{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T23:08:13Z","timestamp":1775862493377,"version":"3.50.1"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004733","name":"Universidade de Macau","doi-asserted-by":"publisher","award":["UM Macao Postdoctoral Associateship"],"award-info":[{"award-number":["UM Macao Postdoctoral Associateship"]}],"id":[{"id":"10.13039\/501100004733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006469","name":"Fundo para o Desenvolvimento das Ci\u00eancias e da Tecnologia","doi-asserted-by":"publisher","award":["0060\/2020\/AGJ"],"award-info":[{"award-number":["0060\/2020\/AGJ"]}],"id":[{"id":"10.13039\/501100006469","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Chin Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Implantation of a biomaterial may induce the foreign-body reaction to the host tissue that determines the outcome of the integration and the biological performance of the implants. The foreign-body reaction can be modulated by control of the material properties of the implants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      First, we synthesized methacrylated\n                      <jats:italic>Bletilla striata<\/jats:italic>\n                      Polysaccharide (BSP-MA) and constructed a series of open porous cryogels utilizing this material via the freezing-thawing treatment of solvent-precursors systems. Second, Pore size and modulus were measured to characterize the properties of BSP cryogels. Live\/dead staining of cells and CCK-8 were performed to test the cytocompatibility of the scaffolds. In addition, the Real-Time qPCR experiments were carried for the tests. Finally, the BSP scaffolds were implanted subcutaneously to verify the foreign-body reaction between host tissue and materials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our data demonstrated that cryogels with different pore sizes and modulus can be fabricated by just adjusting the concentration. Besides, the cryogels showed well cytocompatibility in the in vitro experiments and exhibited upregulated expression levels of pro-inflammation-related genes (\n                      <jats:italic>Tnfa<\/jats:italic>\n                      and\n                      <jats:italic>Il1b<\/jats:italic>\n                      ) with the increase of pore size. In vivo experiments further proved that with the increase of pore size, more immune cells infiltrated into the inner zone of materials. The foreign-body reaction and the distribution of immune-regulatory cells could be modulated by tuning the material microstructure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Collectively, our findings revealed\n                      <jats:italic>Bletilla striata<\/jats:italic>\n                      polysaccharide cryogel scaffold with different pore sizes can spatially control foreign-body reaction. The microstructure of cryogels could differentially guide the distribution of inflammatory cells, affect the formation of blood vessels and fibrous capsules, which eventually influence the material-tissue integration. This work demonstrates a practical strategy to regulate foreign body reaction and promote the performance of medical devices.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13020-021-00526-y","type":"journal-article","created":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T04:02:48Z","timestamp":1638590568000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Bletilla striata polysaccharide cryogel scaffold for spatial control of foreign-body reaction"],"prefix":"10.1186","volume":"16","author":[{"given":"Jiaxi","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiqun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daping","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9845-8295","authenticated-orcid":false,"given":"Yiming","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,4]]},"reference":[{"issue":"3","key":"526_CR1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/85619","volume":"19","author":"S Petit-Zeman","year":"2001","unstructured":"Petit-Zeman S. Regenerative medicine. Nat Biotechnol. 2001;19(3):201\u20136.","journal-title":"Nat Biotechnol"},{"issue":"47","key":"526_CR2","doi-asserted-by":"publisher","first-page":"14452","DOI":"10.1073\/pnas.1508520112","volume":"112","author":"AS Mao","year":"2015","unstructured":"Mao AS, Mooney DJ. Regenerative medicine: Current therapies and future directions. Proc Natl Acad Sci U S A. 2015;112(47):14452\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"526_CR3","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S1074-7613(01)00123-6","volume":"14","author":"E Lagasse","year":"2001","unstructured":"Lagasse E, Shizuru JA, Uchida N, Tsukamoto A, Weissman IL. Toward regenerative medicine. Immunity. 2001;14(4):425\u201336.","journal-title":"Immunity"},{"issue":"8","key":"526_CR4","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/nm.3627","volume":"20","author":"S Dimmeler","year":"2014","unstructured":"Dimmeler S, Ding S, Rando TA, Trounson A. Translational strategies and challenges in regenerative medicine. Nat Med. 2014;20(8):814\u201321.","journal-title":"Nat Med"},{"issue":"10","key":"526_CR5","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1098\/rsif.2006.0124","volume":"3","author":"Y Ikada","year":"2006","unstructured":"Ikada Y. Challenges in tissue engineering. J R Soc Interface. 2006;3(10):589\u2013601.","journal-title":"J R Soc Interface"},{"issue":"5557","key":"526_CR6","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1126\/science.1069210","volume":"295","author":"LG Griffith","year":"2002","unstructured":"Griffith LG, Naughton G. Tissue engineering\u2013current challenges and expanding opportunities. Science. 2002;295(5557):1009\u201314.","journal-title":"Science"},{"issue":"32\u201333","key":"526_CR7","doi-asserted-by":"publisher","first-page":"3307","DOI":"10.1002\/adma.200802106","volume":"21","author":"BV Slaughter","year":"2009","unstructured":"Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA. Hydrogels in regenerative medicine. Adv Mater. 2009;21(32\u201333):3307\u201329.","journal-title":"Adv Mater"},{"key":"526_CR8","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3389\/fbioe.2019.00127","volume":"7","author":"DF Williams","year":"2019","unstructured":"Williams DF. Challenges With the Development of Biomaterials for Sustainable Tissue Engineering. Front Bioeng Biotechnol. 2019;7:127.","journal-title":"Front Bioeng Biotechnol."},{"issue":"1","key":"526_CR9","doi-asserted-by":"publisher","first-page":"014101","DOI":"10.1088\/1748-6041\/8\/1\/014101","volume":"8","author":"SH Oh","year":"2013","unstructured":"Oh SH, Lee JH. Hydrophilization of synthetic biodegradable polymer scaffolds for improved cell\/tissue compatibility. Biomed Mater. 2013;8(1):014101.","journal-title":"Biomed Mater"},{"key":"526_CR10","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.biomaterials.2016.02.003","volume":"86","author":"JM Aamodt","year":"2016","unstructured":"Aamodt JM, Grainger DW. Extracellular matrix-based biomaterial scaffolds and the host response. Biomaterials. 2016;86:68\u201382.","journal-title":"Biomaterials"},{"issue":"22","key":"526_CR11","doi-asserted-by":"publisher","first-page":"8470","DOI":"10.1021\/la300563s","volume":"28","author":"G Cado","year":"2012","unstructured":"Cado G, Kerdjoudj H, Chassepot A, Lefort M, Benmlih K, Hemmerle J, et al. Polysaccharide films built by simultaneous or alternate spray: a rapid way to engineer biomaterial surfaces. Langmuir. 2012;28(22):8470\u20138.","journal-title":"Langmuir"},{"issue":"7","key":"526_CR12","doi-asserted-by":"publisher","first-page":"eabd8217","DOI":"10.1126\/sciadv.abd8217","volume":"7","author":"Y Yu","year":"2021","unstructured":"Yu Y, Dai K, Gao Z, Tang W, Shen T, Yuan Y, et al. Sulfated polysaccharide directs therapeutic angiogenesis via endogenous VEGF secretion of macrophages. Sci Adv. 2021;7(7):eabd8217.","journal-title":"Sci Adv"},{"issue":"5","key":"526_CR13","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1002\/pat.3266","volume":"25","author":"NB Shelke","year":"2014","unstructured":"Shelke NB, James R, Laurencin CT, Kumbar SG. Polysaccharide biomaterials for drug delivery and regenerative engineering. Polym Adv Technol. 2014;25(5):448\u201360.","journal-title":"Polym Adv Technol"},{"issue":"3","key":"526_CR14","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1002\/pi.2378","volume":"57","author":"M Rinaudo","year":"2008","unstructured":"Rinaudo M. Main properties and current applications of some polysaccharides as biomaterials. Polym Int. 2008;57(3):397\u2013430.","journal-title":"Polym Int"},{"key":"526_CR15","doi-asserted-by":"crossref","unstructured":"Jiang Y, Fu X. Traditional Medicine and Tissue Repair and Regeneration, Regenerative Medicine in China. New York: Springer. 2021, pp. 435\u2013446.","DOI":"10.1007\/978-981-16-1182-7_12"},{"key":"526_CR16","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jep.2016.11.026","volume":"195","author":"X He","year":"2017","unstructured":"He X, Wang X, Fang J, Zhao Z, Huang L, Guo H, et al. Bletilla striata: Medicinal uses, phytochemistry and pharmacological activities. J Ethnopharmacol. 2017;195:20\u201338.","journal-title":"J Ethnopharmacol"},{"key":"526_CR17","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.3389\/fphar.2019.01168","volume":"10","author":"D Xu","year":"2019","unstructured":"Xu D, Pan Y, Chen J. Chemical Constituents, Pharmacologic Properties, and Clinical Applications of Bletilla striata. Front Pharmacol. 2019;10:1168.","journal-title":"Front Pharmacol"},{"key":"526_CR18","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1016\/j.carbpol.2016.11.040","volume":"157","author":"L Ding","year":"2017","unstructured":"Ding L, Shan X, Zhao X, Zha H, Chen X, Wang J, et al. Spongy bilayer dressing composed of chitosan\u2013Ag nanoparticles and chitosan\u2013Bletilla striata polysaccharide for wound healing applications. Carbohydr Polym. 2017;157:1538\u201347.","journal-title":"Carbohydr Polym"},{"key":"526_CR19","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/j.ijbiomac.2019.11.049","volume":"155","author":"Y Niu","year":"2020","unstructured":"Niu Y, Zhang Y, He W, Xing P, Dong L, Li Q, et al. Engineering a microcarrier based on a polysaccharide-growth factor complex for enhancing the proliferation of mesenchymal stem cells. Int J Biol Macromol. 2020;155:911\u20138.","journal-title":"Int J Biol Macromol"},{"key":"526_CR20","doi-asserted-by":"publisher","first-page":"115404","DOI":"10.1016\/j.carbpol.2019.115404","volume":"229","author":"C Wang","year":"2020","unstructured":"Wang C, Li B, Chen T, Mei N, Wang X, Tang S. Preparation and bioactivity of acetylated konjac glucomannan fibrous membrane and its application for wound dressing. Carbohydr Polym. 2020;229:115404.","journal-title":"Carbohydr Polym"},{"key":"526_CR21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.actbio.2020.05.023","volume":"111","author":"Y Niu","year":"2020","unstructured":"Niu Y, Wang L, Yu N, Xing P, Wang Z, Zhong Z, et al. An \u201call-in-one\u201d scaffold targeting macrophages to direct endogenous bone repair in situ. Acta Biomater. 2020;111:153\u201369.","journal-title":"Acta Biomater"},{"key":"526_CR22","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.biomaterials.2017.05.042","volume":"139","author":"Y Niu","year":"2017","unstructured":"Niu Y, Li Q, Xie R, Liu S, Wang R, Xing P, et al. Modulating the phenotype of host macrophages to enhance osteogenesis in MSC-laden hydrogels: design of a glucomannan coating material. Biomaterials. 2017;139:39\u201355.","journal-title":"Biomaterials"},{"issue":"4","key":"526_CR23","doi-asserted-by":"publisher","first-page":"1800114","DOI":"10.1002\/adtp.201800114","volume":"2","author":"A Memic","year":"2019","unstructured":"Memic A, Colombani T, Eggermont LJ, Rezaeeyazdi M, Steingold J, Rogers ZJ, et al. Latest advances in cryogel technology for biomedical applications. Adv Ther. 2019;2(4):1800114.","journal-title":"Adv Ther"},{"issue":"5154","key":"526_CR24","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1126\/science.8134835","volume":"263","author":"NA Peppas","year":"1994","unstructured":"Peppas NA, Langer R. New challenges in biomaterials. Science. 1994;263(5154):1715\u201320.","journal-title":"Science"},{"key":"526_CR25","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.smim.2007.11.004","volume":"23","author":"JM Anderson","year":"2008","unstructured":"Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Semin Immunol. 2008;23:86\u2013100.","journal-title":"Semin Immunol"},{"issue":"6","key":"526_CR26","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1177\/193229680800200610","volume":"2","author":"Y Onuki","year":"2008","unstructured":"Onuki Y, Bhardwaj U, Papadimitrakopoulos F, Burgess DJ. A review of the biocompatibility of implantable devices: current challenges to overcome foreign body response. J Diabetes Sci Technol. 2008;2(6):1003\u201315.","journal-title":"J Diabetes Sci Technol"},{"issue":"28","key":"526_CR27","doi-asserted-by":"publisher","first-page":"6692","DOI":"10.1016\/j.biomaterials.2011.05.078","volume":"32","author":"S Franz","year":"2011","unstructured":"Franz S, Rammelt S, Scharnweber D, Simon JCJB. Immune responses to implants\u2013a review of the implications for the design of immunomodulatory biomaterials. Biomaterials. 2011;32(28):6692\u2013709.","journal-title":"Biomaterials"},{"key":"526_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/B978-0-12-800196-7.00001-3","volume-title":"Factors which affect the host response to biomaterials","author":"R Londono","year":"2015","unstructured":"Londono R, Badylak SF. Factors which affect the host response to biomaterials. Host response to biomaterials: Elsevier; 2015. p. 1\u201312."},{"issue":"3","key":"526_CR29","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ijbiomac.2012.05.016","volume":"51","author":"R Tanaka","year":"2012","unstructured":"Tanaka R, Saito T, Isogai A. Cellulose nanofibrils prepared from softwood cellulose by TEMPO\/NaClO\/NaClO(2) systems in water at pH 48 or 68. Int J Biol Macromol. 2012;51(3):228\u201334.","journal-title":"Int J Biol Macromol"},{"issue":"21","key":"526_CR30","doi-asserted-by":"publisher","first-page":"2682","DOI":"10.1039\/c3tb20280a","volume":"1","author":"TMA Henderson","year":"2013","unstructured":"Henderson TMA, Ladewig K, Haylock DN, McLean KM, O\u2019Connor AJ. Cryogels for biomedical applications. J Mater Chem B. 2013;1(21):2682\u201395.","journal-title":"J Mater Chem B"},{"issue":"21","key":"526_CR31","doi-asserted-by":"publisher","first-page":"11247","DOI":"10.1073\/pnas.1922364117","volume":"117","author":"NL Cuccia","year":"2020","unstructured":"Cuccia NL, Pothineni S, Wu B, Mendez HJ, Burton JC. Pore-size dependence and slow relaxation of hydrogel friction on smooth surfaces. Proc Natl Acad Sci U S A. 2020;117(21):11247\u201356.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"526_CR32","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1177\/0883911510377254","volume":"25","author":"S Van Vlierberghe","year":"2010","unstructured":"Van Vlierberghe S, Dubruel P, Schacht EJJ, Polymers C. Effect of cryogenic treatment on the rheological properties of gelatin hydrogels. J Bioact Compatible Polym. 2010;25(5):498\u2013512.","journal-title":"J. Bioact. Compatible Polym."},{"issue":"9","key":"526_CR33","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.3390\/ma8095269","volume":"8","author":"Z Sheikh","year":"2015","unstructured":"Sheikh Z, Brooks PJ, Barzilay O, Fine N, Glogauer M. Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials. Materials (Basel). 2015;8(9):5671\u2013701.","journal-title":"Materials (Basel)"},{"issue":"13","key":"526_CR34","doi-asserted-by":"publisher","first-page":"3479","DOI":"10.1016\/j.biomaterials.2010.01.074","volume":"31","author":"S Chen","year":"2010","unstructured":"Chen S, Jones JA, Xu Y, Low HY, Anderson JM, Leong KW. Characterization of topographical effects on macrophage behavior in a foreign body response model. Biomaterials. 2010;31(13):3479\u201391.","journal-title":"Biomaterials"},{"issue":"11","key":"526_CR35","doi-asserted-by":"publisher","first-page":"e110945","DOI":"10.1371\/journal.pone.0110945","volume":"9","author":"TO Socarras","year":"2014","unstructured":"Socarras TO, Vasconcelos AC, Campos PP, Pereira NB, Souza JP, Andrade SP. Foreign body response to subcutaneous implants in diabetic rats. PLoS. 2014;9(11):e110945.","journal-title":"PLoS"},{"issue":"6085","key":"526_CR36","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1126\/science.1214804","volume":"336","author":"D Seliktar","year":"2012","unstructured":"Seliktar D. Designing cell-compatible hydrogels for biomedical applications. Science. 2012;336(6085):1124\u20138.","journal-title":"Science"},{"key":"526_CR37","first-page":"e53606","volume":"110","author":"A Skardal","year":"2016","unstructured":"Skardal A, Devarasetty M, Kang HW, Seol YJ, Forsythe SD, Bishop C, et al. Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink. J Visualized Exp. 2016;110:e53606.","journal-title":"J. Visualized Exp."},{"issue":"7","key":"526_CR38","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1021\/cr000108x","volume":"101","author":"KY Lee","year":"2001","unstructured":"Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev. 2001;101(7):1869\u201380.","journal-title":"Chem Rev"},{"key":"526_CR39","unstructured":"Sun H, Song X-L, Mao L-L, Li JJMC. New progress and application of polysaccharides from marine organism in biomaterial. Modern Chem Ind 2010 S2."},{"key":"526_CR40","first-page":"1837","volume":"2","author":"J Venkatesan","year":"2014","unstructured":"Venkatesan J, Lowe B, Pallela R, Kim S-KJPB. Polysaccharides. 2014;2:1837\u201350.","journal-title":"Polysaccharides"},{"issue":"12","key":"526_CR41","doi-asserted-by":"publisher","first-page":"4255","DOI":"10.1016\/j.bioactmat.2021.04.028","volume":"6","author":"MC Wan","year":"2021","unstructured":"Wan MC, Qin W, Lei C, Li QH, Meng M, Fang M, et al. Biomaterials from the sea: future building blocks for biomedical applications. Bioact Mater. 2021;6(12):4255\u201385.","journal-title":"Bioact Mater"},{"issue":"1","key":"526_CR42","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1080\/14756366.2019.1660654","volume":"34","author":"Y Liu","year":"2019","unstructured":"Liu Y, Huang G. Extraction and derivatisation of active polysaccharides. J Enzyme Inhib Med Chem. 2019;34(1):1690\u20136.","journal-title":"J Enzyme Inhib Med Chem"},{"key":"526_CR43","volume-title":"Difficulties in research of Chinese medicine polysaccharides","author":"L Li-Feng","year":"2019","unstructured":"Li-Feng L, Tin-Long W, Quan-Bin H. Difficulties in research of Chinese medicine polysaccharides. New York: Elsevier; 2019."},{"issue":"1","key":"526_CR44","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13020-018-0166-0","volume":"13","author":"Q Li","year":"2018","unstructured":"Li Q, Niu Y, Xing P, Wang C. Bioactive polysaccharides from natural resources including Chinese medicinal herbs on tissue repair. Chin Med. 2018;13(1):7.","journal-title":"Chin Med"},{"key":"526_CR45","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.biomaterials.2016.06.028","volume":"102","author":"K Wang","year":"2016","unstructured":"Wang K, Hou WD, Wang X, Han C, Vuletic I, Su N, et al. Overcoming foreign-body reaction through nanotopography: Biocompatibility and immunoisolation properties of a nanofibrous membrane. Biomaterials. 2016;102:249\u201358.","journal-title":"Biomaterials"},{"issue":"1","key":"526_CR46","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.1038\/ncomms3275","volume":"4","author":"H Qi","year":"2013","unstructured":"Qi H, Ghodousi M, Du Y, Grun C, Bae H, Yin P, et al. DNA-directed self-assembly of shape-controlled hydrogels. Nat Commun. 2013;4(1):2275.","journal-title":"Nat Commun"}],"container-title":["Chinese Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13020-021-00526-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13020-021-00526-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13020-021-00526-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T02:08:38Z","timestamp":1675994918000},"score":1,"resource":{"primary":{"URL":"https:\/\/cmjournal.biomedcentral.com\/articles\/10.1186\/s13020-021-00526-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,4]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["526"],"URL":"https:\/\/doi.org\/10.1186\/s13020-021-00526-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-999929\/v1","asserted-by":"object"}]},"ISSN":["1749-8546"],"issn-type":[{"value":"1749-8546","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,4]]},"assertion":[{"value":"20 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal care and experimental procedures used in this study were approved by the Animal Ethics Committee, University of Macau.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflict of interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"131"}}