Extracellular Particles as Carriers of Cholesterol Not Associated with Lipoproteins

Exosomes and exomeres are the smallest microparticles ranging from 20 to 130 nm in diameter. They are found in almost all biological fluids. Exosomes and exomeres are of considerable interest since they can be involved in intercellular signaling and are biological markers of the state of cells, whic...

Full description

Saved in:
Bibliographic Details
Published in:Membranes (Basel) 2022-06, Vol.12 (6), p.618
Main Authors: Landa, Sergey, Verlov, Nicolay, Fedorova, Natalia, Filatov, Mikhail, Pantina, Rimma, Burdakov, Vladimir, Varfolomeeva, Elena, Emanuel, Vladimir
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Biomarkers
Biomechanics
CD63 antigen
CD81 antigen
CD9 antigen
Cell culture
Cholesterol
dynamic light scattering
exomeres
Exosomes
Lipid composition
Lipid metabolism
Lipids
Lipoproteins
Medical research
Membranes
Mevalonic acid
Microparticles
Microscopy
Morphology
Plasma
Proteins
Synthesis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c470t-bc0f2a38f7e1d3bb1fd5df221d42e18cfe625a8792e881654cceddc9acca68183
cites cdi_FETCH-LOGICAL-c470t-bc0f2a38f7e1d3bb1fd5df221d42e18cfe625a8792e881654cceddc9acca68183
container_end_page
container_issue 6
container_start_page 618
container_title Membranes (Basel)
container_volume 12
creator Landa, Sergey
Verlov, Nicolay
Fedorova, Natalia
Filatov, Mikhail
Pantina, Rimma
Burdakov, Vladimir
Varfolomeeva, Elena
Emanuel, Vladimir
description Exosomes and exomeres are the smallest microparticles ranging from 20 to 130 nm in diameter. They are found in almost all biological fluids. Exosomes and exomeres are of considerable interest since they can be involved in intercellular signaling and are biological markers of the state of cells, which can be used for diagnostics. The nomenclature of exosomes remains poorly developed. Most researchers try to classify them based on the mode of formation, physicochemical characteristics, and the presence of tetrasporin markers CD9, CD63, and CD81. The data presented in this work show that although exomeres carry tetrasporin biomarkers, they differ from exosomes strongly in lipid composition, especially in cholesterol content. The production of exomeres by cells is associated with the synthesis of cholesterol in cells and is expressed or suppressed by regulators of the synthesis of mevalonate, an intermediate product of cholesterol metabolism. In addition, the work shows that the concentration of extracellular particles in the body correlates with the concentration of cholesterol in the plasma, but weakly correlates with the concentration of cholesterol in lipoproteins. This suggests that not all plasma cholesterol is associated with lipoproteins, as previously thought.
doi_str_mv 10.3390/membranes12060618
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_88241a31d2cc4e7b8a85b79057ef3d5e</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_88241a31d2cc4e7b8a85b79057ef3d5e</doaj_id><sourcerecordid>2680238132</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-bc0f2a38f7e1d3bb1fd5df221d42e18cfe625a8792e881654cceddc9acca68183</originalsourceid><addsrcrecordid>eNplkl1rHCEUhqWkNCHND-idkJvcbOrH-DE3gbAkaWBpC22vxdFj1mVm3OhM0v77ut2lNKk3yvHhQd9zEPpAySXnLfk4wNBlO0KhjEgiqX6DThhRakG4Ekf_nI_RWSkbUpckQnLyDh1zobjkrDlB325-Ttk66Pu5txl_tXmKroeCbcFLm3OEXHAKeLlOtTpBTj3-nCZ8XUpy0U7g8XOc1ngVt2mb0wRxLO_R22D7AmeH_RT9uL35vvy0WH25u19erxauUWRadI4EZrkOCqjnXUeDFz4wRn3DgGoXQDJhtWoZaE2laJwD711rnbNSU81P0f3e65PdmG2Og82_TLLR_Cmk_GAO3zFas4ZaTj1zrgHVaatFp1oiFATuBVTX1d61nbsBvIOxxtK_kL68GePaPKQn0zKmajuq4OIgyOlxrlGZIZZdrrVFaS6GSU0Y15Szip6_QjdpzmONqlKqVdWndxTdUy6nUjKEv4-hxOwmwPw3Afw3EXGmWg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2679773982</pqid></control><display><type>article</type><title>Extracellular Particles as Carriers of Cholesterol Not Associated with Lipoproteins</title><source>Publicly Available Content (ProQuest)</source><source>PubMed Central</source><creator>Landa, Sergey ; Verlov, Nicolay ; Fedorova, Natalia ; Filatov, Mikhail ; Pantina, Rimma ; Burdakov, Vladimir ; Varfolomeeva, Elena ; Emanuel, Vladimir</creator><creatorcontrib>Landa, Sergey ; Verlov, Nicolay ; Fedorova, Natalia ; Filatov, Mikhail ; Pantina, Rimma ; Burdakov, Vladimir ; Varfolomeeva, Elena ; Emanuel, Vladimir</creatorcontrib><description>Exosomes and exomeres are the smallest microparticles ranging from 20 to 130 nm in diameter. They are found in almost all biological fluids. Exosomes and exomeres are of considerable interest since they can be involved in intercellular signaling and are biological markers of the state of cells, which can be used for diagnostics. The nomenclature of exosomes remains poorly developed. Most researchers try to classify them based on the mode of formation, physicochemical characteristics, and the presence of tetrasporin markers CD9, CD63, and CD81. The data presented in this work show that although exomeres carry tetrasporin biomarkers, they differ from exosomes strongly in lipid composition, especially in cholesterol content. The production of exomeres by cells is associated with the synthesis of cholesterol in cells and is expressed or suppressed by regulators of the synthesis of mevalonate, an intermediate product of cholesterol metabolism. In addition, the work shows that the concentration of extracellular particles in the body correlates with the concentration of cholesterol in the plasma, but weakly correlates with the concentration of cholesterol in lipoproteins. This suggests that not all plasma cholesterol is associated with lipoproteins, as previously thought.</description><identifier>ISSN: 2077-0375</identifier><identifier>EISSN: 2077-0375</identifier><identifier>DOI: 10.3390/membranes12060618</identifier><identifier>PMID: 35736324</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Antibodies ; Apoptosis ; Biomarkers ; Biomechanics ; CD63 antigen ; CD81 antigen ; CD9 antigen ; Cell culture ; Cholesterol ; dynamic light scattering ; exomeres ; Exosomes ; Lipid composition ; Lipid metabolism ; Lipids ; Lipoproteins ; Medical research ; Membranes ; Mevalonic acid ; Microparticles ; Microscopy ; Morphology ; Plasma ; Proteins ; Synthesis</subject><ispartof>Membranes (Basel), 2022-06, Vol.12 (6), p.618</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-bc0f2a38f7e1d3bb1fd5df221d42e18cfe625a8792e881654cceddc9acca68183</citedby><cites>FETCH-LOGICAL-c470t-bc0f2a38f7e1d3bb1fd5df221d42e18cfe625a8792e881654cceddc9acca68183</cites><orcidid>0000-0002-2419-1935 ; 0000-0002-3756-0701</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2679773982/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2679773982?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768,74869</link.rule.ids></links><search><creatorcontrib>Landa, Sergey</creatorcontrib><creatorcontrib>Verlov, Nicolay</creatorcontrib><creatorcontrib>Fedorova, Natalia</creatorcontrib><creatorcontrib>Filatov, Mikhail</creatorcontrib><creatorcontrib>Pantina, Rimma</creatorcontrib><creatorcontrib>Burdakov, Vladimir</creatorcontrib><creatorcontrib>Varfolomeeva, Elena</creatorcontrib><creatorcontrib>Emanuel, Vladimir</creatorcontrib><title>Extracellular Particles as Carriers of Cholesterol Not Associated with Lipoproteins</title><title>Membranes (Basel)</title><description>Exosomes and exomeres are the smallest microparticles ranging from 20 to 130 nm in diameter. They are found in almost all biological fluids. Exosomes and exomeres are of considerable interest since they can be involved in intercellular signaling and are biological markers of the state of cells, which can be used for diagnostics. The nomenclature of exosomes remains poorly developed. Most researchers try to classify them based on the mode of formation, physicochemical characteristics, and the presence of tetrasporin markers CD9, CD63, and CD81. The data presented in this work show that although exomeres carry tetrasporin biomarkers, they differ from exosomes strongly in lipid composition, especially in cholesterol content. The production of exomeres by cells is associated with the synthesis of cholesterol in cells and is expressed or suppressed by regulators of the synthesis of mevalonate, an intermediate product of cholesterol metabolism. In addition, the work shows that the concentration of extracellular particles in the body correlates with the concentration of cholesterol in the plasma, but weakly correlates with the concentration of cholesterol in lipoproteins. This suggests that not all plasma cholesterol is associated with lipoproteins, as previously thought.</description><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biomarkers</subject><subject>Biomechanics</subject><subject>CD63 antigen</subject><subject>CD81 antigen</subject><subject>CD9 antigen</subject><subject>Cell culture</subject><subject>Cholesterol</subject><subject>dynamic light scattering</subject><subject>exomeres</subject><subject>Exosomes</subject><subject>Lipid composition</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Lipoproteins</subject><subject>Medical research</subject><subject>Membranes</subject><subject>Mevalonic acid</subject><subject>Microparticles</subject><subject>Microscopy</subject><subject>Morphology</subject><subject>Plasma</subject><subject>Proteins</subject><subject>Synthesis</subject><issn>2077-0375</issn><issn>2077-0375</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNplkl1rHCEUhqWkNCHND-idkJvcbOrH-DE3gbAkaWBpC22vxdFj1mVm3OhM0v77ut2lNKk3yvHhQd9zEPpAySXnLfk4wNBlO0KhjEgiqX6DThhRakG4Ekf_nI_RWSkbUpckQnLyDh1zobjkrDlB325-Ttk66Pu5txl_tXmKroeCbcFLm3OEXHAKeLlOtTpBTj3-nCZ8XUpy0U7g8XOc1ngVt2mb0wRxLO_R22D7AmeH_RT9uL35vvy0WH25u19erxauUWRadI4EZrkOCqjnXUeDFz4wRn3DgGoXQDJhtWoZaE2laJwD711rnbNSU81P0f3e65PdmG2Og82_TLLR_Cmk_GAO3zFas4ZaTj1zrgHVaatFp1oiFATuBVTX1d61nbsBvIOxxtK_kL68GePaPKQn0zKmajuq4OIgyOlxrlGZIZZdrrVFaS6GSU0Y15Szip6_QjdpzmONqlKqVdWndxTdUy6nUjKEv4-hxOwmwPw3Afw3EXGmWg</recordid><startdate>20220614</startdate><enddate>20220614</enddate><creator>Landa, Sergey</creator><creator>Verlov, Nicolay</creator><creator>Fedorova, Natalia</creator><creator>Filatov, Mikhail</creator><creator>Pantina, Rimma</creator><creator>Burdakov, Vladimir</creator><creator>Varfolomeeva, Elena</creator><creator>Emanuel, Vladimir</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8D</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>M7S</scope><scope>P64</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2419-1935</orcidid><orcidid>https://orcid.org/0000-0002-3756-0701</orcidid></search><sort><creationdate>20220614</creationdate><title>Extracellular Particles as Carriers of Cholesterol Not Associated with Lipoproteins</title><author>Landa, Sergey ; Verlov, Nicolay ; Fedorova, Natalia ; Filatov, Mikhail ; Pantina, Rimma ; Burdakov, Vladimir ; Varfolomeeva, Elena ; Emanuel, Vladimir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-bc0f2a38f7e1d3bb1fd5df221d42e18cfe625a8792e881654cceddc9acca68183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Biomarkers</topic><topic>Biomechanics</topic><topic>CD63 antigen</topic><topic>CD81 antigen</topic><topic>CD9 antigen</topic><topic>Cell culture</topic><topic>Cholesterol</topic><topic>dynamic light scattering</topic><topic>exomeres</topic><topic>Exosomes</topic><topic>Lipid composition</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Lipoproteins</topic><topic>Medical research</topic><topic>Membranes</topic><topic>Mevalonic acid</topic><topic>Microparticles</topic><topic>Microscopy</topic><topic>Morphology</topic><topic>Plasma</topic><topic>Proteins</topic><topic>Synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Landa, Sergey</creatorcontrib><creatorcontrib>Verlov, Nicolay</creatorcontrib><creatorcontrib>Fedorova, Natalia</creatorcontrib><creatorcontrib>Filatov, Mikhail</creatorcontrib><creatorcontrib>Pantina, Rimma</creatorcontrib><creatorcontrib>Burdakov, Vladimir</creatorcontrib><creatorcontrib>Varfolomeeva, Elena</creatorcontrib><creatorcontrib>Emanuel, Vladimir</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics &amp; Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical &amp; Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>ANTE: Abstracts in New Technology &amp; Engineering</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>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Civil Engineering Abstracts</collection><collection>ProQuest Engineering Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Biological Sciences</collection><collection>Computer and Information Systems Abstracts – Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering collection</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Membranes (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Landa, Sergey</au><au>Verlov, Nicolay</au><au>Fedorova, Natalia</au><au>Filatov, Mikhail</au><au>Pantina, Rimma</au><au>Burdakov, Vladimir</au><au>Varfolomeeva, Elena</au><au>Emanuel, Vladimir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extracellular Particles as Carriers of Cholesterol Not Associated with Lipoproteins</atitle><jtitle>Membranes (Basel)</jtitle><date>2022-06-14</date><risdate>2022</risdate><volume>12</volume><issue>6</issue><spage>618</spage><pages>618-</pages><issn>2077-0375</issn><eissn>2077-0375</eissn><abstract>Exosomes and exomeres are the smallest microparticles ranging from 20 to 130 nm in diameter. They are found in almost all biological fluids. Exosomes and exomeres are of considerable interest since they can be involved in intercellular signaling and are biological markers of the state of cells, which can be used for diagnostics. The nomenclature of exosomes remains poorly developed. Most researchers try to classify them based on the mode of formation, physicochemical characteristics, and the presence of tetrasporin markers CD9, CD63, and CD81. The data presented in this work show that although exomeres carry tetrasporin biomarkers, they differ from exosomes strongly in lipid composition, especially in cholesterol content. The production of exomeres by cells is associated with the synthesis of cholesterol in cells and is expressed or suppressed by regulators of the synthesis of mevalonate, an intermediate product of cholesterol metabolism. In addition, the work shows that the concentration of extracellular particles in the body correlates with the concentration of cholesterol in the plasma, but weakly correlates with the concentration of cholesterol in lipoproteins. This suggests that not all plasma cholesterol is associated with lipoproteins, as previously thought.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>35736324</pmid><doi>10.3390/membranes12060618</doi><orcidid>https://orcid.org/0000-0002-2419-1935</orcidid><orcidid>https://orcid.org/0000-0002-3756-0701</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2077-0375
ispartof Membranes (Basel), 2022-06, Vol.12 (6), p.618
issn 2077-0375
2077-0375
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_88241a31d2cc4e7b8a85b79057ef3d5e
source Publicly Available Content (ProQuest); PubMed Central
subjects Antibodies
Apoptosis
Biomarkers
Biomechanics
CD63 antigen
CD81 antigen
CD9 antigen
Cell culture
Cholesterol
dynamic light scattering
exomeres
Exosomes
Lipid composition
Lipid metabolism
Lipids
Lipoproteins
Medical research
Membranes
Mevalonic acid
Microparticles
Microscopy
Morphology
Plasma
Proteins
Synthesis
title Extracellular Particles as Carriers of Cholesterol Not Associated with Lipoproteins
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T02%3A58%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Extracellular%20Particles%20as%20Carriers%20of%20Cholesterol%20Not%20Associated%20with%20Lipoproteins&rft.jtitle=Membranes%20(Basel)&rft.au=Landa,%20Sergey&rft.date=2022-06-14&rft.volume=12&rft.issue=6&rft.spage=618&rft.pages=618-&rft.issn=2077-0375&rft.eissn=2077-0375&rft_id=info:doi/10.3390/membranes12060618&rft_dat=%3Cproquest_doaj_%3E2680238132%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c470t-bc0f2a38f7e1d3bb1fd5df221d42e18cfe625a8792e881654cceddc9acca68183%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2679773982&rft_id=info:pmid/35736324&rfr_iscdi=true