DNA N4-胞嘧啶甲基化(N4-methylcytosine,4mC)是一种重要的表观遗传修饰,能在基因表达、细胞修复、DNA复制及保护等方面发挥作用.机器学习算法在预测4mC位点时,一个重要的环节是特征提取,为更充分地提取数据特征,进一步提高4mC位点的预...DNA N4-胞嘧啶甲基化(N4-methylcytosine,4mC)是一种重要的表观遗传修饰,能在基因表达、细胞修复、DNA复制及保护等方面发挥作用.机器学习算法在预测4mC位点时,一个重要的环节是特征提取,为更充分地提取数据特征,进一步提高4mC位点的预测准确率,提出了一种基于双层卷积神经网络的4mC位点预测模型.首先,将序列数据进行特征编码,搭建具有双卷积层和双池化层的卷积神经网络模型,采用L2范式正则化避免模型过拟合,并采用10折交叉验证保证模型预测的稳定性;其次,对模型参数进行调试,选取预测能力较高的参数组合进行模型训练;最后,将模型的4mC位点预测能力与几种已有算法进行比较.结果表明,双层卷积神经网络模型具有较好的预测性能和鲁棒性,优于基于一般机器学习和单层卷积神经网络的4mC位点预测算法,有效提高了4mC位点的预测能力.展开更多
Objective: To investigate protective effect of Cordyceps sinensis(CS) through autophagyassociated adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway in acute k...Objective: To investigate protective effect of Cordyceps sinensis(CS) through autophagyassociated adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway in acute kidney injury(AKI)-induced acute lung injury(ALI). Methods: Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline(NS)-treated sham group(sham group), NS-treated ischemia reperfusion injury(IRI) group(IRI group), and low-(5 g/kg·d) and high-dose(10 g/kg·d) CS-treated IRI groups(CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry(W/D) ratio of lung, levels of serum creatinine(Scr), blood urea nitrogen(BUN), inflammatory cytokines such as interleukin-βand tumor necrosis factor-α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde(MDA) and myeloperoxidase(MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 Ⅱ/light chain 3 Ⅰ(LC3-Ⅱ/LC3-Ⅰ), uncoordinated-51-like kinase 1(ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively. Results: The renal IRI induced pulmonary injury following AKI,resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO(P<0.01);all of these were reduced in the CS groups(P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower(P<0.05 or P<0.01), while those of LC3-Ⅱ/LC3-Ⅰ, ULK1, and AMPK were significantly higher in the CS2 group(P<0.05 or P<0.01). Conclusion:CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.展开更多
基金the National Natural Science Foundation of China(No.81460682)the Natural Science Foundation of Guangdong Province(No.2020A1515010566)the Shenzhen Foundation of Science and Technology Research and Development(No.JCYJ20190809102413156)。
文摘Objective: To investigate protective effect of Cordyceps sinensis(CS) through autophagyassociated adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway in acute kidney injury(AKI)-induced acute lung injury(ALI). Methods: Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline(NS)-treated sham group(sham group), NS-treated ischemia reperfusion injury(IRI) group(IRI group), and low-(5 g/kg·d) and high-dose(10 g/kg·d) CS-treated IRI groups(CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry(W/D) ratio of lung, levels of serum creatinine(Scr), blood urea nitrogen(BUN), inflammatory cytokines such as interleukin-βand tumor necrosis factor-α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde(MDA) and myeloperoxidase(MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 Ⅱ/light chain 3 Ⅰ(LC3-Ⅱ/LC3-Ⅰ), uncoordinated-51-like kinase 1(ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively. Results: The renal IRI induced pulmonary injury following AKI,resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO(P<0.01);all of these were reduced in the CS groups(P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower(P<0.05 or P<0.01), while those of LC3-Ⅱ/LC3-Ⅰ, ULK1, and AMPK were significantly higher in the CS2 group(P<0.05 or P<0.01). Conclusion:CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.
