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Background: Alzheimer's disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in the protective effect of myricetin. Methods: The effect of myricetin was assessed on Aβ42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. Behavioral tests were performed to assess the cognitive effects of myricetin (14 days, ip) in 3×Tg mice. The levels of beta-amyloid precursor protein (APP), synaptic and mitochondrial proteins, glycogen synthase kinase3β (GSK3β) and extracellular regulated kinase (ERK) 2 were assessed via Western blotting. Flow cytometry assays, immunofluorescence staining, and transmission electron microscopy were used to assess mitochondrial dysfunction and reactive oxidative stress. Results: We found that, compared with control treatment, myricetin treatment improved spatial cognition and learning and memory in 3×Tg mice. Myricetin ameliorated tau phosphorylation and the reduction in pre- and postsynaptic proteins in Aβ42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation, and rescued mitochondrial dysfunction via the associated GSK3β and ERK 2 signalling pathways. Conclusions: This study provides new insight into the neuroprotective mechanism of myricetin in vitro in cell culture and in vivo in a mouse model of Alzheimer’s disease.

Background: Although the changes of mitogen-activated protein kinase (MAPK) pathway in the central nervous system (CNS) induced by excessive fluoride has been confirmed by our previous findings, the underlying mechanism(s) of the action remains unclear. Here, we investigate the possibility that microRNAs (miRNAs) are involved in the aspect. Methods: As a model of chronic fluorosis, SD rats received different concentrations of fluoride in their drinking water for 3 or 6 months and SH-SY5Y cells were exposed to fluoride. Literature reviews and bioinformatics analyses were used to predict and real-time PCR to measure the expression of 12 miRNAs; an algorithm-based approach was applied to identify multiply potential target-genes and pathways; the dual-luciferase reporter system to detect the association of miR-132–3p with MAPK1; and fluorescence in situ hybridization to detect miR-132–3p localization. The miR-132–3p inhibitor or mimics or MAPK1 silencing RNA were transfected into cultured cells. Expression of protein components of the MAPK pathway was assessed by immunofluorescence or Western blotting. Results: In the rat hippocampus exposed with high fluoride, ten miRNAs were down-regulated and two up-regulated. Among these, miR-132–3p expression was down-regulated to the greatest extent and MAPK1 level (selected from the 220 genes predicted) was corelated with the alteration of miR-132–3p. Furthermore, miR-132–3p level was declined, whereas the protein levels MAPK pathway components were increased in the rat brains and SH-SY5Y cells exposed to high fluoride. MiR-132–3p up-regulated MAPK1 by binding directly to its 3′-untranslated region. Obviously, miR-132–3p mimics or MAPK1 silencing RNA attenuated the elevated expressions of the proteins components of the MAPK pathway induced by fluorosis in SH-SY5Y cells, whereas an inhibitor of miR-132–3p just played the opposite effect. Conclusion: MiR-132–3p appears to modulate the changes of MAPK signaling pathway in the CNS associated with chronic fluorosis.

In this study, 316L stainless steel repaired layers were fabricated on a 27SiMn steel substrate using weld surfacing and laser cladding, respectively. The microstructures of repaired layers were subjected to dedicated characterizations using X-ray diffraction, electron backscatter diffraction and energy dispersive spectrometry, with their surface properties (corrosion and wear performances) measured and correlated with the revealed microstructure features. Both the weld-surfacing and the laser-cladding repaired layers (RLs) are found to be mainly comprised of columnar-grained γ-Fe phase, with their average grain widths measured as 17.0 ± 20 μm and 15.3 ± 13.7 μm, respectively. Between their RLs and substrates, an unreported transition layer (∼50 μm in thickness) jointly composed of γ-Fe and α-Fe is identified. After surface property tests, the RL fabricated by the laser cladding shows superior corrosion and wear resistance to that of the weld surfacing. Comprehensive analyses based on their microstructure features suggest that the better performance of the laser-cladding RL can be ascribed to the laser-induced ultrafast cooling that allows denser and finer grain structures to be produced.

Renal fibrosis (RF) is a common pathological feature of chronic kidney disease (CKD), which remains a major public health problem. As now, there is still lack of chemical or biological drugs to reverse RF. Shen-shuai-yi Recipe (SSYR) is a classical Chinese herbal formula for the treatment of CKD. However, the effects and mechanisms of SSYR in treating RF are still not clear. In this study, the active constituents SSYR for treating RF were explored by UHPLC-Q-Orbitrap HRMS. Bioinformatics analyses were employed to analyze the key pharmacological targets and the core active constituents of SSYR in the treatment of RF. In experimental validation, vehicle or SSYR at doses of 2.12 g/kg/d and 4.25 g/kg/d were given by orally to unilateral ureteric obstruction (UUO) mice. 13 days after treatment, we detected the severity of renal fibrosis, extracellular collagen deposition and pre-fibrotic signaling pathways. Bioinformatics analysis suggested that signal transducer and activator of transcription 3 (STAT3) was the core target and lenticin, luteolin-7-O-rutinoside, hesperidin, kaempferol-3-O-rutinoside, and 3,5,6,7,8,3′,4′-heptamethoxyflavone were the key constituents in SSYR for treating RF. SSYR significantly reduced the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), collagen-I and alleviated renal interstitial collagen deposition in UUO kidneys. In mechanism, SSYR potently blocked the phosphorylation of STAT3 and Smad3 and suppressed the expression of connective tissue growth factor (CTGF). Collectively, SSYR can ameliorate RF via inhibiting the phosphorylation of STAT3 and its downstream and reducing the collagen deposition, suggesting that SSYR can be developed as a novel medicine for treating RF.

We present a protocol for the hierarchical controlled joint remote implementation of the partially unknown operations of m qudits belonging to some restricted sets by using m multiparticle high-dimensional entangled states as the quantum channel. All the senders share the information of the partially unknown operations and cooperate with each other to implement the partially unknown operations on the remote receiver's quantum system. The receivers are hierarchized in accordance with their abilities to reconstruct the desired state. The agents in the upper grade need only cooperate with one of the lower-grade agents, and the agents in the lower grade need the cooperation of all the other agents. The protocol has the advantage of having high channel capacity by using a high-dimensional entangle state as the quantum channel for the hierarchial controlled joint remote implementation of partially unknown quantum operations of m qudits. [ABSTRACT FROM AUTHOR]

Object detection can accurately identify and locate targets in images, serving basic industries such as agricultural monitoring and urban planning. However, targets in remote sensing images have random rotation angles, which hinders the accuracy of remote sensing image object detection algorithms. In addition, due to the long-tailed distribution of detected objects in remote sensing images, the network finds it difficult to adapt to imbalanced datasets. In this article, we designed and proposed the Dynamic Optimization and Update network (DOUNet). By introducing adaptive rotation convolution to replace 2D convolution in the Region Proposal Network (RPN), the features of rotating targets are effectively extracted. To address the issues caused by imbalanced data, we have designed a long-tail data detection module to collect features of tail categories and guide the network to output more balanced detection results. Various experiments have shown that after two stages of feature learning and classifier learning, our designed network can achieve optimal performance and perform better in detecting imbalanced data. [ABSTRACT FROM AUTHOR]