Melanosomes are specialized membrane-bound organelles within which melanin is synthesized and stored.The levels of melanin can be effectively reduced by inhibiting melanin synthesis or promoting melanosome degradation...Melanosomes are specialized membrane-bound organelles within which melanin is synthesized and stored.The levels of melanin can be effectively reduced by inhibiting melanin synthesis or promoting melanosome degradation via autophagy.Ceramide,a central molecule in sphingolipid metabolism,has been widely implicated in the regulation of autophagy.Few researchers have addressed the potential effects of ceramide analogs on suppressing melanin synthesis.However,whether ceramide can induce melanosome autophagy and the potential autophagy-dependent mechanism underlying this phenomenon remain unknown.Here,an active compound from the marine microalgae Emiliania huxleyi extract was firstly isolated and identified as a long-chain C22-ceramide(C22-Cer).In vitro results of mouse B16 melanoma cell experiments showed that treatment with 2-5µmol/L C22-Cer significantly suppressed the increase ofα-MSH-induced melanin levels and tyrosinase activity without cytotoxicity.C22-Cer induced typical hallmarks of autophagy such as accumulation of autophagosomes,enhanced autophagic flux and microtubule-associated protein light chain 3,LC3-II expression,and p62 degradation through activating c-Jun N-terminal kinase(JNK)directly.Furthermore,C22-Cer activated JNK-Bcl-2 signaling,dissociated the Beclin1/Bcl-2 complex,and induced melanosome autophagy without affecting the expression of MITF.Besides,the Ca^(2+)influx induced by treatment with C22-Cer further increased the substantial accumulation of autophagosomes.Together,we found a novel marine-derived compound,C22-Cer,targeting JNK pathway and Ca^(2+)signaling to induce melanosome autophagy and suppress melanin accumulation in B16 cells.This study implicates that C22-Cer might be a potential therapeutic mediator against skin pigmentation in mammals.展开更多
基金supported by the National Natural Science Foundation of China(Nos.42076086 and 32202068)Fujian Province Natural Science Foundation of China(Nos.2019J01696 and 2022J01332)the Fujian Province Young and Middle-Aged Teacher Education Research Project(No.JAT200247).
文摘Melanosomes are specialized membrane-bound organelles within which melanin is synthesized and stored.The levels of melanin can be effectively reduced by inhibiting melanin synthesis or promoting melanosome degradation via autophagy.Ceramide,a central molecule in sphingolipid metabolism,has been widely implicated in the regulation of autophagy.Few researchers have addressed the potential effects of ceramide analogs on suppressing melanin synthesis.However,whether ceramide can induce melanosome autophagy and the potential autophagy-dependent mechanism underlying this phenomenon remain unknown.Here,an active compound from the marine microalgae Emiliania huxleyi extract was firstly isolated and identified as a long-chain C22-ceramide(C22-Cer).In vitro results of mouse B16 melanoma cell experiments showed that treatment with 2-5µmol/L C22-Cer significantly suppressed the increase ofα-MSH-induced melanin levels and tyrosinase activity without cytotoxicity.C22-Cer induced typical hallmarks of autophagy such as accumulation of autophagosomes,enhanced autophagic flux and microtubule-associated protein light chain 3,LC3-II expression,and p62 degradation through activating c-Jun N-terminal kinase(JNK)directly.Furthermore,C22-Cer activated JNK-Bcl-2 signaling,dissociated the Beclin1/Bcl-2 complex,and induced melanosome autophagy without affecting the expression of MITF.Besides,the Ca^(2+)influx induced by treatment with C22-Cer further increased the substantial accumulation of autophagosomes.Together,we found a novel marine-derived compound,C22-Cer,targeting JNK pathway and Ca^(2+)signaling to induce melanosome autophagy and suppress melanin accumulation in B16 cells.This study implicates that C22-Cer might be a potential therapeutic mediator against skin pigmentation in mammals.
文摘基于深度学习的鸟鸣声识别是当前研究的热点,现有基于语谱图的识别方法无法提取帧间的时序信息,文章提出了一种基于C-LSTM(CNN-Long Short-Term Memory)的鸟鸣声识别方法,该方法以梅尔语谱图为输入,通过CNN提取谱图特征后,输入到LSTM模型中,进一步提取不同帧之间的时序特征,基于该特征实现鸟鸣声的分类。选择Xeno-Canto中的5种鸟类作为研究对象,对比了VGG16模型和C-LSTM模型的平均识别准确率(Mean Average Precision,MAP)值。结果表明,以VGG16和C-LSTM作为识别模型时,测试集的MAP值分别为0.8628和0.9147,文章提出模型的MAP提升5.19%。说明文章提出的C-LSTM更适合于鸟类物种识别,具有更高的识别性能。