Regulated cell death pathways in cardiomyopathy.

Heart disease is a worldwide health menace. Both intractable primary and secondary cardiomyopathies contribute to malignant cardiac dysfunction and mortality. One of the key cellular processes associated with cardiomyopathy is cardiomyocyte death. Cardiomyocytes are terminally differentiated cells with very limited regenerative capacity. Various insults can lead to irreversible damage of cardiomyocytes, contributing to progression of cardiac dysfunction. Accumulating evidence indicates that majority of cardiomyocyte death is executed by regulating molecular pathways, including apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis. Importantly, these forms of regulated cell death (RCD) are cardinal features in the pathogenesis of various cardiomyopathies, including dilated cardiomyopathy, diabetic cardiomyopathy, sepsis-induced cardiomyopathy, and drug-induced cardiomyopathy. The relevance between abnormity of RCD with adverse outcome of cardiomyopathy has been unequivocally evident. Therefore, there is an urgent need to uncover the molecular and cellular mechanisms for RCD in order to better understand the pathogenesis of cardiomyopathies. In this review, we summarize the latest progress from studies on RCD pathways in cardiomyocytes in context of the pathogenesis of cardiomyopathies, with particular emphasis on apoptosis, necroptosis, ferroptosis, autophagy, and pyroptosis. We also elaborate the crosstalk among various forms of RCD in pathologically stressed myocardium and the prospects of therapeutic applications targeted to various cell death pathways

Wrinkling of a film/substrate bilayer with periodic material properties: An assessment of the Winkler foundation model

The Winkler foundation model is often used to analyze the wrinkling of a film/substrate bilayer under compression, and it can be rigorously justified when both the film and substrate are homogeneous and the film is much stiffer than the substrate. We assess the validity of this model when the substrate is still homogeneous but the film has periodic material properties in the direction parallel to the interface. More precisely, we assume that each unit cell is piecewise homogeneous, and each piece can be described by the Euler-Bernoulli beam theory. We provide analytical results for the critical compression when the substrate is viewed as a Winkler foundation with stiffness modeled either approximately (as in some previous studies) or exactly (using the Floquet theory). The analytical results are then compared with those from Abaqus simulations based on the three-dimensional nonlinear elasticity theory in order to assess the validity of the Euler-Bernoulli beam theory and the Winkler foundation model in the current context

Exact eigenvalue spectrum of a class of fractal scale-free networks

The eigenvalue spectrum of the transition matrix of a network encodes important information about its structural and dynamical properties. We study the transition matrix of a family of fractal scale-free networks and analytically determine all the eigenvalues and their degeneracies. We then use these eigenvalues to evaluate the closed-form solution to the eigentime for random walks on the networks under consideration. Through the connection between the spectrum of transition matrix and the number of spanning trees, we corroborate the obtained eigenvalues and their multiplicities.Comment: Definitive version accepted for publication in EPL (Europhysics Letters

Bear bile: dilemma of traditional medicinal use and animal protection

Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with "Free-dripping Fistula Technique". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future

Atomization Characteristics of Hydrogen Peroxide Solutions in Electrostatic Field

Hydrogen peroxide (H2O2) can be considered as a sterilant or a green propellant. For a common use in industrial application, spray is an effective method to form fine H2O2 droplets. In this paper, electrostatic atomization based on the configuration of needle ring electrodes is proposed to produce H2O2 spray by minimizing its effective surface tension. The breakup performances of H2O2 ligaments can be improved by increasing the electric field intensity, reducing the nozzle size, and adjusting suitable volume flow rate. The smallest average diameter of breakup droplets for 35 wt. % concentration H2O2 solution reached 92.8 μm under optimum operation conditions. The H2O2 concentration significantly influenced the breakup performance owing to the concentration effect on comprehensive physical properties such as density, surface tension, viscosity, and permittivity. The average diameters of breakup droplets decreased with decreasing H2O2 concentration. At 8 wt. % concentration, the average breakup droplet diameter was reduced to 67.4 μm. Finally, electrostatic atomization mechanism of H2O2 solution was analyzed by calculating dimensionless parameters of Re, We, and Oh numbers with the combination of the operation conditions and physical properties for in-depth understanding the breakup behaviors. The calculation showed that the minimum average diameter of breakup droplets was obtained at 8 wt. % concentration at the investigated range of H2O2 concentration, which kept in agreement with the experimental results

The mitochondrial genome of Hua aristarchorum (Heude, 1889) (Gastropoda, Cerithioidea, Semisulcospiridae) and its phylogenetic implications

Research on complete mitochondrial genomes can help in understanding the molecular evolution and phylogenetic relationships of various species. In this study, the complete mitogenome of Hua aristarchorum was characterized to supplement the limited mitogenomic information on the genus Hua. Three distinct assembly methods, GetOrganelle, NovoPlasty and SPAdes, were used to ensure reliable assembly. The 15,691 bp mitogenome contains 37 genes and an AT-rich region. Notably, the cytochrome c oxidase subunit I (COX1) gene, commonly used for species identification, appears to be slow-evolving and less variable, which may suggest the inclusion of rapidly evolving genes (NADH dehydrogenase subunit 6 [ND6] or NADH dehydrogenase subunit 2 [ND2]) as markers in diagnostic, detection, and population genetic studies of Cerithioidea. Moreover, we identified the unreliability of annotations (e.g., the absence of annotations for NADH dehydrogenase subunit 4L [ND4L] in NC_037771) and potential misidentifications (NC_023364) in public databases, which indicate that data from public databases should be manually curated in future research. Phylogenetic analyses of Cerithioidea based on different datasets generated identical trees using maximum likelihood and Bayesian inference methods. The results confirm that Semisulcospiridae is closely related to Pleuroceridae. The sequences of Semisulcospiridae clustered into three clades, of which H. aristarchorum is one; H. aristarchorum is sister to the other two clades. The findings of this study will contribute to a better understanding of the characteristics of the H. aristarchorum mitogenome and the phylogenetic relationships of Semisulcospiridae. The inclusion of further mitochondrial genome sequences will improve knowledge of the phylogeny and origin of Cerithioidea