Optimization design of the sound absorbing structure of double-layer porous metal material with air layer based on genetic algorithm.

An acoustic absorption structure of a double-layer porous metal material with air layers is proposed. The Johnson-Champoux-Allard (JCA) model combined with the transfer matrix method (TMM) was used to establish the theoretical calculation model of the sound absorption coefficient (SAC). Meanwhile, the SAC between 500 and 6300 Hz were measured with an impedance tube. The errors between the theoretical and experimental values were compared to illustrate the good predictability of the theoretical model within the inverse estimations of the transport properties. The effects of the material placement order, material thickness, and cavity depth on the sound absorption performance from 200 to 5000 Hz were analyzed using the theoretical model. Further, a multi-objective function genetic algorithm was used to optimize the porous material's thickness and SAC to obtain an acoustic structure with a smaller thickness and higher sound absorption. A series of optimal solutions were obtained for acoustic structures with a total thickness of less than 70 mm. When the total thickness of the foam metal was 33.57 mm, the average SAC reached 0.853, which was significantly lower than the total thickness of the previous experiments. The multi-objective function genetic algorithm can provide a reliable solution for the optimal design of most sound-absorbing structures.

Novel melatonin-trientine conjugate as potential therapeutic agents for Alzheimer's disease.

Researchers continue to explore drug targets to treat the characteristic pathologies of Alzheimer's disease (AD). Some drugs relieve the pathological processes of AD to some extent, but the failed clinical trials indicate that multifunctional agents seem more likely to achieve the therapy goals for this neurodegenerative disease. Herein, a novel compound named melatonin-trientine (TM) has been covalently synthesized with the natural antioxidant compounds melatonin and the metal ion chelator trientine. After toxicological and pharmacokinetic verification, we elucidated the effects of intraperitoneal administration of TM on AD-like pathology in 6-month-old mice that express both the ß-amyloid (Aß) precursor protein and presenilin-1 (APP/PS1). We found that TM significantly decreased Aß deposition and neuronal degeneration in the brains of the APP/PS1 double transgenic mice. This result may be due to the upregulation of iron regulatory protein-2 (IRP2), insulin degrading enzyme (IDE), and low density lipoprotein receptor related protein 1 (LRP1), which leads to decreases in APP and Aß levels. Additionally, TM may promote APP non-amyloidogenic processing by activating the melatonin receptor-2 (MT2)-dependent signaling pathways, but not MT1. In addition, TM plays an important role in blocking γ-secretase, tau hyperphosphorylation, neuroinflammation, oxidative stress, and metal ion dyshomeostasis. Our results suggest that TM may effectively maximize the therapeutic efficacy of targeting multiple mechanisms associated with AD pathology.

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The high-efficiency phosphate solubilizing mutants of Penicillium oxalicum YTY were screened by mutagenesis of ion beam combined with UV. We analyzed the changes and correlation of phosphate solubilizing ability, pH, and organic acid for YTY and its mutants, and examined the phosphate solubilizing mechanism of P. oxalicum YTY. The results showed that five high-efficiency mutants, P9-8, P9-9, P15-4, P15-6, and P15-7 were screened, and that the phosphate solubili-zing ability of mutants was increased by more than 60% compared with YTY. In the process of pho-sphorus solubilization, both phosphorus solubilizing ability and rate of mutants were higher than that of YTY, and the mutants pH was significantly lower than YTY. The type and content of organic acids secreted by the mutants showed some variations. All mutants and YTY could secrete lactic acid, acetic acid and oxalic acid, while P9-8 also produced citric acid. The pH and the phosphate solubilizing ability of YTY and its mutants had a significant negative correlation. Phosphate solubilizing ability with organic acid and pH were all significantly correlated for YTY and the mutants, except P15-4. Organic acids and low environmental pH reduced by organic acids were the probable mechanism for P. oxalicum to dissolve phosphorus. Radiation of ion beam combined with UV could change the type and content of organic acids of P. oxalicum YTY, and initiate other H+ releasing pathways to lower pH, and participate phosphorus dissolution. The study provided biological mate-rials and theoretical basis for the research and development of high-efficiency phosphate solubilizing P. oxalicum and understanding the phosphate solubilizing mechanism of P. oxalicum.

α-Lipoic Acid Maintains Brain Glucose Metabolism via BDNF/TrkB/HIF-1α Signaling Pathway in P301S Mice.

The microtubule-associated protein tau is closely correlated with hypometabolism in Alzheimer's disease (AD). α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research. However, if LA affects glucose metabolism when it reverses tau pathology remains unclear, especially concerning the potential mechanism. Therefore, we make a further study using the P301S mouse model (a tauopathy and AD mouse model which overexpressing fibrillary tau) to gain a clear idea of the aforementioned problems. Here, we found chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brains. Meanwhile, we found that LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and DNA repair enzymes (OGG1/2 and MTH1). Further, we found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway by LA treatment.

Iron Pathophysiology in Alzheimer's Diseases.

Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. Increasing evidence suggests that disorders of metal ion metabolism in the brain are one of the risk factors for the pathogenesis of AD. Iron, one of the endogenous metal ions, involves in many important physiological activities in the brain. Iron metabolism mainly depends on iron regulatory proteins including ferritin, transferrin and transferrin receptor, hepcidin, ferroportin, lactoferrin. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, leads to cell death, and ultimately influences the process of ß-amyloid (Aß) misfolding and plaque aggregation. Although the results are different, in general, iron has deposition in different brain regions of AD patients, which may impair normal cognitive function and behavior. Therefore, neuroimaging changes have so far been largely attributed to focal iron deposition accompanying the plaques at preclinical stages of AD, and iron-targeted therapeutic strategies have become a new direction. Iron chelators have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Future research will also focus on iron as an opportunity to study the mechanism of the occurrence and development of AD from the iron steady state to more fully clarify the etiology and prevention strategies.

Iron Exposure and the Cellular Mechanisms Linked to Neuron Degeneration in Adult Mice.

Although the causal relationship between Alzheimer's disease (AD) and iron overload remains unclear, iron dyshomeostasis or improper transport mechanisms are speculated to lead to the accumulation of this neurotoxic metal in the hippocampal formation and other cerebral areas related to neurodegenerative diseases, resulting in the formation of reactive oxygen species (ROS) and, ultimately, cell death. In this study, exposure to high dietary iron (HDI) revealed no significant difference in the number of iron-positive cells and iron content in the cortex and hippocampal region between wild-type (WT) and APP/PS1 mice; however, compared with the control mice, the HDI-treated mice exhibited upregulated divalent metal transporter 1 (DMT1) and ferroportin (Fpn) expression, and downregulated transferrin receptor (TFR) expression. Importantly, we confirmed that there were significantly fewer NeuN-positive neurons in both APP/PS1 and WT mice given HDI, than in the respective controls. Moreover, this iron-induced neuron loss may involve increased ROS and oxidative mitochondria dysfunction, decreased DNA repair, and exacerbated apoptosis and autophagy. Although HDI administration might trigger protective antioxidant, anti-apoptosis, and autophagy signaling, especially in pathological conditions, these data clearly indicate that chronic iron exposure results in neuronal loss due to apoptosis, autophagy, and ferroptosis, hence increasing the risk for developing AD.

Disruption of brain zinc homeostasis promotes the pathophysiological progress of Alzheimer's disease.

Zinc is abundant in the brain, where it plays an important role in synaptic plasticity and in learning; however, excessive zinc is toxic to neuronal cells, and dyshomeostasis of zinc in the brain is a contributing factor for Alzheimer's disease (AD). Deposition of zinc has been detected in senile plaques in the form of zinc-Aß (ß-amyloid) complexes. Recent studies have demonstrated that zinc exposure to the brain enhances ß-amyloid precursor protein (APP) expression, amyloidogenic APP cleavage and plaque burden. Furthermore, alterations in zinc transporters, which are responsible for zinc homeostasis, occur in AD human brain and transgenic mouse models. These suggest that abnormal brain zinc homeostasis is involved in the pathophysiological progress of AD.