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eLife：通过RNF145依赖性SCAP泛素化抑制胆固醇生物合成

2017-11-02 MedSci MedSci原创

SCAPRNF145胆固醇
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胆固醇体内平衡是通过SREBPs和LXRs的协同作用来维持的。本研究中，研究人员发现，RNF145一种ER膜泛素连接酶，参与这些关键信号通路之间的串扰。LXR激活和高胆固醇饮食可诱导RNF145的表达。将RNF145转导入小鼠肝脏可抑制参与胆固醇生物合成的基因的表达，并降低血浆胆固醇水平。相反，通过shRNA介导的RNF145敲低或通过遗传删除的RNF145的慢性失活来急性抑制RNF145可增强胆

胆固醇体内平衡是通过SREBPs和LXRs的协同作用来维持的。本研究中，研究人员发现，RNF145一种ER膜泛素连接酶，参与这些关键信号通路之间的串扰。LXR激活和高胆固醇饮食可诱导RNF145的表达。将RNF145转导入小鼠肝脏可抑制参与胆固醇生物合成的基因的表达，并降低血浆胆固醇水平。

相反，通过shRNA介导的RNF145敲低或通过遗传删除的RNF145的慢性失活来急性抑制RNF145可增强胆固醇生物合成基因的表达并增加肝脏和血浆中的胆固醇水平。机制研究表明，RNF145引发SCAP对于COPII结合所必需的细胞质环内的赖氨酸残基的泛素化，潜在地抑制其转运到高尔基体并随后进行SREBP-2的加工。

总之，该研究发现定义了一种将胆固醇水平与SREBP-2和LXR通路的相互作用联系起来的另外一种机制。

原始出处：

Li Zhang, Prashant Rajbhandari, Christina Priest, et al. Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP. eLife. 2017; 6: e28766. Published online 2017 Oct 25. doi: 10.7554/eLife.28766

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    2017-12-12 膀胱癌

    #eLife#

    0

  2. 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    2018-08-21 smlt2008

    #CAP#

    0

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    2017-11-10 clmlylxy

    #Life#

    0

  4. 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topicName=null, topicId=null, topicList=[TopicDto(id=12739, encryptionId=ed8712e399b, topicName=NF1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f34c147, createdName=ay2000fy, createdTime=Sun Jun 17 13:14:00 CST 2018, time=2018-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260200, encodeId=aa382602008f, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Fri Nov 10 07:57:38 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260079, encodeId=9c952600e903, content=继续努力.加油加油!, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Thu Nov 09 21:27:55 CST 2017, time=2017-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259730, encodeId=02cf259e30f7, content=继续努力加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Wed Nov 08 14:52:05 CST 2017, time=2017-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259493, encodeId=24692594934a, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Tue Nov 07 17:45:47 CST 2017, time=2017-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259239, encodeId=2c422592391f, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Mon Nov 06 20:28:00 CST 2017, time=2017-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=258597, encodeId=d0ee25859e09, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Sat Nov 04 12:13:45 CST 2017, time=2017-11-04, status=1, ipAttribution=)]
    2018-06-17 ay2000fy

    #NF1#

    0

  5. 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    2017-11-10 七九九八

    继续努力.加油加油

    0

  6. 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GetPortalCommentsPageByObjectIdResponse(id=258597, encodeId=d0ee25859e09, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Sat Nov 04 12:13:45 CST 2017, time=2017-11-04, status=1, ipAttribution=)]
    2017-11-09 七九九八

    继续努力.加油加油!

    0

  7. 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topicName=null, topicId=null, topicList=[TopicDto(id=12739, encryptionId=ed8712e399b, topicName=NF1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f34c147, createdName=ay2000fy, createdTime=Sun Jun 17 13:14:00 CST 2018, time=2018-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260200, encodeId=aa382602008f, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Fri Nov 10 07:57:38 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260079, encodeId=9c952600e903, content=继续努力.加油加油!, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Thu Nov 09 21:27:55 CST 2017, time=2017-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259730, encodeId=02cf259e30f7, content=继续努力加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Wed Nov 08 14:52:05 CST 2017, time=2017-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259493, encodeId=24692594934a, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Tue Nov 07 17:45:47 CST 2017, time=2017-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259239, encodeId=2c422592391f, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Mon Nov 06 20:28:00 CST 2017, time=2017-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=258597, encodeId=d0ee25859e09, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Sat Nov 04 12:13:45 CST 2017, time=2017-11-04, status=1, ipAttribution=)]
    2017-11-08 七九九八

    继续努力加油加油

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1973030, encodeId=1cab19e3030ea, content=<a href='/topic/show?id=72d566e3a6' target=_blank style='color:#2F92EE;'>#eLife#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6673, encryptionId=72d566e3a6, topicName=eLife)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Tue Dec 12 16:14:00 CST 2017, time=2017-12-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1898004, encodeId=77e018980041b, content=<a href='/topic/show?id=832c404308' target=_blank style='color:#2F92EE;'>#CAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4043, encryptionId=832c404308, topicName=CAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c39f145, createdName=smlt2008, createdTime=Tue Aug 21 22:14:00 CST 2018, time=2018-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2068534, encodeId=98c82068534b2, content=<a href='/topic/show?id=59371088215' target=_blank style='color:#2F92EE;'>#Life#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10882, encryptionId=59371088215, topicName=Life)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Fri Nov 10 18:14:00 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1927982, encodeId=2311192e982c0, content=<a href='/topic/show?id=ed8712e399b' target=_blank style='color:#2F92EE;'>#NF1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12739, encryptionId=ed8712e399b, topicName=NF1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f34c147, createdName=ay2000fy, createdTime=Sun Jun 17 13:14:00 CST 2018, time=2018-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260200, encodeId=aa382602008f, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Fri Nov 10 07:57:38 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260079, encodeId=9c952600e903, content=继续努力.加油加油!, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Thu Nov 09 21:27:55 CST 2017, time=2017-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259730, encodeId=02cf259e30f7, content=继续努力加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Wed Nov 08 14:52:05 CST 2017, time=2017-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259493, encodeId=24692594934a, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Tue Nov 07 17:45:47 CST 2017, time=2017-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259239, encodeId=2c422592391f, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Mon Nov 06 20:28:00 CST 2017, time=2017-11-06, status=1, ipAttribution=), 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    2017-11-07 七九九八

    继续努力.加油加油

    0

  9. 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objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Tue Nov 07 17:45:47 CST 2017, time=2017-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259239, encodeId=2c422592391f, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Mon Nov 06 20:28:00 CST 2017, time=2017-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=258597, encodeId=d0ee25859e09, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Sat Nov 04 12:13:45 CST 2017, time=2017-11-04, status=1, ipAttribution=)]
    2017-11-06 七九九八

    继续努力.加油加油

    0

  10. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Thu Nov 09 21:27:55 CST 2017, time=2017-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259730, encodeId=02cf259e30f7, content=继续努力加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Wed Nov 08 14:52:05 CST 2017, time=2017-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259493, encodeId=24692594934a, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Tue Nov 07 17:45:47 CST 2017, time=2017-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259239, encodeId=2c422592391f, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Mon Nov 06 20:28:00 CST 2017, time=2017-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=258597, encodeId=d0ee25859e09, content=继续努力.加油加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCcmyvDOwDu2ZpuYyovmsD12IBHmUCwr5bZqNic2p50ogCxUAIj4YqJ3PsGwoXOhJPQAvicmu6RqOww/0, createdBy=a0bf1958339, createdName=七九九八, createdTime=Sat Nov 04 12:13:45 CST 2017, time=2017-11-04, status=1, ipAttribution=)]
    2017-11-04 七九九八

    继续努力.加油加油

    0

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