Optimization of the extraction process of polyphenols from Allium cepa using response surface methodology and assessment of its antioxidant and lipid-lowering action

Non-alcoholic fatty liver disease (NAFLD) development and progression is closely associated with oxidative stress (OS). The main objective of this research was to optimize the extraction process of Allium cepa polyphenols using a response surface methodology (RSM) and evaluate its antioxidant and li...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of food measurement & characterization 2022-04, Vol.16 (2), p.1171-1183
Hauptverfasser: Fan, Kongming, Yang, Xiaoqian, Zhou, Chunyang, Mei, Xue, Yang, Xin, Fu, Qiaofeng, Li, Yan, Lin, Yong, Yang, Chunyan
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1183
container_issue 2
container_start_page 1171
container_title Journal of food measurement & characterization
container_volume 16
creator Fan, Kongming
Yang, Xiaoqian
Zhou, Chunyang
Mei, Xue
Yang, Xin
Fu, Qiaofeng
Li, Yan
Lin, Yong
Yang, Chunyan
description Non-alcoholic fatty liver disease (NAFLD) development and progression is closely associated with oxidative stress (OS). The main objective of this research was to optimize the extraction process of Allium cepa polyphenols using a response surface methodology (RSM) and evaluate its antioxidant and lipid-lowering activity correlated with NAFLD. First of all, ultrasound-assisted extraction (UAE) process of the polyphenols from A. cepa was optimized using a three-factor-three-level Box-Behnken Design (BBD) combined with single factor experiment, among which, the investigation factor was total polyphenol content (TPC) from A. cepa measured by Folin-ciocalteu reagent. Then, the quantification of the main polyphenols from A. cepa was undertaken using high performance liquid chromatography (HPLC). Afterwards, the antioxidant activity of A. cepa extract (ACE) was evaluated using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylrylhydrazyl (DPPH) free radicals. In addition, the in vitro lipid-lowering action was investigated using hepatic steatosis model in HepG2 cells induced by free fatty acid (FFA). As a result, the optimal extraction conditions were extraction time of 30 min, extraction temperature of 53.42 ℃, 1:70 solid-to-solvent ratio and 64.5% ethanol. Under these conditions, the measured TPC was 17.0819 mg/g GAE, which was in agreement with the predicted value, while TPC was 17.2449 mg/g GAE with relative error of 0.96%. Furthermore, HPLC analysis showed that the main polyphenols existed in ACE were isoquercitrin (5.07 mg/g DW) and quercetin (2.03 mg/g DW). In addition, Antioxidant activity showed that the IC 50 values of ACE against ABTS and DPPH free radicals were 84.19 ± 0.03 μg/mL and 171.2 ± 0.02 μg/mL, respectively. Moreover, the in vitro lipid-lowering effect exhibited that ACE reduced the levels of TC and TG ( P  
doi_str_mv 10.1007/s11694-021-01239-4
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_3080910189</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3080910189</sourcerecordid><originalsourceid>FETCH-LOGICAL-c319t-4c21e6fcf2a7e3320443ac09664216403be33c147e8cd49a4a73d3720d2510ea3</originalsourceid><addsrcrecordid>eNp9UcFO3TAQjCoqFQE_0JOlnlN2bTd5OSLUFiQkLvRsuc6GZ5TErtdRef0f_hPnpSq3nnY1OzO7q6mqjwifEaC9ZMSm0zVIrAGl6mr9rjqV2Klao9In_3rZfKgumJ8AALHVulGn1ct9zH7yf2z2YRZhEHlPgp5zsu6IxBQcMa-TGMZD3NMcRhZDCpO4Gke_TMJRtGJhPz-KRBzDzCR4SYN1JCbK-9CHMTwehJ17YZmL20RzXh195oKWPc--L_XIGH30fT2G35RWx-2M8-r9YEemi7_1rPrx7evD9U19d__99vrqrnYKu1xrJ5GawQ3StqSUBK2VddA1jZbYaFA_C-pQt7Rzve6stq3qVSuhl18QyKqz6tPmW97-tRBn8xSWNJeVRsEOOgTcdYUlN5ZLgTnRYGLyk00Hg2DWRMyWiCmJmGMiRheR2kQc18covVn_R_UKEyySGw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3080910189</pqid></control><display><type>article</type><title>Optimization of the extraction process of polyphenols from Allium cepa using response surface methodology and assessment of its antioxidant and lipid-lowering action</title><source>SpringerLink Journals - AutoHoldings</source><creator>Fan, Kongming ; Yang, Xiaoqian ; Zhou, Chunyang ; Mei, Xue ; Yang, Xin ; Fu, Qiaofeng ; Li, Yan ; Lin, Yong ; Yang, Chunyan</creator><creatorcontrib>Fan, Kongming ; Yang, Xiaoqian ; Zhou, Chunyang ; Mei, Xue ; Yang, Xin ; Fu, Qiaofeng ; Li, Yan ; Lin, Yong ; Yang, Chunyan</creatorcontrib><description>Non-alcoholic fatty liver disease (NAFLD) development and progression is closely associated with oxidative stress (OS). The main objective of this research was to optimize the extraction process of Allium cepa polyphenols using a response surface methodology (RSM) and evaluate its antioxidant and lipid-lowering activity correlated with NAFLD. First of all, ultrasound-assisted extraction (UAE) process of the polyphenols from A. cepa was optimized using a three-factor-three-level Box-Behnken Design (BBD) combined with single factor experiment, among which, the investigation factor was total polyphenol content (TPC) from A. cepa measured by Folin-ciocalteu reagent. Then, the quantification of the main polyphenols from A. cepa was undertaken using high performance liquid chromatography (HPLC). Afterwards, the antioxidant activity of A. cepa extract (ACE) was evaluated using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylrylhydrazyl (DPPH) free radicals. In addition, the in vitro lipid-lowering action was investigated using hepatic steatosis model in HepG2 cells induced by free fatty acid (FFA). As a result, the optimal extraction conditions were extraction time of 30 min, extraction temperature of 53.42 ℃, 1:70 solid-to-solvent ratio and 64.5% ethanol. Under these conditions, the measured TPC was 17.0819 mg/g GAE, which was in agreement with the predicted value, while TPC was 17.2449 mg/g GAE with relative error of 0.96%. Furthermore, HPLC analysis showed that the main polyphenols existed in ACE were isoquercitrin (5.07 mg/g DW) and quercetin (2.03 mg/g DW). In addition, Antioxidant activity showed that the IC 50 values of ACE against ABTS and DPPH free radicals were 84.19 ± 0.03 μg/mL and 171.2 ± 0.02 μg/mL, respectively. Moreover, the in vitro lipid-lowering effect exhibited that ACE reduced the levels of TC and TG ( P  &lt;  0.05 ) compared with model group. Accordingly, the results indicated that A. cepa might be a potential strategy for NAFLD intervention.</description><identifier>ISSN: 2193-4126</identifier><identifier>EISSN: 2193-4134</identifier><identifier>DOI: 10.1007/s11694-021-01239-4</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Allium cepa ; Antioxidants ; Chemistry ; Chemistry and Materials Science ; Chemistry/Food Science ; Design factors ; Engineering ; Error analysis ; Ethanol ; Fatty liver ; Food Science ; Free radicals ; High performance liquid chromatography ; Hypolipidemic activity ; Lipids ; Liquid chromatography ; Liver diseases ; Optimization ; Original Paper ; Oxidative stress ; Polyphenols ; Quercetin ; Reagents ; Response surface methodology ; Steatosis ; Sulfonic acid</subject><ispartof>Journal of food measurement &amp; characterization, 2022-04, Vol.16 (2), p.1171-1183</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c319t-4c21e6fcf2a7e3320443ac09664216403be33c147e8cd49a4a73d3720d2510ea3</citedby><cites>FETCH-LOGICAL-c319t-4c21e6fcf2a7e3320443ac09664216403be33c147e8cd49a4a73d3720d2510ea3</cites><orcidid>0000-0002-4536-6378</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11694-021-01239-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11694-021-01239-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27915,27916,41479,42548,51310</link.rule.ids></links><search><creatorcontrib>Fan, Kongming</creatorcontrib><creatorcontrib>Yang, Xiaoqian</creatorcontrib><creatorcontrib>Zhou, Chunyang</creatorcontrib><creatorcontrib>Mei, Xue</creatorcontrib><creatorcontrib>Yang, Xin</creatorcontrib><creatorcontrib>Fu, Qiaofeng</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Lin, Yong</creatorcontrib><creatorcontrib>Yang, Chunyan</creatorcontrib><title>Optimization of the extraction process of polyphenols from Allium cepa using response surface methodology and assessment of its antioxidant and lipid-lowering action</title><title>Journal of food measurement &amp; characterization</title><addtitle>Food Measure</addtitle><description>Non-alcoholic fatty liver disease (NAFLD) development and progression is closely associated with oxidative stress (OS). The main objective of this research was to optimize the extraction process of Allium cepa polyphenols using a response surface methodology (RSM) and evaluate its antioxidant and lipid-lowering activity correlated with NAFLD. First of all, ultrasound-assisted extraction (UAE) process of the polyphenols from A. cepa was optimized using a three-factor-three-level Box-Behnken Design (BBD) combined with single factor experiment, among which, the investigation factor was total polyphenol content (TPC) from A. cepa measured by Folin-ciocalteu reagent. Then, the quantification of the main polyphenols from A. cepa was undertaken using high performance liquid chromatography (HPLC). Afterwards, the antioxidant activity of A. cepa extract (ACE) was evaluated using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylrylhydrazyl (DPPH) free radicals. In addition, the in vitro lipid-lowering action was investigated using hepatic steatosis model in HepG2 cells induced by free fatty acid (FFA). As a result, the optimal extraction conditions were extraction time of 30 min, extraction temperature of 53.42 ℃, 1:70 solid-to-solvent ratio and 64.5% ethanol. Under these conditions, the measured TPC was 17.0819 mg/g GAE, which was in agreement with the predicted value, while TPC was 17.2449 mg/g GAE with relative error of 0.96%. Furthermore, HPLC analysis showed that the main polyphenols existed in ACE were isoquercitrin (5.07 mg/g DW) and quercetin (2.03 mg/g DW). In addition, Antioxidant activity showed that the IC 50 values of ACE against ABTS and DPPH free radicals were 84.19 ± 0.03 μg/mL and 171.2 ± 0.02 μg/mL, respectively. Moreover, the in vitro lipid-lowering effect exhibited that ACE reduced the levels of TC and TG ( P  &lt;  0.05 ) compared with model group. Accordingly, the results indicated that A. cepa might be a potential strategy for NAFLD intervention.</description><subject>Allium cepa</subject><subject>Antioxidants</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chemistry/Food Science</subject><subject>Design factors</subject><subject>Engineering</subject><subject>Error analysis</subject><subject>Ethanol</subject><subject>Fatty liver</subject><subject>Food Science</subject><subject>Free radicals</subject><subject>High performance liquid chromatography</subject><subject>Hypolipidemic activity</subject><subject>Lipids</subject><subject>Liquid chromatography</subject><subject>Liver diseases</subject><subject>Optimization</subject><subject>Original Paper</subject><subject>Oxidative stress</subject><subject>Polyphenols</subject><subject>Quercetin</subject><subject>Reagents</subject><subject>Response surface methodology</subject><subject>Steatosis</subject><subject>Sulfonic acid</subject><issn>2193-4126</issn><issn>2193-4134</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp9UcFO3TAQjCoqFQE_0JOlnlN2bTd5OSLUFiQkLvRsuc6GZ5TErtdRef0f_hPnpSq3nnY1OzO7q6mqjwifEaC9ZMSm0zVIrAGl6mr9rjqV2Klao9In_3rZfKgumJ8AALHVulGn1ct9zH7yf2z2YRZhEHlPgp5zsu6IxBQcMa-TGMZD3NMcRhZDCpO4Gke_TMJRtGJhPz-KRBzDzCR4SYN1JCbK-9CHMTwehJ17YZmL20RzXh195oKWPc--L_XIGH30fT2G35RWx-2M8-r9YEemi7_1rPrx7evD9U19d__99vrqrnYKu1xrJ5GawQ3StqSUBK2VddA1jZbYaFA_C-pQt7Rzve6stq3qVSuhl18QyKqz6tPmW97-tRBn8xSWNJeVRsEOOgTcdYUlN5ZLgTnRYGLyk00Hg2DWRMyWiCmJmGMiRheR2kQc18covVn_R_UKEyySGw</recordid><startdate>20220401</startdate><enddate>20220401</enddate><creator>Fan, Kongming</creator><creator>Yang, Xiaoqian</creator><creator>Zhou, Chunyang</creator><creator>Mei, Xue</creator><creator>Yang, Xin</creator><creator>Fu, Qiaofeng</creator><creator>Li, Yan</creator><creator>Lin, Yong</creator><creator>Yang, Chunyan</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X2</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>HCIFZ</scope><scope>L6V</scope><scope>M0K</scope><scope>M7S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><orcidid>https://orcid.org/0000-0002-4536-6378</orcidid></search><sort><creationdate>20220401</creationdate><title>Optimization of the extraction process of polyphenols from Allium cepa using response surface methodology and assessment of its antioxidant and lipid-lowering action</title><author>Fan, Kongming ; Yang, Xiaoqian ; Zhou, Chunyang ; Mei, Xue ; Yang, Xin ; Fu, Qiaofeng ; Li, Yan ; Lin, Yong ; Yang, Chunyan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c319t-4c21e6fcf2a7e3320443ac09664216403be33c147e8cd49a4a73d3720d2510ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Allium cepa</topic><topic>Antioxidants</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Chemistry/Food Science</topic><topic>Design factors</topic><topic>Engineering</topic><topic>Error analysis</topic><topic>Ethanol</topic><topic>Fatty liver</topic><topic>Food Science</topic><topic>Free radicals</topic><topic>High performance liquid chromatography</topic><topic>Hypolipidemic activity</topic><topic>Lipids</topic><topic>Liquid chromatography</topic><topic>Liver diseases</topic><topic>Optimization</topic><topic>Original Paper</topic><topic>Oxidative stress</topic><topic>Polyphenols</topic><topic>Quercetin</topic><topic>Reagents</topic><topic>Response surface methodology</topic><topic>Steatosis</topic><topic>Sulfonic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fan, Kongming</creatorcontrib><creatorcontrib>Yang, Xiaoqian</creatorcontrib><creatorcontrib>Zhou, Chunyang</creatorcontrib><creatorcontrib>Mei, Xue</creatorcontrib><creatorcontrib>Yang, Xin</creatorcontrib><creatorcontrib>Fu, Qiaofeng</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Lin, Yong</creatorcontrib><creatorcontrib>Yang, Chunyan</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Agricultural Science Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Engineering Collection</collection><collection>Agricultural Science Database</collection><collection>Engineering Database</collection><collection>Publicly Available Content Database</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>Engineering Collection</collection><jtitle>Journal of food measurement &amp; characterization</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fan, Kongming</au><au>Yang, Xiaoqian</au><au>Zhou, Chunyang</au><au>Mei, Xue</au><au>Yang, Xin</au><au>Fu, Qiaofeng</au><au>Li, Yan</au><au>Lin, Yong</au><au>Yang, Chunyan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimization of the extraction process of polyphenols from Allium cepa using response surface methodology and assessment of its antioxidant and lipid-lowering action</atitle><jtitle>Journal of food measurement &amp; characterization</jtitle><stitle>Food Measure</stitle><date>2022-04-01</date><risdate>2022</risdate><volume>16</volume><issue>2</issue><spage>1171</spage><epage>1183</epage><pages>1171-1183</pages><issn>2193-4126</issn><eissn>2193-4134</eissn><abstract>Non-alcoholic fatty liver disease (NAFLD) development and progression is closely associated with oxidative stress (OS). The main objective of this research was to optimize the extraction process of Allium cepa polyphenols using a response surface methodology (RSM) and evaluate its antioxidant and lipid-lowering activity correlated with NAFLD. First of all, ultrasound-assisted extraction (UAE) process of the polyphenols from A. cepa was optimized using a three-factor-three-level Box-Behnken Design (BBD) combined with single factor experiment, among which, the investigation factor was total polyphenol content (TPC) from A. cepa measured by Folin-ciocalteu reagent. Then, the quantification of the main polyphenols from A. cepa was undertaken using high performance liquid chromatography (HPLC). Afterwards, the antioxidant activity of A. cepa extract (ACE) was evaluated using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylrylhydrazyl (DPPH) free radicals. In addition, the in vitro lipid-lowering action was investigated using hepatic steatosis model in HepG2 cells induced by free fatty acid (FFA). As a result, the optimal extraction conditions were extraction time of 30 min, extraction temperature of 53.42 ℃, 1:70 solid-to-solvent ratio and 64.5% ethanol. Under these conditions, the measured TPC was 17.0819 mg/g GAE, which was in agreement with the predicted value, while TPC was 17.2449 mg/g GAE with relative error of 0.96%. Furthermore, HPLC analysis showed that the main polyphenols existed in ACE were isoquercitrin (5.07 mg/g DW) and quercetin (2.03 mg/g DW). In addition, Antioxidant activity showed that the IC 50 values of ACE against ABTS and DPPH free radicals were 84.19 ± 0.03 μg/mL and 171.2 ± 0.02 μg/mL, respectively. Moreover, the in vitro lipid-lowering effect exhibited that ACE reduced the levels of TC and TG ( P  &lt;  0.05 ) compared with model group. Accordingly, the results indicated that A. cepa might be a potential strategy for NAFLD intervention.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s11694-021-01239-4</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-4536-6378</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2193-4126
ispartof Journal of food measurement & characterization, 2022-04, Vol.16 (2), p.1171-1183
issn 2193-4126
2193-4134
language eng
recordid cdi_proquest_journals_3080910189
source SpringerLink Journals - AutoHoldings
subjects Allium cepa
Antioxidants
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
Design factors
Engineering
Error analysis
Ethanol
Fatty liver
Food Science
Free radicals
High performance liquid chromatography
Hypolipidemic activity
Lipids
Liquid chromatography
Liver diseases
Optimization
Original Paper
Oxidative stress
Polyphenols
Quercetin
Reagents
Response surface methodology
Steatosis
Sulfonic acid
title Optimization of the extraction process of polyphenols from Allium cepa using response surface methodology and assessment of its antioxidant and lipid-lowering action
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T20%3A36%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Optimization%20of%20the%20extraction%20process%20of%20polyphenols%20from%20Allium%20cepa%20using%20response%20surface%20methodology%20and%20assessment%20of%20its%20antioxidant%20and%20lipid-lowering%20action&rft.jtitle=Journal%20of%20food%20measurement%20&%20characterization&rft.au=Fan,%20Kongming&rft.date=2022-04-01&rft.volume=16&rft.issue=2&rft.spage=1171&rft.epage=1183&rft.pages=1171-1183&rft.issn=2193-4126&rft.eissn=2193-4134&rft_id=info:doi/10.1007/s11694-021-01239-4&rft_dat=%3Cproquest_cross%3E3080910189%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3080910189&rft_id=info:pmid/&rfr_iscdi=true