Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor
Platelet-activating factor (PAF) is a unique phosphoglycerine that mediates the biological functions of both immune and nervous systems. Excessive PAF plays an important role in neural injury via its specific receptor (PAFR). In this study, we hypothesized that PAF signaling activates reactive glios...
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| Veröffentlicht in: | Molecular neurobiology 2016-07, Vol.53 (5), p.3448-3461 |
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| creator | Wang, Yuanyi Gao, Zhongwen Zhang, Yiping Feng, Shi-Qing Liu, Yulong Shields, Lisa B. E. Zhao, Ying-Zheng Zhu, Qingsan Gozal, David Shields, Christopher B. Cai, Jun |
| description | Platelet-activating factor (PAF) is a unique phosphoglycerine that mediates the biological functions of both immune and nervous systems. Excessive PAF plays an important role in neural injury via its specific receptor (PAFR). In this study, we hypothesized that PAF signaling activates reactive gliosis after spinal cord injury (SCI), and blocking the PAF pathway would modify the glia scar formation and promote functional recovery. PAF microinjected into the normal wild-type spinal cord induced a dose-dependent activation of microglia and astrocytes. In the SCI mice,
PAFR
null mutant mice showed a better functional recovery in grip and rotarod performances than wild-type mice. Although both microglia and astrocytes were activated after SCI in wild-type and
PAFR
null mutant mice, expressions of IL-6, vimentin, nestin, and GFAP were not significantly elevated in
PAFR
null mutants. Disruption of PAF signaling inhibited the expressions of proteoglycan CS56 and neurocan (CSPG3). Intriguingly, compared to the wild-type SCI mice, less axonal retraction/dieback at 7 dpi but more NFH-labeled axons at 28 dpi was found in the area adjacent to the epicenter in
PAFR
null mutant SCI mice. Moreover, treatment with PAFR antagonist Ginkgolide B (GB) at the chronic phase rather than acute phase enhanced the functional recovery in the wild-type SCI mice. These findings suggest that PAF signaling participates in reactive gliosis after SCI, and blocking of this signaling enhances functional recovery and to some extent may promote axon regrowth. |
| doi_str_mv | 10.1007/s12035-015-9263-6 |
| format | Article |
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PAFR
null mutant mice showed a better functional recovery in grip and rotarod performances than wild-type mice. Although both microglia and astrocytes were activated after SCI in wild-type and
PAFR
null mutant mice, expressions of IL-6, vimentin, nestin, and GFAP were not significantly elevated in
PAFR
null mutants. Disruption of PAF signaling inhibited the expressions of proteoglycan CS56 and neurocan (CSPG3). Intriguingly, compared to the wild-type SCI mice, less axonal retraction/dieback at 7 dpi but more NFH-labeled axons at 28 dpi was found in the area adjacent to the epicenter in
PAFR
null mutant SCI mice. Moreover, treatment with PAFR antagonist Ginkgolide B (GB) at the chronic phase rather than acute phase enhanced the functional recovery in the wild-type SCI mice. These findings suggest that PAF signaling participates in reactive gliosis after SCI, and blocking of this signaling enhances functional recovery and to some extent may promote axon regrowth.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-015-9263-6</identifier><identifier>PMID: 26084439</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Astrocytes - drug effects ; Astrocytes - metabolism ; Astrocytes - pathology ; Axons - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Cervical Vertebrae - drug effects ; Cervical Vertebrae - pathology ; Cervical Vertebrae - physiopathology ; Extracellular Matrix - drug effects ; Extracellular Matrix - metabolism ; Female ; Forelimb - physiopathology ; Gliosis - etiology ; Gliosis - pathology ; Gliosis - physiopathology ; Inflammation - pathology ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia - drug effects ; Microglia - metabolism ; Microglia - pathology ; Mutation ; Myelin Sheath - metabolism ; Neurobiology ; Neurology ; Neuronal Plasticity - drug effects ; Neurons ; Neurosciences ; Platelet Activating Factor - pharmacology ; Platelet Membrane Glycoproteins - antagonists & inhibitors ; Platelet Membrane Glycoproteins - deficiency ; Platelet Membrane Glycoproteins - metabolism ; Receptors, G-Protein-Coupled - antagonists & inhibitors ; Receptors, G-Protein-Coupled - deficiency ; Receptors, G-Protein-Coupled - metabolism ; Recovery of Function - drug effects ; Rice ; Spinal cord injuries ; Spinal Cord Injuries - complications ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - physiopathology</subject><ispartof>Molecular neurobiology, 2016-07, Vol.53 (5), p.3448-3461</ispartof><rights>Springer Science+Business Media New York 2015</rights><rights>Springer Science+Business Media New York 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-abb7ac349ac96e114ba8a3033797f0ad5ad71696516fdcf7db1f7bc7b2a67aa33</citedby><cites>FETCH-LOGICAL-c471t-abb7ac349ac96e114ba8a3033797f0ad5ad71696516fdcf7db1f7bc7b2a67aa33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-015-9263-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-015-9263-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26084439$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yuanyi</creatorcontrib><creatorcontrib>Gao, Zhongwen</creatorcontrib><creatorcontrib>Zhang, Yiping</creatorcontrib><creatorcontrib>Feng, Shi-Qing</creatorcontrib><creatorcontrib>Liu, Yulong</creatorcontrib><creatorcontrib>Shields, Lisa B. E.</creatorcontrib><creatorcontrib>Zhao, Ying-Zheng</creatorcontrib><creatorcontrib>Zhu, Qingsan</creatorcontrib><creatorcontrib>Gozal, David</creatorcontrib><creatorcontrib>Shields, Christopher B.</creatorcontrib><creatorcontrib>Cai, Jun</creatorcontrib><title>Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Platelet-activating factor (PAF) is a unique phosphoglycerine that mediates the biological functions of both immune and nervous systems. Excessive PAF plays an important role in neural injury via its specific receptor (PAFR). In this study, we hypothesized that PAF signaling activates reactive gliosis after spinal cord injury (SCI), and blocking the PAF pathway would modify the glia scar formation and promote functional recovery. PAF microinjected into the normal wild-type spinal cord induced a dose-dependent activation of microglia and astrocytes. In the SCI mice,
PAFR
null mutant mice showed a better functional recovery in grip and rotarod performances than wild-type mice. Although both microglia and astrocytes were activated after SCI in wild-type and
PAFR
null mutant mice, expressions of IL-6, vimentin, nestin, and GFAP were not significantly elevated in
PAFR
null mutants. Disruption of PAF signaling inhibited the expressions of proteoglycan CS56 and neurocan (CSPG3). Intriguingly, compared to the wild-type SCI mice, less axonal retraction/dieback at 7 dpi but more NFH-labeled axons at 28 dpi was found in the area adjacent to the epicenter in
PAFR
null mutant SCI mice. Moreover, treatment with PAFR antagonist Ginkgolide B (GB) at the chronic phase rather than acute phase enhanced the functional recovery in the wild-type SCI mice. These findings suggest that PAF signaling participates in reactive gliosis after SCI, and blocking of this signaling enhances functional recovery and to some extent may promote axon regrowth.</description><subject>Animals</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - pathology</subject><subject>Axons - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Cervical Vertebrae - drug effects</subject><subject>Cervical Vertebrae - pathology</subject><subject>Cervical Vertebrae - physiopathology</subject><subject>Extracellular Matrix - drug effects</subject><subject>Extracellular Matrix - metabolism</subject><subject>Female</subject><subject>Forelimb - physiopathology</subject><subject>Gliosis - etiology</subject><subject>Gliosis - pathology</subject><subject>Gliosis - physiopathology</subject><subject>Inflammation - pathology</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Microglia - pathology</subject><subject>Mutation</subject><subject>Myelin Sheath - metabolism</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neuronal Plasticity - drug effects</subject><subject>Neurons</subject><subject>Neurosciences</subject><subject>Platelet Activating Factor - pharmacology</subject><subject>Platelet Membrane Glycoproteins - antagonists & inhibitors</subject><subject>Platelet Membrane Glycoproteins - deficiency</subject><subject>Platelet Membrane Glycoproteins - metabolism</subject><subject>Receptors, G-Protein-Coupled - antagonists & inhibitors</subject><subject>Receptors, G-Protein-Coupled - deficiency</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Recovery of Function - drug effects</subject><subject>Rice</subject><subject>Spinal cord injuries</subject><subject>Spinal Cord Injuries - complications</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - physiopathology</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc1q3DAUhUVpaCZpH6CbIuimGyW6li3Zy2HIJIGkLf1Zm2tZTj1opKkkp-Q9-sCRcVpKoXQlwfnOOXAPIa-BnwHn6jxCwUXFOFSsKaRg8hlZQVU1DKAunpMVrxvBlCzrY3IS447zogCuXpDjQvK6LEWzIj_XKRk3YTI9_WRQp_He0Es7-jhGiq6nF-4bOp3V7eSy6h3aDGp_b8ID3Xpr_Y_R3dHPh3FWNj709NrtpiyOjr6frKW3U0KX6O2oDfUD_WhzmTWJrecyTLN7m4t9mHPNIX9ekqMBbTSvnt5T8nV78WVzxW4-XF5v1jdMlwoSw65TqEXZoG6kASg7rFFwIVSjBo59hb0C2cgK5NDrQfUdDKrTqitQKkQhTsm7JfcQ_PfJxNTux6iNteiMn2ILNa-lKBSv_o-qpqpryHfN6Nu_0J2fQr7OQklQJfBMwULp4GMMZmgPYdxjeGiBt_O67bJum9dt53VbmT1vnpKnbm_6345fc2agWICYJXdnwh_V_0x9BAAYsQg</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Wang, Yuanyi</creator><creator>Gao, Zhongwen</creator><creator>Zhang, Yiping</creator><creator>Feng, Shi-Qing</creator><creator>Liu, Yulong</creator><creator>Shields, Lisa B. E.</creator><creator>Zhao, Ying-Zheng</creator><creator>Zhu, Qingsan</creator><creator>Gozal, David</creator><creator>Shields, Christopher B.</creator><creator>Cai, Jun</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20160701</creationdate><title>Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor</title><author>Wang, Yuanyi ; Gao, Zhongwen ; Zhang, Yiping ; Feng, Shi-Qing ; Liu, Yulong ; Shields, Lisa B. E. ; Zhao, Ying-Zheng ; Zhu, Qingsan ; Gozal, David ; Shields, Christopher B. ; Cai, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-abb7ac349ac96e114ba8a3033797f0ad5ad71696516fdcf7db1f7bc7b2a67aa33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Astrocytes - pathology</topic><topic>Axons - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Cervical Vertebrae - drug effects</topic><topic>Cervical Vertebrae - pathology</topic><topic>Cervical Vertebrae - physiopathology</topic><topic>Extracellular Matrix - drug effects</topic><topic>Extracellular Matrix - metabolism</topic><topic>Female</topic><topic>Forelimb - physiopathology</topic><topic>Gliosis - etiology</topic><topic>Gliosis - pathology</topic><topic>Gliosis - physiopathology</topic><topic>Inflammation - pathology</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>Microglia - pathology</topic><topic>Mutation</topic><topic>Myelin Sheath - metabolism</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neuronal Plasticity - drug effects</topic><topic>Neurons</topic><topic>Neurosciences</topic><topic>Platelet Activating Factor - pharmacology</topic><topic>Platelet Membrane Glycoproteins - antagonists & inhibitors</topic><topic>Platelet Membrane Glycoproteins - deficiency</topic><topic>Platelet Membrane Glycoproteins - metabolism</topic><topic>Receptors, G-Protein-Coupled - antagonists & inhibitors</topic><topic>Receptors, G-Protein-Coupled - deficiency</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Recovery of Function - drug effects</topic><topic>Rice</topic><topic>Spinal cord injuries</topic><topic>Spinal Cord Injuries - complications</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yuanyi</creatorcontrib><creatorcontrib>Gao, Zhongwen</creatorcontrib><creatorcontrib>Zhang, Yiping</creatorcontrib><creatorcontrib>Feng, Shi-Qing</creatorcontrib><creatorcontrib>Liu, Yulong</creatorcontrib><creatorcontrib>Shields, Lisa B. E.</creatorcontrib><creatorcontrib>Zhao, Ying-Zheng</creatorcontrib><creatorcontrib>Zhu, Qingsan</creatorcontrib><creatorcontrib>Gozal, David</creatorcontrib><creatorcontrib>Shields, Christopher B.</creatorcontrib><creatorcontrib>Cai, Jun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yuanyi</au><au>Gao, Zhongwen</au><au>Zhang, Yiping</au><au>Feng, Shi-Qing</au><au>Liu, Yulong</au><au>Shields, Lisa B. E.</au><au>Zhao, Ying-Zheng</au><au>Zhu, Qingsan</au><au>Gozal, David</au><au>Shields, Christopher B.</au><au>Cai, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>53</volume><issue>5</issue><spage>3448</spage><epage>3461</epage><pages>3448-3461</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Platelet-activating factor (PAF) is a unique phosphoglycerine that mediates the biological functions of both immune and nervous systems. Excessive PAF plays an important role in neural injury via its specific receptor (PAFR). In this study, we hypothesized that PAF signaling activates reactive gliosis after spinal cord injury (SCI), and blocking the PAF pathway would modify the glia scar formation and promote functional recovery. PAF microinjected into the normal wild-type spinal cord induced a dose-dependent activation of microglia and astrocytes. In the SCI mice,
PAFR
null mutant mice showed a better functional recovery in grip and rotarod performances than wild-type mice. Although both microglia and astrocytes were activated after SCI in wild-type and
PAFR
null mutant mice, expressions of IL-6, vimentin, nestin, and GFAP were not significantly elevated in
PAFR
null mutants. Disruption of PAF signaling inhibited the expressions of proteoglycan CS56 and neurocan (CSPG3). Intriguingly, compared to the wild-type SCI mice, less axonal retraction/dieback at 7 dpi but more NFH-labeled axons at 28 dpi was found in the area adjacent to the epicenter in
PAFR
null mutant SCI mice. Moreover, treatment with PAFR antagonist Ginkgolide B (GB) at the chronic phase rather than acute phase enhanced the functional recovery in the wild-type SCI mice. These findings suggest that PAF signaling participates in reactive gliosis after SCI, and blocking of this signaling enhances functional recovery and to some extent may promote axon regrowth.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>26084439</pmid><doi>10.1007/s12035-015-9263-6</doi><tpages>14</tpages></addata></record> |
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| issn | 0893-7648 1559-1182 |
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| subjects | Animals Astrocytes - drug effects Astrocytes - metabolism Astrocytes - pathology Axons - metabolism Biomedical and Life Sciences Biomedicine Cell Biology Cervical Vertebrae - drug effects Cervical Vertebrae - pathology Cervical Vertebrae - physiopathology Extracellular Matrix - drug effects Extracellular Matrix - metabolism Female Forelimb - physiopathology Gliosis - etiology Gliosis - pathology Gliosis - physiopathology Inflammation - pathology Mice, Inbred C57BL Mice, Knockout Microglia - drug effects Microglia - metabolism Microglia - pathology Mutation Myelin Sheath - metabolism Neurobiology Neurology Neuronal Plasticity - drug effects Neurons Neurosciences Platelet Activating Factor - pharmacology Platelet Membrane Glycoproteins - antagonists & inhibitors Platelet Membrane Glycoproteins - deficiency Platelet Membrane Glycoproteins - metabolism Receptors, G-Protein-Coupled - antagonists & inhibitors Receptors, G-Protein-Coupled - deficiency Receptors, G-Protein-Coupled - metabolism Recovery of Function - drug effects Rice Spinal cord injuries Spinal Cord Injuries - complications Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology |
| title | Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor |
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