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1.
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.  相似文献   
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Mealworms (Tenebrio molitor larva) are an edible insect and a protein-rich food; however, research on mealworms as a substitute protein is insufficient. In this study, mealworm fermentation extract (TMP) was assessed as a replacement for soy protein (SP) in a control diet (CON) or a high-fat diet (HFD) of mice for 12 weeks. TMP substitution reduced body weight, body weight gain, body fat mass (perirenal and mesenteric), fat size, glucose intolerance, and insulin resistance compared to the HFD-SP group. TMP alleviated hepatic steatosis (lipid contents and lipid droplets) in high-fat-fed mice and down-regulated the PPARγ, CD36, and DGAT2 gene levels. Proteomic analysis showed that a HFD for 12 weeks up-regulated 20 proteins and down-regulated 17 proteins in mice fed SP. On the other hand, TMP reversed the protein profiles. TMP significantly down-regulated KHK, GLO1, ATP5H, SOD, and DDAH1 and up-regulated DLD, Mup1, CPS1, Ces3b, PDI, and HYOU1 compared to the HFD-SP group. These proteins are involved in the glucose, lipid, and amino acid metabolism, as well as in oxidative stress and endoplasmic reticulum stress. Thus, substituting SP for TMP helped improve HFD-induced obesity, steatosis, and insulin resistance in mice. These results suggest that TMP is a potential substitute for commonly used protein sources.  相似文献   
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Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O2 hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Cav 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Cav 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Cav 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.  相似文献   
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Hypertension induces renal fibrosis or tubular interstitial fibrosis, which eventually results in end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is one of the underlying mechanisms of renal fibrosis. Though previous studies showed that Ecklonia cava extracts (ECE) and dieckol (DK) had inhibitory action on angiotensin (Ang) I-converting enzyme, which converts Ang I to Ang II. It is known that Ang II is involved in renal fibrosis; however, it was not evaluated whether ECE or DK attenuated hypertensive nephropathy by decreasing EMT. In this study, the effect of ECE and DK on decreasing Ang II and its down signal pathway of angiotensin type 1 receptor (AT1R)/TGFβ/SMAD, which is related with the EMT and restoring renal function in spontaneously hypertensive rats (SHRs), was investigated. Either ECE or DK significantly decreased the serum level of Ang II in the SHRs. Moreover, the renal expression of AT1R/TGFβ/SMAD was decreased by the administration of either ECE or DK. The mesenchymal cell markers in the kidney of SHRs was significantly decreased by ECE or DK. The fibrotic tissue of the kidney of SHRs was also significantly decreased by ECE or DK. The ratio of urine albumin/creatinine of SHRs was significantly decreased by ECE or DK. Overall, the results of this study indicate that ECE and DK decreased the serum levels of Ang II and expression of AT1R/TGFβ/SMAD, and then decreased the EMT and renal fibrosis in SHRs. Furthermore, the decrease in EMT and renal fibrosis could lead to the restoration of renal function. It seems that ECE or DK could be beneficial for decreasing hypertensive nephropathy by decreasing EMT and renal fibrosis.  相似文献   
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Templated grain growth is beneficial for piezoelectric materials, the properties of which become the best in their single crystalline form. Nevertheless, a textured ceramic prepared by a templated grain growth technique often fails in exhibiting as good properties as expected in single crystals even with a high degree of orientation factor. Here, we propose a new strategy for maximizing texturing effect by suppressing the growth of untextured matrix grains. The textured ceramics made by our method, so-called bi-templated grain growth, are featured by ultrahigh piezoelectric properties (d33 = ~1,031 pC/N, d?g = ~59,000, kp = ~0.76). A special emphasis is on the achieved electric-field-induced strain of 0.13 % at 1 kV/mm, which is as high as that of single crystals. This work demonstrates that not only the degree of texture but also the coarsening of untextured matrix grains should be well-controlled to best exploit the templated grain growth technique.  相似文献   
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In metal oxide nanofiber fabrication using the electrospinning method, heat treatment is performed at temperatures of 500°C or higher for crystallization and polymer desorption. Therefore, it is difficult to fabricate low-temperature phase metal oxides that crystallize at low temperatures. TiO2, a representative metal oxide often used as photocatalysts, is known to have higher photocatalytic activity in the low-temperature phase (anatase structure) than in the high-temperature phase (rutile structure). Studies on the fabrication of TiO2 anatase nanofibers using conventional electrospinning have reported disadvantages such as the partial expression of rutile structures and low crystallinity. This study developed an anatase TiO2 nanofiber as a high-efficiency catalyst based on the electrospinning method and a residual organic matter cleaning method that employs ultra-violet (UV) light. We fabricated nanofibers using the electrospinning method and implemented TiO2 nanofibers with the anatase structure through heat treatment at 260°C. Residual organics remaining after heat treatment of the fabricated crystalized TiO2 nanofibers were removed by exposing them to UV light, thereby improving photocatalytic efficiency. The photocatalytic efficiency of the fabricated TiO2 nanofibers was confirmed through a methylene blue (MB) decomposition experiment under visible light irradiation. The photocatalytic efficiency (time taken for the concentration of the MB solution to reach 50%) of the UV-treated TiO2 nanofibers was approximately six times higher than of P25 and the heat-treated nanofibers.  相似文献   
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Yb3+/Er3+codoped La10W22O81 (LWO) nanophosphor rods have been successfully synthesized by a facile hydrothermal assisted solid state reaction method, and their upconversion photoluminescence properties were systematically studied. X-ray diffraction patterns revealed that the nanophosphors have an orthorhombic structure with space group Pbcn (60). A microflowers-like morphology with irregular hexagonal nanorods was observed using field emission scanning electron microscopy for the Yb3+(2 mol%)/Er3+(2 mol%):LWO nanophosphor. The shape and size of the nanophosphor and the elements along with their ionic states in the material were confirmed by TEM and XPS studies, respectively. A green upconversion emission was observed in the Er3+: LWO nanophosphors under 980 nm laser excitation. A significant improvement in upconversion emission has been observed in the Er3+: LWO nanophosphors by increasing the Er3+ ion concentration. A decrease in the upconversion emission occurred due to concentration quenching when the doping concentration of Er3+ ions was greater than 2 mol%. An optimized Er3+(2 mol%): LWO nanophosphor exhibited a strong near infrared emission at 1.53 μm by 980 nm excitation. The green upconversion emission of Er3+(2 mol%): LWO was remarkably enhanced by co-doping with Yb3+ ions under 980 nm excitation because of energy transfer from Yb3+ to Er3+. The naked eye observed this upconversion emission when co-doping with 2 mol% Yb3+. In order to obtain the high upconversion green emission, the optimized sensitizer concentration of Yb3+ ions was found to be 2 mol%. The upconversion emission trends were studied as a function of stimulating laser power for an optimized sample. Moreover, the NIR emission intensity has also been enhanced by co-doping with Yb3+ ions due to energy transfer from Yb3+ to Er3+. The energy transfer dynamics were systematically elucidated by energy level scheme. Colorimetric coordinates were determined for Er3+ and Yb3+/Er3+: LWO nanophosphors. The energy transfer mechanism was well explained and substantiated by several fluorescence dynamics of upconversion emission spectra and CIE coordinates. The results demonstrated that the co-doped Yb3+(2 mol%)/Er3+(2 mol%): LWO nanophosphor material is found to be a suitable candidate for the novel upconversion photonic devices.  相似文献   
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