4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway. 相似文献
Machine Learning - Traditional clustering algorithms focus on a single clustering result; as such, they cannot explore potential diverse patterns of complex real world data. To deal with this... 相似文献
With the emergence of large-scale knowledge base, how to use triple information to generate natural questions is a key technology in question answering systems. The traditional way of generating questions require a lot of manual intervention and produce lots of noise. To solve these problems, we propose a joint model based on semi-automated model and End-to-End neural network to automatically generate questions. The semi-automated model can generate question templates and real questions combining the knowledge base and center graph. The End-to-End neural network directly sends the knowledge base and real questions to BiLSTM network. Meanwhile, the attention mechanism is utilized in the decoding layer, which makes the triples and generated questions more relevant. Finally, the experimental results on SimpleQuestions demonstrate the effectiveness of the proposed approach. 相似文献
To overcome the drawbacks of solid microporous materials for CO2 capture, this proof‐of‐concept study demonstrates a low‐cost and rapid method for producing composites consisting of hypercrosslinked polymers (HCP) with a polyethyleneimine (PEI) binder. The resulting materials capture CO2 through physical and chemical absorption simultaneously. Compared with HCP, the composites exhibit higher CO2 uptake, higher volumetric density, and improved tolerance to water which is attributed to the PEI binder. 相似文献
Malondialdehyde (MDA) was selected to represent a secondary by-product of lipid peroxidation during rice ageing. This study aimed to investigate the effects of MDA modification on the structural characteristics of rice protein. The results showed that as MDA concentration increased, rice protein carbonyl and disulphide groups increased, but sulphydryl content decreased. The blue shift of maximum fluorescence peak, the decrease of rice protein intrinsic fluorescence intensity and the reduction of surface hydrophobicity indicated the formation of protein aggregates caused by MDA oxidative modification. The results of molecular weight distribution and particle size distribution showed that MDA modification resulted in the formation of soluble protein aggregates, and the decrease of rice protein solubility indicated that insoluble protein aggregates were formed. Results of protein electrophoresis showed that MDA modification contributed to rice protein aggregation via non-disulphide covalent bonds. The results showed that rice protein gradually aggregated with increasing MDA concentration. 相似文献
Two-dimensional (2D) nanomaterials have attracted a great deal of attention since the discovery of graphene in 2004, due to their intriguing physicochemical properties and wide-ranging applications in catalysis, energy-related devices, electronics and optoelectronics. To maximize the potential of 2D nanomaterials for their technological applications, controlled assembly of 2D nanobulding blocks into integrated systems is critically needed. This mini review summarizes the reported strategies of 2D materials-based assembly into integrated functional nanostructures, from in-situ assembly method to post-synthesis assembly. The applications of 2D assembled integrated structures are also covered, especially in the areas of energy, electronics and sensing, and we conclude with discussion on the remaining challenges and potential directions in this emerging field.