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Myocardial ischemia/reperfusion (I/R) injury is recognized as the leading cause of death worldwide. However, the molecular mechanisms involved in this process are still not fully understood. We previously reported that the combined action of Notch1 and Keap1-NRF2 signaling pathway can significantly increase the activity of cardiomyocytes, inhibit the apoptosis of cardiomyocytes, reduce the formation of reactive oxygen species, and improve the antioxidant activity in neonate rat myocardial cells. However, the regulatory mechanism of Notch1 signaling pathway on the NRF2 signaling pathway and its actual role on I/R injury are still unclear. Herein, we found that Keap-NRF2 signaling is activated by Notch1 in RBP-Jκ dependent manner, thus protects the heart against I/R injury via inhibiting the mitochondrial ROS generation and improves the mitochondrial bioenergetics in vitro and in vivo. These results suggest that Keap-NRF2 signaling might become a promising therapeutic strategy for treating myocardial I/R injury.

Mounting evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and tumor progression. SNHG12 has been identified in multiple types of malignant tumors. However, the role of SNHG12 in human non‐small cell lung cancer (NSCLC) is poorly characterized, and the relevant underlying mechanism remains unclear. The expression levels of SNHG12, miR‐101‐3p, and CUL4B in collected human NSCLC tumor tissues and NSCLC cell lines were tested via qRT‐PCR. Then, NSCLC cellular proliferation, migration and invasion were determined, followed by MTT, scratch and Transwell assays. Dual‐luciferase reporter assays and RNA pulldown assays were adopted to explore the target site. Moreover, western blotting was performed to detect the relevant protein expression concerning the CUL4B/PI3K/AKT pathway. This study clarified that SNHG12 knockdown significantly reduced proliferation, migration, invasion and EMT of NSCLC cells. Our data indicated that SNHG12 targeted and negatively regulated miR‐101‐3p, and this depletion reversed the inhibitory effect of si‐SNHG12 on NSCLC cells. Furthermore, CUL4B was confirmed as a functional target of miR‐101‐3p, and its knockdown resulted in a strong alleviation of the NSLCL cell phenotype, which was enhanced by the silencing of miR‐101‐3p. Mechanistically, we found that SNHG12 regulated miR‐101‐3p to modulate the PI3K/AKT pathway mediated by CUL4B.These observations suggested that lncRNA SNHG12‐mediated miR‐101‐3p downregulation regulated the malignant phenotype of NSCLC cells by targeting CUL4B through the PI3K/AKT pathway, which may present a path to novel therapeutic strategies for NSCLC therapy.

Li-Jun Wang,1,* Bai-Quan Qiu,1,* Ming-Ming Yuan,2,* Hua-Xi Zou,1 Cheng-Wu Gong,1 Huang Huang,2 Song-Qing Lai,3 Ji-Chun Liu1 1Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Institute of Cardiovascular Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ji-Chun Liu, Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Tel +86 13907913502, Email liujichun999@yeah.net Song-Qing Lai, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Tel +86 13699562160, Email ndyfy03743@ncu.edu.cnPurpose: Dilated cardiomyopathy (DCM) is a type of cardiomyopathy that can easily cause heart failure and has a high mortality rate. Therefore, there is an urgent need to study the underlying mechanism of action of dilated cardiomyopathy. In the present study, we aimed to explore potential miRNA–mRNA pairs and drugs related to DCM.Methods: The Microarray data were collected from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis differentially expressed miRNAs and mRNAs in each microarray were obtained. The target genes of miRNAs were obtained from the miRWalk 2.0 database, and the intersection of these two gene sets (miRNA target genes and differentially expressed mRNAs in the microarray) was obtained. Pathway and Gene Ontology (GO) enrichment analyses were performed in the KOBAS database. Cytoscape software was used to construct the miRNA–mRNA network, and the final hub genes were obtained. Furthermore, we predicted several candidate drugs related to hub genes using DSigDB database. To confirm the abnormal expression of hub genes, qRT-PCR was performed.Results: In total, eight differentially expressed miRNAs and 92 differentially expressed mRNAs were identified. In addition, 47 differentially expressed miRNA target genes were identified. According to the analysis results of the miRNA-mRNA network, we identified hsa-miR-551b-3p, hsa-miR-770-5p, hsa-miR-363-3p, PIK3R1, DDIT4, and CXCR4 as hub genes in DCM. Several candidate drugs, which are related to the hug genes, were identified.Conclusion: In conclusion, in our study, we identified several hub genes that may be involved in the pathogenesis of DCM. Several drugs related to these hub genes may be used as clinical therapeutic candidates.Keywords: dilated cardiomyopathy, miRNA, mRNA, public database, drugs

BackgroundMyocardial ischemia/reperfusion injury is associated with adverse cardiovascular outcomes after acute myocardial infarction. However, the molecular mechanism of ischemia/reperfusion injury remains unclear. Mitochondria dysfunction have become important participants and regulators of myocardial ischemia-reperfusion injury. However, the molecular mechanisms involved in this process are still not fully understood. We previously reported that Notch1 can reduce mitochondrial lysis, reduce myocardial infarct size and inhibit ventricular remodeling. Herein, we tried to explore the downstream target of Notch1 on the mitochondrial regulation. MethodsIschemic/reperfusion injury rat model and hypoxia/reoxygenation cell model were constructed in this study. The expression of PTEN was detected by real-time PCR, Western Blot and immunofluorescence staining. The cell viability was analyzed by CCK-8. The apoptosis level was detected by TUNEL assay. The mitochondrial fission/fusion were analyzed by Mito-Tracker Green staining. Measurement of cardiac troponin I (cTnI), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and CK levels creatine kinase-MB (CK) were detected by ELISA Kits.ResultsWe found that PETN-Pink1-Parkin signaling is inhibited by Notch1 I/R injured neonatal cardiomyocytes and hearts, thus via inhibiting the mitochondrial dysfunction and fragmentation. With the recure of PTEN or Pink1, the protective effect of Notch1 was largely diminished. ConclusionThese results suggest that N1ICD protective against ischemic reperfusion injury via suppressing PTEN-Pink1 mediated mitochondrial dysfunction and fragmentation.

Aortic dissection (AD) is a catastrophic cardiovascular emergency with a poor prognosis, and little preceding symptoms. Abnormal lipid metabolism is closely related to the pathogenesis of AD. However, comprehensive lipid alterations related to AD pathogenesis remain unclear. Moreover, there is an urgent need for new or better biomarkers for improved risk assessment and surveillance of AD. Therefore, an untargeted lipidomic approach based on ultra-high-performance liquid chromatograph-mass spectrometry was employed to unveil plasma lipidomic alterations and potential biomarkers for AD patients in this study. We found that 278 of 439 identified lipid species were significantly altered in AD patients (n = 35) compared to normal controls (n = 32). Notably, most lipid species, including fatty acids, acylcarnitines, cholesteryl ester, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatidylinositols, diacylglycerols, and triacylglycerols with total acyl chain carbon number ≥54 and/or total double bond number ≥4 were decreased, whereas phosphatidylethanolamines and triacylglycerols with total double bond number

Currently, the role of Notch signaling during myocardial infarction (MI) remains controversy. In this study we used in vitro and in vivo approaches to investigate the role of Notch signaling in MI. Using cultured human umbilical vein endothelial cells exposed to hypoxia/reoxygenation (H/R), we demonstrated that H/R inhibited the proliferation, VEGF secretion, and tube formation of HUVECs, and these effects were correlated with the inhibition of Notch signaling. Furthermore, these effects were antagonized by overexpression of NICD but aggravated by knockdown of NICD. In addition, in MI model rats we found that heart dysfunction and angiogenesis in model rats was partly improved by NICD overexpression but was aggravated by knockdown of NICD. In conclusion, these data demonstrate that Notch signaling is downregulated in H/R injury in the hearts. Artificial activation of Notch signaling could promote myocardial survival and angiogenesis and improve cardiac function following H/R injury.

Calcific aortic valve disease (CAVD) currently lacks a highly effective in vitro model. The presence of high concentrations of serum inorganic phosphate in patients with end-stage renal disease leads to calcification of vascular and aortic valves. Therefore, we applied inorganic phosphate to induce the osteogenic differentiation of valvular interstitial cells (VICs) and mimic its in vivo pathophysiological effects. Calcification and inflammatory response assays determined that inorganic phosphate-osteogenic induction medium (IP-OIM) was more efficient than classic osteogenic induction medium (OIM) containing organic glycerophosphate. Levels of BMP-2, RhoA, and ROCK-1 were significantly increased in IP-OIM cells. Knockdown efficiency of BMP-2- and RhoA-siRNA in VICs was evaluated, and expression of RhoA and its downstream target ROCK-1 was decreased after BMP-2-siRNA transfection. Moreover, ROCK-1 was significantly downregulated after RhoA knockdown, whereas expression of BMP-2 was unchanged. Interference of BMP-2 had a stronger anti-calcification effect than RhoA, further identifying BMP-2 as an upstream regulator of RhoA/ROCK-1. Stimulation of VICs by IP-OIM led to increased Smad1/5/9 phosphorylation, which peaked at 60 min, while pre-treatment of VICs with the Smad1/5/9 inhibitor Compound C attenuated VICs calcification. These results suggest that IP-OIM induced VICs osteogenic differentiation via Smad1/5/9 signaling. Knockdown of BMP-2 or RhoA also decreased Smad1/5/9 phosphorylation also decreased. We conclude that the RhoA/ROCK-1 axis participates in VICs osteogenic differentiation as a “bypass mediator” of the BMP-2/Smad1/5/9 signaling pathway.

ObjectiveTo discuss the effect and molecular mechanism of miR-146a on the proliferation of lung cancer cells by targeting and regulating the macrophage migration inhibitory factor (MIF) gene.MethodsRT-PCR was employed to detect expression of miR-146a; immunohistochemistry was used to detect the expression of MIF. The luciferase reporter gene technique was adopted to verify that MIF was the specific reverse target gene of miR-146a and the liposome Lipofectamine™2000 was employed to transfer the modeled miR-146a mimics, and miR-146a negative control (NC) in NSCLC cells to detect the expression of MIF mRNA and protein. MTT assay was used to detect cell viability, cloning technique to detect cell proliferation ability, AnnexinV-PI to detect cell apoptosis, UV spectrophotometry to detect viability of cysteinyl aspartate specific proteinase 3 (Caspase 3), and western blot to detect expression of nuclear factor-κB (NF-κB) in cells.ResultsThe expression of miR-146a in NSCLC lung tissues was lower than that in the normal lung tissues besides the lung cancer; while the expression of miR-146a in NSCLC cells was lower than that in normal human embryonic lung tissues. It was chosen as the subsequent cell line for its appropriate expression in A549. The expression of MIF protein in NSCLC lung tissues was higher than that in the normal lung tissues besides the lung cancer. The luciferase reporter gene proved that MIF was the reverse target gene of miR-146a. The miR-146a mimics were transfected into A549 cells through the liposome. Compared with NC group, the expression of MIF protein and mRNA was significantly decreased (P

This paper proposes a Bayesian semiparametric modeling approach for the return distribution in double autoregressive models. Monte Carlo investigation of finite sample properties and an empirical application are presented. The results indicate that the semiparametric model developed in this paper is valuable and competitive.

Reports have highlighted an association between connexins (CXs) or gap junction proteins and non-small cell lung cancer (NSCLC). In the present study, it was aimed to elucidate the regulatory mechanism of CX26 and CX43 under hypoxic conditions in NSCLC. Clinical samples were collected for analysis of CX26 and CX43 expression and clinical cancerization followed by quantification of CX26 and CX43 expression. Following the establishment of an in vitro hypoxia model, P53/murine double minute-2 (MDM2) signaling pathway-, proliferation- and epithelial-mesenchymal transition (EMT)-related genes were quantified to evaluate the influence of CX26 and CX43 on the biological functions of pulmonary epithelial cells in NSCLC. In addition, the proliferation and tumorigenicity of cancer cells were assessed by EdU staining and xenograft tumors, respectively. Decreased expression of CX26 and CX43 was found in cancer tissues compared with surrounding normal tissue. Hypoxia was shown to activate the P53/MDM2 axis and stimulate the downregulation, ubiquitination and degradation of CX26 and CX43, which were translocated from the membrane to the cytoplasm. Low levels of CX26 and CX43 were demonstrated to further promote EMT and the induction of the proliferation and tumorigenicity of cancer cells. These results were reflected by decreased E-cadherin expression and increased N-cadherin expression, along with increased cell migration, promoted cell proliferation ability and elevated relative protein expression of Oct4 and Nanog, and accelerated tumor growth, accompanied by a higher number of metastatic nodes. Taken together, the key observations of the present study demonstrate that the internalization of CX26 and CX43 promoted proliferation, EMT and migration and thus induced NSCLC via aberrant activation of the P53/MDM2 signaling pathway under hypoxic conditions.

We consider a multivariate Markov-switching GARCH model which allows for regime-specific volatility dynamics, leverage effects, and correlation structures. Conditions for stationarity and expressions for the moments of the process are derived. A Lagrange Multiplier test against misspecification of the within-regime correlation dynamics is proposed, and a simple recursion for multi-step-ahead conditional covariance matrices is deduced. We use this methodology to model the dynamics of the joint distribution of global stock market and real estate equity returns. The empirical analysis highlights the importance of the conditional distribution in Markov-switching time series models. Specifications with Student’s t innovations dominate their Gaussian counterparts both in- and out-of-sample. The dominating specification appears to be a two-regime Student’s t process with correlations which are higher in the turbulent (high-volatility) regime.

A new zinc coordination polymer, [Zn(L)(bpp)·H2O]n, was synthesized using 5-dimethylamino-isophthalic acid (H2L) and 1,3-bis(4-pyridyl)propane (bpp) as organic linkers. In the complex, adjacent Zn2+ ions are linked by L2− anions to form a one-dimensional (1D) [ZnL]n chain. Then bpp ligands expand the 1D chains into a corrugated two-dimensional (2D) layer network by linking neighboring Zn2+ ions. These adjacent layers are further stacked together by direct C−H···π supramolecular interactions, generating a three-dimensional (3D) supramolecular structure. From the viewpoint of topology, the 2D network can be rationalized to a uninodal four-connected non-interpenetrated sql/Shubnikov tetragonal plane net with {44.62} topology. Moreover, the solid state properties such as thermogravimetric analysis and luminescence were also investigated.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Elucidation of the pathogenesis and biology of lung cancer is critical for the design of an effective treatment for patients. Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases. The abnormal expression of Notch signaling pathway members is a relatively frequent event in NSCLC. The Notch signaling pathway serves important roles in cell fate determination, proliferation, differentiation and apoptosis. Increasing evidence supports the association of Notch signaling dysregulation with various types of malignant tumor, including NSCLC. Several studies have demonstrated that members of the Notch signaling pathway may be potential biomarkers for predicting the progression and prognosis of patients with NSCLC. Furthermore, Notch signaling serves critical roles in the tumorigenesis and treatment resistance of NSCLC cells by promoting the proliferation or inhibiting the apoptosis of NSCLC cells. The present review provides a detailed summary of the roles of Notch signaling in NSCLC.

Tou price is based on the price as the guidance, guiding power users according to their own electricity utilization way of flexibility and interest adjustment behavior to realize the purpose of peak peel and improve the load rate. This paper is on the basis of considering the user satisfaction, using plastic load capacity and power generation side coal saving benefit after two measures of implementing peak valley price demand response potential quantitative analysis, and feasibility of implementing peak valley price for a specific region. At last, a big industrial user in a certain area as an example for analysis, the result shows that the implementation of peak valley price can bring potential benefits, and provide a guide that the feasibility of implementing peak valley price in the region.

With the development of electric power system, the people pay more attention to demand-side management. Valid for load classification is an important prerequisite for improving demand side management level. Based on common indicators and load clustering algorithms, new SVC algorithm, cluster validity analysis and similarity measurement of the impact of the judgment are proposed based on load clustering method, and finally the effectiveness of the method is demonstrated by an example.

With the rise of micro-grid, renewable energy such as wind and solar power is introduced to the electric power grid, which has the random and intermittent characteristics, thus having great impact on the safety and stability for the electric power grid. This paper deeply analyzes the situation where multiple micro-grids are connected to power grid and establishes a scheme of joint scheduling model for micro-grids and distribution network, which considers network loss, load fluctuation and operation economy. Then a combined bi-level optimization algorithm is introduced to solve this model. The simulation result shows that reasonable scheduling of micro-grid and distribution network not only can smooth the load curve but also reduce network loss and achieve load shifting result.

High penetration of electric vehicles has brought huge impact on the safe and stable operation of power grid. How to effectively improve the comprehensive utilization rate of electric vehicle charging and discharging has become the most important problem for the grid operation. In this paper, we establish the centralized station model which takes the minimal real power loss as its objective and bring variance optimization function. Using IEEE 30-bus system as simulation system, this paper uses genetic algorithm to find the best solution of the above model. The result shows that reasonable arrangement of charge and discharge plans not only smoothes the load curve, but reduces real power loss.

In the coordination development course between wind power and power grid, because of flexible operation ability, the combined cycle gas turbine (CCGT) can strength the inherent unit commitment performance such as reserve security and ramp limit with the result of improving the power grids wind power absorption capacity. Thus, CCGT included wind power system is one way of sustainable development for civil energy and environment. Because the price of gas is much more expensive than that of coal, taking aspects of economy, technique and environment into account, this paper sets up comprehensive risk evaluation for combined cycle gas turbine involved wind power system, which includes index such as system operation cost, environmental benefit, unit capacity utilization rate, heavy ramping rate lasting time, wind power utilization rate, et al. The exact index calculation method is focused on. The case study shows that the large volume of wind power could spoil the trend of system evaluation index and introducing CCGT could enhance the economy and reliability of power system and thus has superior practical value for grid-source coordination with large volume of wind power injection and refined management of generation schedule.

Firstly, taking into account the load forecasting error and uncertainty of wind power, the coal saving benefit and network loss of the reserve are combined into integrated coal consumption of thermal units. Then, the consistency constraints of reserve capacity are derived. On the basis of the work mentioned above, the optimal reserve distribution model for power system with large scale wind power integration is proposed. This model is used to compare the network loss, integrated coal consumption and the allocation of reserve before and after adding consistency constraints. Finally, simulation results on the IEEE-RTS24 system verify the effectiveness of the algorithm in solving reserve transfer between units, ensuring the fairness of market and providing a reference to dispatchers.

An optimal assignment algorithm of emergency power supply considering V2G is proposed with a necessary concern for its effect on society. Firstly, the comprehensive index weight coefficients are proposed according to the priority. Next, this paper establishes the network minimum total cost objective function based on constraints such as time and capacity limit, using symmetric triangular fuzzy numbers to simulate the uncertainties in emergency logistics on the condition that ensuring the normal work of EV in next day which is used to search for the best logistics path. Finally the optimal algorithm of emergency power supply is developed based on genetic algorithm. The model and algorithm are proved by a numerical example, and the study helps to reduce the investment and operating cost of power system and improve the ability of urban electric network in emergency situation.

Based on the characteristics of current China's electricity power market, it is necessary to develop the self-regulation system for all market participants. This paper sets up index system based comprehensive risk evaluation for self-regulation construction, which covers market infrastructure stability, schedule fairness,trade compliance, electricity bill settlement risk. The evaluation criterion for each indicator is given afterwards. The key self-regulation information and subsequent trade behavior improvement measures can be attained after making the evaluation by calculating each index value, thus conducive to achieving the power market transaction stability and efficiency.

To promote the development of energy-saving dispatch under the pressure of energy saving and environmental protection, this paper proposes an energy-saving dispatch method based on considering demand response, which establishes a bi-level optimization model based on the optimal allocation plan of thermal units and interruptible loads, and solve the problem with improved NSGA-II and sensitivity analysis between unit interrupt capacity and thermal unit output. The case study shows that this model can decrease the pollutants at both generation side and demand side significantly with guaranteeing the economic of power grid operation. The model can also give the dispatch schedule of thermal units and interruptible loads accurately and thus has some use value.

In the emergency management of power system, there are many uncertain factors, such as wind power of the generation side and electric vehicle charging of the demand side. Firstly, the probability statistics model of PEVs charging demands was established, which considered the random factors of the probability distribution of PEVs charging. Then, we used scenarios generation and reduction techniques to predict the output of wind generators. The uncertainty of wind power was described by scenarios set. On this basis, the dispatch model considering PEVs charging and wind power was proposed. Finally, simulation results on the 5-generator system indicated the effectiveness of the proposed method. The synergistic dispatch model considering wind power and PEVs charging can effectively improve the utilization of wind power and the safety and economic benefits of the power system.

To investigate in vitro effects of nicotine on the non-small-cell lung cancer line A549.The case-control study was conducted at the First Affiliated Hospital of Nanchang University from 1st January to 30th June, 2014 and comprised A549 cells which were treated with a series of concentrations of nicotine (0.01 µM, 0.1 µM, 1 µM and 10 µM) for 24 hours. Control cells were incubated under the same conditions without the addition of nicotine. Cell growth was detected by monotetrazolium salt [3-(4, 5-dimethyl-2-thiazolyl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. Cell apoptosis was detected by Haematoxylin and Eosin staining, immunofluorescence analysis of Filamentous actin and electron microscope observation.Nicotine had no significant effect on A549 cell growth at the dose of 0.01µM (p0.05), but had significant growth inhibitory effects at the doses of 0.1µM, 1µM and 10µM (p0.05 each). A significant decrease in cell numbers was observed on staining (p0.05). Significant changes in the size and shape of cells and concomitant changes in cytoskeletons and organelles were observed by immunofluorescence and electron microscope observation (p0.05).The growth inhibitory effects of nicotine on A549 cells were found to be dose-dependent.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Elucidation of the pathogenesis and biology of lung cancer is critical for the design of an effective treatment for patients. Non-small cell lung cancer (NSCLC) accounts for 80–85% of lung cancer cases. The abnormal expression of Notch signaling pathway members is a relatively frequent event in NSCLC. The Notch signaling pathway serves important roles in cell fate determination, proliferation, differentiation and apoptosis. Increasing evidence supports the association of Notch signaling dysregulation with various types of malignant tumor, including NSCLC. Several studies have demonstrated that members of the Notch signaling pathway may be potential biomarkers for predicting the progression and prognosis of patients with NSCLC. Furthermore, Notch signaling serves critical roles in the tumorigenesis and treatment resistance of NSCLC cells by promoting the proliferation or inhibiting the apoptosis of NSCLC cells. The present review provides a detailed summary of the roles of Notch signaling in NSCLC.

This paper considers a new so-called autoregressive process with ARCH(1) errors driven by a hidden Markov chain, X t + 1 = α ( Δ t + 1 ) X t + η t + 1 β ( Δ t + 1 ) + λ ( Δ t + 1 ) X t 2 , t ∈ N , where ( η t ) is a sequence of independent and identically distributed standard normal random variables, and ( Δ t ) is a Markov chain with finite state space. Some structural properties of this new autoregressive process are considered. A sufficient condition for the existence of the strictly stationary and geometrically ergodic solution of the process is presented. The condition for this is only E [ ln | α ( Δ t ) + η t λ ( Δ t ) | ] 0 . Moreover, some simple conditions for the existence of the moments of the process are also derived.

This paper develops a family of Markov-switching GARCH (MSG) processes that not only encompasses some specifications in the literature, but also can be regarded as a Markov-switching version of the family of GARCH processes introduced by He and Terasvirta (J. Econometrics, 1999, 92, 173–192). Some structural properties of this new family of MSG processes are considered. First, a sufficient and necessary condition for the existence of the strictly stationary solution of the family of MSG processes is presented. Moreover, we also give a sufficient and necessary condition for the existence of the strictly stationary solution of the family of MSG processes with finite δ-order moment. In particular, a definition of so-called family of integrated MSG processes is introduced and its stationarity is also discussed. Next, the general conditions for the existence of any order moment of the family of MSG processes are derived. Finally, by means of a new renewal theorem, we describe the tail of the marginal distribution of the family of MSG processes.

Summary A natural generalization of the first-order GARCH processes family introduced in 1999 to allow for higher-order past errors and conditional variances on the current conditional variance equation is proposed. This new family of GARCH processes includes many well-known GARCH processes. A sufficient and necessary condition for the existence of stationary solution of the family of GARCH processes is given. In particular, we proved the stationarity of the so-called family of IGARCH processes.

This paper investigates stationarity of the so-called integrated Markov-switching generalized autoregressive conditionally heteroskedastic (GARCH) process, which is an important subclass of the Markov-switching GARCH process introduced by Francq, Roussignol, and Zakoïan (2001,Journal of Time Series Analysis22,197–220) and a Markov-switching version of the integrated GARCH (IGARCH) process. We show that, like the classical IGARCH process, a stationary solution with infinite variance for the integrated Markov-switching GARCH process may exist. To this purpose, an alternative condition for the existence of a strictly stationary solution of the Markov-switching GARCH process is presented, and some results obtained in Hennion (1997,Annals of Probability25, 1545–1587) are employed. In addition, we also discuss conditions for the existence of a strictly stationary solution of the Markov-switching GARCH process with finite variance, which is a modification of Theorem 2 in Francq et al. (2001).

In order to capture three important dynamic characteristics of time series, the asymmetry, regimes, and conditional heteroskedasticity, based on Hwang and Basawa’s [2004. Stationarity and moment structure for Box–Cox transformed threshold GARCH(1,1) processes. Statist. Probab. Lett. 68, 209–220] and Haas et al. [2004. A new approach to Markovswitching GARCH models. J. Financial Econometrics 2, 493–530] models, this paper proposes a Markov-switching Box–Cox transformed threshold GARCH model. Some structural properties of this new GARCH process are considered. First, a sufficient and necessary condition for the existence of the weakly and strictly stationary solution of the process is presented, respectively. Second, the general conditions for the existence of high-order moments of the process are derived. The technique used in this paper for the weak stationarity and the high-order moments of the process is different from that used in Haas et al. [2004. A new approach to Markov-switching GARCH models. J. Financial Econometrics 2, 493–530], and avoids the assumption that the process started in the infinite past with finite variance. r 2007 Elsevier B.V. All rights reserved. MSC: primary 60G10; secondary 60G70; 93E15

Background Coronary artery bypass grafting is employed for the treatment of multiple-vessel lesions. Studies have shown that continued maladaptive remodelling expedites atherosclerosis and that excessive remodelling leads to graft restenosis. However, few studies have focussed on mechanistic target of rapamycin (mTOR) signalling involved during remodelling of transplanted veins. Methods Rabbits were randomly allocated to groups undergoing vein-graft restenosis or sham surgery. At 1, 3, 7, 14, 28 and 90 days after surgery, we removed bypassed grafts and placed them in groups named T 1 , T 2 , T 3 , T 4 , T 5 and T 6 , respectively. Group T 0 denoted the control group. Analysis included vessel thickness, electron microscope data, TUNEL staining, and expression of the proliferation-associated gene proliferating cell nuclear antigen (PCNA). We chose specific time-points of gene expression, and then observed changes in the mTOR signalling. Results The early stage of vein grafting (one to three days after surgery) led to apoptosis and degradation of the extracellular matrix. Seven days after surgery, cells began to proliferate. RICTOR expression in mTOR complex 2 (mTORC2) and that of its downstream substrate protein kinase C was enhanced in the early stage (T 1 and T 3 ), and was higher in T 1 . mTORC1's upstream gene regulation decreased in T 1 and increased in T 3 . Its downstream genes eIF4b and 4E-BP showed similar changes. Expression of eIF4e and eIF4b increased, and led to an increase in protein composition. Conclusions After transplantation, mTORC1 function and its upstream and downstream genes were inhibited on the first day after grafting, but mTORC2 function was enhanced. One week after surgery, mTORC2 was still overexpressed when mTORC1 function had recovered and became enhanced. Hence, mTORC2 plays a major role in arterialisation of veins.

This article investigates some structural properties of the Markov-switching GARCH process introduced by Haas, Mittnik, and Paolella. First, a sufficient and necessary condition for the existence of the weakly stationary solution of the process is presented. The solution is weakly stationary, and the causal expansion of the Markov-switching GARCH process is also established. Second, the general conditions for the existence of any integer-order moment of the square of the process are derived. The technique used in this article for the weak stationarity and the high-order moments of the process is different from that used by Haas, Mittnik, and Paolella and avoids the assumption that the process started in the infinite past with finite variance. Third, a sufficient and necessary condition for the strict stationarity of the Markov-switching GARCH process with possibly infinite variance is given. Finally, the strict stationarity of the so-called integrated Markov-switching GARCH process is also discussed. Copyright 2006, Oxford University Press.

This paper considers some structural properties of Box-Cox transformed threshold GARCH(1,1) process. First, a sufficient and necessary condition for the strict stationarity of this threshold GARCH process is given. Second, some simple conditions for the existence of the moments of the threshold GARCH process are also derived. Finally, we describe the tail of the marginal distribution of the threshold GARCH process. It gives a precise meaning to the statement “light-tailed input causes heavy-tailed output”.

The expression of Hes1 is increased following myocardial infarct and other ischemic cardiomyopathies, but the role of Hes1 in cardioprotection provided by ischemic postconditioning (IPost) remains unclear. In this study, we used gain and loss of function approaches to investigate the role of Hes1 in cardioprotection during IPost. Primary cardiac myocytes exposed to ischemia reperfusion injury (IRI) and IPost were used as the experimental model. The results showed that Hes1 expression was increased during myocardial IPost, and Hes1 promoted the viability while inhibited the apoptosis of cardiomyocytes. Moreover, Hes1 inhibited the opening of mitochondrial permeability transition pore (mPTP) and the generation of reactive oxygen species in primary cardiac myocytes exposed to IRI. Mechanistically, we found that Hes1-mediated cardioprotection was related to the downregulation of phosphatase and tensin homolog and the activation of phosphatidylinositol 3-kinase/Akt and signal transducer and activator of transcription 3 signalling. These data demonstrate that Hes1 is upregulated and mediates cardioprotection provided by IPost and suggest that Hes1 is a potential new target for the treatment of ischemic cardiomyopathy.

Ischemic postconditioning (IPost), able to significantly attenuate myocardial ischemia reperfusion injury, is dependent on RISK signaling. Studies have shown that Notch signaling repairs damaged myocardium, and this study aimed to investigate the effect of Notch signaling in myocardial IPost.We used H9c2 cells to establish the myocardial IPost and Hypoxia/Reoxygenation (H/R) model in vitro. which were randomly divided into control, H/R, IPost, Hepatocyte growth factor (HGF)+IPost and DAPT+IPost, N1ICD+IPost, miRNA+IPost, and Mock treatment groups. The myocardial cell viability was assessed by MTT, the cell apoptosis was detected using Annexin V/PI double staining and flow cytometry analyses. The expression of N1ICD, Hes1, PTEN Phospho-Akt/Akt, Phospho-GSK-3β/GSK-3β were detected by Western blotting. Finally, we assessed the changes in ψm using the potential-sensitive dye JC-1 and measured using flow cytometry analyses.The Notch1 signaling is activated by HGF and ectopic expression of N1ICD during myocardial IPost, which increased myocardial cell viability, prevented cardiomyocyte apoptosis, and reduced loss of the mitochondrial membrane potential. However, myocardial ischemia reperfusion injury was increased in IPost when Notch1 signaling was inhibited using DAPT or with knockdown by Notch1-miRNA. Western blotting found that PTEN was down-regulated by Hes1 when Notch1 was activated, which consequently promoted Akt and GSK-3β phosphorylation.Notch1 crosstalk with RISK signaling may be dependent on PTEN, which plays a cardioprotective role during IPost. This mechanism could provide a promising therapeutic target for the treatment of ischemic heart disease.

Ras is best known for its ability to regulate cell growth, proliferation and differentiation. Mutations in Ras are associated with the abnormal cell proliferation which can result in incidence of all human cancers. Extracellular signal-regulated kinase (ERK) is a downstream effector of Ras and plays important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that there are other effectors between Ras and ERK, these proteins interact each other and constitute the thorough Ras/Raf/MEK/ERK signaling pathway. The pathway has profound effects on incidence of esophageal carcinoma and clinical applications of some chemotherapeutic drugs targeting the pathway. Further understanding of the relevant molecular mechanisms of Ras/Raf/MEK/ERK signaling pathway can be helpful for the development of efficient targeting therapeutic approaches which contribute to the treatment of esophageal cancer. In this article, roles of Ras/Raf/MEK/ERK signaling pathway in esophageal carcinoma as well as pharmacological targeting point in the pathway are reviewed.

To investigate the impact of fluid resuscitation with different ratio of crystalloid-colloid in early resuscitation stage on prognosis of patients with severe acute pancreatitis (SAP).A retrospective analysis was made by reviewing clinical data of 47 patients with SAP from January 2001 to December 2011. According to crystalloid-colloid ratio 1.5 or 3, which was the input volume of crystalloid fluid versus colloid fluid in the first 24 hours, patients were divided into low ratio group (crystalloid-colloid ratio1.5, n=13), middle ratio group (crystalloid-colloid ratio 1.5-3, n=15) and high ratio group (crystalloid-colloid ratio3, n=19). Among the patients who had been successfully resuscitated, rate of mechanical ventilation, the oxygenation index, intra-abdominal pressure (IAP), and the amount of fluid retention in the third space within the first 24 hours, as well as the parameters of fluid resuscitation and the survival rate within 2 weeks were collected and analyzed.(1) In the first 24 hours, the rate of mechanical ventilation in the high ratio group was significantly higher than that in the middle ratio group and the low ratio group (68.4% vs. 20.0%, 23.1%, both P0.05); the oxygenation index was significantly lower than that in the middle ratio group and in the low ratio group (180.7±26.3 mm Hg vs. 280.6±24.8 mm Hg, 260.3±25.7 mm Hg, both P0.05); the IAP was significantly higher than that in the middle ratio group and the low ratio group (16.8±3.6 cm H(2)O vs. 13.4±3.5 cm H(2)O, 13.1±3.3 cm H(2)O, both P0.05); the amount of fluid retention in the third space was significant higher than that in the middle ratio group and the low ratio group (2834±631 ml vs. 1887±282 ml, 1865±300 ml, both P0.05). There was no significant difference in above indexes between middle ratio group and low ratio group (all P0.05). (2) In the first 24 hours, the volume of crystalloid in high ratio group was significantly larger than that in the middle ratio group and the low ratio group (3611±798 ml vs. 2308±416 ml, 2124±477 ml, both P0.05); and the volume of colloid in high ratio group and middle ratio group was significantly lower than that in the low ratio group (993±233 ml, 948±140 ml vs. 1506±332 ml, both P0.05); and the mean crystalloid-colloid rate in the high ratio group was significantly higher than that in the middle ratio group and the low ratio group (3.65±0.13 vs. 2.43±0.13, 1.41±0.08, both P0.05). The volume of infused fluid during the first 72 hours in the high ratio group was significantly higher than that in the middle and low ratio groups (11 941±1161 ml vs. 9036±982 ml, 9400±1051 ml, both P0.05). (3) The survival rate in the high ratio group (36.8%) was significantly lower than that in the middle ratio group (86.7%, P0.05) and the low ratio group (61.5%, P0.05).A suitable crystalloid-colloid ratio should be considered in the early stage of resuscitation in patients with severe acute pancreatitis, which would result in a decrease in the fluid retention in the third space as well as an improvement of survival rate in return. It is suggested that the middle ratio of crystalloid-colloid fluid resuscitation should be the optimal strategy.