Abstract Previous studies have demonstrated that pioglitazone (Piog), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. Piog has also been ...shown to exert anti-inflammatory effects by attenuation of nuclear factor-κB (NF-κB) activation after myocardial ischemia/reperfusion injury. Because NF-κB is known to play a major role in the pathophysiology of brain ischemia, the present study was undertaken to elucidate whether pioglitazone attenuates ischemic neuronal damage through PPARγ-mediated suppression of NF-κB apoptotic signaling pathway. Permanent middle cerebral artery occlusion (pMCAO) model was induced by using an intraluminal filament technique in rats. Piog was administrated i.p. twice (24 h before and at the time of ischemia insult) or once (10 min after ischemia). The neuroprotection of Piog was analyzed by assessing neurological deficits, infarction volume and morphological changes. The inhibition of NF-κB signaling pathway by Piog was evaluated by detecting the nuclear translocation of NF-κB p65 with immunohistochemistry and its target gene p53 by real-time PCR, and the expression of phospholated NF-κB p65 (p- NF-κB p65) in primary cultured neurons and the protein levels of IκBα and p-ERK in the ischemic cortex or striatum with Western blotting analysis. The contribution of a PPARγ mechanism to Piog's inhibitory effects on NF-κB and neuroprotection was evaluated by pretreatment with the PPARγ irreversible antagonist GW9662. In vitro ischemia in cultured primary neurons was induced by the oxygen-glucose deprivation (OGD) and the protective effect of Piog on cultured neurons was measured by lactate dehydrogenase (LDH) assay. Piog (0.5, 1, 2 mg/kg) reduced infarction volume, and improved morphological changes and motor deficits. Piog markedly up-regulated the protein levels of IκBα or p-ERK 6 h or 12 h after ischemia. Piog reduced the nuclear translocation of NF-κB p65 in the ischemic cortical cells and repressed the expression of p53 12 h after ischemia. Pre-treatment with GW9662 blocked Piog-elicited reduction in infarction volume, the increase in protein levels of IκBα and p-ERK, the reduction in the nuclear translocation of NF-κB subunit p65 and the repression of p53 mRNA expression. In addition, Piog attenuated the OGD-induced neuronal damage and inhibited the OGD-induced increases in p- NF-κB p65 in neurons. The present findings suggest that Piog's neuroprotection appears to be associated with PPARγ-mediated suppression of NF-κB signaling pathway.
The blades that play a key role to collect wind energy are the most critical components of a wind turbine system. Meanwhile, they are also the parts most susceptible to damage. Structural health ...monitoring (SHM) system has been proposed to continuously monitor the wind turbine. Nevertheless, no system has yet been developed to a stage compatible with the requirements of commercial wind turbines. Therefore, full-scale structural testing is the main means available so far for validating the comprehensive performance of wind turbine blades. It is now normally used as part of a blade certification process. It also allows an insight into the failure mechanisms of wind turbine blades, which are essential to the success of SHM. Furthermore, it provides a unique opportunity to exercise SHM and non-destructive testing (NDT) techniques. Recognizing these practical significances, this paper therefore aims to carry out an extensive review of full-scale structural testing of wind turbine blades, including static testing and fatigue testing. In particular, the current status in China is presented. One focus of this review is on the failure mechanisms of wind turbine blades, which are vital for optimizing the design of themselves as well as the design of their SHM system. Another focus is on the strengths and weaknesses of various SHM and NDT techniques, which are useful for evaluating their applicability on wind turbine blades. In addition, recent advances in photogrammetry and digital image correlation have allowed new opportunities for blade monitoring. These techniques are currently being explored on a few wind turbine blade applications and can provide a wealth of additional information that was previously unobtainable. These works are also summarized in this paper in order to discover the pros and cons of these techniques.
From Nitrate to Nitric Oxide Qu, X.M.; Wu, Z.F.; Pang, B.X. ...
Journal of dental research,
12/2016, Volume:
95, Issue:
13
Journal Article
Peer reviewed
The salivary glands and oral bacteria play an essential role in the conversion process from nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO) in the human body. NO is, at present, recognized as ...a multifarious messenger molecule with important vascular and metabolic functions. Besides the endogenous L-arginine pathway, which is catalyzed by complex NO synthases, nitrate in food contributes to the main extrinsic generation of NO through a series of sequential steps (NO3--NO2--NO pathway). Up to 25% of nitrate in circulation is actively taken up by the salivary glands, and as a result, its concentration in saliva can increase 10- to 20-fold. However, the mechanism has not been clearly illustrated until recently, when sialin was identified as an electrogenic 2NO3-/H+ transporter in the plasma membrane of salivary acinar cells. Subsequently, the oral bacterial species located at the posterior part of the tongue reduce nitrate to nitrite, as catalyzed by nitrate reductase enzymes. These bacteria use nitrate and nitrite as final electron acceptors in their respiration and meanwhile help the host to convert nitrate to NO as the first step. This review describes the role of salivary glands and oral bacteria in the metabolism of nitrate and in the maintenance of NO homeostasis. The potential therapeutic applications of oral inorganic nitrate and nitrite are also discussed.
Bone defect repair is challenging in orthopaedic clinics. For treatment of large bone defects, bone grafting remains the method of choice for the majority of surgeons, as it fills spaces and provides ...support to enhance biological bone repair. As therapeutic agents are desirable for enhancing bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier, incorporating a phytomolecule icaritin (ICT), i.e., a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high-dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of these bioactive scaffolds with slow release of osteogenic ICT, the authors established a 12mm ulnar bone defect model in rabbits. X-ray and high-resolution peripheral quantitative computed tomography results at weeks 2, 4 and 8 post-surgery showed more newly formed bone within bone defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized bone in PLGA/TCP/ICT groups, especially in the PLGA/TCP/MICT group, with correspondingly more new vessel ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with the proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications.
Background
Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our ...objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients.
Methods
The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro.
Results
The patients were well‐controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL‐5, IL‐13 and IL‐9 in response to IL‐25, IL‐33 plus IL‐2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL‐5, IL‐13 and IL‐9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment.
Conclusion
The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK‐STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.
High circulating ILC2s were found in asthma and asthma with allergic rhinitis patients, and significantly decreased after treatment of glucocorticoid. High levels of IL‐5, IL‐13 and IL‐9 in response to epithelium‐derived cytokines were mostly produced by the increased ILC2s from asthma patients. Glucocorticoid treatment is able to reverse the high levels of IL‐5 and IL‐13 produced by ILC2s via STAT3, STAT5 and STAT6 signalling pathways.
Objective
The purposes of this study were to explore both the prognostic value of pathologic grade and the relationships between differentiation and clinicopathological characteristics in oral ...squamous cell carcinoma.
Methods
This retrospective cohort study included the records of 2036 patients with oral squamous cell carcinoma who were surgically treated from June 1999 to December 2011. Chi‐square test, Kaplan–Meier analysis, and Cox proportional hazards regression model were performed for statistical analysis.
Results
Many clinicopathological characteristics were associated with pathologic grade. Kaplan–Meier analysis showed that well‐differentiated tumors had a better prognosis than the other two grades. Cox regression model showed that differentiation was an independent risk factor for prognosis in patients with early stage, but not with advanced stage. The predictive abilities of pathologic grade, T stage, N status, and lymph node ratio were similar, but the presence of extracapsular spread and perineural invasion were stronger prognostic factors than pathologic differentiation.
Conclusions
Pathologic grade was found to be an independent risk factor for early‐stage oral squamous cell carcinoma, but not for advanced stage. Many important clinicopathological characteristics were associated with histological classification; however, its prognostic value was limited.
Using a low background data sample of 9.7×10^{5} J/ψ→γη^{'}, η^{'}→γπ^{+}π^{-} events, which are 2 orders of magnitude larger than those from the previous experiments, recorded with the BESIII ...detector at BEPCII, the decay dynamics of η^{'}→γπ^{+}π^{-} are studied with both model-dependent and model-independent approaches. The contributions of ω and the ρ(770)-ω interference are observed for the first time in the decays η^{'}→γπ^{+}π^{-} in both approaches. Additionally, a contribution from the box anomaly or the ρ(1450) resonance is required in the model-dependent approach, while the process specific part of the decay amplitude is determined in the model-independent approach.
The cross sections of e^{+}e^{-}→π^{+}π^{-}h_{c} at center-of-mass energies from 3.896 to 4.600 GeV are measured using data samples collected with the BESIII detector operating at the Beijing ...Electron Positron Collider. The cross sections are found to be of the same order of magnitude as those of e^{+}e^{-}→π^{+}π^{-}J/ψ and e^{+}e^{-}→π^{+}π^{-}ψ(2S), but the line shape is inconsistent with the Y states observed in the latter two modes. Two structures are observed in the e^{+}e^{-}→π^{+}π^{-}h_{c} cross sections around 4.22 and 4.39 GeV/c^{2}, which we call Y(4220) and Y(4390), respectively. A fit with a coherent sum of two Breit-Wigner functions results in a mass of (4218.4_{-4.5}^{+5.5}±0.9) MeV/c^{2} and a width of (66.0_{-8.3}^{+12.3}±0.4) MeV for the Y(4220), and a mass of (4391.5_{-6.8}^{+6.3}±1.0) MeV/c^{2} and a width of (139.5_{-20.6}^{+16.2}±0.6) MeV for the Y(4390), where the first uncertainties are statistical and the second ones systematic. The statistical significance of Y(4220) and Y(4390) is 10σ over one structure assumption.
•8% Ag/ZnO has a positive displacement of 590 mV compared with floral ZnO when the current density is 2.5 mA/cm2 for ORR.•Citric acid is effective in controlling the morphology of zinc ...oxide.•Flower-like zinc oxide with good dispersion was successfully synthesized.
ZnO is one of the third generation semiconductors and has excellent photoelectric properties. In the paper, floral ZnO and Ag/ZnO were synthesized by hydrothermal method. The effect of sample morphology and silver doping was studied on catalytic performance. X-ray diffraction (XRD) results show that the synthesized ZnO and Ag/ZnO are of pure and high crystallinity. 8% Ag/ZnO has the best catalytic activity for oxygen reduction reaction (ORR) and has a positive displacement of 590 mV compared with floral ZnO when the current density is 2.5 mA/cm2.
The effects of C, Zr and Y/Ce on the microstructures and stress rupture properties of a directionally solidified Ni-based superalloys were investigated. The morphology of MC carbides does not change ...in as-cast alloys, as the C content is increased or the Zr is added. However, the Y/Ce additions promote the transformation of MC carbide morphology from blocky to script-like type. Compared with that in as-cast alloys, there is no obvious change in the morphologies of MC carbide or chemical compositions after heat treatment. The increasing of C content and the addition of Zr or Y/Ce significantly decreases and increases the amount of the γ/γ′ eutectic, respectively. After a solid solution treatment and subsequently a two-stage aging treatment, the γ′ phase is characteristic with two kinds of shapes and sizes, and the volume fraction of cuboidal γ′ phase is much larger than that of spherical γ′ phases. More MC carbide and residual eutectic result from the decreasing of cuboidal γ′ phase volume fraction. The decrease in volume fraction of cuboidal γ′ phase is principally responsible for the reduction of the stress rupture property. In addition, script-like carbide and residual eutectic remaining after heat treatment play the secondary role in the degradation of the stress rupture properties. The less regularly arranged cuboidal γ′ phase can damage the stress rupture life to some extent. The spherical γ′ phase re-dissolves into γ′ matrix widening the spacing between large cuboidal γ′ phase, and the addition of Zr inhibits grain boundary sliding and cracking; these two facts are beneficial to the rupture elongation.
PDF
