RSC Chemical Biology最新文献

{"title":"Macrocyclic peptides as a new class of targeted protein degraders.","authors":"Xuefei Jing, Joel P Mackay, Toby Passioura","doi":"10.1039/d4cb00199k","DOIUrl":"10.1039/d4cb00199k","url":null,"abstract":"<p><p>Targeted protein degraders, in the form of proteolysis targeting chimaeras (PROTACs) and molecular glues, leverage the ubiquitin-proteasome system to catalytically degrade specific target proteins of interest. Because such molecules can be extremely potent, they have attracted considerable attention as a therapeutic modality in recent years. However, while targeted degraders have great potential, they are likely to face many of the same challenges as more traditional small molecules when it comes to their development as therapeutics. In particular, existing targeted degrader design is largely only applicable to the same set of protein targets as traditional small molecules (<i>i.e.</i>, ∼15% of the human proteome). Here, we consider the potential of macrocyclic peptides to overcome this limitation. Such molecules possess several features that make them well-suited for the role, including the ability to induce the formation of ternary protein complexes that can involve relatively flat surfaces and their structural commonality with E3 ligase-recruiting peptide degrons. For these reasons, macrocyclic peptides provide the opportunity both to broaden the number of targets accessible to degrader activity and to broaden the number of E3 ligases that can be harnessed to mediate that activity.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the substrate of olefin synthase loading domains in cyanobacteria Picosynechococcus sp. strain PCC 7002†","authors":"Audrey E. Yñigez-Gutierrez, Erin Conley, Michael G. Thomas and Brian F. Pfleger","doi":"10.1039/D4CB00234B","DOIUrl":"10.1039/D4CB00234B","url":null,"abstract":"<p >Cyanobacteria are widespread, photosynthetic, gram-negative bacteria that generate numerous bioactive secondary metabolites <em>via</em> complex biosynthetic enzymatic machinery. The model cyanobacterium <em>Picosynechococcus</em> sp. strain PCC 7002, hereafter referred to as PCC 7002, contains a type I polyketide synthase (PKS), termed olefin synthase (OlsWT), that synthesizes 1-nonadecene and 1,14-nonadecadiene: α-olefins that are important for growth at low temperatures. The putative biochemistry encoded by the PKS domains suggests that OlsWT will create an olefin with one additional carbon relative to the original substrate (+1 mechanism). The first domain in the multi-module OlsWT protein has homology to fatty acyl-AMP ligases (FAALs) that typically activate free fatty acids prior to creating novel thioester linkages. Paradoxically, unmodified wildtype PCC 7002 is not known to maintain a substantial pool of free fatty acids, and prior work demonstrated conversion of exogenous pentadecanoic acid to 1-octadecene instead of the expected 1-hexadecene. In this study, we developed PCC 7002 as a heterologous host to facilitate the expression and study of Ols proteins in effort to discover their true substrates. Here, we report the successful expression of two Ols homologs from <em>Geminocystis</em> sp. NIES-3709 and <em>Xenococcus</em> sp. PCC 7305 in PCC 7002 that generated 1-heptadecene and 1-pentadecene, respectively. Through the additional deletion of a gene encoding an acyl–acyl carrier protein (ACP) synthetase (Aas) responsible for activation of exogenous free fatty acids, we demonstrated the expected conversion of exogenously provided odd-chain fatty acids to α-olefins containing one additional carbon. These data suggest that short-lived fatty acids liberated from lipid membranes are the Ols substrate. We subsequently confirmed OlsWT activity on octadecanoic acid <em>via in vitro</em> chrome azurol S assay using a purified FAAL module. Collectively, this work clarifies the <em>in vivo</em> substrate of Ols FAAL domains and identifies the FAAL module as a target for future bioengineering to allow access to desired α-olefins.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 2","pages":" 307-316"},"PeriodicalIF":4.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using environment-sensitive tetramethylated thiophene-BODIPY fluorophores in DNA probes for studying effector-induced conformational changes of protein-DNA complexes.","authors":"Markéta Šoltysová, Pedro Güixens-Gallardo, Irena Sieglová, Anna Soldánová, Veronika Krejčiříková, Milan Fábry, Jiří Brynda, Petro Khoroshyy, Michal Hocek, Pavlína Řezáčová","doi":"10.1039/d4cb00260a","DOIUrl":"10.1039/d4cb00260a","url":null,"abstract":"<p><p>The LutR protein represses the transcription of genes encoding enzymes for the utilization of l-lactate in <i>Bacillus subtilis</i> through binding to a specific DNA region. In this study, we employed oligonucleotide probes modified by viscosity-sensitive tetramethylated thiophene-BODIPY fluorophores to investigate the impact of selected metabolites on the LutR-DNA complex. Our goal was to identify the effector molecule whose binding alters the protein-DNA affinity, thereby enabling gene transcription. The designed DNA probes exhibited distinctive responses to the binding and release of the protein, characterized by significant alterations in fluorescence lifetime. Through this method, we have identified l-lactate as the sole metabolite exerting a substantial modulating effect on the protein-DNA interaction and thus confirmed its role as an effector molecule. Moreover, we showed that our approach was able to follow conformation changes affecting affinity, which were not captured by other methods commonly used to study the protein-DNA interaction, such as electro-mobility shift assays and florescence anisotropy binding studies. This work underlines the potential of environment-sensitive fluorophore-linked nucleotide modifications, <i>i.e.</i> dC^TBdp, for studying the dynamics and subtle changes of protein-DNA interactions.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An expanded substrate scope for cross-chiral ligation enables efficient synthesis of long l-RNAs†","authors":"Xuan Han and Jonathan T. Sczepanski","doi":"10.1039/D4CB00253A","DOIUrl":"10.1039/D4CB00253A","url":null,"abstract":"<p >Despite the growing interest in mirror-image <small>L</small>-oligonucleotides, both as a robust nucleic acid analogue and as an artificial genetic polymer, their broader adoption in biochemical research and medicine remains hindered by challenges associated with the synthesis of long sequences, especially for <small>L</small>-RNA. Herein, we present a novel strategy for assembling long <small>L</small>-RNAs <em>via</em> the joining of two or more shorter fragments using cross-chiral ligase ribozymes together with new substrate activation chemistry. We show that 5′-monophosphorylated <small>L</small>-RNA, which is readily prepared by solid-phase synthesis, can be activated by chemical attachment of a 5′-adenosine monophosphate (AMP) or diphosphate (ADP), yielding 5′-adenosyl(di- or tri-)phosphate <small>L</small>-RNA. The activation reaction is performed in mild aqueous conditions, proceeds efficiently with short or large <small>L</small>-RNA, and, yielding few byproducts, requires little or no further purification after activation. Importantly, both groups, when added to <small>L</small>-RNA, are compatible with ribozyme-mediated ligation, with the 5′-adenosyltriphosphate permitting rapid and efficient joining of two long <small>L</small>-RNA strands. This is exemplified by the assembly of a 129-nt <small>L</small>-RNA molecule <em>via</em> a single cross-chiral ligation event. Overall, by relying on ribozymes that can be readily prepared by <em>in vitro</em> transcription and <small>L</small>-RNA substrates that can be activated through simple chemistry, these methods are expected to make long <small>L</small>-RNAs more accessible to a wider range of researchers and facilitate the expansion of <small>L</small>-ON-based technologies.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 2","pages":" 209-217"},"PeriodicalIF":4.2,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular features of non-peptidic nucleophilic substrates and acceptor proteins determine the efficiency of sortagging†","authors":"Tetiana Bondarchuk, Elena Zhuravel, Oleh Shyshlyk, Mykhaylo O. Debelyy, Oleksandr Pokholenko, Diana Vaskiv, Alla Pogribna, Mariana Kuznietsova, Yevhenii Hrynyshyn, Oleksandr Nedialko, Volodymyr Brovarets and Sergey A. Zozulya","doi":"10.1039/D4CB00246F","DOIUrl":"10.1039/D4CB00246F","url":null,"abstract":"<p >Sortase A-mediated ligation (SML) or “sortagging” has become a popular technology to selectively introduce structurally diverse protein modifications. Despite the great progress in the optimization of the reaction conditions and design of miscellaneous C- or N-terminal protein modification strategies, the reported yields of conjugates are highly variable. In this study, we have systematically investigated C-terminal protein sortagging efficiency using a combination of several rationally selected and modified acceptor proteins and a panel of incoming surrogate non-peptidic amine nucleophile substrates varying in the structural features of their amino linker parts and cargo molecules. Our data suggest that the sortagging efficiency is modulated by the combination of molecular features of the incoming nucleophilic substrate, including the ionization properties of the reactive amino group, structural recognition of the nucleophilic amino linker by the enzyme, as well as the molecular nature of the attached payload moiety. Previous reports have confirmed that the steric accessibility of the C-terminal SrtA recognition site in the acceptor protein is also the critical determinant of sortase reaction efficiency. We suggest a computational procedure for simplifying <em>a priori</em> predictions of sortagging outcomes through the structural assessment of the acceptor protein and introduction of a peptide linker, if deemed necessary.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 2","pages":" 295-306"},"PeriodicalIF":4.2,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A one-step route for the conversion of Cd waste into CdS quantum dots by Acidithiobacillus sp. via unique biosynthesis pathways†","authors":"Xiao-Ju Li, Tian-Qi Wang, Lu Qi, Feng-Wei Li, Yong-Zhen Xia, Bin-Jin, Cheng-Jia Zhang, Lin-Xu Chen and Jian-Qun Lin","doi":"10.1039/D4CB00195H","DOIUrl":"10.1039/D4CB00195H","url":null,"abstract":"<p >Microorganisms serve as biological factories for the synthesis of nanomaterials such as CdS quantum dots. Based on the uniqueness of <em>Acidithiobacillus</em> sp., a one-step route was explored to directly convert cadmium waste into CdS QDs using these bacteria. First, an exhaustive study was conducted to reveal the specific pathways involved in the biosynthesis of CdS QDs. The widely known homologous enzyme, cysteine desulfhydrase, which catalyzes the synthesis of CdS QDs from a cysteine substrate, is also present in <em>Acidithiobacillus</em> sp. and is referred to as the OSH enzyme. The structure of the OSH enzyme was determined through X-ray crystallography. Moreover, we identified two new pathways. One involved the SQR enzyme in <em>Acidithiobacillus</em> sp., which catalyzed the formation of sulfur globules and subsequently catalyzed further reactions with GSH to release H<small>₂</small>S; subsequently, a CdS QD biosynthesis pathway was successfully constructed. The other pathway involved extracellular polyphosphate, a bacterial metabolic product, which with the addition of GSH and Cd<small>²⁺</small>, resulted in the formation of water-soluble fluorescent CdS QDs in the supernatant. Based on the above-described mechanism, after the bioleaching of Cd<small>²⁺</small> from cadmium waste by <em>Acidithiobacillus</em> sp., CdS QDs were directly obtained from the bacterial culture supernatants. This work provides important insights into cleaner production and cadmium bioremediation with potential industrial applications.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 2","pages":" 281-294"},"PeriodicalIF":4.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the promise of peptide nucleic acids as functional linkers for an RNA imaging platform†","authors":"Aleksandra J. Wierzba, Erin M. Richards, Shelby R. Lennon, Robert T. Batey and Amy E. Palmer","doi":"10.1039/D4CB00274A","DOIUrl":"10.1039/D4CB00274A","url":null,"abstract":"<p >Linkers in chemical biology provide more than just connectivity between molecules; their intrinsic properties can be harnessed to enhance the stability and functionality of chemical probes. In this study, we explored the incorporation of a peptide nucleic acid (PNA)-based linker into RNA-targeting probes to improve their affinity and specificity. By integrating a PNA linker into a small molecule probe of the Riboglow platform, we enabled dual binding events: cobalamin (Cbl)–RNA structure-based recognition and sequence-specific PNA–RNA interaction. We show that incorporating a six-nucleotide PNA sequence complementary to a region of wild type RNA aptamer (<em>env</em>8) results in a 30-fold improvement in binding affinity compared to the probe with a nonfunctional PEG linker. Even greater improvements are observed when the PNA probe was tested against truncated versions of the RNA aptamer, with affinity increasing by up to 280-fold. Additionally, the PNA linker is able to rescue the Cbl–RNA interaction even when the cobalamin binding pocket is compromised. We demonstrate that PNA probes effectively bind RNA both <em>in vitro</em> and in live cells, enhancing visualization of RNA in stress granules and U-bodies at low concentrations. The modular nature of the Riboglow platform allows for flexible modifications of the PNA linker, fluorophore, and RNA tag, while maintaining high specificity and affinity. This work establishes a new approach for enhancing RNA imaging platforms through the use of PNA linkers, highlighting the potential of combining short oligonucleotides with small molecules to improve the affinity and specificity of RNA-targeting probes. Furthermore, this dual-binding approach presents a promising strategy for driving advancements in RNA-targeted drug development.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 2","pages":" 249-262"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein stabilization in spray drying and solid-state storage by using a ‘molecular lock’ – exploiting bacterial adaptations for industrial applications†","authors":"Wiktoria Brytan, Tewfik Soulimane and Luis Padrela","doi":"10.1039/D4CB00202D","DOIUrl":"10.1039/D4CB00202D","url":null,"abstract":"<p >Small, stable biomedicines, like peptides and hormones, are already available on the market as spray dried formulations, however large biomolecules like antibodies and therapeutic enzymes continue to pose stability issues during the process. Stresses during solid-state formation are a barrier to formulation of large biotherapeutics as dry powders. Here, we explore an alternative avenue to protein stabilisation during the spray drying process, moving away from the use of excipients. In thermophilic proteins, the presence of C-termini extensions can add to their stability by increasing molecular rigidity. Hence, we explored a unique thermostable amino acid extension in the C-terminal of an aldehyde dehydrogenase tetramer originating from <em>Thermus thermophilus</em> HB27 (ALDH<em>Tt</em>), and its ability to stabilise the large enzyme against drying stresses. The presence of the C-terminal extension was found to act like a ‘molecular lock’ of the oligomeric state of the ALDH tetramer upon spray drying. Removal of the extension, mimicking the structure of mesophilic ALDHs, promoted the formation of aggregates and dissociative states. The ALDH protein with the ‘molecular lock’ retained ∼24% more activity after spray drying and retained up to 16% more activity during solid state storage than its mutant. We proposed a mechanism for the protection of oligomeric proteins by the distinct C-terminal extension under stresses involved in solid formation. Additionally, the process of spray drying an excipient-free ALDH is achieved using a design of experiments approach, increasing its breadth of application in the biocatalysis of aldehydes.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 2","pages":" 263-272"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-enzymatic posttranslational protein modifications in protein aggregation and neurodegenerative diseases","authors":"Tim Baldensperger, Miriam Preissler and Christian F. W. Becker","doi":"10.1039/D4CB00221K","DOIUrl":"10.1039/D4CB00221K","url":null,"abstract":"<p >Highly reactive metabolic intermediates and other small molecules frequently react with amino acid side chains, leading to non-enzymatic posttranslational modifications (nPTMs) of proteins. The abundance of these modifications increases under high metabolic activity or stress conditions and can dramatically impact protein structure and function. Although protein quality control mechanisms typically mitigate the effects of these impaired proteins, in long-lived and degradation-resistant proteins, nPTMs accumulate. In some cases, such as cataract development and diabetes, clear links between nPTMs, aging, and disease progression have been established. In neurodegenerative diseases such as Alzheimer's and Parkinson's disease, a key question is whether accumulation of nPTMs is a cause or consequence of protein aggregation. This review focuses on major nPTMs found on proteins with central roles in neurodegenerative diseases such as α-synuclein, β-amyloid, and tau. We summarize current knowledge on the formation of these modifications and discuss their potential impact on disease onset and progression. Additionally, we examine what is known to date about how nPTMs impair cellular detoxification, repair, and degradation systems. Finally, we critically discuss the available methodologies to systematically investigate nPTMs at the molecular level and outline suitable approaches to study their effects on protein aggregation. We aim to foster more research into the role of nPTMs in neurodegeneration by adapting methodologies that have proven successful in studying enzymatic posttranslational modifications. Specifically, we advocate for site-specific incorporation of these modifications into target proteins using advanced chemical and molecular biology techniques.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 2","pages":" 129-149"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calmodulin interacts with androglobin and regulates the nitrite reductase activity†","authors":"Lv-Suo Nie, Xi-Chun Liu, Hui Han, Zhi-Hao Ren, Shu-Qin Gao and Ying-Wu Lin","doi":"10.1039/D4CB00245H","DOIUrl":"10.1039/D4CB00245H","url":null,"abstract":"<p >Androglobin (Adgb) was discovered as the fifth mammalian globin, but its structure and function remain elusive. In this study, the heme-binding globin domain of Adgb was expressed and its interaction with calmodulin (CaM) was investigated. The protein structure of Adgb and its complex with CaM were predicted using AlphaFold3 and HDOCK. The circularly permutated globin domain of Adgb was well folded with a heme group, which can interact with CaM <em>via</em> the IQ motif. In experimental studies, two mutants of CaM (G41C and G114C) were constructed and labeled with a fluorescent molecule (fluorescein-5-maleimide) in the N-lobe and C-lobe, respectively. Upon binding to Adgb, a greater fluorescence quenching effect was observed for the labeling of Cys41 in the N-lobe due to energy transfer to the heme group, which is consistent with the predicted structure of the Adgb–CaM complex. Furthermore, as shown by UV-vis kinetic studies, the binding of CaM enhanced the nitrite reductase activity of Adgb. This study reveals a regulatory role of CaM for the unique Adgb and provides valuable information for understanding the structure–function relationship.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 2","pages":" 175-181"},"PeriodicalIF":4.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}