Phosphatidylinositol-3 kinases (PI3K)-Protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway plays an important role in the synthesis and secretion of triacylglycerol. However, the ...mechanism of PI3K-Akt-mTOR pathway in regulating lipid metabolism of goose liver was poorly understood. The purpose of this study was to determine how PI3K-Akt-mTOR pathway regulating lipid metabolic homeostasis in goose hepatocytes. Goose primary hepatocytes were treated with different PI3K-Akt-mTOR signal inhibitors (LY294002, rapamycin and NVP-BEZ235) for 24 h. The results showed that these inhibitors evidently inhibited PI3K-Akt-mTOR downstream signaling. Meanwhile, these PI3K-Akt-mTOR inhibitors reduced intracellular lipid accumulation, decreased the mRNA expression and protein content of genes involved in the de novo fatty acid synthesis, while increased the transcriptional and protein level of key factors involved in fatty acid oxidation and very low density lipoprotein (VLDL) assembly and secretion.
These findings suggested that the reduction of lipids accumulation induced-by inhibiting PI3K-Akt-mTOR pathway was closely linked to the decrease of lipogenesis, the increase of fatty acids oxidation, and the increase of VLDL assembly and secretion in goose hepatocytes.
•We developed a modeling and resolution framework for wrinkling and restabilization in both compressible and incompressible hyperelastic sheets.•2D hyperelastic plate models were systematically ...derived from general 3D strain energy functions.•A novel, efficient and robust numerical algorithm through coupling of a spectral collocation method and Asymptotic Numerical Method was proposed.•The first attempt to ameliorate a spectral method for nonlinear instability resolution with real boundary conditions was achieved.•Effects of Poisson’s ratio and strain-stiffening behavior on post-buckling evolution were investigated.
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Wrinkles commonly occur in uniaxially stretched rectangular hyperelastic membranes with clamped-clamped boundaries, and can vanish upon excess stretching. Here we develop a modeling and resolution framework to solve this complex instability problem with highly geometric and material nonlinearities. We extend the nonlinear Föppl-von Kármán thin plate model to finite membrane strain regime for various compressible and incompressible hyperelastic materials. Under plane stress condition, 2D hyperelastic constitutive models can be systematically deduced based on general 3D strain energy potentials, e.g., Saint-Venant Kirchhoff, neo-Hookean, Mooney-Rivlin, Gent model and Gent-Gent model. Moreover, we establish a novel and efficient numerical resolution framework combining a path-following continuation technique by Asymptotic Numerical Method (ANM) and a discretization by a spectral method. The main advantages of this framework include the generality for both compressible and incompressible materials, ease of programming, high precision and efficient continuation predictor. Based on the proposed approach, effect of different incompressible constitutive models on the post-buckling response is investigated, which shows that restabilization points and wrinkling amplitudes are quantitatively influenced. However, for compressible materials, Poisson’s ratio plays a critical role in the wrinkling and restabilization behavior. We find that smaller Poisson’s ratio makes later onset of wrinkling, lower amplitude and earlier disappearance of wrinkles. Besides, severe strain-stiffening phenomena are explored by accounting for phenomenological models such as Gent model and Gent-Gent model. Efficiency and accuracy of the proposed modeling and resolution framework were examined by comparing with some benchmarks.
Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we ...examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China.
The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed.
Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15-40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15-30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids.
Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also, recommendations are developed to reduce prevalence of metabolic syndrome and its components in rural Chinese populations.
Abstract
Polymer composites are gradually replacing traditional metal materials in the fields of aviation, aerospace, automotive and medicine due to their corrosion resistance, light weight and high ...strength. Moulding technology and organization morphology of polymer composite are key elements affecting the quality of products and their application, so a vacuum hot pressing process for graphene
x
/poly(ether ketone ketone) (PEKK) (x = 0%, 2%, 3%, 4%, 5%, 6%) composite powders is explored with particularly designed moulding parameters to achieve high conductive properties and good mechanical properties in graphene/PEKK composite sheet with thickness of 1.25 mm and diameter of 80 mm. The vacuum environment ensures that the graphene is not oxidized by air during hot pressing molding, which is essential for achieving conductive property in the graphene/PEKK composite; The hot pressing temperature of each graphene/PEKK composite powder is higher than glass transition temperature but lower than melting temperature, which ensures the graphene/PEKK composite powders is fully compacted and then graphene is fully lapped in the composite sheet. In addition, the graphene/PEKK composite sheet shows conductive property when the graphene content increases to 3wt%, and then the conductivity of the composites increases and then decreases with a peak value at 5wt% with increasing graphene content. By comparing the mechanical properties and microstructure morphology of the graphene/PEKK composite sheets, it was obtained that graphene content has an obvious effect on the mechanical properties of the composites, e.g., the mechanical properties will be increased as the graphene content increasing when graphene content is more than 3%. The graphene distribution law of the composite material with different graphene contents is analysed using a scanning electron microscope (SEM).
Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein ...expression. Here, we describe design principles that overcome these barriers. We develop an RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that highly structured "superfolder" mRNAs can be designed to improve both stability and expression with further enhancement through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.
Polymer-based graphene composite products with high mechanical properties, heat resistance, corrosion resistance and electrical conductivity are obtained by different molding technologies. Although ...these processes conveniently realize the molding of polymer composites, it is often difficult to control the product quality because of the fluctuation of the temperature and pressure threshold. At the same time, a high temperature or external load will carbonize polymer composites or cause excessive porosity to influence the compacted density and electrical conductivity. In this review, additive manufacturing, injection molding, extrusion molding, hot pressing, spark plasma sintering, electromagnetic-assisted molding and other processing methods were introduced. Meanwhile, the powder molding mechanism and material constitutive model were introduced, providing appropriate molding methods and theoretical guidance based on the performance of raw materials and the performance requirements of products.
Polymer-based graphene composite products with high mechanical properties, heat resistance, corrosion resistance and electrical conductivity are obtained by different molding technologies.
Current treatments have limited effectiveness in treating tumors. The combination of multiple drugs or treatment strategies is widely studied to improve therapeutic effect and reduce adverse effects ...of cancer therapy. The codelivery system is the key to realize combined therapies. It is necessary to design and construct different codelivery systems in accordance with the variable structures and properties of cargoes and vectors. This review presented the typical design considerations about codelivery vectors for cancer therapy and described the current state of codelivery systems from two aspects: different types of vectors and collaborative treatment strategies. The commonly used loading methods of cargoes into the vectors, including physical and chemical processes, are discussed in detail. Finally, we outline the challenges and perspectives about the improvement of codelivery systems.
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Knowledge and investigation of therapeutic targets (responsible for drug efficacy) and the targeted drugs facilitate target and drug discovery and validation. Therapeutic Target Database (TTD, ...http://bidd.nus.edu.sg/group/ttd/ttd.asp) has been developed to provide comprehensive information about efficacy targets and the corresponding approved, clinical trial and investigative drugs. Since its last update, major improvements and updates have been made to TTD. In addition to the significant increase of data content (from 1894 targets and 5028 drugs to 2025 targets and 17 816 drugs), we added target validation information (drug potency against target, effect against disease models and effect of target knockout, knockdown or genetic variations) for 932 targets, and 841 quantitative structure activity relationship models for active compounds of 228 chemical types against 121 targets. Moreover, we added the data from our previous drug studies including 3681 multi-target agents against 108 target pairs, 116 drug combinations with their synergistic, additive, antagonistic, potentiative or reductive mechanisms, 1427 natural product-derived approved, clinical trial and pre-clinical drugs and cross-links to the clinical trial information page in the ClinicalTrials.gov database for 770 clinical trial drugs. These updates are useful for facilitating target discovery and validation, drug lead discovery and optimization, and the development of multi-target drugs and drug combinations.
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