Aging-associated Alteration in the Cardiac MIF-AMPK Cascade in Response to Ischemic Stress

An important role for a macrophage migration inhibitory factor (MIF)-AMP-activated protein kinase (AMPK) signaling pathway in ameliorating myocardial damage following ischemia/reperfusion has been described. An aging-associated reduction in AMPK activity may be associated with a decline in the ability of cardiac cells to activate the MIF-AMPK cascade, thereby resulting in reduced tolerance to ischemic insults. To test this hypothesis, _in vivo_ regional ischemia was induced by occlusion of the left anterior descending (LAD) coronary artery in young (4-6 months) and aged (24-26 months) mice. The ischemic AMPK activation response was impaired in aged hearts compared to young ones (p<0.01). Notably, cardiac MIF expression in aged hearts was lower than in young hearts (p<0.01). Dual staining data clearly demonstrated larger infarct size in aged hearts following ischemia and reperfusion compared to young hearts (p<0.05). Ischemia-induced AMPK activation in MIF knock out (MIF KO) hearts was blunted, leading to greater contractile dysfunction of MIF KO cardiomyocytes during hypoxia than that of wild type (WT) cardiomyocytes. Finally exogenous recombinant MIF significantly reversed the contractile dysfunction of aged cardiomyocytes in response to hypoxia. We conclude that an aging-associated reduction in ischemic AMPK activation contributes to ischemic intolerance in aged hearts

Genome-wide analysis for the melatonin trait associated genes and SNPs in dairy goat (Capra hircus) as the molecular breeding markers

Previous studies have reported that the endogenous melatonin level is positively associated with the quality and yield of milk of cows. In the current study, a total of 34,921 SNPs involving 1,177 genes were identified in dairy goats by using the whole genome resequencing bulked segregant analysis (BSA) analysis. These SNPs have been used to match the melatonin levels of the dairy goats. Among them, 3 SNPs has been identified to significantly correlate with melatonin levels. These 3 SNPs include CC genotype 147316, GG genotype 147379 and CC genotype 1389193 which all locate in the exon regions of ASMT and MT2 genes. Dairy goats with these SNPs have approximately 5-fold-higher melatonin levels in milk and serum than the average melatonin level detected in the current goat population. If the melatonin level impacts the milk production in goats as in cows, the results strongly suggest that these 3 SNPs can serve as the molecular markers to select the goats having the improved milk quality and yield. This is a goal of our future study

Dynamic analysis and circuit realization of a novel variable-wing 5D memristive hyperchaotic system with line equilibrium

By introducing flux-controlled memristor and linear feedback term into the three-dimensional (3D) chaotic system, and using the state feedback control method to increase dimension, a novel variable-wing 5D memristive hyperchaotic system has been proposed in this paper. The proposed memristive hyperchaotic system has a line equilibrium point whose position is directly determined by the control parameter. The remarkable feature of the system is that the influence of positive feedback memristor and negative feedback memristor on the system and their similarities and differences are considered. Meanwhile, by analyzing the complex dynamic behavior of the system under different control parameters and initial values, it can be found that the proposed memristive hyperchaotic system shows many interesting phenomena including hidden extreme multistability, transient chaotic transition behavior and variable-wing characteristics. Finally, the hardware electronic circuit of the memristive hyperchaotic system is designed. The hardware experimental results are highly consistent with the numerical simulation ones, which demonstrate the physical realizability of the proposed system

MIF-AMPK cascades

Withdrawn for publicatio

Brown adipose tissue-derived Nrg4 alleviates non-alcoholic fatty liver disease in mice

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, seriously affecting human health. Carnosine, which widely exists in the skeletal muscle of marine migratory fish, birds, and chickens, is a non-protein histidine dipeptide with anti-inflammatory properties. To investigate whether carnosine can alleviate high-fat diet (HFD)-induced NAFLD. Mice were fed a HFD and orally administered with carnosine at doses of 60, 120, and 240 mg/kg/day for 16 weeks. Its lipid content, liver oxidative damage, neuregulin 4 (Nrg4), lipid-associated protein, and inflammation-related protein content in mice were measured and its brown fat morphology were observed by microscope. Results showed that carnosine significantly inhibited mice body weight gain (reduced by 28.90%, 25.43%, and 42.34%, respectively), liver oxidative damage, and lipid metabolism and decreased its serum interleukin-1β (IL-1β) content in HFD-induced obese mice (P < 0.05). Western blot analysis showed that carnosine could activate brown adipose tissue and upregulate Nrg4 to inhibit sterol regulatory element binding protein-1 (SREBP-1) expression and the NOD-like receptor thermal protein domain associated protein 3/ nuclear factor kappa-B (NLRP3/NF-κB) pathway. These results indicated that carnosine could lessen the effects of a HFD on NAFLD in mice

Three-dimensional simulation of gas-solid flow in a fluidised bed with flexible ribbon particles

Fluidisation is a widely used process in the industry as it offers high solid-gas contact efficiency and high heat and mass transfer, hence making it the unit operation of choice for drying. For instance, in the tobacco industry, drying of cut-tobacco is usually performed in fluidised beds. Unlike other particle materials, cut-tobacco exhibit ribbon-like morphology and are highly flexible. The high tendency of such particles to intertwine and form clusters could significantly influence the hydrodynamic characteristics and equipment performance. Therefore, it is of great significance to understand the dynamic behaviours of flexible ribbon particles in the fluidised bed. However, reported studies on such particles in the literature are scarce, and there is no large-scale numerical calculation for that matter. In this paper, the dynamic behaviours of flexible ribbon particles in a fluidised bed are investigated numerically using a two-way coupling of Discrete Element Method (DEM) and Computational fluid dynamics (CFD). A flexible ribbon chain model is used. The spring force constants is proposed and validated reasonably. Compared to other models, the flexible ribbon particle model provides better flexibility. It could also accurately reflect the flow properties of flexible ribbon particles to a certain extent. The effects of particle mass flow rate, superficial gas velocity and other process parameters on the particle dynamics in a fluidised bed are thoroughly studied in this paper. The numerical simulations are validated with experimental data, and the results show a very good agreement. (C) 2019 Elsevier Ltd. All rights reserved

Analysis of flexible ribbon particle residence time distribution in a fluidised bed riser using three-dimensional CFD-DEM simulation

Fluidised bed technology is a very common industrial process and has a wide range of applications in process engineering. Though indirectly, a common way to infer the end product uniformity is through investigating the solid residence time distribution (RTD) in the system. A good understanding of the particle RTD is crucial for the proper design, optimisation, and scale-up of a fluidisation process. Flexible ribbon particles have a very different flow behaviour in a fluidised bed compared to that of spheres which in turn influences the RID of the particles. However, this issue is still not very well addressed to date. In this paper, a double chain model is adopted to model cut tobacco strips in a fluidised bed riser. The spring constants of this chain model are calibrated, and the model is validated against experimental datum. Finally, the particle RID as a function of different process parameters is investigated. (C) 2020 Elsevier B.V. All rights reserved.</p

The Uterine Melatonergic Systems of AANAT and Melatonin Membrane Receptor 2 (MT2) Are Essential for Endometrial Receptivity and Early Implantation in Mice

In the current study, using Aanat and Mt2 KO mice, we observed that the preservation of the melatonergic system is essential for successful early pregnancy in mice. We identified that aralkylamine N-acetyltransferase (AANAT), melatonin receptor 1A (MT1), and melatonin receptor 1B (MT2) were all expressed in the uterus. Due to the relatively weak expression of MT1 compared to AANAT and MT2, this study focused on AANAT and MT2. Aanat and Mt2 KO significantly reduced the early implantation sites and the abnormal morphology of the endometrium of the uterus. Mechanistical analysis indicated that the melatonergic system is the key player in the induction of the normal nidatory estrogen (E2) response for endometrial receptivity and functions by activating the STAT signaling pathway. Its deficiency impaired the interactions between the endometrium, the placenta, and the embryo. The reduction in melatonin production caused by Aanat KO and the impairment of signal transduction caused by Mt2 KO reduced the uterine MMP-2 and MMP-9 activity, resulting in a hyperproliferative endometrial epithelium. In addition, melatonergic system deficiency also increased the local immunoinflammatory reaction with elevated local proinflammatory cytokines leading to early abortion in the Mt2 KO mice compared to the WT mice. We believe that the novel data obtained from the mice might apply to other animals including humans. Further investigation into the interaction between the melatonergic system and reproductive effects in different species would be worthwhile

Investigation of SNP markers for the melatonin production trait in the Hu sheep with bulked segregant analysis

Abstract Background As an important reproductive hormone, melatonin plays an important role in regulating the reproductive activities of sheep and other mammals. Hu sheep is a breed favoring for meat, with prolific traits. In order to explore the relationship between melatonin and reproductive function of Hu sheep, 7,694,759 SNPs were screened out through the whole genome sequencing analysis from high and low melatonin production Hu sheep. Results A total of 68,673 SNPs, involving in 1126 genes, were identified by ED association analysis. Correlation analysis of SNPs of AANAT/ASMT gene and MTNR1A/MTNR1B gene were carried out. The melatonin level of CG genotype 7,981,372 of AANAT, GA genotype 7,981,866 of ASMT and GG genotype 17,355,171 of MTNR1A were higher than the average melatonin level of 1.64 ng/mL. High melatonin Hu sheep appear to have better multiple reproductive performance. Conclusions By using different methods, three SNPs which are associated with high melatonin production trait have been identified in Hu sheep. These 3 SNPs are located in melatonin synthetase AANAT/ASMT and receptor MTNR1A, respectively. Considering the positive association between melatonin production and reproductive performance in ruminants, these three SNPs can be served as the potential molecular markers for breading Hu sheep with the desirable reproductive traits