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Cytocompatibility, Antimicrobial and Antioxidant Activity of a Mucoadhesive Biopolymeric Hydrogel Embedding Selenium Nanoparticles Phytosynthesized by Sea Buckthorn Leaf Extract
Phytosynthesized selenium nanoparticles (SeNPs) are less toxic than the inorganic salts of selenium and show high antioxidant and antibacterial activity. Chitosan prevents microbial biofilm formation and can also determine microbial biofilm dispersal. Never-dried bacterial nanocellulose (NDBNC) is a...
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Published in: | Pharmaceuticals (Basel, Switzerland) Switzerland), 2023-12, Vol.17 (1), p.23 |
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creator | Tritean, Naomi Dimitriu, Luminița Dima, Ștefan-Ovidiu Stoica, Rusăndica Trică, Bogdan Ghiurea, Marius Moraru, Ionuț Cimpean, Anisoara Oancea, Florin Constantinescu-Aruxandei, Diana |
description | Phytosynthesized selenium nanoparticles (SeNPs) are less toxic than the inorganic salts of selenium and show high antioxidant and antibacterial activity. Chitosan prevents microbial biofilm formation and can also determine microbial biofilm dispersal. Never-dried bacterial nanocellulose (NDBNC) is an efficient carrier of bioactive compounds and a flexible nanofibrillar hydrophilic biopolymer. This study aimed to develop a selenium-enriched hydrogel nanoformulation (Se-HNF) based on NDBNC from kombucha fermentation and fungal chitosan with embedded biogenic SeNPs phytosynthesized by an aqueous extract of sea buckthorn leaves (SbLEx)-SeNPsSb-in order to both disperse gingival dysbiotic biofilm and prevent its development. We determined the total phenolic content and antioxidant activity of SbLEx. Liquid chromatography-mass spectrometry (LC-MS) and high-performance liquid chromatography (HPLC) were used for the identification of polyphenols from SbLEx. SeNPsSb were characterized by transmission electron microscopy-energy-dispersive X-ray spectroscopy (TEM-EDX), dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) in small- and wide-angle X-ray scattering (SAXS and WAXS). The hydrogel nanoformulation with embedded SeNPsSb was characterized by SEM, FTIR, XRD, rheology, mucin binding efficiency, contact angle and interfacial tension measurements. We also assessed the in vitro biocompatibility, antioxidant activity and antimicrobial and antibiofilm potential of SeNPsSb and Se-HNF. TEM, DLS and SAXS evidenced polydisperse SeNPsSb, whereas FTIR highlighted a heterogeneous biocorona with various biocompounds. The contact angle on the polar surface was smaller (52.82 ± 1.23°) than that obtained on the non-polar surface (73.85 ± 0.39°). The interfacial tension was 97.6 ± 0.47 mN/m. The mucin binding efficiency of Se-HNF decreased as the amount of hydrogel decreased, and the SEM analysis showed a relatively compact structure upon mucin contact. FTIR and XRD analyses of Se-HNF evidenced an interaction between BNC and CS through characteristic peak shifting, and the rheological measurements highlighted a pseudoplastic behavior, 0.186 N adhesion force and 0.386 adhesion energy. The results showed a high degree of cytocompatibility and the significant antioxidant and antimicrobial efficiency of SeNPsSb and Se-HNF. |
doi_str_mv | 10.3390/ph17010023 |
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Chitosan prevents microbial biofilm formation and can also determine microbial biofilm dispersal. Never-dried bacterial nanocellulose (NDBNC) is an efficient carrier of bioactive compounds and a flexible nanofibrillar hydrophilic biopolymer. This study aimed to develop a selenium-enriched hydrogel nanoformulation (Se-HNF) based on NDBNC from kombucha fermentation and fungal chitosan with embedded biogenic SeNPs phytosynthesized by an aqueous extract of sea buckthorn leaves (SbLEx)-SeNPsSb-in order to both disperse gingival dysbiotic biofilm and prevent its development. We determined the total phenolic content and antioxidant activity of SbLEx. Liquid chromatography-mass spectrometry (LC-MS) and high-performance liquid chromatography (HPLC) were used for the identification of polyphenols from SbLEx. SeNPsSb were characterized by transmission electron microscopy-energy-dispersive X-ray spectroscopy (TEM-EDX), dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) in small- and wide-angle X-ray scattering (SAXS and WAXS). The hydrogel nanoformulation with embedded SeNPsSb was characterized by SEM, FTIR, XRD, rheology, mucin binding efficiency, contact angle and interfacial tension measurements. We also assessed the in vitro biocompatibility, antioxidant activity and antimicrobial and antibiofilm potential of SeNPsSb and Se-HNF. TEM, DLS and SAXS evidenced polydisperse SeNPsSb, whereas FTIR highlighted a heterogeneous biocorona with various biocompounds. The contact angle on the polar surface was smaller (52.82 ± 1.23°) than that obtained on the non-polar surface (73.85 ± 0.39°). The interfacial tension was 97.6 ± 0.47 mN/m. The mucin binding efficiency of Se-HNF decreased as the amount of hydrogel decreased, and the SEM analysis showed a relatively compact structure upon mucin contact. FTIR and XRD analyses of Se-HNF evidenced an interaction between BNC and CS through characteristic peak shifting, and the rheological measurements highlighted a pseudoplastic behavior, 0.186 N adhesion force and 0.386 adhesion energy. The results showed a high degree of cytocompatibility and the significant antioxidant and antimicrobial efficiency of SeNPsSb and Se-HNF.</description><identifier>ISSN: 1424-8247</identifier><identifier>EISSN: 1424-8247</identifier><identifier>DOI: 10.3390/ph17010023</identifier><identifier>PMID: 38256857</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Analysis ; Anti-infective agents ; Antimicrobial agents ; Antioxidants ; bacterial nanocellulose ; Biofilms ; Biopolymers ; Cellulose ; Chemical properties ; Cocoa ; Flavonoids ; fungal chitosan ; gingival dysbiotic biofilm ; Gum disease ; Health aspects ; High performance liquid chromatography ; Hydrogels ; Hydrogen bonds ; Inflammation ; Leaves ; Medicine, Botanic ; Medicine, Herbal ; Nanoparticles ; phytosynthesized selenium nanoparticles ; Polyphenols ; Risk factors ; sea buckthorn leaf extract ; Selenium ; Selenium compounds ; Spectrum analysis ; Structure ; Testing</subject><ispartof>Pharmaceuticals (Basel, Switzerland), 2023-12, Vol.17 (1), p.23</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 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/). 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Chitosan prevents microbial biofilm formation and can also determine microbial biofilm dispersal. Never-dried bacterial nanocellulose (NDBNC) is an efficient carrier of bioactive compounds and a flexible nanofibrillar hydrophilic biopolymer. This study aimed to develop a selenium-enriched hydrogel nanoformulation (Se-HNF) based on NDBNC from kombucha fermentation and fungal chitosan with embedded biogenic SeNPs phytosynthesized by an aqueous extract of sea buckthorn leaves (SbLEx)-SeNPsSb-in order to both disperse gingival dysbiotic biofilm and prevent its development. We determined the total phenolic content and antioxidant activity of SbLEx. Liquid chromatography-mass spectrometry (LC-MS) and high-performance liquid chromatography (HPLC) were used for the identification of polyphenols from SbLEx. SeNPsSb were characterized by transmission electron microscopy-energy-dispersive X-ray spectroscopy (TEM-EDX), dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) in small- and wide-angle X-ray scattering (SAXS and WAXS). The hydrogel nanoformulation with embedded SeNPsSb was characterized by SEM, FTIR, XRD, rheology, mucin binding efficiency, contact angle and interfacial tension measurements. We also assessed the in vitro biocompatibility, antioxidant activity and antimicrobial and antibiofilm potential of SeNPsSb and Se-HNF. TEM, DLS and SAXS evidenced polydisperse SeNPsSb, whereas FTIR highlighted a heterogeneous biocorona with various biocompounds. The contact angle on the polar surface was smaller (52.82 ± 1.23°) than that obtained on the non-polar surface (73.85 ± 0.39°). The interfacial tension was 97.6 ± 0.47 mN/m. The mucin binding efficiency of Se-HNF decreased as the amount of hydrogel decreased, and the SEM analysis showed a relatively compact structure upon mucin contact. FTIR and XRD analyses of Se-HNF evidenced an interaction between BNC and CS through characteristic peak shifting, and the rheological measurements highlighted a pseudoplastic behavior, 0.186 N adhesion force and 0.386 adhesion energy. The results showed a high degree of cytocompatibility and the significant antioxidant and antimicrobial efficiency of SeNPsSb and Se-HNF.</description><subject>Analysis</subject><subject>Anti-infective agents</subject><subject>Antimicrobial agents</subject><subject>Antioxidants</subject><subject>bacterial nanocellulose</subject><subject>Biofilms</subject><subject>Biopolymers</subject><subject>Cellulose</subject><subject>Chemical properties</subject><subject>Cocoa</subject><subject>Flavonoids</subject><subject>fungal chitosan</subject><subject>gingival dysbiotic biofilm</subject><subject>Gum disease</subject><subject>Health aspects</subject><subject>High performance liquid chromatography</subject><subject>Hydrogels</subject><subject>Hydrogen bonds</subject><subject>Inflammation</subject><subject>Leaves</subject><subject>Medicine, Botanic</subject><subject>Medicine, Herbal</subject><subject>Nanoparticles</subject><subject>phytosynthesized selenium nanoparticles</subject><subject>Polyphenols</subject><subject>Risk factors</subject><subject>sea buckthorn leaf extract</subject><subject>Selenium</subject><subject>Selenium compounds</subject><subject>Spectrum analysis</subject><subject>Structure</subject><subject>Testing</subject><issn>1424-8247</issn><issn>1424-8247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkt9u0zAUhyMEYmNwwwMgS9wgRIed2LFzhbqqsEnljwRcRyf2SeuS2CVxqoW34g1x17KtCPnC1vHnTz5HvyR5zuh5lhX07WbFJGWUptmD5JTxlE9UyuXDe-eT5EnfrykVknH2ODnJVCpyJeRp8ns2Bq99u4FgK9vYML4hUxdsa3XnKwsNAWduKv7aGnCBTHWw28gRXxMgHwftwaywt1skF9ZvfDO22FlNLkfT-SU2ZN5WaIx1S_IVG3R2aMkncH4DXbC6wZ58WcU_9KMLO80vNKQaIwrkYtA_wsp3jiwQajK_Dh3o8DR5VEPT47PDfpZ8fz__NrucLD5_uJpNFxMtOA0TDZoXUhteKWRaUMkqqHVtoBJZxilmUggAamTFRSXzOEFMKUfGOaBmtczOkqu913hYl5vOttCNpQdb3hR8tywPHZSZFrJIKQphGM8ghdrUoihyhWkmZa6j693etRmqFo1GF1tpjqTHN86uyqXflowqVsgij4ZXB0Pnfw7Yh7K1vcamAYd-6Mu0YFLlMpVFRF_-g6790Lk4qx2lpJIxB3fUEmIH1tV-N92dtJxKRZWiudq5zv9DxWUwJsQ7rG2sHz14vX8Q49P3Hda3TTJa7tJa3qU1wi_uj-UW_RvP7A-tdehS</recordid><startdate>20231222</startdate><enddate>20231222</enddate><creator>Tritean, Naomi</creator><creator>Dimitriu, Luminița</creator><creator>Dima, Ștefan-Ovidiu</creator><creator>Stoica, Rusăndica</creator><creator>Trică, Bogdan</creator><creator>Ghiurea, Marius</creator><creator>Moraru, Ionuț</creator><creator>Cimpean, Anisoara</creator><creator>Oancea, Florin</creator><creator>Constantinescu-Aruxandei, Diana</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</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>GNUQQ</scope><scope>GUQSH</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2902-1537</orcidid><orcidid>https://orcid.org/0000-0003-1770-0890</orcidid><orcidid>https://orcid.org/0000-0002-9948-6914</orcidid><orcidid>https://orcid.org/0000-0001-6442-8389</orcidid><orcidid>https://orcid.org/0000-0003-1068-1439</orcidid><orcidid>https://orcid.org/0000-0002-3548-8443</orcidid><orcidid>https://orcid.org/0000-0003-1970-0552</orcidid><orcidid>https://orcid.org/0000-0002-5833-3110</orcidid><orcidid>https://orcid.org/0000-0002-7723-1814</orcidid></search><sort><creationdate>20231222</creationdate><title>Cytocompatibility, Antimicrobial and Antioxidant Activity of a Mucoadhesive Biopolymeric Hydrogel Embedding Selenium Nanoparticles Phytosynthesized by Sea Buckthorn Leaf Extract</title><author>Tritean, Naomi ; Dimitriu, Luminița ; Dima, Ștefan-Ovidiu ; Stoica, Rusăndica ; Trică, Bogdan ; Ghiurea, Marius ; Moraru, Ionuț ; Cimpean, Anisoara ; Oancea, Florin ; Constantinescu-Aruxandei, Diana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-cac497cd4b8e1c5071bafcfdab53340e3755aa0d7b45b76170e204e144aec1f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Anti-infective agents</topic><topic>Antimicrobial agents</topic><topic>Antioxidants</topic><topic>bacterial nanocellulose</topic><topic>Biofilms</topic><topic>Biopolymers</topic><topic>Cellulose</topic><topic>Chemical properties</topic><topic>Cocoa</topic><topic>Flavonoids</topic><topic>fungal chitosan</topic><topic>gingival dysbiotic biofilm</topic><topic>Gum disease</topic><topic>Health aspects</topic><topic>High performance liquid chromatography</topic><topic>Hydrogels</topic><topic>Hydrogen bonds</topic><topic>Inflammation</topic><topic>Leaves</topic><topic>Medicine, Botanic</topic><topic>Medicine, Herbal</topic><topic>Nanoparticles</topic><topic>phytosynthesized selenium nanoparticles</topic><topic>Polyphenols</topic><topic>Risk factors</topic><topic>sea buckthorn leaf extract</topic><topic>Selenium</topic><topic>Selenium compounds</topic><topic>Spectrum analysis</topic><topic>Structure</topic><topic>Testing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tritean, Naomi</creatorcontrib><creatorcontrib>Dimitriu, Luminița</creatorcontrib><creatorcontrib>Dima, Ștefan-Ovidiu</creatorcontrib><creatorcontrib>Stoica, Rusăndica</creatorcontrib><creatorcontrib>Trică, Bogdan</creatorcontrib><creatorcontrib>Ghiurea, Marius</creatorcontrib><creatorcontrib>Moraru, Ionuț</creatorcontrib><creatorcontrib>Cimpean, Anisoara</creatorcontrib><creatorcontrib>Oancea, Florin</creatorcontrib><creatorcontrib>Constantinescu-Aruxandei, Diana</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tritean, Naomi</au><au>Dimitriu, Luminița</au><au>Dima, Ștefan-Ovidiu</au><au>Stoica, Rusăndica</au><au>Trică, Bogdan</au><au>Ghiurea, Marius</au><au>Moraru, Ionuț</au><au>Cimpean, Anisoara</au><au>Oancea, Florin</au><au>Constantinescu-Aruxandei, Diana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytocompatibility, Antimicrobial and Antioxidant Activity of a Mucoadhesive Biopolymeric Hydrogel Embedding Selenium Nanoparticles Phytosynthesized by Sea Buckthorn Leaf Extract</atitle><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle><addtitle>Pharmaceuticals (Basel)</addtitle><date>2023-12-22</date><risdate>2023</risdate><volume>17</volume><issue>1</issue><spage>23</spage><pages>23-</pages><issn>1424-8247</issn><eissn>1424-8247</eissn><abstract>Phytosynthesized selenium nanoparticles (SeNPs) are less toxic than the inorganic salts of selenium and show high antioxidant and antibacterial activity. Chitosan prevents microbial biofilm formation and can also determine microbial biofilm dispersal. Never-dried bacterial nanocellulose (NDBNC) is an efficient carrier of bioactive compounds and a flexible nanofibrillar hydrophilic biopolymer. This study aimed to develop a selenium-enriched hydrogel nanoformulation (Se-HNF) based on NDBNC from kombucha fermentation and fungal chitosan with embedded biogenic SeNPs phytosynthesized by an aqueous extract of sea buckthorn leaves (SbLEx)-SeNPsSb-in order to both disperse gingival dysbiotic biofilm and prevent its development. We determined the total phenolic content and antioxidant activity of SbLEx. Liquid chromatography-mass spectrometry (LC-MS) and high-performance liquid chromatography (HPLC) were used for the identification of polyphenols from SbLEx. SeNPsSb were characterized by transmission electron microscopy-energy-dispersive X-ray spectroscopy (TEM-EDX), dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) in small- and wide-angle X-ray scattering (SAXS and WAXS). The hydrogel nanoformulation with embedded SeNPsSb was characterized by SEM, FTIR, XRD, rheology, mucin binding efficiency, contact angle and interfacial tension measurements. We also assessed the in vitro biocompatibility, antioxidant activity and antimicrobial and antibiofilm potential of SeNPsSb and Se-HNF. TEM, DLS and SAXS evidenced polydisperse SeNPsSb, whereas FTIR highlighted a heterogeneous biocorona with various biocompounds. The contact angle on the polar surface was smaller (52.82 ± 1.23°) than that obtained on the non-polar surface (73.85 ± 0.39°). The interfacial tension was 97.6 ± 0.47 mN/m. The mucin binding efficiency of Se-HNF decreased as the amount of hydrogel decreased, and the SEM analysis showed a relatively compact structure upon mucin contact. FTIR and XRD analyses of Se-HNF evidenced an interaction between BNC and CS through characteristic peak shifting, and the rheological measurements highlighted a pseudoplastic behavior, 0.186 N adhesion force and 0.386 adhesion energy. The results showed a high degree of cytocompatibility and the significant antioxidant and antimicrobial efficiency of SeNPsSb and Se-HNF.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38256857</pmid><doi>10.3390/ph17010023</doi><orcidid>https://orcid.org/0000-0003-2902-1537</orcidid><orcidid>https://orcid.org/0000-0003-1770-0890</orcidid><orcidid>https://orcid.org/0000-0002-9948-6914</orcidid><orcidid>https://orcid.org/0000-0001-6442-8389</orcidid><orcidid>https://orcid.org/0000-0003-1068-1439</orcidid><orcidid>https://orcid.org/0000-0002-3548-8443</orcidid><orcidid>https://orcid.org/0000-0003-1970-0552</orcidid><orcidid>https://orcid.org/0000-0002-5833-3110</orcidid><orcidid>https://orcid.org/0000-0002-7723-1814</orcidid><oa>free_for_read</oa></addata></record> |
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source | Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central (Open access) |
subjects | Analysis Anti-infective agents Antimicrobial agents Antioxidants bacterial nanocellulose Biofilms Biopolymers Cellulose Chemical properties Cocoa Flavonoids fungal chitosan gingival dysbiotic biofilm Gum disease Health aspects High performance liquid chromatography Hydrogels Hydrogen bonds Inflammation Leaves Medicine, Botanic Medicine, Herbal Nanoparticles phytosynthesized selenium nanoparticles Polyphenols Risk factors sea buckthorn leaf extract Selenium Selenium compounds Spectrum analysis Structure Testing |
title | Cytocompatibility, Antimicrobial and Antioxidant Activity of a Mucoadhesive Biopolymeric Hydrogel Embedding Selenium Nanoparticles Phytosynthesized by Sea Buckthorn Leaf Extract |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T08%3A14%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cytocompatibility,%20Antimicrobial%20and%20Antioxidant%20Activity%20of%20a%20Mucoadhesive%20Biopolymeric%20Hydrogel%20Embedding%20Selenium%20Nanoparticles%20Phytosynthesized%20by%20Sea%20Buckthorn%20Leaf%20Extract&rft.jtitle=Pharmaceuticals%20(Basel,%20Switzerland)&rft.au=Tritean,%20Naomi&rft.date=2023-12-22&rft.volume=17&rft.issue=1&rft.spage=23&rft.pages=23-&rft.issn=1424-8247&rft.eissn=1424-8247&rft_id=info:doi/10.3390/ph17010023&rft_dat=%3Cgale_doaj_%3EA780880689%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c540t-cac497cd4b8e1c5071bafcfdab53340e3755aa0d7b45b76170e204e144aec1f73%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2918787057&rft_id=info:pmid/38256857&rft_galeid=A780880689&rfr_iscdi=true |