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The additive benefits of a PPARα agonist and metformin in a HF-CDAA diet-induced advanced NASH model was firstly demonstrated, possibly through restoration of mitochondrial function and AMPK activation, which finally resulted in suppression of hepatic inflammation, ER stress, then, fibrosis.A Correction to this paper has been published https//doi.org/10.1038/s41467-020-19812-8 .Vimentin is one of the first cytoplasmic intermediate filaments to be expressed in mammalian cells during embryogenesis, but its role in cellular fitness has long been a mystery. Vimentin is acknowledged to play a role in cell stiffness, cell motility, and cytoplasmic organization, yet it is widely considered to be dispensable for cellular function and organismal development. Here, we show that Vimentin plays a role in cellular stress response in differentiating cells, by recruiting aggregates, stress granules, and RNA-binding proteins, directing their elimination and asymmetric partitioning. In the absence of Vimentin, pluripotent embryonic stem cells fail to differentiate properly, with a pronounced deficiency in neuronal differentiation. Our results uncover a novel function for Vimentin, with important implications for development, tissue homeostasis, and in particular, stress response.The disconnect between preclinical and clinical results underscores the imperative for establishing good animal models, then gleaning all available data on efficacy, safety, and potential toxicities associated with a device or drug. Mini pigs are a commonly used animal model for testing orthopedic and dental devices because their skeletons are large enough to accommodate human-sized implants. The challenge comes with the analyses of their hard tissues current methods are time-consuming, destructive, and largely limited to histological observations made from the analysis of very few tissue sections. We developed and employed cryo-based methods that preserved the microarchitecture and the cellular/molecular integrity of mini pig hard tissues, then demonstrated that the results of these histological, histochemical, immunohistochemical, and dynamic histomorphometric analyses e.g., mineral apposition rates were comparable with similar data from preclinical rodent models. Thus, the ability to assess static and dynamic bone states increases the translational value of mini pig and other large animal model studies. In sum, this method represents logical means to minimize the number of animals in a study while simultaneously maximizing the amount of information collected from each specimen.Mass construction and operation of hazardous waste landfill infrastructure has greatly improved China's waste management and environmental safety. However, the deterioration of engineering materials and the failure of landfill may lead to the release of untreated leachate rich in persistent toxic pollutants to the soil and shallow groundwater. Accordingly, we develop the framework and process model to predict landfill life by coupling the landfill hydrological performance model and material degradation model. We found that the decrease rate of the concentration of persistent pollutants in leachate was significantly slower than the deterioration rate of the landfill engineering materials. As a result, when the materials failed, the leachate with high concentrations of persistent pollutants continued to leak, resulting in the pollutants concentration in surrounding groundwater exceeding the acceptable concentration at around 385 a, which is the average life of a landfill. Further simulation indicated that hydrogeological conditions and the initial concentration of leachate will affect landfill lifespan. The correlation coefficients of concentration, the thickness of vadose zone and the thickness of aquifer are - 0.79, 0.99 and 0.72 respectively, so the thickness of vadose zone having the greatest impact on the life of a landfill. selleck inhibitor The results presented herein indicate hazardous waste landfill infrastructure reinvestment should be directed toward long-term monitoring and maintenance, waste second-disposal, and site restoration.Myocardial infarction (MI), the leading cause of mortality and disability worldwide, is a disease in which multiple environmental and genetic factors are involved. Recently, researches suggested that insertion/deletion (ins/del) variation of NFKB1 gene rs28362491 is a functional polymorphism. In the present study, we aimed to explore the relation between variation of NFKB1 gene rs28362491 and MI by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 359 MI patients and 1085 control participants. Gensini score was used to evaluate the degree of coronary artery stenosis in MI patients. The plasma levels of interleukin-6 (IL-6), IL-8, malonaldehyde (MDA) and superoxide dismutase (SOD) were randomly measured by ELISA both in MI patients and control participants. We found that the detected frequencies of D allele (41.2% vs. 36.4%, P = 0.021) and DD genotype (17.5% vs. 12.0%, P = 0.022) were significantly higher in MI patients than in control participants. Compared with II or ID genotype carriers, the Gensini score in MI patients with DD genotype was 32-43% higher (both P less then 0.001). Moreover, DD genotype carries had more diseased coronary arteries (P = 0.001 vs. II or ID genotype). Of note, IL-6 levels in MI patients carrying DD genotype were significantly higher than that in control participants and other genotype carriers in MI patients (both P less then 0.05). In conclusion, NFKB1 gene rs28362491 DD genotype was associated with a higher risk of MI and more severe coronary artery lesion, which also had a potential influence on the level of inflammatory cytokine IL-6.Pachychoroid spectrum diseases have attracted increasing attention, though their pathophysiology has yet to be fully elucidated. In this study, we assessed the vascular diameters of vortex veins in pachychoroid spectrum diseases such as central serous chorioretinopathy (CSC), pachychoroid neovasculopathy without polypoidal lesions (PNV), and pachychoroid neovasculopathy with polypoidal lesions (polypoidal choroidal vasculopathy PCV). In a retrospective case series of 94 eyes with CSC, 60 eyes with PNV and 57 with PCV, we binarized en face optical coherence tomography (OCT) images of choroidal vortex veins and analyzed the mean diameter of vortex veins. The presence of anastomosis between the superior and inferior vortex veins and central choroidal thickness (CCT) were also evaluated using OCT images. CSC showed significantly larger mean diameter of vortex veins than PCV (P less then 0.05). Anastomosis between superior and inferior vortex veins was observed in over 90% of eyes with each pachychoroid spectrum disease. The patients with CSC were the youngest, followed by PNV patients, and then patients with PCV. The largest CCT values were observed in CSC eyes, followed by PNV eyes, and then PCV eyes. CCT correlated with the mean diameter of vortex veins (rs = 0.51, P less then 0.01). These findings suggest that congestion of vortex veins might show gradual amelioration corresponding to the development of anastomosis between the superior and inferior vortex veins during the course of progression of pachychoroid spectrum diseases. Moreover, the mean diameter of vortex veins can be used as a parameter indicating choroidal congestion.Physical reservoir computing is a type of recurrent neural network that applies the dynamical response from physical systems to information processing. However, the relation between computation performance and physical parameters/phenomena still remains unclear. This study reports our progress regarding the role of current-dependent magnetic damping in the computational performance of reservoir computing. The current-dependent relaxation dynamics of a magnetic vortex core results in an asymmetric memory function with respect to binary inputs. A fast relaxation caused by a large input leads to a fast fading of the input memory, whereas a slow relaxation by a small input enables the reservoir to keep the input memory for a relatively long time. As a result, a step-like dependence is found for the short-term memory and parity-check capacities on the pulse width of input data, where the capacities remain at 1.5 for a certain range of the pulse width, and drop to 1.0 for a long pulse-width limit. link2 Both analytical and numerical analyses clarify that the step-like behavior can be attributed to the current-dependent relaxation time of the vortex core to a limit-cycle state.The interocean transfer of thermocline water between the Indian and the Atlantic Oceans known as 'Agulhas leakage' is of global significance as it influences the Atlantic Meridional Overturning Circulation (AMOC) on different time scales. Variability in the Agulhas Current regime is key in shaping hydroclimate on the adjacent coastal areas of the African continent today as well as during past climates. However, the lack of long, continuous records from the proximal Agulhas Current region dating beyond the last glacial cycle prevents elucidation of its role in regional and wider global climate changes. This is the first continuous record of hydrographic variability (SST; δ18Osw) from the Agulhas Current core region spanning the past 270,000 years. link3 The data set is analytical sound and provides a solid age model. As such, it can be used by paleoclimate scientists, archaeologists, and climate modelers to evaluate, for example, linkages between the Agulhas Current system and AMOC dynamics, as well as connections between ocean heat transport and Southern African climate change in the past and its impact on human evolution.Dorsal-ventral patterning of the mammalian telencephalon is fundamental to the formation of distinct functional regions including the neocortex and ganglionic eminence. While Bone morphogenetic protein (BMP), Wnt, and Sonic hedgehog (Shh) signaling are known to determine regional identity along the dorsoventral axis, how the region-specific expression of these morphogens is established remains unclear. Here we show that the Polycomb group (PcG) protein Ring1 contributes to the ventralization of the mouse telencephalon. Deletion of Ring1b or both Ring1a and Ring1b in neuroepithelial cells induces ectopic expression of dorsal genes, including those for BMP and Wnt ligands, as well as attenuated expression of the gene for Shh, a key morphogen for ventralization, in the ventral telencephalon. We observe PcG protein-mediated trimethylation of histone 3 at lysine-27 and binding of Ring1B at BMP and Wnt ligand genes specifically in the ventral region. Furthermore, forced activation of BMP or Wnt signaling represses Shh expression. Our results thus indicate that PcG proteins suppress BMP and Wnt signaling in a region-specific manner and thereby allow proper Shh expression and development of the ventral telencephalon.No previous study has investigated the prevalence and risk factors for primary sarcopenia in outpatient setting. This study aims to evaluate the prevalence and factors associated with primary sarcopenia in outpatient elderly. Additionally, we compared the severity of sarcopenia based on the 2014 and 2019 Asian Working Group for Sarcopenia (AWGS) criteria. This cross-sectional study was performed in 330 subjects aged over 60 years in an outpatient setting. The muscle strength, muscle performance and muscle mass were assessed using the handheld dynamometer, 6-m gait speed, and bioelectrical impedance analysis, respectively. The prevalence of sarcopenia was 10% as per the 2014 and 2019 AWGS criteria. The development of sarcopenia was positively correlated with the age with an odds ratio (OR) of 6.87 [95% confidence interval (CI) 1.63-28.88] in the middle-old group (70-79 years), and 13.71 (95%CI 3.66-51.41; p = 0.009) in the very old group (≥ 80 years). Prefrailty and low physical activity were significantly associated with sarcopenia with an OR of 4.
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