Amyloid precursor protein (APP) is a transmembrane precursor protein that is widely expressed in the central nervous system and peripheral tissues in the liver and pancreas, adipose tissue, and ...myotubes. APP can be cleaved by proteases in two different ways to produce a variety of short peptides, each with different physiological properties and functions. APP peptides generated by non-amyloidogenic processing can positively influence metabolism, while the peptides produced by amyloidogenic processing have the opposite effects. Here, we summarize the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues. In addition, abnormal expression and function of APP and APP-derived peptides are associated with metabolic diseases, such as type 2 diabetes, obesity, non-alcoholic fatty liver disease, and cardiovascular disease, and cancers. Pharmacological intervention of APP function or reduction of the production of peptides derived from amyloidogenic processing may be effective strategies for the prevention and treatment of Alzheimer's disease, and they may also provide new guidance for the treatment of metabolic diseases.
•APP is a transmembrane precursor protein that plays an important role in metabolism of the central nervous system and peripheral tissues.•Peptides produced by APP through non-amyloidogenic pathway have protective effects on metabolism, while peptides produced by the amyloidogenic pathway have detrimental effects.•Pharmacological intervention of APP or reduction of the peptides derived from amyloidogenic processing has benefical effects on AD and metabolic diseases.
Acrylamide (AA) is a toxicant to humans, but the association between AA exposure and the risk of non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, our objective is to examine ...the cross-sectional association between AA exposure and the risk of NAFLD in American adults.
A total of 3234 individuals who took part in the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2013-2016 were enrolled in the study. NAFLD was diagnosed by the U.S. Fatty Liver Index. Multivariable logistic regression models were applied to estimate the association between AA and NAFLD in the whole group and the non-smoking group.
We discovered that in the whole group, serum hemoglobin adducts of AA (HbAA) were negatively associated with the prevalence of NAFLD after adjustment for various covariables (P for trend < 0.001). Compared with individuals in the lowest HbAA quartiles, the odds ratios (ORs) with 95% confidence intervals (CIs) in the highest HbAA quartiles were 0.61 (0.46-0.81) and 0.57 (0.36-0.88) in the whole group and the non-smoking group, respectively. In contrast, HbGA/HbAA showed a significantly positive correlation with the prevalence of NAFLD in both groups (P for trend < 0.001). In addition, HbGA was not significantly associated with NAFLD in the whole group or the non-smoking group.
HbAA is negatively associated with NAFLD whereas HbGA/HbAA is positively associated with NAFLD in adults in the U.S. Further studies are needed to clarify these relationships.
Although the probability of a rollover accident is lower than that of other forms of collision, rollover is a serious accident that can break the symmetry of the vehicle and cause serious loss of ...life and property. There are many factors affecting rollovers, such as the environment, the vehicle, and the driving control. A coach comprises a complex dynamic system; as such, the accuracy and rationality of the used mathematical model are decisive in the study of coach rollover warning and control. By analogy with the modeling method of an automobile collision accident, the general process of a coach rollover accident is analyzed in this study in combination with the contact form and freedom of motion characteristic of the coach body and external environment. According to the principle of conservation of energy, the mathematical models of critical rollover impact force in a collision between vehicles and obstacles and in a collision between two vehicles are established, allowing for analysis of the relationships between the critical tripped rollover impact forces required for a 90° rollover and the continuous action time and collision point height. During the collision between the vehicle and the obstacle, the occurrence of a vehicle rollover is related not only to the impact force in the collision process but also to the collision duration time. Even if the impact force is relatively small, the collision lasts long enough that a second collision may occur until the vehicle rolls over. In the process of a two-vehicle collision, the critical rollover impact force is not only related to the vehicle mass but also to the vehicle wheelbase and the height of the collision point. Based on the law of conservation of momentum, the mathematic models of 90-degree rollover and 180-degree rollover are established, and the critical rollover velocities are calculated. The purpose of this study is to provide reference and guidance for the research methods of vehicle rollover stability and anti-rollover control in the intelligent vehicle era.
Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism ...generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemicals have been shown to induce hormesis. This study aims to investigate whether the neuroprotective activity of BBR is mediated by hormesis and the related signaling pathways in 6-OHDA-induced PC12 cells and zebrafish neurotoxic models. Our results demonstrated that BBR induced a typical hormetic response in PC12 cells, i.e. low dose BBR significantly increased the cell viability, while high dose BBR inhibited the cell viability. Moreover, low dose BBR protected the PC12 cells from 6-OHDA-induced cytotoxicity and apoptosis, whereas relatively high dose BBR did not show neuroprotective activity. The hormetic and neuroprotective effects of BBR were confirmed to be mediated by up-regulated PI3K/AKT/Bcl-2 cell survival and Nrf2/HO-1 antioxidative signaling pathways. In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency in zebrafish, while high dose BBR only slightly exhibited neuroprotective activities. These results strongly suggested that the neuroprotection of BBR were attributable to the hormetic mechanisms via activating cell survival and antioxidative signaling pathways.
Hyperuricemia is a major risk for non-alcoholic fatty liver disease. However, the mechanisms for this phenomenon are not fully understood. This study aimed to investigate whether microRNAs mediated ...the pathogenic effects of uric acid on non-alcoholic fatty liver disease.
Microarray was used to determine the hepatic miRNA expression profiles of male C57BL/6 mice fed on standard chow diet, high fat diet (HFD), and HFD combined with uric acid-lowering therapy by allopurinol. We validated the expression of the most significant differentially expressed microRNAs and explored its role and downstream target in uric acid-induced hepatocytes lipid accumulation.
Microarray analysis and subsequent validation showed that miR-149-5p was significantly up-regulated in the livers of HFD-fed mice, while the expression was down-regulated by allopurinol therapy. MiR-149-5p expression was also significantly up-regulated in uric acid-stimulated hepatocytes. Over-expression of miR-149-5p significantly aggregated uric acid-induced triglyceride accumulation in hepatocytes, while inhibiting miR-149-5p ameliorated the triglyceride accumulation. Luciferase report assay confirmed that FGF21 is a target gene of miR-149-5p. Silencing FGF21 abolished the ameliorative effects of miR-149-5p inhibitor on uric acid-induced hepatocytes lipid accumulation, while overexpression of FGF21 prevented the lipid accumulation induced by miR-149-5p mimics.
Uric acid significantly up-regulated the expression of miR-149-5p in hepatocytes and induced hepatocytes lipid accumulation via regulation of miR-149-5p/FGF21 axis.
Lightweighting of automotives is crucial for the decrease of fuel and energy consumption, as well as CO2 emission and environmental pollution. Polymer composites, especially the high strength glass ...fiber/polyamide (GF/PA) composites, have great potential in lightweight; however, they have not been universally accepted due to their insufficient performance. Here, a stearate‐ended hyperbranched polyester (HBP‐12‐n) is designed and high‐performance GF/PA6 composites with high GF content are prepared. The flowability of the composites can be further increased by combining carboxyl‐ended hyperbranched polymer (HyPer C181) with HBP‐12‐n. Compared with unmodified GF/PA6 composites, the melt flow index (MFI) can be increased remarkably to 587% by adding a 0.7 wt% mixture of HBP‐12‐75 and HyPer C181, and the strength and toughness remain competitive. The simultaneous improvement in MFI and impact strength of GF/PA6 composites is the first discovery of this kind, and a synergistic mechanism of amphiphilic bridging‐deformation slipping‐interfacial strengthening of hyperbranched polymers is proposed to account for this phenomenon. This work provides a simple strategy to fabricate GF/PA6 composites with the extensive application for automotive parts and has great prospects in making automotives lightweight and reduction of CO2 emissions.
A series of stearate‐ended hyperbranched polyester (HBP‐12‐n) by the esterification reaction between the hydroxyl groups of HBP‐12 and stearic acid is synthesized. The melt flow inde of the glass fiber/polyamide 6 (GF/PA6) blends can be increased approximately 5.87 times upon the mixed use of HBP‐12‐75 and carboxyl‐ended hyperbranched polymer (HyPer C181), without sacrificing the strength and toughness of the composites.
Hormesis is an adaptive response of living organisms to a moderate stress. However, its biomedical implication and molecular mechanisms remain to be intensively investigated. Panaxatriol saponins ...(PTS) is the major bioactive components extracted from Panax notoginseng, a widely used herbal medicine for cerebrovascular diseases. This study aims to examine the hormetic and neuroprotective effects of PTS in PC12 cells and zebrafish Parkinson's disease (PD) models. Our results demonstrated that PTS stimulated PC12 cell growth by about 30% at low doses, while PTS at high doses inhibited cell growth, which is a typical hormetic effect. Moreover, we found that low dose PTS pretreatment significantly attenuated 6-OHDA-induced cytotoxicity and up-regulated PI3K/AKT/mTOR cell proliferation pathway and AMPK/SIRT1/FOXO3 cell survival pathway in PC12 cells. These results strongly suggested that neuroprotective effects of PTS may be attributable to the hormetic effect induced by PTS through activating adaptive response-related signaling pathways. Notably, low dose PTS could significantly prevent the 6-OHDA-induced dopaminergic neuron loss and improve the behavior movement deficiency in zebrafish, whereas relative high dose PTS exhibited neural toxicity, further supporting the hormetic and neuroprotective effects of PTS. This study indicates that PTS may have the potential in the development of future therapeutic medicines for PD.
Background and Aims. Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) have become common chronic liver diseases. Recent evidence has shown the value of transient ...elastography (TE) in the context of ALD/NAFLD. The aim of this study is to investigate the accuracy of TE for diagnosing steatosis and fibrosis in ALD/NAFLD patients. Methods. We retrieved relevant English studies from the databases of PubMed, Embase, the Web of Science, and the Cochrane Library through March 31st 2019. We included studies regarding the diagnosis or staging of steatosis or fibrosis by using controlled attenuation parameter (CAP) or liver stiffness measurement (LSM) measured by TE in patients with ALD or NAFLD. The reference standard of all included studies was liver biopsy. A random-effects model was applied. Statistical analyses were performed using STATA. Results. A total of 62 articles were included and analyzed in our meta-analysis. In patients with ALD/NAFLD, the pooled results revealed that the sensitivity and specificity of CAP were 0.84, 0.83, and 0.78 and 0.83, 0.71, and 0.62 for steatosis grades ≥S1, ≥S2, and =S3, respectively. The sensitivity and specificity of LSM for identifying fibrosis grades ≥F1, ≥F2, ≥F3, and =F4 were 0.77, 0.77, 0.83, and 0.91 and 0.80, 0.82, 0.84, and 0.86, respectively. Conclusion. In patients with ALD/NAFLD, CAP was feasible for identifying and screening steatosis, and LSM was accurate for diagnosing fibrosis, especially severe fibrosis and cirrhosis.
In this work, we present the theoretical study of the vibrationally resolved absorption (ABS), electronic circular dichroism (ECD), emission (EMI), and circularly polarized luminescence (CPL) spectra ...of a boron-fused double helicene, with a detailed and complete discussion of the alternative possible approximate methods. Given the fact that few examples of CPL calculations exist, the potential energy surfaces (PESs) have been constructed and compared with Adiabatic (AH) and Vertical Hessian (VH) models. All the vibronic calculations have accounted for Duschinsky mixings, Franck-Condon (FC) effect and Herzberg-Teller (HT) contribution. Moreover, different HT expansions have been checked and compared, by computing the derivatives of the electric and magnetic dipole transition moments around the equilibrium geometries of the initial and final states. Our results show that both AH and VH models have well reproduced the experimental vibronic structures and VH model shows a better performance in the simulation of spectral lineshapes. They also show that HT effects dominate the shapes of EMI and CPL, tuning the relative heights of the different vibronic peaks, improving the agreement with the experiment for EMI. Moreover, HT effects are the main reason for the mirror-symmetry breaking between ECD and CPL spectra. Furthermore, interesting interference effects between FC and HT contributions have also been addressed.
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•Vibrationally Resolved Electronic Circular Dichroism and Circularly Polarized Luminescence have been investigated.•Herzberg-Teller (HT) effects improve the performance by tuning the relative heights of vibronic bands.•HT effects explain the mirror-symmetry breaking down between absorptive and emissive chiroptical spectroscopies.
The pullout process of graphene from an epoxy/graphene composite filled with a carbon nanotube (CNT) was simulated by molecular dynamics simulations. The interaction energy and the interfacial ...adhesion energy were calculated to analyze the effect of CNT addition on the interfacial adhesion between the graphene and the epoxy matrix, with varying CNT radii, distances between the CNT and the graphene sheet, CNT axial directions, and the number of CNT walls. Generally, the addition of a CNT strengthens the interfacial adhesion between the graphene and the polymer matrix. Firstly, a larger CNT radius induces a stronger interfacial adhesion of graphene with the matrix. Secondly, when the CNT is farther away from the graphene sheet, the interfacial adhesion of graphene with the matrix becomes weaker. Thirdly, the CNT axial direction has little effect on the interfacial adhesion of graphene in the equilibrium structure. However, it plays an important role in the graphene pullout process. Finally, compared with a single-walled CNT, the interfacial adhesion between graphene and the matrix is stronger when a double-walled CNT is added to the matrix.
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