Inhibiting oxidative damage in early stage of Alzheimer’s disease (AD) is considered as a strategy for AD treatment. Our previous study has shown that Panax notoginseng saponins (PNS) have an ...antiaging action by increasing the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) in the serum of aged rats. In this study, we aimed to investigate the effects of PNS on antioxidant enzymes and uncoupling proteins (UCPs) involved in oxidative stress in AD mice. The results showed that PNS prevented neuronal loss in hippocampal CA1 region and alleviated pathomorphological change of neurons in CA1 region. Moreover, PNS inhibited the production of 8-hydroxydeoxyguanosine (8-OHdG), enhanced the expressions and activities of SOD, CAT, and GSH-PX, and improved the mRNA and protein levels of UCP4 and UCP5 in the brains of SAMP8 mice. Together, our study shows that PNS has the ability to protect neurons in AD brain from oxidative stress damage through attenuating the production of 8-OHdG, enhancing the activities of antioxidant enzymes and the expressions levels of UCP4 and UCP5. Accordingly, PNS may be a promising agent for AD treatment.
Abstract
Lycium ruthenicum is an important ecoeconomic thorny shrub. In this study, the L. ruthenicum plants of a clone showed two types of ‘fewer leaves without thorn’ and ‘more leaves with thorns’ ...under the same condition after transplanting. Microscopic observation revealed that the apical buds of the thornless (Thless) and thorny (Thorny) branches should be selected as materials for further study. RNA-Seq analysis showed that the KEGG pathway of starch and sucrose metabolism and differentially expressed genes of sugar transport protein 13 (SUT13), sucrose synthase (SUS), trehalose-phosphate phosphatase (TPP) and trehalose-phosphate synthase (TPS) were significantly up-regulated in Thorny. The results of qRT-PCR confirmed the accuracy and credibility of the RNA-Seq. The content of sucrose in Thorny was significantly higher than that in Thless, but the content of trehalose-6-phosphate (T6P) was opposite. Leaf-clipping treatments reduced sucrose content and inhibited the occurrence/development of branch-thorns; exogenous sucrose of 16 g l−1 significantly promoted the occurrence and growth of branch-thorns, and the promotion effects were significantly higher than those treated with non-metabolizable sucrose analogs (isomaltolose and melitose). These findings suggested that sucrose might play a dual role of energy and signal in the occurrence of branch-thorns. Higher sucrose supply in apical buds from more leaves promoted the occurrence of branch-thorns via a lower content of T6P and higher expression levels of SUS, TPP and TPS, whereas fewer leaves inhibited the occurrence. The molecular hypothesis model of the leaf number/sucrose supply regulating the occurrence of branch-thorns in L. ruthenicum was established in the study, which provides foundation for breeding both Thless L. ruthenicum and Thless types of other species.
The effect of pH regulation on schwertmannite bio-synthesis and its As removal ability were investigated in this study. The total Fe precipitation efficiency in a conventional schwertmannite ...bio-synthesis system (CK) reached 26.5%, with a mineral weight of 5.21 g/L and a mineral specific surface area of 3.18 m
2
/g. The total Fe precipitation efficiency increased to 88.4-95.8%, the mineral weight increased to 17.10-18.62 g/L, and the specific surface area increased to 3.61-90.67 m
2
/g of five different treatments in which the system pH was continually adjusted to 2.50, 2.70, 2.90, 3.10, and 3.30 every 3 h, respectively. The very small amounts of schwertmannite were transformed to goethite when the system pH was periodically adjusted to 2.90, 3.10 and 3.30. The increased specific surface area of bio-schwertmannite was due to the contribution of mesopores, with most pores having a diameter of 2-20 nm. For actual As-containing groundwater (27.4 μg/L), the As removal rate was 52.9% for bio-schwertmannite collected from the CK system. However, the removal rate of As increased to 92.7-97.8% for minerals which were collected after five adjusted pH treatments. The outcomes of this study provide a fresh insight into the bio-synthesis regulation of schwertmannite, and have great significance for the treatment of As-containing groundwater.
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•Algorithm for unmixing the flow spectra with partly known components.•Gauss model to fit the spectrum of the unknown component.•GA to optimize the parameters of the Gauss ...models.•Verify the algorithms by the simulated and experimental cyanobacteria data.
Spectral unmixing algorithm is one of the key technologies for spectral flow cytometer in biology, chemistry and medicine. The proposed algorithm can separate the overlapping spectra automatically without the premeasured single stained or un-stained samples as the basic pure spectra. Genetic algorithm is adopted to search the optimal positions and peak sharps of the basic spectra derived from the unknown components, and then the concentration of each component can be estimated simultaneously by least squares method. Compared with conventional methods, the proposed algorithm has a wider application scope, such as the multi-stained samples with unknown components or the samples with auto-fluorescence. In the simulation, the convergence rate, accuracy and stability of the proposed algorithm are evaluated under the conditions of completely and partly unknown components. In the experiment, the flow spectra of cyanobacteria are processed, and the results demonstrate the feasibility and effectiveness of the proposed algorithm.
Previous studies have shown that toxic metal exposure can have adverse effects on the nervous system of children, but the toxicology of metal co-exposure on neurodevelopment remains to be clarified. ...Brain derived neurotrophic factor (BDNF) plays an important role in nervous system development, but the possible effects of metal co-exposure on the serum BDNF concentrations of children remain unknown. A total of 561 children living in Taizhou City, China were recruited to participate in our cross-sectional multicenter survey. We measured their blood Pb, Hg, Al and Mn levels and serum BDNF concentrations as well as determined their associations in the total and within sex subgroups. The geometric means of the blood Pb, Hg, Al and Mn levels in all the participants were 67.18 μg/L, 1.01 μg/L, 52.03 μg/L and 18.26 μg/L, respectively. The serum BDNF concentration in children was 19.45 ng/mL. After adjusting for confounders, the blood Pb levels were significantly negatively associated with the serum BDNF concentrations in all the subjects and boys but not in girls. In addition, a significantly negative interaction between blood Pb and blood Hg and a positive interaction between blood Pb and blood Al on serum BDNF concentrations were also observed in boys but not in girls. Our findings highlight the toxic effects of metal co-exposure on serum BDNF levels in pre-school children and indicate that these effects might differ by gender, which suggest that special attention should be paid to the sex-specific effects of metal exposure.
•The blood Pb levels were negatively associated with the serum BDNF concentrations in boys, but not in girls.•A negative interaction between the blood Pb and Hg levels on serum BDNF concentrations was found in boys, but not in girls.•A positive interaction between the blood Pb and Al levels on serum BDNF concentrations was found in boys, but not in girls.•Boys are more susceptible to environmental toxic exposure in pre-school children.
•Lead exposure induced early AD-like pathology by increasing Aβ accumulation and amyloid plaque deposition.•Lead exposure increased APP expression and activation of the SREBP2-BACE1 pathway in young ...rat brains.•Lead exposure potentiated early AD-like pathology by disrupting brain cholesterol metabolism.•Lead exposure disturbed cholesterol metabolism via affecting the expression of LXR-a, ABCA1, HMG-CR and LDL-R.
Lead exposure has been evidenced as a risk factor for Alzheimer’s disease (AD), mainly affecting the ageing. However, the early manifestation and mechanisms of AD-like pathology induced by lead exposure remains to be elucidated. Considering the fact that impaired cholesterol metabolism is associated with many neurodegenerative disorders including AD, in this study we focused on the role of cholesterol metabolism in lead induced premature AD-like pathology. We treated weaning rats with lead at different concentrations for 4 weeks. We found that developmental lead exposure increased amyloid-beta (Aβ) accumulation and amyloid plaque deposition in the cortex and hippocampus. Lead exposure increased amyloid precursor protein (APP) expression and activated the sterol regulatory element binding protein 2 (SREBP2)-beta secretase (BACE1) pathway. In addition, we found that lead exposure decreased cholesterol levels by upregulating the expression of liver X receptor-a (LXR-a) and ATP-binding cassette transporter protein family member A1 (ABCA1) and decreasing the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low density lipoprotein receptor (LDL-R) in young rat brain tissues. Taken together, our data demonstrated that developmental lead exposure induced early manifestation of AD-like pathology and disturbed cholesterol metabolism in young rat brains.
Technology selection is an important part of enterprises sustainable development. The best technologies could create significant competitive advantages for an enterprise to realize its profit growth ...and capability improvement, and then realize its sustainable development. However, due to the complexity of technology selection, decision makers are faced with a difficult task, therefore, to select the best technologies, we introduce the evaluation based on distance from average solution (EDAS) method to aggregate ultimate cross-efficiency scores. By calculating the positive distance from average solution (PDA) and the negative distance from average solution (NDA), we can get the appraisal scores (AS) to rank for each rated decision making unit (DMU). Finally, an example of technology selection is illustrated to examine the validity of the proposed method.
Early molecular events after the exposure of heavy metals, such as aberrant DNA methylation, suggest that DNA methylation was important in regulating physiological processes for animals and ...accordingly could be used as environmental biomarkers. In the present study, we found that copper (Cu) exposure increased lipid content and induced the DNA hypermethylation at the whole genome level. Especially, Cu induced hypermethylation of glucose-regulated protein 78 (grp78) and peroxisome proliferator-activated receptor gamma coactivator-1α (pgc1α). CCAAT/enhancer binding protein α (C/EBPα) could bind to the methylated sequence of grp78, whereas C/EBPβ could not bind to the methylated sequence of grp78. These synergistically influenced grp78 expression and increased lipogenesis. In contrast, DNA methylation of PGC1α blocked the specific protein 1 (SP1) binding and interfered mitochondrial function. Moreover, Cu increased reactive oxygen species (ROS) production, activated endoplasmic reticulum (ER) stress and damaged mitochondrial function, and accordingly increased lipid deposition. Notably, we found a new toxicological mechanism for Cu-induced lipid deposition at DNA methylation level. The measurement of DNA methylation facilitated the use of these epigenetic biomarkers for the evaluation of environmental risk.
•Cu elevated the lipid content, oxidative and ER stress and damaged mitochondrial role.•Cu induced the genome-wide methylation and hypermethylation of GRP78 and PGC1α.•ROS mediated Cu-induced changes of DNA methylation, ER stress and mitochondrial function.•GRP78 and PGC1α transcription was affected by the promoter hypermethylation.
Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In ...this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-β levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.
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•Lead (Pb)-induced neurotoxicity might be associated with imbalance of cholesterol homeostasis.•Supplementation of cholesterol ameliorated Pb-induced learning and memory impairments.•Amelioration of Pb-induced injury may be linked with activation of BDNF signaling and cholesterol metabolism.
The green supplier selection has gradually become a hot topic around the world. To achieve the purpose of optimal decision-making, it is of great importance to process the imprecise and ambiguous ...information that may exist in the evaluation and selection of green suppliers. In the present article, first, converting the imprecise and ambiguous information into interval-valued Pythagorean fuzzy numbers (IVPFNs) through the Likert scale. Then, using the interval-valued Pythagorean fuzzy weighted average (IVPFWA) operator and multiplicative theory to introduce the IVPFNs into the non-radial SE-BCC model of Data Envelopment Analysis (DEA), we developed the DEA model in the interval-valued Pythagorean fuzzy environment. Later, ranking all decision-making units (DMUs) to be evaluated and selecting the best of them. Moreover, The proposed model can not only deal with the case where the quantitative indicators are interval-valued numbers, but also solve the problem of qualitative analysis in the evaluation process. Finally, a numerical example of green suppliers selection is provided to demonstrate the feasibility and usefulness of the model.
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