepared with 0.3 wt% of PAM and 0.1 g/L as Fe of magnetite. The results indicated that treating the soil with 5.985 g/m2 of PAM-MAG was able to decrease cumulative soil mass loss in the runoff by 90.8% (from 254.50 ±â€¯0.10 g to 23.35 ±â€¯3.19 g), or turbidity of the runoff by 79.9% (from 244.5 ±â€¯27.5 NTU to 49.2 ±â€¯22.5 NTU). Compared to PAM only, the PAM-MAG suspension showed a 30% reduction of viscosity, allowing for easier application and transport of the nanoparticles in soil. Concurrently, the PAM-MAG treatment also immobilized 82.5% of water-leachable arsenate compared to untreated controls. Fourier-transform infrared (FTIR) spectroscopy analyses revealed that arsenate was immobilized by magnetite nanoparticles through inner sphere surface complexation (Fe-O-As). Overall, the PAM-MAG based technology holds the promise for simultaneously controlling soil erosion and metal/metalloid releases from disturbed land.

5.
J Control Release ; 315: 40-54, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669212

RESUMO

Dry eye (DE) disease is an uprising health epidemic that directly affects the surface of the eye. We developed a water soluble cerium oxide loaded glycol chitosan nanoparticle as a new type of eye drop, namely GCCNP (glycol chitosan cerium oxide nanoparticles). GCCNP is capable of scavenging cellular reactive oxygen species (ROS) for the treatment of DE disease. The antioxidative effects of GCCNP were assessed in mice primary corneal and conjunctival cells in vitro and in a DE murine model in vivo. GCCNP's effect on the DE models was assessed via histological evaluations, migration assays, cell viability assays, cellular uptake analyses, intracellular ROS scavenging assays, wound healing assays, mitochondrial membrane potential readings, corneal fluorescein staining, tear volume concentrations, tear film break up time analyses, and lastly, analytical/spectroscopic analyses of GCCNP eye drop formulations. Spectroscopic analysis showed that cerium oxide was entrapped into the glycol chitosan (GC). The solubility of cerium in GC (GCCNP) increased to 709.854±24.3µg/ml compared to its original solubility in cerium oxide, which was measured as 0.020±0.002µg/ml. GCCNP had no cytotoxic effect and showed improvements on dry eye disease models by stabilizing the tear film, scavenging ROS, up-regulating SOD, promoting and maintaining corneal and conjunctival cell growth and integrity. We provided convincing evidence that GCCNP is an effective treatment for DE and may represent a potential new class of drug for DE disease.

6.
Med Sci Monit ; 25: 8492-8498, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710020

RESUMO

BACKGROUND More and more patients with lung adenocarcinoma were detected with ground glass nodule (GGN) due to the popularity of low-dose spiral computed tomography (LDCT) recently. The clinicopathological characteristics and epidermal growth factor receptor (EGFR) mutation features were unclear. MATERIAL AND METHODS This retrospective study enrolled patients with surgical resected primary lung adenocarcinomas with GGN component. The clinicopathological data included age, gender, smoking history, tumor staging, lymph node staging, surgical methods, subtypes, thyroid transcription factor-1 (TTF-1) expression, EGFR gene mutation and follow-up records were investigated. RESULTS There were 338 lung adenocarcinoma patients with GGN component eligible for our analysis: 219 patients (64.8%) harbored the EGFR mutation. In addition, the EGFR mutation rate was higher in patients with TTF-1+ than in patients with TTF-1- (72 out of 108 patients, 66.7% versus 147 out of 231 patients, 63.6%). In multivariable analysis, surgical procedure, tumor size, nodal stage, and subtype were still significant factors for relapse-free survival (RFS) while only subtype acted as the significant factor for overall survival (OS). In subgroup analyses, patients with TTF-1- had better prognosis in RFS (log-rank P=0.0142) when compared with those with TTF-1+ but not in OS (log-rank P=0.1113). Furthermore, patients with high-risk subtype had worse outcomes than those with low-risk subtype (RFS: log-rank P<0.0001; OS: log-rank P<0.0001). Patients who underwent limited resection experienced high risk of relapse (log-rank P<0.0001) while there was no statistical significance in OS (log-rank P=0.1644) between patients underwent lobectomy and those underwent limited resection. CONCLUSIONS The prognosis of lung adenocarcinomas with GGN component depends mainly on the pathological subtype and there is no significant correlation between EGFR mutation and prognosis. Lobectomy should be performed actively in patients whose preoperative puncture biopsy or intraoperative freezing indicates an invasive or worse subtype. For postoperative patients, we should consider follow-up more frequently.

7.
Can J Cardiol ; 35(11): 1523-1533, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31679622

RESUMO

BACKGROUND: The diagnostic performance of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) in detecting ischemia in myocardial bridging (MB) has not been investigated to date. METHODS: This retrospective multicentre study included 104 patients with left anterior descending MBs. MB was classified as either superficial or deep, short, or long, whereas all MB vessels were further divided into <50%, 50% to 69%, and ≥70% groups, according to proximal lumen stenosis on invasive coronary angiography. Diagnostic performance and receiver operating characteristics (ROC) of CT-FFR to detect lesion-specific ischemia was assessed on a per-vessel level, using invasive FFR as reference standard. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used for agreement measurement. RESULTS: Forty-eight MB vessels (46.2%) showed ischemia by invasive FFR (≤0.80). Sensitivity, specificity, and accuracy of CT-FFR to detect functional ischemia were 0.96 (0.85 to 0.99), 0.84 (0.71 to 0.92), and 0.89 (0.81 to 0.94), respectively, in all MB vessels. There were no differences in diagnostic performance between superficial and deep MB or between short and long MB (all P > 0.05). The accuracy of CT-FFR was 0.96 (0.85 to 0.99) in ≥70% stenosis, 0.82 (0.67 to 0.91) in 50% to 69% stenosis, and 0.89 (0.51 to 0.99) in <50% stenosis (P = 0.081). Bland-Altman analysis showed a slight mean difference between CT-FFR and invasive FFR of 0.014 (95% limit of agreement, -0.117 to 0.145). The ICC was 0.775 (95% confidence interval, 0.685-0.842, P < 0.001). CONCLUSIONS: CT-FFR demonstrated high diagnostic performance for identifying functional ischemia in vessels with MB and concomitant proximal atherosclerotic disease when compared with invasive FFR. However, the clinical use of CT-FFR in patients with MB needs further study for stronger and more robust results.

8.
Appl Microbiol Biotechnol ; 103(23-24): 9711-9722, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31705181

RESUMO

As the key organism for enhanced biological phosphorus removal, Accumulibacter has shown high intragenus diversity based on the phylogeny of polyphosphate kinase1 gene (ppk1) and many clade-specific features related to performance of wastewater treatment. However, the widely used molecular approaches are deficient or cost-inefficient in providing a comprehensive and quantitative population-level profile for Accumulibacter in complex community. In this study, we introduced a pipeline to analyze the population-level diversity and dynamics of Accumulibacter via high throughput sequencing (HTS) of ppk1 and 16S rRNA gene simultaneously. The HTS approach was assessed by testing primer coverage, performing sample replication, and comparing with a traditional clone library. Based on survey on full-scale activated sludge samples, unexpected high microdiversity in Accumulibacter and a tendency of exclusivity between two phylogenetic types were discovered. Moreover, the pipeline facilitated monitoring the population-level dynamics and co-occurrence pattern under various laboratory enriching conditions. The results revealed previously uncharacterized intraclade dynamics during enrichment, little effect of denitrifying process on the Accumulibacter diversity, and the niche adaption of Clade IIC on propionate as sole carbon source. Co-occurrence of Accumulibacter populations further partially supported the exclusivity of two types. A few bacterial taxa, including Cytophagaceae-, Prosthecobacter-, and Compteibacter-related taxa, showed co-occurrence with many Accumulibacter populations, suggesting their niche co-selection or potential metabolic interactions with Accumulibacter. The present pipeline is transplantable for studying microdiversity and niche differentiation of other functional microorganisms in complex microbial systems.

9.
Cell Death Dis ; 10(12): 869, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740664

RESUMO

Extracellular vesicles (EVs) including exosomes can serve as mediators of cell-cell communication under physiological and pathological conditions. However, cargo molecules carried by EVs to exert their functions, as well as mechanisms for their regulated release and intake, have been poorly understood. In this study, we examined the effects of endothelial cells-derived EVs on neurons suffering from oxygen-glucose deprivation (OGD), which mimics neuronal ischemia-reperfusion injury in human diseases. In a human umbilical endothelial cell (HUVEC)-neuron coculture assay, we found that HUVECs reduced apoptosis of neurons under OGD, and this effect was compromised by GW4869, a blocker of exosome release. Purified EVs could be internalized by neurons and alleviate neuronal apoptosis under OGD. A miRNA, miR-1290, was highly enriched in HUVECs-derived EVs and was responsible for EV-mediated neuronal protection under OGD. Interestingly, we found that OGD enhanced intake of EVs by neurons cultured in vitro. We examined the expression of several potential receptors for EV intake and found that caveolin-1 (Cav-1) was upregulated in OGD-treated neurons and mice suffering from middle cerebral artery occlusion (MCAO). Knock-down of Cav-1 in neurons reduced EV intake, and canceled EV-mediated neuronal protection under OGD. HUVEC-derived EVs alleviated MCAO-induced neuronal apoptosis in vivo. These findings suggested that ischemia likely upregulates Cav-1 expression in neurons to increase EV intake, which protects neurons by attenuating apoptosis via miR-1290.

10.
Arch Biochem Biophys ; 677: 108185, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31704100

RESUMO

Endothelial senescence is the main risk factor that contributes to vascular dysfunction and the progression of vascular disease. Carbon monoxide (CO) plays an important role in preventing vascular dysfunction and in maintaining vascular physiology or homeostasis. The application of exogenous CO has been shown to confer protection in several models of cardiovascular injury or disease, including hypertension, atherosclerosis, balloon-catheter injury, and graft rejection. However, the mechanism by which CO prevents endothelial senescence has been largely unexplored. The aim of this study was to evaluate the effects of CO on endothelial senescence and to investigate the possible mechanisms underlying this process. We measured the levels of senescence-associated-ß-galactosidase activity, senescence-associated secretory phenotype, reactive oxygen species (ROS) production, and stress granule in human umbilical vein endothelial cells and the WI-38 human diploid fibroblast cell line. We found that 5-fluorouracil (5FU)-induced ROS generation was inhibited by CO-releasing molecules (CORM)-A1 treatment, and endothelial senescence induced by 5FU was attenuated by CORM-A1 treatment. The SIRT1 inhibitor EX527 reversed the inhibitory effect of CO on the 5FU-induced endothelial senescence. Furthermore, SIRT1 deficiency abolished the stress granule formation by CO. Our results suggest that CO alleviates the endothelial senescence induced by 5FU through SIRT1 activation and may hence have therapeutic potential for the treatment of vascular diseases.

11.
Life Sci ; : 117094, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31760101

RESUMO

The liver serves as a central participant in immune system owing to its particular blood supply and large amounts of immune cells, in which macrophages play a significant role in liver homeostasis and disorders. Extracellular vesicles (EVs), membrane-defined nanometer-sized vesicles released by cells in a tightly controlled manner, have attracted intensive research attention as a critical vehicle for cell-cell communication in the pathophysiology of liver. Accumulating evidence has proved that extracellular vesicles are frequently involved in macrophage-mediated biological behaviors. Not only can macrophages produce and secrete EVs containing multifarious cargo themselves to exert immunomodulatory functions, but also macrophages may serve as target cells of EVs from other cells eliciting the alteration of their phenotype and function. Since both macrophage as well as EVs show pleiotropic and central effects in the progression of liver diseases, their roles in adjusting innate immunity of liver often present a crossover. In this review we are dedicated to deciphering the complex immunological network constituted by macrophages and EVs in several common liver diseases, including acute liver injury or failure and a set of chronic liver diseases such as viral hepatitis B and C, metabolic and alcoholic liver diseases, as well as hepatocellular carcinoma (HCC). From the aspect of immunology, we integrate the mechanism of EVs and hepatic macrophages in the setting of liver diseases and show a promising significance of utilizing this association into clinical immunotherapy.

12.
J Dermatolog Treat ; : 1-26, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31689127

RESUMO

Background: To investigate the efficacy and safety of Dermalax in the correction of moderate to severe nasolabial folds (NLFs) compared to Restylane.Methods: A total of 324 subjects with moderate to severe NLFs were enrolled in this multicenter, randomized, double-blind, active-controlled clinical study. Eligible subjects were randomly assigned to the test group received Dermalax injection (n = 162) or control group received Restylane injection (n = 162). Clinical efficacy and safety were assessed based on the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale(GAIS) at weeks 2, 8, 16, 24, 36 and 48 weeks after injection.Results: At week 24, similar improvements of effective rate were obtained on the Dermalax group (93.75%) and Restylane group (89.44%). Significances were found at 36 weeks and 48 weeks after injection, Dermalax seemed be better than Restylane in maintaining the effect in the later period. The improvement of mean WSRS score for test group was superior to that of control group with significance. GAIS scores rated at week 24 were 1.65 VS 1.94 (p < 0.001) and 2.10 VS 2.27 (p = 0.060), seperately.Conclusions: Dermalax was no inferior to or better than that of the control filler Restylane in correcting of moderate to severe NLFs in Chinese subjects.

13.
Microb Pathog ; 138: 103816, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655218

RESUMO

Duckling short beak and dwarfism syndrome virus (SBDSV), a newly identified goose parvovirus, causes devastating disease in domestic waterfowl and considerable economic losses to Chinese waterfowl industry. The molecular pathogenesis of SBDSV infection, nature and dynamics of host immune responses against SBDSV infection remained elusive. In this study, we systematically explored the relative mRNA expression profiles of major innate immune-related genes in SBDSV infected duck embryo fibroblasts. We found that SBDSV infection effectively activated host innate immune responses and resulted in significant up-regulation of IFN-ß and several vital IFN-stimulated genes (ISGs). These up-regulation responses were mainly attributed to viral genomic DNA and dsRNA replication intermediates. Importantly, the expression of cGAS was significantly induced, whereas the expression of other DNA receptors including DDX41, STING, ZBP1, LSM14A and LRRFIP1 have no significant change. Furthermore, SBDSV infection also activates the up-regulation of TLR3 and inhibited the expression of TLR2 and TLR4; however, no effect was observed on the expression of TLR1, TLR5, TLR7, TLR15 and TLR21. Intriguingly, SBDSV infection significantly up-regulated the expression of RNA sensors such as MDA5 and LGP2, and resulted in a delayed but significant up-regulation of RIG-I gene. Taken together, these data indicate that host multiple sensors including DNA sensor (cGAS) and RNA sensors (TLR3, MDA5 and LGP2) are involved in recognizing a variety of different pathogen associated molecular patterns (PAMPs) including viral genomic ssDNA and dsRNA replication intermediates, which trigger an effective antiviral innate immune response.

14.
Sci Rep ; 9(1): 15163, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31619747

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

15.
Sci Rep ; 9(1): 14573, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601909

RESUMO

Elevated oxidative stress and associated reactive oxygen species (ROS) accumulation are hallmarks in the induction and progression of age-related macular degeneration (AMD). By exposing nuclear factor erythroid 2-related factor (Nrf2) knockout (Nrf2-/-) mice to mild white light, we were able to generate a new dry-AMD like murine model to the study. This animal model developed phenotypes of photoreceptor degeneration, retinal function impairment, ROS accumulation, and inflammation reaction in a relatively shorter time. In the treatment of this animal model we utilized an antioxidative and water soluble nanoparticle known as glycol chitosan coated cerium oxide nanoparticles (GCCNP). The delivery of GCCNP protected retina against progressive retinal oxidative damage. Further combination of GCCNP with alginate-gelatin based injectable hydrogel provided synergistic antioxidant effects and achieved a more rapid recovery of the retinal pigment epithelium and photoreceptor cells. This combined treatment technique has the potential to translate into a clinical intervention for the treatment of AMD.

16.
Microb Pathog ; 137: 103764, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31585153

RESUMO

Novel duck reovirus (NDRV) is pathogenic to young ducks, which is characterized by hemorrhagic spots and necrotic foci of the livers and necrotic foci of spleens. However, the effect of NDRV infection on the composition of the host's intestinal microbiota remains poorly understood. In this study, three-day-old Muscovy ducklings were inoculated with either the virulent NDRV strain NP03 or sterile Hank's solution. Through Illumina MiSeq sequencing, the whole cecal microbiota of healthy and NDRV infected ducklings was examined. The results showed that the gut microbiota was mainly dominated by Firmicutes, Proteobacteria and Bacteroidestes in both healthy and NDRV infected ducks. NDRV infection altered the relative abundance of bacteria. Specifically, families Ruminococcaceae and Lachnospiraceae were remarkably reduced, whereas Escherichia_Shigella belonging to family Enterobacteriaceae was significantly increased. Collectively, NDRV infection in Muscovy ducks resulted in a shift of the gut microbiota, including a net loss of probiotic bacteria with a compensatory expansion of pathogenic bacteria. These results provide new insights into the potential pathogenic mechanisms of NDRV.

17.
ACS Nano ; 13(11): 13374-13381, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31639293

RESUMO

Nanofluidic osmotic power, which converts a difference in salinity between brine and fresh water into electricity with nanoscale channels, has received more and more attention in recent years. It is long believed that to gain high-performance osmotic power, highly charged channel materials should be exploited so as to enhance the ion selectivity. In this paper, we report counterintuitive surface-charge-density-dependent osmotic power in a single funnel-shaped nanochannel (FSN), violating the previous viewpoint. For the highly charged nanochannel, the performance of osmotic power decreases with a further increase in its surface charge density. With increasing pH (surface charge density), the FSN enables a local maximum power density as high as ∼3.5 kW/m2 in a 500 mM/1 mM KCl gradient. This observation is strongly supported by our rigorous model where the equilibrium chemical reaction between functional carboxylate ion groups on the channel wall and protons is taken into account. The modeling reveals that for a highly charged nanochannel, a significant increase in the surface charge density amplifies the ion concentration polarization effect, thus weakening the effective salinity ratio across the channel and undermining the osmotic power generated.

18.
Toxicol Lett ; 316: 49-59, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520698

RESUMO

Epidemiological studies have established the correlations between PM2.5 and a wide variety of pulmonary diseases. However, their underlying pathogeneses have not been clearly elucidated yet. In the present study, the epithelial-mesenchymal transition (EMT) phenotype with enhanced proliferation and migration activity of human pulmonary epithelial cell line BEAS-2B was observed after exposure to low dose PM2.5 exposure (50 µg/ml) for 30 passages. Then, epithelial cells derived-exosomal micro-RNA (miRNA) and intracellular total RNA were extracted, and the differentially expressed exosomal miRNAs (DE-Exo-MiRs) as well as differentially expressed protein coding genes (DEGs) were identified by RNA sequencing (RNA-seq) and transcriptome analysis. We found that chronic PM2.5 exposure stimulated the release of pulmonary epithelium derived exosomes. 45 DE-Exo-MiRs including 32 novelly predicted miRNAs and 843 DEGs between PM2.5 exposed group and the normal control were detected. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs were significantly enriched in extracellular matrix organization, focal adhesion and cancer related terms. Besides, the enrichment analyses on 7774 mRNA targets of 27 DE-Exo-MiRs predicted by MiRanda software also revealed the potential regulatory role of exosomal miRNAs in pathways in cancer, Wingless/Integrated (Wnt) signaling pathway, focal adhesion related genes and other multiple pathogenic pathways. Moreover, the interactive exosomal miRNA-mRNA pair networks were constructed using Cytoscape software. Our results provided a novel basis for a better understanding of the mechanisms of chronic PM2.5 exposure induced pulmonary disorders including pulmonary fibrosis and cancer, in which exosomal miRNAs (Exo-MiRs) potentially functions by dynamically regulating gene expressions.


Assuntos
Células Epiteliais/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Pulmão/efeitos dos fármacos , MicroRNAs/genética , Material Particulado/toxicidade , RNA Mensageiro/genética , Transcriptoma/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Biologia Computacional , Bases de Dados Genéticas , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Redes Reguladoras de Genes , Humanos , Pulmão/metabolismo , Pulmão/ultraestrutura , MicroRNAs/metabolismo , Tamanho da Partícula , RNA Mensageiro/metabolismo , Medição de Risco , Fatores de Tempo , Testes de Toxicidade Crônica
19.
Plant Sci ; 287: 110183, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31481206

RESUMO

In plants, sugar acts as an essential signaling molecule that modulates various aspects of metabolism, growth and development, which are also controlled by phytohormones. However, the molecular mechanism of cross-talk between sugar and phytohormones still remains to be elucidated. We have identified gsm1 (glucose-hypersensitive mutant 1) as a mutant with impaired cotyledon development that shows sensitivity to exogenous abscisic acid (ABA). The addition of fluridone can reverse the glucose (Glc) inhibitory effect in gsm1, implying that endogenous ABA is involved in the Glc response of gsm1. In 4.5% Glc, the expression of Glc-induced ABA-responsive genes in gsm1-1 was nearly two times higher than that in the wild type. Compared to gsm1-1, the gsm1-1 abi4-1 double mutant exhibited reduced sensitivity to Glc and ABA, which was similar to the Glc and ABA insensitive phenotype of abi4-1, suggesting that ABI4 is epistatic to GSM1. In the treatment with 4.5% Glc, the GSM1 transcript level was greatly increased in abi4-1 by almost 4-fold of that in the wild type. These data suggest that GSM1 plays an important role in the ABI4-regulated Glc-ABA signaling cascade during Arabidopsis early seedling growth.

20.
MBio ; 10(5)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530680

RESUMO

Nonstructural protein 1 (NS1) of influenza virus is a key virulence element with multifunctional roles in virus replication and a potent antagonist of host immune response. Deletion of NS1 (DelNS1) would create a safer and more extensively immunogenic live attenuated influenza virus (LAIV) vaccine. However, DelNS1 viruses are very difficult to grow in regular vaccine-producing systems, which has hampered the application of DelNS1 LAIV vaccines in humans. We have developed two master backbones of deleted-NS1 (DelNS1) viral genomes from influenza A or B viruses which contain novel adaptive mutations to support DelNS1-LAIV replication. These DelNS1-LAIVs are highly attenuated in human cells in vitro and nonpathogenic in mice but replicate well in vaccine-producing cells. Both influenza A and influenza B DelNS1 LAIVs grow better at 33°C than at 37 to 39°C. Vaccination with DelNS1 LAIV performed once is enough to provide potent protection against lethal challenge with homologous virus and strong long-lasting cross protection against heterosubtypic or antigenically distantly related influenza viruses in mice. Mechanistic investigations revealed that DelNS1-LAIVs induce cross protective neutralizing antibody and CD8+ and CD4+ T cell immunities. Importantly, it has been shown that DelNS1-LAIV can be used to enhance specific anti-influenza immunity through expression of additional antigens from the deleted-NS1 site. Generation of DelNS1 viruses which are nonpathogenic and able to grow in vaccine-producing systems is an important strategy for making highly immunogenic LAIV vaccines that induce broad cross protective immunity against seasonal and emerging influenza.IMPORTANCE Current seasonal influenza vaccines are suboptimal and low in immunogenicity and do not provide long-lasting immunity and cross protection against influenza virus strains that have antigenically drifted. More-effective influenza vaccines which can induce both humoral immunity and T cell immunity are needed. The NS1 protein of influenza virus is a virulence element and the critical factor for regulation of the host immune response during virus infection. Deletion of the NS1 protein is a strategy to make an optimal LAIV vaccine. However, DelNS1 viruses are very difficult to grow in regular vaccine-producing systems, hampering the application of DelNS1 LAIV vaccines in humans. We have generated a panel of both influenza A and influenza B DelNS1 LAIVs which are able to grow in regular vaccine-producing cells. These DelNS1 LAIV vaccines are completely nonpathogenic, exhibit potent and long-lasting immunity, and can be used to express extra viral antigen to induce cross protective immunity against seasonal and emerging influenza.

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