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1.
Mater Sci Eng C Mater Biol Appl ; 106: 110230, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753349

RESUMO

There is an urgent need for new antibacterial strategies to overcome the emergence of antibiotic resistance. Antibacterial photodynamic therapy (APDT) may be an effective method to deliver photosensitizers for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report that the photosensitizer hypocrellin A (HA) loaded into lipase-sensitive methoxy poly (ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) micelles showed high anti-MRSA activity in vitro and in vivo by PDT. Once the micelles come into contact with bacteria that secrete lipase, the PCL is degraded to release HA. Our results showed that the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of mPEG-PCL/HA micelles after light irradiation were 0.69 and 1.38 mg/L (HA concentration), respectively. In the dark, the MIC and MBC of the micelles were 250 and 500 mg/L (HA concentration), respectively. The fluorescent stain results further demonstrated the photodynamic antibacterial activity of mPEG-PCL/HA micelles. The survival rate of mice subjected to experimental acute peritonitis increased to 86% after treated with the micelles. The polymeric micelles showed low hemolytic activity and biocompatibility, simultaneously preventing aggregation in vivo and enhancing the water solubility of HA. Thus, the photosensitizer HA loaded micelles could be used as APDT for infections caused by bacteria without antibiotic resistance.

2.
Biomed Pharmacother ; 121: 109669, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31766100

RESUMO

Oxidative stress is closely associated to the onset and progression of many human diseases. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway using naturally-derived molecules is an efficient strategy for alleviating the intracellular oxidative insults, and thus blocking the pathogenesis of oxidative stress-induced diseases. In the present study, a naturally-derived isopimarane-type diterpenoid sphaeropsidin C (SC) was identified to be an activator of Nrf2/ARE signaling pathway. Our data indicated that SC was able to stimulate Nrf2-mediated defensive system through promoting Nrf2 translocation, inhibiting Nrf2 ubiquitination, and enhancing Nrf2 stability in normal human lung epithelial Beas-2B cells. Furthermore, SC-induced Nrf2 activation required the involvement of protein kinases, exemplified by protein kinase C (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). It alleviated sodium arsenite [As(III)]-induced intracellular oxidative stress in an Nrf2-dependent manner. These results suggested that SC displayed potential application for the prevention and therapy against oxidative stress-induced diseases. Moreover, isopimarane-type diterpenoid represents a promising skeleton for developing Nrf2 activators.

3.
Talanta ; 206: 120211, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514873

RESUMO

Urinary glucose determination using a glucose test strip is simple and convenient in daily self-monitoring of diabetes. However, diabetic patients exhibit acquired impaired color vision (ICV), which results in the inability to discriminate between hues. Even with the assistance of a color chart, it is still not easy for these patients to read the urinary glucose results with the naked eye. In this study, a smartphone camera using an image-based colorimetric detection method was successfully developed for quantitative analysis of urine glucose. A horseradish peroxidase-hydrogen peroxide-3,3'5,5'-tetramethylbenzidine (HRP-H2O2-TMB) system was optimized for a reliable and gradual color fading process via a glucose oxidase (GOD) catalyzed oxidation reaction. The color changes of the peroxidase-H2O2 enzymatic reactions in the 96-well microplate were captured by a smartphone RGB camera with subsequent detection of red, green, and blue (RGB) intensities decreasing at each image pixel. The highly quantitative relationships between the glucose concentrations and the color characteristic values of the blue channel of the captured images were successfully established. The high accuracy of this method was demonstrated in urine glucose measurements with a linear response over the 0.039 mg mL-1 to 10.000 mg mL-1 glucose concentration range and a 0.009 mg mL-1 detection limit. The method has great potential as a point-of-need platform for diabetic patients with defective color vision and features high accuracy and low cost.

4.
Adv Healthc Mater ; : e1901224, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793757

RESUMO

Osteosarcoma is an aggressive tumor of mesenchymal origin that is more likely to spread to the lung than others, with a major impact on patients' prognosis. The optimal imaging method that can reliably detect or exclude pulmonary metastases from osteosarcoma is still scarce. Herein, two homologous types of fluorescent probes CH1055-PEG-PT and CH1055-PEG-Affibody, which show highly promising results for targeting imaging of osteosarcoma and its lung metastasis, respectively, are designed and synthesized. It is found that the NIR-II imaging quality of CH1055-PEG-PT is far superior to that of computed tomography for the early in vivo 143B tumor imaging, and this probe-guided surgery for accurate resection of 143B tumor is further performed. The high-resolution visualization of primary and micrometastatic lung lesions of osteosarcoma by using CH1055-PEG-Affibody is also demonstrated. Therefore, the attractive imaging properties of CH1055-PEG-PT and CH1055-PEG-Affibody, including high levels of uptakes, and high spatial and temporal resolution, open up opportunities for molecular imaging and clinical translation of osteosarcoma and its lung metastasis in the unique second near-infrared window.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31802535

RESUMO

BACKGROUND AND AIM: Endoscopic stenting for unresectable malignant hilar biliary strictures (MHBS) remains challenging. Post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis (PEC) can be the most common and fatal adverse event. In the present study, we aimed to systematically evaluate the incidence, severity, risk factors and consequences of PEC after endoscopic procedures for advanced MHBS. METHODS: Of 924 patients, we identified 502 patients with MHBS (Bismuth type II to IV) who underwent endoscopic stenting as the primary therapy at two centers over 16 years. PEC and its severity were verified according to the current Tokyo guidelines. RESULTS: A total of 108 patients (21.5%) experienced acute PEC. Mild, moderate and severe cholangitis was encountered in 51 (10.1%), 42 (8.4%) and 15 (3.0%) patients, respectively. Multivariate analyses showed that metal stenting (verse plastic stenting) (OR 0.328, 95% CI 0.200-0.535, p<0.001) and Bismuth classification (IV vs. III/II) (OR 2.499, 95% CI 1.150-5.430) were independent predictors for PEC and the moderate/severe type. Patients with PEC had significantly lower clinical success rates (86.3% vs 41.7%, p<0.001), a higher rate of early death (6.5% vs. 0.5%, p<0.001), a shorter median stent patency (4.9 vs. 6.4 months, p<0.001), and shorter overall survival (2.6 vs. 5.2 months, p<0.001) compared to the noncholangitis group. CONCLUSIONS: After endoscopic stenting for advanced MHBS, cholangitis may occur in as many as 21.5% of patients, which may be associated with a poor prognosis. The risk is high in patients with Bismuth type IV and may be reduced by using metal stents.

6.
Curr Mol Med ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31804167

RESUMO

INTRODUCTION: Pain is one of the most common symptoms in clinical. This review is to describe researches on herbs and their active ingredients in treating pain and provide valuable reference for the development and utilization of analgesic traditional Chinese medicine (TCM). Areas covered: The literature search was performed from 1995 to October 2016, covering the relevant literatures that concern the treatment of pain with TCM. Active ingredients extracted from TCM with analgesic activity are summarized and classified into six categories, including polysaccharides, saponins, alkaloids, flavonoids, terpenoids and other constituents. Expert opinions: There are two pathways constituting the analgesic mechanisms of TCM: through the central nervous system and through the peripheral nervous system. The former pathway includes increasing the content of endogenous analgesic substances like opiate peptide, cutting down the second messenger of neurotransmitter like nitric oxide (NO), reducing the content of prostaglandin E2 (PGE2) in brain tissue, blocking the central calcium channel, reducing excitatory amino acids in brain tissue, inhibiting their receptors and raising the content of the central 5-hydroxytryptamine (5-HT). The latter one usually contains the decrease in secretion of peripheral algogenic substances, the induction of pain-sensitive substances and the accumulation of local algogenic substance, the increase in release of peripheral endogenous analgesia materials and the regulation of c-Fos gene (immediate early gene).

8.
Artigo em Inglês | MEDLINE | ID: mdl-31707019

RESUMO

Heat shock is a potentially fatal condition characterized by high body temperature (>40 °C), which may lead to physical discomfort and dysfunctions of organ systems. Acidic pH environment in lysosomes can activate enzymes, thus facilitating the degradation of proteins in cellular metabolism. Owing to the lack of a practical research tool, it remains difficult to exploit relationship between heat shock and lysosome. Herein, a NIR lysosomal pH chemosensor (NRLH) was developed. One typical lysosome-locating group, morpholine, was incorporated into NRLH. The fluorescence intensity showed pH-dependent characteristics and responded sensitively to pH fluctuations in the pH range of 3.0-5.5. NRLH with a pKa of 4.24 displayed rapid response and high selectivity for H+ among common species. We also demonstrated NRLH was capable of targeting lysosomes. Importantly, NRLH was applied in cellular imaging and the data revealed that lysosomal pH increased but never decreased during the heat shock. Therefore, NRLH may act as an effective molecular tool for exploring the mechanisms of heat-related pathology in bio-systems.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31713080

RESUMO

An obligately anaerobic, nitrate-reducing bacterial strain (MJB2T) was isolated from sediments of saline in Xinjiang province of China. Cells were Gram-stain-positive rods and motile by means of flagella and formed endospores. The novel strain MJB2T was able to grow at 15-37 °C (optimum 28-30 °C), pH 5.8-9.4 (optimum 7.8) and with 1.0-7.0% NaCl (optimum 5.0-6.0%, w/v). Sulfate, sulfite, thiosulfate, elemental sulfur, nitrite and Fe(III) were not used as terminal electron acceptors. Oxidase and catalase reactions were positive. H2S was producted from L-cystine. Complex substrates such as beef extract, peptone and yeast extract can be used as sole energy sources. The DNA G+C content was 29.4 mol%. The major cellular fatty acids (> 10%) were C14:0, C16:1 cis 7 and C16:1 cis 9. The main polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, three unidentified amino lipids, one unidentified amino glycolipid, two unidentified glycolipid, one unidentified aminophospholipid and two unidentified lipids. No respiratory quinones were detected. According to phylogenetic analysis based on 16S rRNA gene sequences, strain MJB2T was affiliated to the family Clostridiaceae (order Clostridiales) with highest 16S rRNA gene sequence similarity of 95.3% to Crassaminicella profunda Ra1766HT. Strain MJB2T exhibited 74.9% ANI values to C. profunda Ra1766HT. In silico DNA-DNA relatedness value between strain MJB2T and C. profunda Ra1766HT was 19.5%. The distinct biochemical, chemotaxonomic and phylogenetic differences from the previously described taxa supported that strain MJB2T represents a novel species of a new genus, for which the name Anaerophilus nitritogenes gen. nov., sp. nov. is proposed. The type strain is MJB2T (=KCTC 15800T=MCCC 1K03631T).

10.
Mol Med Rep ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31746388

RESUMO

The epithelial­to­mesenchymal transition (EMT) has been reported to serve vital roles in regulating the progress of cancer metastasis. In addition, lipid rafts enriched in sphingolipids and cholesterol serve important roles in physiological and biochemical processes as a signaling platform. The present study explored the effects of hydroxypropyl­ß­cyclodextrin (HP­ß­CD), a cholesterol­depleting agent of lipid rafts, on the transforming growth factor (TGF)­ß/Smad signaling pathway and endoplasmic reticulum (ER) stress in mediating EMT in MDA­MB­231 breast cancer cells. HP­ß­CD treatment inhibited TGF­ß1­induced EMT, based on increased expression of E­cadherin and decreased expression of vimentin. HP­ß­CD reduced the expression of the TGF receptor TßRI and blocked the phosphorylation of Smad2. In addition, HP­ß­CD increased the expression of ER stress­related proteins (binding immunoglobulin protein and activating transcription factor 6), but TGF­ß1 could reverse these changes. Sodium 4­phenylbutyrate, an inhibitor of ER stress, suppressed these effects of HP­ß­CD on EMT and TGF­ß/Smad signaling pathway inhibition in breast cancer cells. Thus, HP­ß­CD can block the TGF­ß/Smad signaling pathway via diminishing the expression of TßRI which helps to activate ER stress and attenuate EMT in MDA­MB­231 cells, highlighting a potential target of lipid rafts for breast cancer treatment.

11.
J Affect Disord ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31759667

RESUMO

BACKGROUND: Depressive symptoms among adolescents are common. This study aimed to assess, among Chinese adolescents, the associations of habitual weekday sleep duration with depressive symptoms and whether these associations varied with the mode of birth delivery. METHODS: Data were from the 2015 School-based Chinese Adolescents Health Survey, and 150,053 students' questionnaires were qualified for analysis. Multi-level logistic regression models were performed. RESULTS: A weekday sleep duration of ≤5 h/night was associated with depressive symptoms (adjusted odds ratio [aOR]=2.98, 95% CI=2.75-3.24), and adolescents who reported a weekday sleep duration of 5-7 h/night (aOR=1.69, 95% CI=1.60-1.79) and >9 h/night (aOR=1.28, 95% CI=1.11-1.45) were also at a higher risk of depressive symptoms. Stratification analyses showed that in both adolescents delivered by vaginal birth and cesarean section (CS), a weekday sleep duration of ≤5 h/night, 5-7 h/night, and >9 h/night were associated with the increased risk of depressive symptoms in the adjusted models, and the magnitudes of the aORs in adolescents delivered by CS were slightly higher than those in adolescents delivered by vaginal birth. LIMITATIONS: The cross-sectional study design and self-reported sleep duration and depressive symptoms. CONCLUSION: This study demonstrates a significant U-shaped association between weekday sleep duration and depressive symptoms among Chinese adolescents. In both adolescents delivered by vaginal birth and CS, those who reported having abnormal sleep duration were at a high risk of depressive symptoms. Based on the findings of this study, we suggest sleep duration and mode of delivery should be a matter of concern for public health authorities.

12.
J Hazard Mater ; : 121670, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31761646

RESUMO

Pertechnetate (TcO4-) is a component of low-activity waste (LAW) fractions of legacy nuclear waste, and the adsorption removal of TcO4- from LAW effluents would greatly benefit the site remediation process. However, available adsorbent materials lack the desired combination of low cost, radiolytic stability, and high selectivity. In this study, a ZnO nanoparticle-anchored biochar composite (ZBC) was fabricated and applied to potentially separate TcO4- from radioactive effluents. The as-synthesized material exhibited γ radiation resistance and superhydrophobicity, with a strong sorption capacity of 25,916 mg/kg for perrhenate (ReO4-), which was used in this study as a surrogate for radioactive pertechnetate (TcO4-). Additionally, the selectivity for ReO4- exceeded that for the competing ions I-, NO2-, NO3-, SO42-, PO43-, Cu2+, Fe3+, Al3+, and UO22+. These unique features show that ZBC is capable of selectively removing ReO4- from Hanford LAW melter off-gas scrubber simulant effluent. This selectivity stems from the synergistic effects of both the superhydrophobic surface of the sorbent and the inherent nature of sorbates. Furthermore, density functional theory (DFT) calculations indicated that ReO4- can form stable complexes on both the (100) and (002) planes of ZnO, of which, the (002) complexes have greater stability. Electron transfer from ReO4- on (002) was greater than that on (100). These phenomena may be because (002) has a lower surface energy than (100). Partial density of state (PDOS) analysis further confirms that ReO4- is chemisorbed on ZBC, which agrees with the findings of the Elovich kinetic model. This work provides a feasible pathway for scale-up to produce high-efficiency and cost-effective biosorbents for the removal of radionuclides.

13.
Neurobiol Dis ; 134: 104648, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31676238

RESUMO

Accumulation of DNA damage has been detected in the spinal cord of patients as well as in the G93A mouse model of amyotrophic lateral sclerosis (ALS). Wild-type p53-induced phosphatase 1 (Wip1) is a p53-inducible serine/threonine phosphatase that terminates DNA-damage responses via dephosphorylation of DNA-damage response proteins, namely ataxia-telangiectasia mutated (ATM) kinase, checkpoint kinase 2, and p53, thus enhancing cell proliferation. However, the role of Wip1, DNA-damage responses, and their interaction in ALS development remains to be elucidated. Here, we showed that Wip1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro. The DNA-damage response was activated in superoxide dismutase 1 (SOD1) G93A-transfected cells. However, increased expression of Wip1 improved cell viability and inhibited the DNA-damage response in mutated SOD1G93A cells. Further studies demonstrated that decreased Wip1 expression reduced cell viability and further activated the DNA-damage response in chronic H2O2-treated NSC34 cells. In contrast, Wip1 promoted cell survival and suppressed DNA damage-induced apoptosis during persistent DNA damage conditions. Over-expression of Wip1 in the central nervous system (CNS) can delay the onset of disease symptoms, extended the survival, decreased MN loss improved motor function and inhibit the DNA-damage response in SOD1 G93A mice. Furthermore, homeodomain-interacting protein kinase 2 (HIPK2) promoted the degradation of Wip1 via the ubiquitin-proteasome system during chronic stress. These findings indicate that persistent accumulation of DNA damage and subsequent chronic activation of the downstream DNA damage-response ATM and p53 pro-apoptotic signaling pathways may trigger neuronal dysfunction and neuronal death in ALS. Wip1 may play a protective role by targeting the DNA-damage response in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS.

14.
Free Radic Biol Med ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31760092

RESUMO

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease resulted from airflow obstructions, and there is a driving requirement for novel and effective preventive and therapeutic agents of COPD. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been regarded to be a promising therapeutic target for COPD. Resveratrol is a natural Nrf2 activator with antioxidant and anti-inflammatory properties, however, its application is limited by its relative low efficiency and poor bioavailability. Herein, based on the skeleton of resveratrol, trans-4,4'-dihydroxystilbene (DHS) has been firstly identified to be an Nrf2 activator, which is more potent than the well-known sulforaphane (SF) and resveratrol. Our results indicate that DHS blocks Nrf2 ubiquitylation through specifically reacting with Cys151 cysteine in Keap1 protein to activate Nrf2-regulated defensive response, and thus enhances intracellular antioxidant capability. Furthermore, DHS relieves lipopolysaccharide (LPS)-stimulated inflammatory response via inhibition of NF-κB. Importantly, DHS significantly ameliorates pathological alterations (e.g. infiltration of leukocytes and fibrosis), downregulates the levels of oxidant biomarkers malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'-deoxyguanosin (8-oxo-dG), and inhibits the overproductions of inflammatory mediators [e.g. tumor necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9)] in a cigarette smoke (CS)-induced pulmonary impairment mice model. Taken together, this study demonstrates that DHS attenuates the CS-induced pulmonary impairments through inhibitions of oxidative stress and inflammatory response targeting Nrf2 and NF-κB in vitro and in vivo, and could be developed into a preventive agent against pulmonary impairments induced by CS.

15.
Clin Exp Med ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745677

RESUMO

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

16.
Biotechnol Lett ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776751

RESUMO

OBJECTIVES: Previously, we have found that the matrix attachment region (MAR) may confer a 'distance effect' on transgene expression. This work aims to systematically explore the increased transgene expression in transfected Chinese hamster ovary (CHO) cells due to the characteristics of MAR and its mechanism. RESULTS: Compared with the control vector, 500 and 1000 bp DNA distances between MAR and the cytomegalovirus promoter can increase transgene expression by 1.77- and 1.56-fold, respectively. Meanwhile, transgene expression was not affected when 2000 and 2500 bp spacer DNAs were inserted, but a declining trend was observed when a 1500 bp spacer DNA was inserted. The vector containing a 500 bp DNA distance significantly increased the expression of the enhanced green fluorescent protein, and this increase was not related to transgene copy numbers. CONCLUSIONS: A short DNA distance-containing MAR confers high transgene expression level in transfected CHO cells, but a distance threshold does not exist in the vector system.

17.
Biomater Sci ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31777865

RESUMO

On account of the biological significance of self-assembling peptides in blocking the cellular mass exchange as well as impeding the formation for actin filaments resulting in program cell death, stimuli-responsive polypeptide nanoparticles have attracted more and more attention. In this work, we successfully fabricated doxorubicin-loaded polyethylene glycol-block-peptide (FFKY)-block-tetraphenylethylene (PEG-Pep-TPE/DOX) nanoparticles, where the aggregation-induced emission luminogens (AIEgen, TPE-CHO) can become a fluorescence resonance energy transfer (FRET) pair with the entrapped antitumor drug DOX to detect the release of drugs dynamically. This is the first successful attempt to detect and quantify the change of FRET signals in A549 cells via three methods to monitor the cellular uptake of nanoprobes and intracellular drug molecule release intuitively. As we proposed here, the combination of free DOX and the self-assembling peptide could achieve the synergistic anticancer efficacy. The multifunctional PEG-Pep-TPE/DOX nanoparticles may provide a new opportunity for combination cancer therapy and real-time detection of the drug release from stimuli-responsive nanomedicine.

18.
Vaccine ; 37(48): 7155-7164, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31611100

RESUMO

Although West Nile virus (WNV) causes annual cases of neurological disease and deaths in humans, a vaccine has not been licensed for human use. Several WNV genes have been targeted for mutagenesis in attempts to generate live attenuated vaccine candidates, including the non-structural protein NS5. Specifically, mutation of WNV NS5-K61A or NS5-E218A in the catalytic tetrad of the methyltransferase decreases enzyme activity of the NS5 protein and correspondingly attenuates the virus in mice. In this report, NS5-K61A, NS5-E218A, and a double mutant encoding both mutations (NS5-K61A/E218A) were compared both in vitro and in vivo. Each single mutant was strongly attenuated in highly susceptible outbred mice, whereas the double mutant unexpectedly was not attenuated. Sequencing analysis demonstrated that the double mutant was capable of reversion at both residues NS5-61 and NS5-218, whereas the genotype of the single mutants did not show evidence of reversion. Overall, either NS5-K61A or NS5-E218A methyltransferase mutations could be potential mutations to include in a candidate live WNV vaccine; however, multiple mutations in the catalytic tetrad of the methyltransferase are not tolerated.

19.
Nanoscale ; 11(42): 19783-19790, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612184

RESUMO

Developing robust and inexpensive non-noble metal based anode electrocatalysts is highly desirable for alkaline direct methanol fuel cells (ADMFCs). Herein, we successfully develop a facile self-template synthetic strategy for gram-grade porous NiO nanotubes (NTs) by pyrolyzing a nanorod-like Ni-dimethylglyoxime complex. The pyrolysis temperature highly correlates with the morphology and crystallinity of NiO NTs. The optimal NiO NTs exhibit a large electrochemically active surface area, a fast catalytic kinetics, and a small charge transfer resistance, which induce an outstanding electrocatalytic activity for the methanol oxidation reaction (MOR). Compared with conventional NiO nanoparticles, NiO NTs achieve a 11.5-fold increase in mass activity at 1.5 V for the MOR due to nanotubal morphology and abundant non-vacancy defects on the NiO NT surface. Moreover, NiO NTs have a higher electrocatalytic activity for the intermediates of the MOR (such as formaldehyde and formate) than conventional NiO nanoparticles, which also contribute to MOR activity enhancement. Given the facile synthesis and enhanced electrocatalytic performance, NiO NTs may be promising anode electrocatalysts for ADMFCs.

20.
Nat Commun ; 10(1): 4458, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575867

RESUMO

The use of anion redox reactions is gaining interest for increasing rechargeable capacities in alkaline ion batteries. Although anion redox coupling of S2- and (S2)2- through dimerization of S-S in sulfides have been studied and reported, an anion redox process through electron hole formation has not been investigated to the best of our knowledge. Here, we report an O3-NaCr2/3Ti1/3S2 cathode that delivers a high reversible capacity of ~186 mAh g-1 (0.95 Na) based on the cation and anion redox process. Various charge compensation mechanisms of the sulfur anionic redox process in layered NaCr2/3Ti1/3S2, which occur through the formation of disulfide-like species, the precipitation of elemental sulfur, S-S dimerization, and especially through the formation of electron holes, are investigated. Direct structural evidence for formation of electron holes and (S2)n- species with shortened S-S distances is obtained. These results provide valuable information for the development of materials based on the anionic redox reaction.

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