RESUMO
BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating medical emergency with high mortality and severe neurological deficit. ICH-related poor outcomes are due to a combination of pathological processes that could be complicated by secondary insults. TWIK-related K+ channel 1 (TREK-1) is a two-pore-domain potassium channel that is highly expressed in the mammalian nervous system. Previous studies have shown that TREK-1 channels play important roles in various central nervous system diseases. However, its role in the secondary injuries after intracerebral hemorrhage remains unknown. In this study, we explored the function of TREK-1 in secondary blood-brain barrier injuries and neuroinflammation after intracerebral hemorrhage in mice. METHODS: Adult male TREK-1-/- mice and WT mice were subjected to a collagenase-induced ICH model. Immunostaining, western blot, and enzyme-linked immunosorbent assay were used to assess inflammatory infiltration and neuronal death. Blood-brain barrier compromise was assessed using electron microscopy and Evans Blue dye injection on days 1 and 3 after intracerebral hemorrhage. Magnetic resonance imaging and behavioral assessments were conducted to evaluate the neurologic damage and recovery after intracerebral hemorrhage. RESULTS: Genetic deficiency of TREK-1 channel exacerbated blood-brain barrier impairment and promoted cerebral edema after intracerebral hemorrhage. Meanwhile, TREK-1 deficiency aggravated focal inflammatory featured by the increased recruitment of microglia and neutrophils, the enhanced secretion of proinflammatory factors interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and cell adhesion molecules (CAMs). Furthermore, TREK-1 deficiency promoted neuronal injury and neurological impairment. CONCLUSIONS: These results establish the first in vivo evidence for the protective role of TREK-1 in blood-brain barrier injury and neuroinflammation after intracerebral hemorrhage. TREK-1 may thereby be harnessed to a potential therapeutical target for the treatment of intracerebral hemorrhage.
Assuntos
Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Animais , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
This study focuses on the financing difficulties of small and medium enterprises (SMEs) in China to study the application of blockchain technology in developing the real economy. Deep learning neural network is applied to the vulnerability analysis and detection of smart contracts in blockchain technology by analyzing the connotation of blockchain technology and deep learning. A multiparty joint financial service platform based on blockchain technology is established to help SMEs financing institutions reduce transaction costs, thereby helping them reduce loan interest rates. Finally, Jiangsu Province is studied as a pilot unit. The results show that the Recall and F-score of Bidirectional Neural Network for smart contract vulnerability detection are higher than those of the original neural network. The Recall rate and F-score value of the Wide and Deep model are up to 96.2% and 94.7%, which are higher than those of other vulnerability detection schemes. The Timestamp vulnerability has the highest Recall rate, 94.2%, which can rely on a large amount of valid data to improve detection efficiency. The distribution of financing needs of SMEs in Jiangsu Province from 2020 to 2021 shows that the loan number of SMEs is generally not high. Still, financial institutions and enterprises must spend the same transaction cost. After a technology company in Nanjing made a loan through a blockchain financial service platform, its financing cost decreased by 0.5331%. Blockchain technology has played a great role in the financing process of SMEs, reducing intermediate links and credit costs, and promoting the development of SMEs and the real economy.