AIM:To investigate the hepatic protective effects of 5-methoxypsoralen(5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS:C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5...AIM:To investigate the hepatic protective effects of 5-methoxypsoralen(5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS:C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5,25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen(APAP) subcutaneously at a dose of 500 mg/kg.The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP.Twenty-four hours after APAP administration,blood samples of mice were analyzed for serum enzyme alanine transaminase(ALT),aspartate transaminase(AST),lactate dehydrogenase(LDH) levels,and malondialdehyde(MDA),reduced glutathione(GSH) and oxidized glutathione(GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS:Compared with the vehicle control group,the serum levels(IU/L) of ALT,AST and LDH were all increased significantly in APAP group(8355 ± 3940 vs 30 ± 21,P < 0.05;6482 ± 4018 vs 146 ± 58,P <0.05;24627 ± 10975 vs 1504 ± 410,P < 0.05).Compared with APAP group,the serum ALT levels(IU/L)(1674 ± 1810 vs 8355 ± 3940,P < 0.05;54 ± 39 vs 8355 ± 3940,P < 0.05;19 ± 9 vs 8355 ± 3940,P < 0.05),AST levels(IU/L)(729 ± 685 vs 6482 ± 4108,P < 0.05;187 ± 149 vs 6482 ± 4108,P < 0.05;141 ± 12 vs 6482 ± 4108,P < 0.05) and LDH levels(IU/L)(7220 ± 6317 vs 24 627 ± 10 975,P < 0.05;1618 ± 719 vs 24 627 ± 10 975,P < 0.05;1394 ± 469 vs 24 627 ± 10 975,P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups.Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP,including hepatocellular necrosis and infiltration of inflammatory cells,and the effect was dose-dependent.MDA levels(nmol/mg) were decreased by 5-MOP in a dose-dependent manner(0.98 ± 0.45 vs 2.15 ± 1.07,P > 0.05;0.59 ± 0.07 vs 2.15 ± 1.07,P < 0.05;0.47 ± 0.06 vs 2.15 ± 1.07,P < 0.05).The pretreatment of 5-MOP could also increase the GSH/GSSG ratio(3.834 ± 0.340 vs 3.306 ± 0.282,P > 0.05;5.330 ± 0.421 vs 3.306 ± 0.282,P < 0.05;6.180 ± 0.212 vs 3.306 ± 0.282,P < 0.05).In the group treated with 5-MOP but without APAP,the serum enzyme levels,the liver histopathologic manifestation,and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION:5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity,and does not cause liver injury at the protective doses.展开更多
目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的s...目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的shRNA(shRNA-METTL5)转染TNBC细胞后,用CCK-8、集落形成、伤口愈合以及Transwell实验分别检测细胞增殖活性、迁移与侵袭,Western blot检测Wnt/β-catenin信号关键蛋白的表达。构建异种移植瘤模型,验证敲降METTL5对TNBC细胞在体内生长以及Wnt/β-catenin信号活性的影响。结果METTL5在TNBC肿瘤组织和细胞系中表达上调(P<0.01)。敲降METTL5可抑制TNBC细胞的增殖、迁移和侵袭并降低了Wnt/β-catenin信号分子β-catenin、细胞周期蛋白(Cyclin)D1、基质金属蛋白酶(MMP)-2和MMP-7的表达(均P<0.01)。体内实验显示,敲降METTL5减缓了移植瘤生长和Wnt/β-catenin信号活性。结论敲降METTL5能抑制TNBC细胞的增殖、迁移与侵袭,其作用可能与抑制Wnt/β-catenin信号通路有关。展开更多
目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结...目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结肠癌组织、正常结肠细胞系(NCM460)和结直肠癌细胞系(SW620、HCT116、HT29、Lovo和SW480)中的表达。将SCL6A9过表达质粒及阴性对照(SLC6A9 OE、Vector)转染HT29细胞,将SCL6A9小干扰RNA及阴性对照(SLC6A9 siRNA1#、siRNA2#和Scramble)转染SW620细胞。划痕愈合实验和Transwell实验检测各组细胞的迁移、侵袭能力。Western blot和细胞免疫荧光检测EMT相关蛋白E-cadherin、Vimentin的表达水平。利用CCK-8法和构建裸鼠移植瘤模型检测SLC6A9过表达对结直肠癌细胞5-FU药物敏感性的影响。结果:与正常结肠组织和NCM460细胞相比,SLC6A9在结肠癌组织和结直肠癌细胞系中低表达(均P<0.05)。SLC6A9过表达引起E-cadherin蛋白表达增加,Vimentin蛋白水平降低,抑制结直肠癌细胞的迁移、侵袭(P<0.05)。SLC6A9低表达引起E-cadherin蛋白表达降低,Vimentin蛋白水平增加,促进结直肠癌细胞的迁移、侵袭能力(P<0.05)。SLC6A9过表达提高了5-FU的药物敏感性,并使肿瘤生长缓慢,质量减轻(P<0.05)。而SLC6A9低表达降低了5-FU的药物敏感性(P<0.05)。结论:SLC6A9过表达能够抑制结直肠癌细胞的迁移、侵袭和EMT进程,并增强5-FU对结直肠癌细胞的药物敏感性。展开更多
在复杂的自然环境中绿色柑橘生长形态各异,颜色与背景色相近,为有效识别绿色柑橘,提出一种基于混合注意力机制并改进YOLOv5模型的柑橘识别方法。首先,改进YOLOv5的网络结构,在主干网络中添加混合注意力机制,即在主干网络中的第2层嵌入SE...在复杂的自然环境中绿色柑橘生长形态各异,颜色与背景色相近,为有效识别绿色柑橘,提出一种基于混合注意力机制并改进YOLOv5模型的柑橘识别方法。首先,改进YOLOv5的网络结构,在主干网络中添加混合注意力机制,即在主干网络中的第2层嵌入SE(squeeze and excitation)注意力,第11层嵌入CA(coordinate attention)注意力;其次,改进网络模型特征融合结构,将YOLOv5模型Concat特征融合操作的下层分支放在模型C3模块之前,再与另一条上层分支进行特征融合;最后,改进模型分类损失函数,将YOLOv5模型的分类损失函数改成Varifocal Loss函数,加强绿色柑橘特征信息的提取,提高绿色柑橘检测精度。根据自然环境和柑橘自身的特点,对自建数据集进行分类,设计3组不同分类场景下柑橘的对比试验以验证其有效性。试验结果表明,改进后的YOLOv5-SC模型准确率为91.74%,平均精度为95.09%,F1为89.56%,在自然环境下对绿色柑橘的识别具有更高的准确率和更好的鲁棒性,为绿色水果智能采摘提供技术支持。展开更多
基金Supported by Drug Innovation Program of National Science and Technology Project,No.2009ZX09103-007
文摘AIM:To investigate the hepatic protective effects of 5-methoxypsoralen(5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS:C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5,25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen(APAP) subcutaneously at a dose of 500 mg/kg.The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP.Twenty-four hours after APAP administration,blood samples of mice were analyzed for serum enzyme alanine transaminase(ALT),aspartate transaminase(AST),lactate dehydrogenase(LDH) levels,and malondialdehyde(MDA),reduced glutathione(GSH) and oxidized glutathione(GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS:Compared with the vehicle control group,the serum levels(IU/L) of ALT,AST and LDH were all increased significantly in APAP group(8355 ± 3940 vs 30 ± 21,P < 0.05;6482 ± 4018 vs 146 ± 58,P <0.05;24627 ± 10975 vs 1504 ± 410,P < 0.05).Compared with APAP group,the serum ALT levels(IU/L)(1674 ± 1810 vs 8355 ± 3940,P < 0.05;54 ± 39 vs 8355 ± 3940,P < 0.05;19 ± 9 vs 8355 ± 3940,P < 0.05),AST levels(IU/L)(729 ± 685 vs 6482 ± 4108,P < 0.05;187 ± 149 vs 6482 ± 4108,P < 0.05;141 ± 12 vs 6482 ± 4108,P < 0.05) and LDH levels(IU/L)(7220 ± 6317 vs 24 627 ± 10 975,P < 0.05;1618 ± 719 vs 24 627 ± 10 975,P < 0.05;1394 ± 469 vs 24 627 ± 10 975,P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups.Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP,including hepatocellular necrosis and infiltration of inflammatory cells,and the effect was dose-dependent.MDA levels(nmol/mg) were decreased by 5-MOP in a dose-dependent manner(0.98 ± 0.45 vs 2.15 ± 1.07,P > 0.05;0.59 ± 0.07 vs 2.15 ± 1.07,P < 0.05;0.47 ± 0.06 vs 2.15 ± 1.07,P < 0.05).The pretreatment of 5-MOP could also increase the GSH/GSSG ratio(3.834 ± 0.340 vs 3.306 ± 0.282,P > 0.05;5.330 ± 0.421 vs 3.306 ± 0.282,P < 0.05;6.180 ± 0.212 vs 3.306 ± 0.282,P < 0.05).In the group treated with 5-MOP but without APAP,the serum enzyme levels,the liver histopathologic manifestation,and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION:5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity,and does not cause liver injury at the protective doses.
文摘目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结肠癌组织、正常结肠细胞系(NCM460)和结直肠癌细胞系(SW620、HCT116、HT29、Lovo和SW480)中的表达。将SCL6A9过表达质粒及阴性对照(SLC6A9 OE、Vector)转染HT29细胞,将SCL6A9小干扰RNA及阴性对照(SLC6A9 siRNA1#、siRNA2#和Scramble)转染SW620细胞。划痕愈合实验和Transwell实验检测各组细胞的迁移、侵袭能力。Western blot和细胞免疫荧光检测EMT相关蛋白E-cadherin、Vimentin的表达水平。利用CCK-8法和构建裸鼠移植瘤模型检测SLC6A9过表达对结直肠癌细胞5-FU药物敏感性的影响。结果:与正常结肠组织和NCM460细胞相比,SLC6A9在结肠癌组织和结直肠癌细胞系中低表达(均P<0.05)。SLC6A9过表达引起E-cadherin蛋白表达增加,Vimentin蛋白水平降低,抑制结直肠癌细胞的迁移、侵袭(P<0.05)。SLC6A9低表达引起E-cadherin蛋白表达降低,Vimentin蛋白水平增加,促进结直肠癌细胞的迁移、侵袭能力(P<0.05)。SLC6A9过表达提高了5-FU的药物敏感性,并使肿瘤生长缓慢,质量减轻(P<0.05)。而SLC6A9低表达降低了5-FU的药物敏感性(P<0.05)。结论:SLC6A9过表达能够抑制结直肠癌细胞的迁移、侵袭和EMT进程,并增强5-FU对结直肠癌细胞的药物敏感性。
文摘在复杂的自然环境中绿色柑橘生长形态各异,颜色与背景色相近,为有效识别绿色柑橘,提出一种基于混合注意力机制并改进YOLOv5模型的柑橘识别方法。首先,改进YOLOv5的网络结构,在主干网络中添加混合注意力机制,即在主干网络中的第2层嵌入SE(squeeze and excitation)注意力,第11层嵌入CA(coordinate attention)注意力;其次,改进网络模型特征融合结构,将YOLOv5模型Concat特征融合操作的下层分支放在模型C3模块之前,再与另一条上层分支进行特征融合;最后,改进模型分类损失函数,将YOLOv5模型的分类损失函数改成Varifocal Loss函数,加强绿色柑橘特征信息的提取,提高绿色柑橘检测精度。根据自然环境和柑橘自身的特点,对自建数据集进行分类,设计3组不同分类场景下柑橘的对比试验以验证其有效性。试验结果表明,改进后的YOLOv5-SC模型准确率为91.74%,平均精度为95.09%,F1为89.56%,在自然环境下对绿色柑橘的识别具有更高的准确率和更好的鲁棒性,为绿色水果智能采摘提供技术支持。
