Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity

Crystalline metal–organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2022-08, Vol.23 (16), p.9098
Main Authors: Lee, Do Nam, Kim, Yeong Rim, Yang, Sohyeon, Tran, Ngoc Minh, Park, Bong Joo, Lee, Su Jung, Kim, Youngmee, Yoo, Hyojong, Kim, Sung-Jin, Shin, Jae Ho
Format: Article
Language:English
Subjects:
Adsorption
Antibacterial activity
Ball milling
Benzene
Biocompatibility
Biological activity
Catalysis
Crystal structure
Crystallography
Drug delivery
Gram-negative bacteria
Hydrocarbons
Metal-organic frameworks
MOFs
Morphology
Nitric oxide
Nitrogen
Single crystals
Spectrum analysis
Synergistic effect
X-ray diffraction
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-c455t-69d0902095bb1ae7eea1aa29bc261cf06c60ea83346d0def741441e59afa93043
cites cdi_FETCH-LOGICAL-c455t-69d0902095bb1ae7eea1aa29bc261cf06c60ea83346d0def741441e59afa93043
container_end_page
container_issue 16
container_start_page 9098
container_title International journal of molecular sciences
container_volume 23
creator Lee, Do Nam
Kim, Yeong Rim
Yang, Sohyeon
Tran, Ngoc Minh
Park, Bong Joo
Lee, Su Jung
Kim, Youngmee
Yoo, Hyojong
Kim, Sung-Jin
Shin, Jae Ho
description Crystalline metal–organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg−1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.
doi_str_mv 10.3390/ijms23169098
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_a65b678c6ba14ac895326906b8d71b1f</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_a65b678c6ba14ac895326906b8d71b1f</doaj_id><sourcerecordid>2706251402</sourcerecordid><originalsourceid>FETCH-LOGICAL-c455t-69d0902095bb1ae7eea1aa29bc261cf06c60ea83346d0def741441e59afa93043</originalsourceid><addsrcrecordid>eNpdkk1v1DAQhi0EomXhxg-IxIUDAX_FiTkgtREfK1VUgnK2xs4k61U2XmynYv892W6FWk4e2c88st4ZQl4z-l4ITT_47S5xwZSmunlCzpnkvKRU1U8f1GfkRUpbSrnglX5OzoSijAslzoltw5RjGEewIxbffY7eFdd_fIfFzxwiDFjA1BU_cERIWPipaOfy8qb9WLTxkDKMYxgi7DdL13pKftjkdNdw6QO47G99Prwkz3oYE766P1fk15fPN-238ur667q9uCqdrKpcKt1RTTnVlbUMsEYEBsC1dVwx11PlFEVohJCqox32tWRSMqw09KAFlWJF1idvF2Br9tHvIB5MAG_uLkIcDMTs3YgGVGVV3ThlgUlwja4EXwJUtulqZlm_uD6dXPvZ7rBzuIQE4yPp45fJb8wQbo2WVDNdL4K394IYfs-Ystn55HDJecIwJ8NrWqsFZUf0zX_oNsxxWqI6UopXTC6DW5F3J8rFkFLE_t9nGDXHRTAPF0H8Be7LpNE</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2706251402</pqid></control><display><type>article</type><title>Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity</title><source>PubMed (Medline)</source><source>Publicly Available Content Database</source><creator>Lee, Do Nam ; Kim, Yeong Rim ; Yang, Sohyeon ; Tran, Ngoc Minh ; Park, Bong Joo ; Lee, Su Jung ; Kim, Youngmee ; Yoo, Hyojong ; Kim, Sung-Jin ; Shin, Jae Ho</creator><creatorcontrib>Lee, Do Nam ; Kim, Yeong Rim ; Yang, Sohyeon ; Tran, Ngoc Minh ; Park, Bong Joo ; Lee, Su Jung ; Kim, Youngmee ; Yoo, Hyojong ; Kim, Sung-Jin ; Shin, Jae Ho</creatorcontrib><description>Crystalline metal–organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg−1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms23169098</identifier><identifier>PMID: 36012363</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Adsorption ; Antibacterial activity ; Ball milling ; Benzene ; Biocompatibility ; Biological activity ; Catalysis ; Crystal structure ; Crystallography ; Drug delivery ; Gram-negative bacteria ; Hydrocarbons ; Metal-organic frameworks ; MOFs ; Morphology ; Nitric oxide ; Nitrogen ; Single crystals ; Spectrum analysis ; Synergistic effect ; X-ray diffraction</subject><ispartof>International journal of molecular sciences, 2022-08, Vol.23 (16), p.9098</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-c455t-69d0902095bb1ae7eea1aa29bc261cf06c60ea83346d0def741441e59afa93043</citedby><cites>FETCH-LOGICAL-c455t-69d0902095bb1ae7eea1aa29bc261cf06c60ea83346d0def741441e59afa93043</cites><orcidid>0000-0002-4932-3885 ; 0000-0002-3959-4956 ; 0000-0003-2116-6707 ; 0000-0002-6117-6910</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2706251402/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2706251402?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids></links><search><creatorcontrib>Lee, Do Nam</creatorcontrib><creatorcontrib>Kim, Yeong Rim</creatorcontrib><creatorcontrib>Yang, Sohyeon</creatorcontrib><creatorcontrib>Tran, Ngoc Minh</creatorcontrib><creatorcontrib>Park, Bong Joo</creatorcontrib><creatorcontrib>Lee, Su Jung</creatorcontrib><creatorcontrib>Kim, Youngmee</creatorcontrib><creatorcontrib>Yoo, Hyojong</creatorcontrib><creatorcontrib>Kim, Sung-Jin</creatorcontrib><creatorcontrib>Shin, Jae Ho</creatorcontrib><title>Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity</title><title>International journal of molecular sciences</title><description>Crystalline metal–organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg−1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.</description><subject>Adsorption</subject><subject>Antibacterial activity</subject><subject>Ball milling</subject><subject>Benzene</subject><subject>Biocompatibility</subject><subject>Biological activity</subject><subject>Catalysis</subject><subject>Crystal structure</subject><subject>Crystallography</subject><subject>Drug delivery</subject><subject>Gram-negative bacteria</subject><subject>Hydrocarbons</subject><subject>Metal-organic frameworks</subject><subject>MOFs</subject><subject>Morphology</subject><subject>Nitric oxide</subject><subject>Nitrogen</subject><subject>Single crystals</subject><subject>Spectrum analysis</subject><subject>Synergistic effect</subject><subject>X-ray diffraction</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkk1v1DAQhi0EomXhxg-IxIUDAX_FiTkgtREfK1VUgnK2xs4k61U2XmynYv892W6FWk4e2c88st4ZQl4z-l4ITT_47S5xwZSmunlCzpnkvKRU1U8f1GfkRUpbSrnglX5OzoSijAslzoltw5RjGEewIxbffY7eFdd_fIfFzxwiDFjA1BU_cERIWPipaOfy8qb9WLTxkDKMYxgi7DdL13pKftjkdNdw6QO47G99Prwkz3oYE766P1fk15fPN-238ur667q9uCqdrKpcKt1RTTnVlbUMsEYEBsC1dVwx11PlFEVohJCqox32tWRSMqw09KAFlWJF1idvF2Br9tHvIB5MAG_uLkIcDMTs3YgGVGVV3ThlgUlwja4EXwJUtulqZlm_uD6dXPvZ7rBzuIQE4yPp45fJb8wQbo2WVDNdL4K394IYfs-Ystn55HDJecIwJ8NrWqsFZUf0zX_oNsxxWqI6UopXTC6DW5F3J8rFkFLE_t9nGDXHRTAPF0H8Be7LpNE</recordid><startdate>20220813</startdate><enddate>20220813</enddate><creator>Lee, Do Nam</creator><creator>Kim, Yeong Rim</creator><creator>Yang, Sohyeon</creator><creator>Tran, Ngoc Minh</creator><creator>Park, Bong Joo</creator><creator>Lee, Su Jung</creator><creator>Kim, Youngmee</creator><creator>Yoo, Hyojong</creator><creator>Kim, Sung-Jin</creator><creator>Shin, Jae Ho</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4932-3885</orcidid><orcidid>https://orcid.org/0000-0002-3959-4956</orcidid><orcidid>https://orcid.org/0000-0003-2116-6707</orcidid><orcidid>https://orcid.org/0000-0002-6117-6910</orcidid></search><sort><creationdate>20220813</creationdate><title>Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity</title><author>Lee, Do Nam ; Kim, Yeong Rim ; Yang, Sohyeon ; Tran, Ngoc Minh ; Park, Bong Joo ; Lee, Su Jung ; Kim, Youngmee ; Yoo, Hyojong ; Kim, Sung-Jin ; Shin, Jae Ho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-69d0902095bb1ae7eea1aa29bc261cf06c60ea83346d0def741441e59afa93043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adsorption</topic><topic>Antibacterial activity</topic><topic>Ball milling</topic><topic>Benzene</topic><topic>Biocompatibility</topic><topic>Biological activity</topic><topic>Catalysis</topic><topic>Crystal structure</topic><topic>Crystallography</topic><topic>Drug delivery</topic><topic>Gram-negative bacteria</topic><topic>Hydrocarbons</topic><topic>Metal-organic frameworks</topic><topic>MOFs</topic><topic>Morphology</topic><topic>Nitric oxide</topic><topic>Nitrogen</topic><topic>Single crystals</topic><topic>Spectrum analysis</topic><topic>Synergistic effect</topic><topic>X-ray diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Do Nam</creatorcontrib><creatorcontrib>Kim, Yeong Rim</creatorcontrib><creatorcontrib>Yang, Sohyeon</creatorcontrib><creatorcontrib>Tran, Ngoc Minh</creatorcontrib><creatorcontrib>Park, Bong Joo</creatorcontrib><creatorcontrib>Lee, Su Jung</creatorcontrib><creatorcontrib>Kim, Youngmee</creatorcontrib><creatorcontrib>Yoo, Hyojong</creatorcontrib><creatorcontrib>Kim, Sung-Jin</creatorcontrib><creatorcontrib>Shin, Jae Ho</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Research Library</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Do Nam</au><au>Kim, Yeong Rim</au><au>Yang, Sohyeon</au><au>Tran, Ngoc Minh</au><au>Park, Bong Joo</au><au>Lee, Su Jung</au><au>Kim, Youngmee</au><au>Yoo, Hyojong</au><au>Kim, Sung-Jin</au><au>Shin, Jae Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity</atitle><jtitle>International journal of molecular sciences</jtitle><date>2022-08-13</date><risdate>2022</risdate><volume>23</volume><issue>16</issue><spage>9098</spage><pages>9098-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Crystalline metal–organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg−1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>36012363</pmid><doi>10.3390/ijms23169098</doi><orcidid>https://orcid.org/0000-0002-4932-3885</orcidid><orcidid>https://orcid.org/0000-0002-3959-4956</orcidid><orcidid>https://orcid.org/0000-0003-2116-6707</orcidid><orcidid>https://orcid.org/0000-0002-6117-6910</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1422-0067
ispartof International journal of molecular sciences, 2022-08, Vol.23 (16), p.9098
issn 1422-0067
1661-6596
1422-0067
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_a65b678c6ba14ac895326906b8d71b1f
source PubMed (Medline); Publicly Available Content Database
subjects Adsorption
Antibacterial activity
Ball milling
Benzene
Biocompatibility
Biological activity
Catalysis
Crystal structure
Crystallography
Drug delivery
Gram-negative bacteria
Hydrocarbons
Metal-organic frameworks
MOFs
Morphology
Nitric oxide
Nitrogen
Single crystals
Spectrum analysis
Synergistic effect
X-ray diffraction
title Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T12%3A26%3A17IST&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=Controllable%20Nitric%20Oxide%20Storage%20and%20Release%20in%20Cu-BTC:%20Crystallographic%20Insights%20and%20Bioactivity&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Lee,%20Do%20Nam&rft.date=2022-08-13&rft.volume=23&rft.issue=16&rft.spage=9098&rft.pages=9098-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms23169098&rft_dat=%3Cproquest_doaj_%3E2706251402%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c455t-69d0902095bb1ae7eea1aa29bc261cf06c60ea83346d0def741441e59afa93043%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2706251402&rft_id=info:pmid/36012363&rfr_iscdi=true