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1.
N Engl J Med ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374959

RESUMO

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

2.
Polymers (Basel) ; 12(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244649

RESUMO

A novel torsion screw has been proposed to resolve the inadequate control of mass transfer and the thermal management of two component polymer blends and their carbon fiber composites. The novel torsional screw distinctly introduced radial flow in the torsion screw channel, which is a significant improvement over the flow pattern developed by the conventional screw. The heat transfer and mixing behavior of melt mixtures are enhanced by adapting screws with torsion elements compared with the traditional screw elements. Heat transfer efficacy in the polypropylene-polystyrene bi-phasic extrusion process improved with the increase in torsion element numbers. An increased number of newly designed torsional elements also improved the dispersion of minor phase in bi-phase polypropylene-polystyrene composition and their carbon fiber composites. The unique flow pattern induced by the torsion elements shows a synergistic effect on the melt-phase mass flow and the thermal flow field facilitating phase-to-phase thermal and molecular mobility and enhanced fiber orientation, crystallinity and mechanical properties of composite made from recycled carbon fiber/polypropylene. Microtomographs of recycled carbon fiber demonstrated the extraordinary ability of a torsion screw element to orient carbon fiber in both axial and radial directions.

3.
Am Surg ; 86(2): 164-170, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167047

RESUMO

Tumor deposits in colon cancer are related to poor prognosis, whereas the prognostic power of tumor deposits in combination with lymph node metastasis (LNM) is controversial. This study aimed to compare the overall survival between LNM alone and LNM in combination with tumor deposits, and to verify whether the number of tumor deposits can be considered LNM in patients with both LNM and tumor deposits in stage III colon cancer by propensity score matching (PSM). Patients carrying resected stage III adenocarcinoma of colon cancer were identified from the Surveillance, Epidemiology, and End Results database (2010-2015). The Kaplan-Meier method, Cox proportional hazard models and PSM were used. On the whole, 23,168 patients (20,451 (88.3%) with only LNM and 2,717 (11.7%) with both LNM and tumor deposits) were selected. After undergoing PSM, patients with both LNM and tumor deposits showed worse overall survival (hazard ratio = 1.33, 95% confidence interval: 1.20-1.47, P < 0.001). After the number of tumor deposits was added with that of positive regional lymph nodes, patients with both LNM and tumor deposits seemed to have prognostic implications similar to those with LNM alone (hazard ratio = 1.02, 95% confidence interval: 0.93-1.12, P = 0.66). The simultaneous presence of LNM and tumor deposits, as compared with the presence of only LNM, had an association with a worse outcome. Tumor deposits should be considered as LNM in patients with both tumor deposits and LNM in stage III colon cancer.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Adenocarcinoma/secundário , Idoso , Intervalos de Confiança , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Programa de SEER , Taxa de Sobrevida
4.
Acta Pharmacol Sin ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32203078

RESUMO

Gastrodin (GAS) is the main bioactive component of Tianma, a traditional Chinese medicine widely used to treat neurological disorders as well as cardio- and cerebrovascular diseases. In the present study, the protective effects of GAS on H9c2 cells against ischemia-reperfusion (IR)-like injury were found to be related to decreasing of oxidative stress. Furthermore, GAS could protect H9c2 cells against oxidative injury induced by H2O2. Pretreatment of GAS at 20, 50, and 100 µM for 4 h significantly ameliorated the decrease in cell viability and increase in apoptosis of H9c2 cells treated with 400 µM H2O2 for 3 h. Furthermore, we showed that H2O2 treatment induced fragmentation of mitochondria and significant reduction in networks, footprint, and tubular length of mitochondria; H2O2 treatment strongly inhibited mitochondrial respiration; H2O2 treatment induced a decrease in the expression of mitochondrial fusion factors Mfn2 and Opa1, and increase in the expression of mitochondrial fission factor Fis1. All these alterations in H2O2-treated H9c2 cells could be ameliorated by GAS pretreatment. Moreover, we revealed that GAS pretreatment enhanced the nuclear translocation of Nrf2 under H2O2 treatment. Knockdown of Nrf2 expression abolished the protective effects of GAS on H2O2-treated H9c2 cells. Our results suggest that GAS may protect H9c2 cardiomycytes against oxidative injury via increasing the nuclear translocation of Nrf2, regulating mitochondrial dynamics, and maintaining the structure and functions of mitochondria.

5.
J Am Chem Soc ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32207969

RESUMO

Understanding the reaction mechanism for the catalytic process is essential to the rational design and synthesis of highly efficient catalysts. MoS2 has been reported to be an efficient catalyst toward the electrochemical hydrogen evolution reaction (HER), but it still lacks direct experimental evidence to reveal the mechanism for MoS2-catalyzed electrochemical HER process at the atomic level. In this work, we develop a wet-chemical synthetic method to prepare the single-layer MoS2-coated polyhedral Ag core-shell heterostructure (Ag@MoS2) with tunable sizes as efficient catalysts for the electrochemical HER. The Ag@MoS2 core-shell heterostructures are used as ideal platforms for the real-time surface-enhanced Raman spectroscopy (SERS) study owing to the strong electromagnetic field generated in the plasmonic Ag core. The in situ SERS results provide solid Raman spectroscopic evidence proving the S-H bonding formation on the MoS2 surface during the HER process, suggesting that the S atom of MoS2 is the catalytic active site for the electrochemical HER. It paves the way on the design and synthesis of heterostructures for exploring their catalytic mechanism at atomic level based on the in situ SERS measurement.

6.
Eur J Med Chem ; 191: 112115, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105982

RESUMO

Adenylate cyclases (ACs), play a critical role in the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP). Studies have indicated that adenylyl cyclase type 2 (AC2) is potential drug target for many diseases, however, up to now, there is no AC2-selective agonist reported. In this research, docking-based virtual screening with the combination of cell-based biological assays have been performed for discovering novel potent and selective AC2 agonists. Virtual screening disclosed a novel hit compound 8 as an AC2 agonist with EC50 value of 8.10 µM on recombinant human hAC2 + HEK293 cells. The SAR (structure activity relationship) based on the derivatives of compound 8 was further explored on recombinant AC2 cells and compound 73 was found to be the most active agonist with the EC50 of 90 nM, which is 160-fold more potent than the reported agonist Forskolin and could selectively activate AC2 to inhibit the expression of Interleukin-6. The discovery of a new class of AC2-selective agonists would provide a novel chemical probe to study the physiological function of AC2.

7.
Nanoscale ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32091518

RESUMO

In situ monitoring of electrocatalytic processes at solid-liquid interfaces is essential for the fundamental understanding of reaction mechanisms, yet quite challenging. Herein, Pt-on-Au nanocatalysts with a Au-core Pt-satellite superstructure have been fabricated. In such Pt-on-Au nanocatalysts, the Au cores can greatly amplify the Raman signals of the species adsorbed on Pt, allowing the in situ surface-enhanced Raman spectroscopy (SERS) study of the electrocatalytic reactions on Pt. Using the combination of an electrochemical method and in situ SERS, size effects of Pt on the catalytic performance of the core-satellite nanocomposites towards CO and methanol electrooxidation are revealed. It is found that such Pt-on-Au nanocomposites show improved activity and long-term stability for the electrooxidation of CO and methanol with a decrease in the Pt size. This work demonstrates an effective strategy to achieve the in situ monitoring of electrocatalytic processes and to simultaneously boost their catalytic performance towards electrooxidation.

8.
Virology ; 541: 150-159, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32056713

RESUMO

Hepatitis E virus (HEV) is the main pathogen of hepatitis E infections with multiple extrahepatic replication sites. The presence of HEV RNA in the semen of infertile males suggests HEV replicates in the male genital tract. However, the mechanism is largely remained elusive. A BALB/c-based animal model was used to evaluate the effects of HEV infection on the testicular damage. HEV RNA was detected in feces, blood and livers from 7 to 28 days post-inoculation (dpi), while was positive in male genital tract from 7 to 70 dpi. Positive signals of HEV antigens were observed in testes, epididymides and seminal vesicles (SVs). Impaired sperm quality, destroyed the blood-testis barrier (BTB) and drastically decreased spermatogonia suggested that HEV infection causes testicular damage. Antiviral immune response was barely found in the testes. Results demonstrated that HEV replicates in male genital tract, causes testicular damage, and consequently results in flawed fertility.

9.
Scand J Gastroenterol ; 55(2): 202-208, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32008420

RESUMO

Aim: This study aims to establish and validate an effective nomogram to predict cancer-specific survival (CSS) in elderly patients with stages I-III colon cancer.Methods: The data of elderly colon cancer patients with stages I-III were enrolled from the Surveillance, Epidemiology, and End Results database (SEER) between 2010 and 2015. The eligible patients were randomly divided into a training cohort and a validation cohort (ratio 1:1). All predictors of cancer-specific survival were determined by Cox regression. The concordance index (C-index) and calibration curves were used for validation of nomograms. Decision curve analysis (DCA) was performed to evaluate the clinical net benefit of the nomogram.Results: Cox hazard analysis in the training cohort indicated that grade, tumor stage, node stage, colectomy, and CEA were independent predictors of CSS. Nomogram was constructed based on these predictors. The C-index of nomograms for CSS was 0.728 (95%CI: 0.7133-0.7427), and were superior to that of AJCC TNM Stage (C-index: 0.625, 95%CI: 0.6093-0.6406). The calibration curves showed satisfactory consistency between actual observation and nomogram-predicted CSS probabilities. The validation cohort demonstrated similar results. The DCA showed high net benefit of nomogram in a clinical context. The population was divided into three groups based on the scores of the nomogram, and the survival analysis showed that this prognostic stratification was statistically significant (p < 0.01).Conclusion: The nomograms showed significant accuracy in predicting 1-, 3-, and 5-year CSS in elderly patients with stages I-III colon cancer and may be helpful inpatient counseling clinical decision guidance.

10.
J Chem Phys ; 152(1): 014702, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31914769

RESUMO

Light-matter interactions in nanostructures have shown great potential in physics, chemistry, surface science, materials science, and nanophotonics. Herein, for the first time, the feasibility of strong coupling between plasmon-induced magnetic resonant and propagating surface plasmonic modes at visible light frequencies is theoretically demonstrated. Taking advantage of the strong coupling between these modes allowed for a narrow-linewidth hybrid mode with a huge electromagnetic field enhancement to be acquired. This work can serve as a promising guide for designing a platform with strong coupling based on magnetic resonance at visible and even ultraviolet light frequencies and also offers an avenue for further exploration of strong light-matter interactions at the nanoscale.

11.
Bioorg Med Chem Lett ; 30(2): 126823, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31776060

RESUMO

Adenylyl cyclases (ACs), which are responsible for catalyzing the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP), play a critical role in cell signal transduction. In this study, a combined approach involving docking-based virtual screening, with the combination of homology modeling followed by an in-vitro, and cell-based biological assay have been performed for discovering a class of novel potent and selective isoform adenylyl cyclase type 8 (AC8) agonist. The computer-aided virtual screening was used to identify fourteen virtual cluster compounds as potential hits which were further subjected to rigorous bioassays. A novel hit compound VHC-7 (ethyl 3-(2,4-dichlorobenzyl)-2-oxoindoline-3-carboxylate) was identified as a highly potent selective AC8 agonist with EC50 value of 0.1052 ± 0.038 µM. Remarkably, the molecule herein reported can be explored further to discover greater number of hit compounds with better pharmacokinetic properties as well as to serve as a promising novel hit agonist of AC8 for the treatment of various central nervous system disorders and its associated diseases.

12.
Sensors (Basel) ; 19(23)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31816904

RESUMO

In substations, a localization system based on a wireless sensor network (WSN) is a challenge, because the propagation of the measured signal could be blocked by various devices. In other words, non-line-of-sight (NLOS) propagation, where the signal propagation path is occluded, will affect measurement accuracy. A novel localization method based on a two-step weighted least squares and a probability distribution function is proposed to reduce the influence of NLOS error on the localization result. In this method, the initial multi-group localization result is obtained by the two-step weight weighted least-squares method, and the probability distribution function of the target is constructed by using the initial localization results, which can effectively reduce the influence of the NLOS error on the localization result. The simulation and test results show that the proposed method can keep the coordinate error within 30 cm in the substation. Compared with the localization result of two-step weighted least-squares (TSWLS) method, the average localization error is reduced by more than 1 m. Compared with the other two similar algorithms, the localization accuracy is improved by more than 50%. The tested results show that the localization performance of the method is robustness in the NLOS environment of the substation. While ensuring stability, the proposed algorithm is less efficient than some existing ones. However, under the calculation conditions of ordinary computers, the average single-point calculation time is less than 0.1 s, which can meet the needs of applications in substations.

13.
Pharmacology ; : 1-11, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752010

RESUMO

Vascular dementia (VaD) is the second most common type of dementia and has become a major public health challenge as the global population ages. VaD is caused by cerebrovascular disease, and most patients with VaD have been reported to also have Alzheimer's pathologies, which is the formation of neurofibrillary tangles and amyloid plaques that are mainly composed of hyperphosphorylated Tau and amyloid ß (Aß) respectively. However, the mechanisms of VaD are not completely understood, and very few drugs are available to treat this condition. Gastrodin (Gas) is the main bioactive component of the traditional Chinese herbal plant named Tian Ma (Gastrodia elata), and it has been used to treat neurasthenia in the clinical practice of Chinese Medicine for many years. Here, we hypothesize that Gas alleviates VaD in a rat model of permanent bilateral common carotid artery occlusion (2-VO)-induced VaD. Based on the results of the Morris water maze test and attention set shift test, either 22.5 or 90 mg/kg/day Gas improved the executive dysfunction and memory impairment of 2-VO rats following an intragastric administration for 4 weeks. Both 22.5 and 90 mg/kg/day Gas reduced Aß1-40 and Aß1-42 plaques in plasma and hippocampus of 2-VO rats. Mechanistically, in 2-VO rats, treatment with Gas (90 mg/kg/day) suppressed Aß plaque deposition by decreasing the hippocampus levels of phosphorylated Tau. Thus, Gas ameliorated the cognitive deficits of 2-VO rats by inhibiting the abnormal phosphorylation of Aß and Tau.

14.
Urolithiasis ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511921

RESUMO

To perform a systematic review and meta-analysis for the evaluation of 22 drug interventions in the management of ureteral stones, MEDLINE, Web of Science, EMBASE, and Cochrane central databases were searched to identify RCTs focusing on the evaluation of the efficacy of multiple drug interventions in medical expulsive therapy (MET) for ureteral stones, with no restrictions on year or language. Study quality assessment and data extraction were performed by independent reviewers. Major outcome measures were the stone expulsion rate, stone expulsion time, and pain episodes during treatment. A total of 78 RCTs with 14,922 participants were included in the present study. The final comparative results show that naftopidil plus corticosteroids was associated with higher stone expulsion rates than other drug interventions. Silodosin plus tadalafil had the highest probability of reducing stone expulsion time. Tamsulosin plus tadalafil performed better than all the other drug interventions in reducing pain episodes during treatment. However, in terms of all the outcome measures, the ranking plot results demonstrate that silodosin plus tadalafil, in addition to tamsulosin plus tadalafil and corticosteroids, was the best drug intervention as medical expulsive therapy in the management of ureteral stones. In ureteral stones ≤ 10 mm, all active drug interventions were more efficacious than the control; however, not all active drug interventions had an efficacy superior to the placebo. Silodosin plus tadalafil, tamsulosin plus tadalafil and corticosteroids, tamsulosin plus tadalafil, and naftopidil plus corticosteroids were the most effective drug interventions. Considering the choice of treatment, these results should serve as evidence-based practice and be considered by physicians, patients, and guideline developers. However, with respect to the limitations of the present study, further high-quality studies are needed for more in-depth evaluation of both the efficacy and safety of these drug interventions.

15.
Polymers (Basel) ; 11(8)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382528

RESUMO

Numerous jets can be generated simultaneously on a nozzle by needleless melt electrospinning technology which has the advantages of solvent-free residues and environmental friendliness; and potential industrial application prospects. In this paper, the linear annular tip nozzle was taken as the research object, and the high-speed image acquisition of the jets generation and distribution process of annular tip nozzle was carried out and compared with that of straight-line tip nozzle. The results showed that the repulsive force between the jets caused a slight adjustment in the position of the jets on the free surface, the force between the jets on the annular closed curve canceled each other and eventually reached the equilibrium state, making the position of the jets stable and the distance between the jets the same, and the distance between the jets was related to the intensity of the induced electric field at the tip of the nozzle. Relevant conclusions can provide scientific and practical guidance for the design of needleless electrospinning nozzles on free surface in order to achieve uniform and efficient preparation of ultrafine fibers.

16.
Medicine (Baltimore) ; 98(33): e16899, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415434

RESUMO

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive multisystem disorder characterized by oculocutaneous albinism (OCA) and bleeding diathesis, although it displays both genetic and phenotypic heterogeneity. Several genetic subtypes of HPS have been identified in human; however, the characterizations of HPS type 4 (HPS-4) genotype and phenotype remain unclear. This study was aimed to identify gene mutation responsible for HPS-4 with pulmonary fibrosis (PF).Two Chinese siblings in their 50 s afflicted with OCA and progressive dyspnea were recruited and underwent clinical and genetic examinations. In both patients, chest high-resolution computerized tomography showed severe interstitial PF in bilateral lung fields, and the pulmonary function test indicated restrictive lung disease. A novel homozygous frameshift mutation (NM_022081: c.630dupC; p.A211fs) in the HPS4 gene was identified by whole-exome sequencing analysis followed by Sanger DNA sequencing, and it segregated with the phenotypes. The c.630dupC mutation was not found in unaffected healthy controls. The patients were considered as HPS-4 with interstitial PF and eventually died of respiratory failure.This is the first report on the genotype and clinical phenotype of HPS-4 in China. Our results demonstrate the association between a novel frameshift mutation in HPS4 and severe PF with poor prognosis in HPS is presented.


Assuntos
Mutação da Fase de Leitura , Síndrome de Hermanski-Pudlak/genética , Fibrose Pulmonar Idiopática/genética , Proteínas/genética , Adulto , China , Testes Genéticos , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Irmãos
17.
Nanoscale ; 11(35): 16428-16436, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31441473

RESUMO

High-quality and unique surface plasmon resonance (SPR) with a narrow linewidth and controllable resonance energy plays a key role in wide applications including ultrahigh-resolution spectroscopy, on-chip sensing, optical modulation, and solar cell technology. In this work, the response of surface plasmon polariton (SPP) modes in Au nanohole arrays has been effectively tuned by properly adjusting the sample orientation without changing the geometrical parameters, and a very narrow linewidth down to 8 nm is achieved via the strong interference of two (0, -1) and (-1, 0) SPP modes in the Γ-M direction under transverse magnetic polarization. These results have been validated excellently by finite-element-method numerical simulations. More importantly, we have quantitatively investigated the contribution of conduction-band electron distribution to the SPP intensity of the array within a 20 ps timescale with ultrahigh sensitivity by utilizing home-built femtosecond transient absorption spectroscopy, and observed the minimum SPP intensity at ∼700 fs following excitation with a 0.2 µJ pulse. This study may help enhance the understanding toward the intrinsic micromechanism of SPR, thus offering opportunities for potential applications in strong coupling and new-style optical wave manipulations.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31428169

RESUMO

Background: Asthma is a chronic disease that seriously harms the health of patients. Oxidative stress is involved in asthma. As an oxidative stress-inducible protein, sestrin2 is elevated in oxidative stress-related diseases. We aimed to explore whether sestrin2 was involved in asthma. Methods: Seventy-six subjects (44 in the asthma group, 32 in the control group) were recruited in this study. Plasma sestrin2 levels, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % predicted and FEV1/FVC ratio were measured in controls and in asthmatics both during an exacerbation and when controlled after the exacerbation. Results: The asthma group had a significant higher sestrin2 level than the control group (asthmatics during exacerbation, 1.75 ± 0.53 ng/mL vs. 1.32 ± 0.48 ng/mL, p < 0.001; asthmatics when controlled after the exacerbation, 1.56 ± 0.46 ng/mL vs. 1.32 ± 0.48 ng/mL, p = 0.021, respectively). In addition, sestrin2 was negatively correlated with FEV1% predicted and FEV1/FVC ratio in asthmatics during exacerbation (r = - 0.393, p = 0.008; r = - 0.379, p = 0.011; respectively). Moreover, negative correlations between sestrin2 and FEV1% predicted and FEV1/FVC ratio also existed in asthmatics when controlled after the exacerbation (r = - 0.543, p < 0.001; r = - 0.433, p = 0.003 respectively). More importantly, multiple linear regression analysis demonstrated that FEV1% predicted was independently associated with sestrin2 in asthmatics both during exacerbation and when controlled after the exacerbation. Conclusions: Sestrin2 is involved in asthma. Sestrin2 levels increase in asthmatics both during exacerbation and when controlled after the exacerbation. In addition, sestrin2 is independently associated with FEV1% predicted.

19.
J Am Chem Soc ; 141(31): 12192-12196, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31328527

RESUMO

Investigating the chemical nature of the adsorbed intermediate species on well-defined Cu single crystal substrates is crucial in understanding many electrocatalytic reactions. Herein, we systematically study the early stages of electrochemical oxidation of Cu(111) and polycrystalline Cu surfaces in different pH electrolytes using in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). On Cu(111), for the first time, we identified surface OH species which convert to chemisorbed "O" before forming Cu2O in alkaline (0.01 M KOH) and neutral (0.1 M Na2SO4) electrolytes; while at the Cu(poly) surface, we only detected the presence of surface hydroxide. Whereas, in a strongly acidic solution (0.1 M H2SO4), sulfate replaces the hydroxyl/oxy species. This results improves the understanding of the reaction mechanisms of various electrocatalytic reactions.

20.
Mol Vis ; 25: 359-372, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354229

RESUMO

Purpose: Uveitis is a serious inflammatory disease of the uvea, frequently leading to visual impairment and irreversible blindness. Here, we investigated the anti-inflammatory effect of minocycline on rat endotoxin-induced uveitis (EIU) and retinal inflammation. Methods: For in vivo studies, the rat EIU model was induced with intravitreal injection of lipopolysaccharide (LPS). Minocycline was administered intraperitoneally 2 h before and after the LPS injection. The severity of the ocular inflammation was evaluated with slit-lamp photography, aqueous humor cell counting, protein quantitative determination, and histological analysis. Retinal microglia were labeled with a fluorescent dye 4Di-10ASP. Microglial activity and inflammatory cytokine production were analyzed with immunofluorescence and real-time PCR. For the in vitro studies, BV-2 microglia cells were stimulated with LPS or cotreated with minocycline for 6 h. Toll-like receptor (TLR) 2/4 levels were determined with real-time PCR and western blotting. Results: The LPS-challenged eyes displayed severe inflammation in all ocular structures, including a large number of anterior chamber cells, fibrin exudation, hypopyon, and infiltrated inflammatory cells in the vitreous and retina. Immunostaining of the retinal whole-mounts also revealed numerous retinal microglia were activated promptly, and then more and more peripheral leukocytes were recruited and infiltrated in the LPS-injected retinas. Additionally, the production of tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL-2), interleukin-1 beta (IL-1ß), and IL-6 was dramatically increased. However, minocycline treatment strongly inhibited microglia activation, decreased inflammatory cytokine production, prevented peripheral inflammatory cell recruitment, and significantly attenuated ocular inflammation. Finally, we demonstrated the mechanism of the microglia inactivation effect of minocycline is via suppression of TLR4 signaling. Conclusions: This study indicates minocycline is far beyond an antibiotic. It not only attenuates rat EIU but also inhibits retinal inflammation through inactivating microglia, inhibiting inflammatory cell recruitment and inflammatory cytokine production.

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