Inhibition of Autophagy Signaling via 3-methyladenine Rescued Nicotine-Mediated Cardiac Pathological Effects and Heart Dysfunctions.

Rationale: Cigarette smoking is a well-established risk factor for myocardial infarction and sudden cardiac death. The deleterious effects are mainly due to nicotine, but the mechanisms involved and theranostics remain unclear. Thus, we tested the hypothesis that nicotine exposure increases the heart sensitivity to ischemia/reperfusion injury and dysfunction, which can be rescued by autophagy inhibitor. Methods: Nicotine or saline was administered to adult rats via subcutaneous osmotic minipumps in the absence or presence of an autophagy inhibitor, 3-methyladenine (3-MA). After 30 days of nicotine treatment, the rats underwent the cardiac ischemia/reperfusion (I/R) procedure and echocardiography analysis, and the heart tissues were isolated for molecular biological studies. Results: Nicotine exposure increased I/R-induced cardiac injury and cardiac dysfunction as compared to the control. The levels of autophagy-related proteins including LC3 II, P62, Beclin1, and Atg5 were upregulated in the reperfused hearts isolated from nicotine-treated group. In addition, nicotine enhanced cardiac and plasma ROS production, and increased the phosphorylation of GSK3β (ser9) in the left ventricle tissues. Treatment with 3-MA abolished nicotine-mediated increase in the levels of autophagy-related proteins and phosphorylation of GSK3β, but had no effect on ROS production. Of importance, 3-MA ameliorated the augmented I/R-induced cardiac injury and dysfunction in the nicotine-treated group as compared to the control. Conclusion: Our results demonstrate that nicotine exposure enhances autophagy signaling pathway, resulting in development of ischemic-sensitive phenotype of heart. It suggests a potentially novel therapeutic strategy of autophagy inhibition for the treatment of ischemic heart disease

Model and Application of Risk Degree for Vessel-Bridge Collision Based on Theory of Ship Collision Avoidance

In recent years, there are many ship-bridge collision accidents in the world, which caused huge casualties and property losses. The main risk not only come from itself, but also come from the vessel in the water. Following the development of economy, more and more vessels sailing in higher level inland rivers in China, it causes the traffic density climb sharply, and with the heighten speed of ship, bridges crossing navigational channel be confronted with more higher risk of ship-bridge collision

Progress in anti-HER2 targeted therapy of metastatic lung cancer

Lung cancer is one of the most common malignant tumors in the world and one of the main causes of cancer death. In lung cancer, metastatic stage accounted for a large percentage. It is a global disease affecting human health, with high incidence rate, low malignant degree and other characteristics. After decades of exploration, anti-HER2 targeted therapy in breast has made breakthrough progress, obtained encouraging clinical efficacy, and fully improved the quality of the life of patients. Because of this, more and more researchers are focusing on anti-HER2 in metastatic lung cancer targeting research. For the past few years, new targeted drugs have been constantly developed for anti-HER2 in metastatic lung cancer, and promising data results have been obtained in clinical trials and cohort study. This article provides a review of the clinical research progress of anti-HER2 targeted therapy in metastatic lung cancer in recent years, with a view to further guiding clinical treatment and providing more treatment options for patients

Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice.

Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes

Optimal weighting models based on linear uncertain constraints in intuitionistic fuzzy preference relations

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Although the classic exponential-smoothing models and grey prediction models have been widely used in time series forecasting, this paper shows that they are susceptible to fluctu- ations in samples. A new fractional bidirectional weakening buffer operator for time series prediction is proposed in this paper. This new operator can effectively reduce the negative impact of unavoidable sample fluctuations. It overcomes limitations of existing weakening buffer operators, and permits better control of fluctuations from the entire sample period. Due to its good performance in improving stability of the series smoothness, the new op- erator can better capture the real developing trend in raw data and improve forecast accu- racy. The paper then proposes a novel methodology that combines the new bidirectional weakening buffer operator and the classic grey prediction model. Through a number of case studies, this method is compared with several classic models, such as the exponential smoothing model and the autoregressive integrated moving average model, etc. Values of three error measures show that the new method outperforms other methods, especially when there are data fluctuations near the forecasting horizon. The relative advantages of the new method on small sample predictions are further investigated. Results demonstrate that model based on the proposed fractional bidirectional weakening buffer operator has higher forecasting accuracy

The Application of E-learning in Maritime Education and Training in China

E-learning brings the third wave to Internet applications. E-learning is a new training mode with the open characteristics, which is completely different with traditional training. E-learning teaches students the specialized knowledge of theories, work experience and technology by information networks and computer hardware equipment. Students can through a variety of terminal equipment to learn anytime and anywhere, so as to improve student learning results. Maritime education and training must conform to the trend of times to explore E-learning training to improve the training performance. In this paper, based on the theory of E-learning, comparing the advantages and disadvantages of E-learning training. By analyzing current status of maritime education and training, using E-learning to establish China's maritime education and training of the lifelong education system, using E-learning to promote the internationalization of navigation education and training

Inflammatory bowel disease and prostate cancer risk: a two-sample Mendelian randomization analysis

BackgroundPrevious epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis.MethodsWe performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.ResultsGenetically determined IBD did not have a causal effect on PCa (IVW P > 0.05). Additionally, there was no causal effect of Crohn’s disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P > 0.05). Results of complementary methods were consistent with those of the IVW method.ConclusionsThis study does not support a causal association of IBD on PCa, which is in contrast to most observational studies

Using a novel multi-variable grey model to forecast the electricity consumption of Shandong Province in China

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.The electricity consumption forecasting problem is especially important for policy making in developing region. To properly formulate policies, it is necessary to have reliable forecasts. Electricity consumption forecasting is influenced by some factors, such as economic, population and so on. Considering all factors is a difficult task since it requires much detailed study in which many factors significantly influence on electricity forecasting whereas too many data are unavailable. Grey convex relational analysis is used to describe the relationship between the electricity consumption and its related factors. A novel multi-variable grey forecasting model which considered the total population is developed to forecast the electricity consumption in Shandong Province. The GMC(1,N) model with fractional order accumulation is optimized by changing the order number and the effectiveness of the first pair of original data by the model is proven. The results of practical numerical examples demonstrate that the model provides remarkable prediction performances compared with the traditional grey forecasting model. The forecasted results showed that the increase of electricity consumption will speed up in Shandong Province

Using grey Holt-Winters model to predict the air quality index for cties in China

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linkThe randomness, non-stationarity and irregularity of air quality index series bring the di fficulty of air quality index forecasting. To enhance forecast accuracy, a novel model combining grey accumulated generating technique and Holt-Winters method is developed for air quality index forecasting in this paper. The grey accumulated generating technique is utilized to handle non-stationarity of random and irregular data series and Holt-Winters method is employed to deal with the seasonal e ects. To verify and validate the proposed model, two monthly air quality index series from January in 2014 to December in 2016 collected from Shijiazhuang and Handan in China are taken as the test cases. The experimental results show that the proposed model is remarkably superior to conventional Holt-Winters method for its higher forecast accuracy

Multiple cross-frequency coupling analysis of resting-state EEG in patients with mild cognitive impairment and Alzheimer’s disease

IntroductionElectroencephalographic (EEG) abnormalities are seen in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance.MethodsWe recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function.Results and discussionMultiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology