{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T08:49:47Z","timestamp":1769244587977,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["17181231"],"award-info":[{"award-number":["17181231"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["16171751"],"award-info":[{"award-number":["16171751"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["15161731"],"award-info":[{"award-number":["15161731"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["21778046"],"award-info":[{"award-number":["21778046"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["81703726"],"award-info":[{"award-number":["81703726"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["17119619"],"award-info":[{"award-number":["17119619"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["17100317"],"award-info":[{"award-number":["17100317"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["17146216"],"award-info":[{"award-number":["17146216"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["17120915"],"award-info":[{"award-number":["17120915"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Midstream Research Programme for Universities","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}]},{"name":"Midstream Research Programme for Universities","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}]},{"name":"Midstream Research Programme for Universities","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}]},{"name":"Midstream Research Programme for Universities","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}]},{"name":"Midstream Research Programme for Universities","award":["17181231"],"award-info":[{"award-number":["17181231"]}]},{"name":"Midstream Research Programme for Universities","award":["16171751"],"award-info":[{"award-number":["16171751"]}]},{"name":"Midstream Research Programme for Universities","award":["15161731"],"award-info":[{"award-number":["15161731"]}]},{"name":"Midstream Research Programme for Universities","award":["21778046"],"award-info":[{"award-number":["21778046"]}]},{"name":"Midstream Research Programme for Universities","award":["81703726"],"award-info":[{"award-number":["81703726"]}]},{"name":"Midstream Research Programme for Universities","award":["17119619"],"award-info":[{"award-number":["17119619"]}]},{"name":"Midstream Research Programme for Universities","award":["17100317"],"award-info":[{"award-number":["17100317"]}]},{"name":"Midstream Research Programme for Universities","award":["17146216"],"award-info":[{"award-number":["17146216"]}]},{"name":"Midstream Research Programme for Universities","award":["17120915"],"award-info":[{"award-number":["17120915"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["17181231"],"award-info":[{"award-number":["17181231"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["16171751"],"award-info":[{"award-number":["16171751"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["15161731"],"award-info":[{"award-number":["15161731"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["21778046"],"award-info":[{"award-number":["21778046"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["81703726"],"award-info":[{"award-number":["81703726"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["17119619"],"award-info":[{"award-number":["17119619"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["17100317"],"award-info":[{"award-number":["17100317"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["17146216"],"award-info":[{"award-number":["17146216"]}]},{"name":"Research and Cultivation Plan of High-Level Hospital Construction","award":["17120915"],"award-info":[{"award-number":["17120915"]}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["17181231"],"award-info":[{"award-number":["17181231"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["16171751"],"award-info":[{"award-number":["16171751"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["15161731"],"award-info":[{"award-number":["15161731"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["21778046"],"award-info":[{"award-number":["21778046"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["81703726"],"award-info":[{"award-number":["81703726"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["17119619"],"award-info":[{"award-number":["17119619"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["17100317"],"award-info":[{"award-number":["17100317"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["17146216"],"award-info":[{"award-number":["17146216"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["17120915"],"award-info":[{"award-number":["17120915"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17181231"],"award-info":[{"award-number":["17181231"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["16171751"],"award-info":[{"award-number":["16171751"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["15161731"],"award-info":[{"award-number":["15161731"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["21778046"],"award-info":[{"award-number":["21778046"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["81703726"],"award-info":[{"award-number":["81703726"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17119619"],"award-info":[{"award-number":["17119619"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17100317"],"award-info":[{"award-number":["17100317"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17146216"],"award-info":[{"award-number":["17146216"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17120915"],"award-info":[{"award-number":["17120915"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17181231"],"award-info":[{"award-number":["17181231"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["16171751"],"award-info":[{"award-number":["16171751"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["15161731"],"award-info":[{"award-number":["15161731"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["21778046"],"award-info":[{"award-number":["21778046"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["81703726"],"award-info":[{"award-number":["81703726"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17119619"],"award-info":[{"award-number":["17119619"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17100317"],"award-info":[{"award-number":["17100317"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17146216"],"award-info":[{"award-number":["17146216"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17120915"],"award-info":[{"award-number":["17120915"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17181231"],"award-info":[{"award-number":["17181231"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["16171751"],"award-info":[{"award-number":["16171751"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["15161731"],"award-info":[{"award-number":["15161731"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["21778046"],"award-info":[{"award-number":["21778046"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["81703726"],"award-info":[{"award-number":["81703726"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17119619"],"award-info":[{"award-number":["17119619"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17100317"],"award-info":[{"award-number":["17100317"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17146216"],"award-info":[{"award-number":["17146216"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17120915"],"award-info":[{"award-number":["17120915"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17181231"],"award-info":[{"award-number":["17181231"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["16171751"],"award-info":[{"award-number":["16171751"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["15161731"],"award-info":[{"award-number":["15161731"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21778046"],"award-info":[{"award-number":["21778046"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703726"],"award-info":[{"award-number":["81703726"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17119619"],"award-info":[{"award-number":["17119619"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17100317"],"award-info":[{"award-number":["17100317"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17146216"],"award-info":[{"award-number":["17146216"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17120915"],"award-info":[{"award-number":["17120915"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17181231"],"award-info":[{"award-number":["17181231"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["16171751"],"award-info":[{"award-number":["16171751"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["15161731"],"award-info":[{"award-number":["15161731"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21778046"],"award-info":[{"award-number":["21778046"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703726"],"award-info":[{"award-number":["81703726"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17119619"],"award-info":[{"award-number":["17119619"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17100317"],"award-info":[{"award-number":["17100317"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17146216"],"award-info":[{"award-number":["17146216"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["17120915"],"award-info":[{"award-number":["17120915"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Grants Council","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}]},{"name":"Research Grants Council","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}]},{"name":"Research Grants Council","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}]},{"name":"Research Grants Council","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}]},{"name":"Research Grants Council","award":["17181231"],"award-info":[{"award-number":["17181231"]}]},{"name":"Research Grants Council","award":["16171751"],"award-info":[{"award-number":["16171751"]}]},{"name":"Research Grants Council","award":["15161731"],"award-info":[{"award-number":["15161731"]}]},{"name":"Research Grants Council","award":["21778046"],"award-info":[{"award-number":["21778046"]}]},{"name":"Research Grants Council","award":["81703726"],"award-info":[{"award-number":["81703726"]}]},{"name":"Research Grants Council","award":["17119619"],"award-info":[{"award-number":["17119619"]}]},{"name":"Research Grants Council","award":["17100317"],"award-info":[{"award-number":["17100317"]}]},{"name":"Research Grants Council","award":["17146216"],"award-info":[{"award-number":["17146216"]}]},{"name":"Research Grants Council","award":["17120915"],"award-info":[{"award-number":["17120915"]}]},{"name":"Research Grants Council","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}]},{"name":"Research Grants Council","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}]},{"name":"Research Grants Council","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}]},{"name":"Research Grants Council","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}]},{"name":"Research Grants Council","award":["17181231"],"award-info":[{"award-number":["17181231"]}]},{"name":"Research Grants Council","award":["16171751"],"award-info":[{"award-number":["16171751"]}]},{"name":"Research Grants Council","award":["15161731"],"award-info":[{"award-number":["15161731"]}]},{"name":"Research Grants Council","award":["21778046"],"award-info":[{"award-number":["21778046"]}]},{"name":"Research Grants Council","award":["81703726"],"award-info":[{"award-number":["81703726"]}]},{"name":"Research Grants Council","award":["17119619"],"award-info":[{"award-number":["17119619"]}]},{"name":"Research Grants Council","award":["17100317"],"award-info":[{"award-number":["17100317"]}]},{"name":"Research Grants Council","award":["17146216"],"award-info":[{"award-number":["17146216"]}]},{"name":"Research Grants Council","award":["17120915"],"award-info":[{"award-number":["17120915"]}]},{"name":"Research Grants Council","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}]},{"name":"Research Grants Council","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}]},{"name":"Research Grants Council","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}]},{"name":"Research Grants Council","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}]},{"name":"Research Grants Council","award":["17181231"],"award-info":[{"award-number":["17181231"]}]},{"name":"Research Grants Council","award":["16171751"],"award-info":[{"award-number":["16171751"]}]},{"name":"Research Grants Council","award":["15161731"],"award-info":[{"award-number":["15161731"]}]},{"name":"Research Grants Council","award":["21778046"],"award-info":[{"award-number":["21778046"]}]},{"name":"Research Grants Council","award":["81703726"],"award-info":[{"award-number":["81703726"]}]},{"name":"Research Grants Council","award":["17119619"],"award-info":[{"award-number":["17119619"]}]},{"name":"Research Grants Council","award":["17100317"],"award-info":[{"award-number":["17100317"]}]},{"name":"Research Grants Council","award":["17146216"],"award-info":[{"award-number":["17146216"]}]},{"name":"Research Grants Council","award":["17120915"],"award-info":[{"award-number":["17120915"]}]},{"name":"Research Grants Council","award":["201611159156"],"award-info":[{"award-number":["201611159156"]}]},{"name":"Research Grants Council","award":["053\/18X"],"award-info":[{"award-number":["053\/18X"]}]},{"name":"Research Grants Council","award":["HKUSZH201902040"],"award-info":[{"award-number":["HKUSZH201902040"]}]},{"name":"Research Grants Council","award":["JCYJ20180306173835901"],"award-info":[{"award-number":["JCYJ20180306173835901"]}]},{"name":"Research Grants Council","award":["17181231"],"award-info":[{"award-number":["17181231"]}]},{"name":"Research Grants Council","award":["16171751"],"award-info":[{"award-number":["16171751"]}]},{"name":"Research Grants Council","award":["15161731"],"award-info":[{"award-number":["15161731"]}]},{"name":"Research Grants Council","award":["21778046"],"award-info":[{"award-number":["21778046"]}]},{"name":"Research Grants Council","award":["81703726"],"award-info":[{"award-number":["81703726"]}]},{"name":"Research Grants Council","award":["17119619"],"award-info":[{"award-number":["17119619"]}]},{"name":"Research Grants Council","award":["17100317"],"award-info":[{"award-number":["17100317"]}]},{"name":"Research Grants Council","award":["17146216"],"award-info":[{"award-number":["17146216"]}]},{"name":"Research Grants Council","award":["17120915"],"award-info":[{"award-number":["17120915"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:p>Aberrant microglial activation drives neuroinflammation and neurodegeneration in Alzheimer\u2019s disease (AD). The present study is aimed at investigating whether the herbal formula Qi-Fu-Yin (QFY) could inhibit the inflammatory activation of cultured BV-2 microglia. A network pharmacology approach was employed to predict the active compounds of QFY, protein targets, and affected pathways. The representative pathways and molecular functions of the targets were analyzed by Gene Ontology (GO) and pathway enrichment. A total of 145 active compounds were selected from seven herbal ingredients of QFY. Targets (e.g., MAPT, APP, ACHE, iNOS, and COX-2) were predicted for the selected active compounds based on the relevance to AD and inflammation. As a validation, fractions were sequentially prepared by aqueous extraction, ethanolic precipitation, and HPLC separation, and assayed for downregulating two key proinflammatory biomarkers iNOS and COX-2 in lipopolysaccharide- (LPS-) challenged BV-2 cells by the Western blotting technique. Moreover, the compounds of QFY in 90% ethanol downregulated iNOS in BV-2 cells but showed no activity against COX-2 induction. Among the herbal ingredients of QFY, Angelicae Sinensis Radix and Ginseng Radix et Rhizoma contributed to the selective inhibition of iNOS induction. Furthermore, chemical analysis identified ginsenosides, especially Rg3, as antineuroinflammatory compounds. The herbal formula QFY may ameliorate neuroinflammation via downregulating iNOS in microglia.<\/jats:p>","DOI":"10.1155\/2020\/5780703","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T23:31:30Z","timestamp":1599003090000},"page":"1-15","source":"Crossref","is-referenced-by-count":17,"title":["Network Pharmacology Analysis and Molecular Characterization of the Herbal Medicine Formulation Qi-Fu-Yin for the Inhibition of the Neuroinflammatory Biomarker iNOS in Microglial BV-2 Cells: Implication for the Treatment of Alzheimer\u2019s Disease"],"prefix":"10.1155","volume":"2020","author":[{"given":"Fung Yin","family":"Ngo","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, The University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The University of Hong Kong, Hong Kong 999077, China"},{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qilei","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubiao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4801-6514","authenticated-orcid":true,"given":"Jin-Ming","family":"Gao","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3709-7315","authenticated-orcid":true,"given":"Jianhui","family":"Rong","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The University of Hong Kong, Hong Kong 999077, China"},{"name":"Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen 518057, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1017\/S135561771700100X"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255555"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-013-9398-z"},{"issue":"1","key":"4","first-page":"19","volume":"6","year":"2012","journal-title":"Therapeutic Advances in Neurological Disorders"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)70016-5"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0242-x"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2005.06.004"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(00)00078-1"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00402"},{"issue":"5","key":"10","first-page":"537","volume":"16","year":"2016","journal-title":"Current Topics in Medicinal Chemistry"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-0908-0"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(14)60135-7"},{"key":"13","first-page":"34","volume":"17","year":"2010","journal-title":"Chinese Journal of Information on Traditional Chinese Medicine"},{"key":"14","first-page":"9","volume":"31","year":"2015","journal-title":"Pharmacology and Clinics of Chinese Materia Medica"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2015.05.030"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2020.113467"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2016.08.004"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.08.008"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.3390\/molecules200713041"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2038"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030558"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.118"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1186\/2047-9158-2-6"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1039\/C3MB70507B"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(13)60037-0"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.11.034"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3880"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666151204122017"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200600123"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2170258"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1021\/jf900269r"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1021\/jf801101u"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.3390\/s120709181"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2009.11.029"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/306857"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2015.00129"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.07075.x"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2006.04.021"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.31.1392"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.01.018"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2016.12.012"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.06.080"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1159\/000491651"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00911"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2019.104370"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.01.005"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2020\/5780703.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2020\/5780703.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2020\/5780703.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T23:31:42Z","timestamp":1599003102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/omcl\/2020\/5780703\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":46,"alternative-id":["5780703","5780703"],"URL":"https:\/\/doi.org\/10.1155\/2020\/5780703","relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,1]]}}}