JACS AuPub Date : 2025-02-10eCollection Date: 2025-02-24DOI: 10.1021/jacsau.4c01020
Remy Chiaffarelli, Pedro F Cruz, Jonathan Cotton, Tjark Kelm, Slade Lee, Mohammad Ghaderian, Max Zimmermann, Carlos F G C Geraldes, Paul Jurek, André F Martins
{"title":"Metabolic PCTA-Based Shift Reagents for the Detection of Extracellular Lactate Using CEST MRI.","authors":"Remy Chiaffarelli, Pedro F Cruz, Jonathan Cotton, Tjark Kelm, Slade Lee, Mohammad Ghaderian, Max Zimmermann, Carlos F G C Geraldes, Paul Jurek, André F Martins","doi":"10.1021/jacsau.4c01020","DOIUrl":"10.1021/jacsau.4c01020","url":null,"abstract":"<p><p>Lactate is a key metabolic driver in oncology and immunology. Even in the presence of physiological oxygen levels, most cancer cells upregulate anaerobic glycolysis, resulting in abnormal lactate production and accumulation in the tumor microenvironment. The development of more effective, sensitive, and safe probes for detecting extracellular lactate holds the potential to significantly impact cancer metabolic profiling and staging significantly. Macrocyclic-based PARACEST agents have been reported to act as shift reagents (SRs) and detect extracellular lactate via chemical exchange saturation transfer (CEST) MRI. Here, we introduce a new family of SRs based on the PCTA ligand, an inherently stable and kinetically inert group of molecules with the potential for (pre)clinical translation. We observed that Yb-PCTA and Eu-PCTA can significantly shift lactate -OH signals in the CEST spectra. <i>In vitro</i>, CEST MRI experiments proved that imaging extracellular lactate specifically with these complexes is feasible even in the presence of competing small metabolites in blood and in the tumor microenvironment. <i>In vivo</i> preclinical imaging showed that Yb-PCTA can be safely administered intravenously in mice to detect extracellular lactate noninvasively. This work contributes to the field of precision imaging in medicine and provides evidence that the PCTA-ligand is a valuable scaffold for developing molecular and metabolic imaging sensors.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 2","pages":"779-790"},"PeriodicalIF":8.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525723","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}
JACS AuPub Date : 2025-02-09DOI: 10.1021/jacsau.4c0118910.1021/jacsau.4c01189
Akihito Inoue, Bo Zhu, Keisuke Mizutani, Ken Kobayashi, Takanobu Yasuda, Alon Wellner, Chang C. Liu and Tetsuya Kitaguchi*,
{"title":"Prediction of Single-Mutation Effects for Fluorescent Immunosensor Engineering with an End-to-End Trained Protein Language Model","authors":"Akihito Inoue, Bo Zhu, Keisuke Mizutani, Ken Kobayashi, Takanobu Yasuda, Alon Wellner, Chang C. Liu and Tetsuya Kitaguchi*, ","doi":"10.1021/jacsau.4c0118910.1021/jacsau.4c01189","DOIUrl":"https://doi.org/10.1021/jacsau.4c01189https://doi.org/10.1021/jacsau.4c01189","url":null,"abstract":"<p >A quenchbody (Q-body) is a fluorophore-labeled homogeneous immunosensor in which the fluorophore is quenched by tryptophan (Trp) residues in the vicinity of the antigen-binding paratope and dequenched in response to antigen binding. Developing Q-bodies against targets on demand remains challenging due to the large sequence space of the complementarity-determining regions (CDRs) related to antigen binding and fluorophore quenching. In this study, we pioneered a strategy using high-throughput screening and a protein language model (pLM) to predict the effects of mutations on fluorophore quenching with single amino acid resolution, thereby enhancing the performance of Q-bodies. We collected yeasts displaying nanobodies with high- and low-quenching properties for the TAMRA fluorophore from a modified large synthetic nanobody library followed by next-generation sequencing. The pretrained pLM, connected to a single-layer perceptron, was trained end-to-end on the enriched CDR sequences. The achieved quenching prediction model that focused on CDR1 + 3 performed best in the evaluation with precision-recall curves. Using this model, we predicted and validated the effective mutations in two anti-SARS-CoV-2 nanobodies, RBD1i13 and RBD10i14, which converted them into Q-bodies. For RBD1i13, three Trp mutants were predicted to have high probability scores for quenching through in silico Trp scanning. These mutants were verified via yeast surface display, and all showed enhanced quenching. For RBD10i14, mutations at four positions close to an existing Trp gave high scores through in silico saturation mutagenesis scanning. Six of eight high-score mutants, derived from two mutants at each of the four positions, exhibited deeper quenching on the yeast surface. Next, combined with the investigation of antigen binding of the mutants, we successfully achieved Q-bodies with enhanced responses. Overall, our strategy allows the prediction of fluorescence responses solely on the basis of the antibody sequence and will be essential for the rational selection and design of antibodies to achieve immunosensors with larger responses.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 2","pages":"955–964 955–964"},"PeriodicalIF":8.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c01189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473830","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}
JACS AuPub Date : 2025-02-09DOI: 10.1021/jacsau.4c0127810.1021/jacsau.4c01278
Binming Han, Guorong Hu, Xiaosong Chen, Rui Shi and Jingyuan Li*,
{"title":"Flexibility-Induced Collective Behavior Drives Symmetry Breaking in Discrimination of Undesired Ions","authors":"Binming Han, Guorong Hu, Xiaosong Chen, Rui Shi and Jingyuan Li*, ","doi":"10.1021/jacsau.4c0127810.1021/jacsau.4c01278","DOIUrl":"https://doi.org/10.1021/jacsau.4c01278https://doi.org/10.1021/jacsau.4c01278","url":null,"abstract":"<p >Structure flexibility is essential for the biological function of proteins. At the same time, many proteins need to discriminate ligands with subtle differences, with one example being ion selectivity. Investigating the mechanisms by which flexible proteins achieve such precise discrimination is crucial for advancing our understanding of their functions. In this work, we study transporter KCC4, which undergoes continuous conformation changes during ion transport and can realize K<sup>+</sup> over Na<sup>+</sup> selectivity. Our findings reveal that the center of the binding site no longer represents a stable equilibrium for the undesired Na<sup>+</sup>, and its binding mode exhibits bifurcation. Interestingly, protein conformation fluctuation can induce collective behavior throughout the entire binding region, which contributes to this bifurcation. Thus, the symmetry of the binding mode decreases from the inherent <i>T</i><sub>d</sub> symmetry to a C<sub>2v</sub> symmetry, and the binding stability of Na<sup>+</sup> is largely reduced. A similar phenomenon is observed in a GPCR, β<sub>2</sub>-AR, where a less favored ligand forms a biased binding mode with reduced stability. The mechanism underlying the selectivity in such flexible regions could be interpreted as spontaneous symmetry breaking, which may represent a general mechanism by which flexible proteins achieve efficient ligand discrimination.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 2","pages":"1051–1059 1051–1059"},"PeriodicalIF":8.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c01278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473860","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}
JACS AuPub Date : 2025-02-09eCollection Date: 2025-02-24DOI: 10.1021/jacsau.4c01278
Binming Han, Guorong Hu, Xiaosong Chen, Rui Shi, Jingyuan Li
{"title":"Flexibility-Induced Collective Behavior Drives Symmetry Breaking in Discrimination of Undesired Ions.","authors":"Binming Han, Guorong Hu, Xiaosong Chen, Rui Shi, Jingyuan Li","doi":"10.1021/jacsau.4c01278","DOIUrl":"10.1021/jacsau.4c01278","url":null,"abstract":"<p><p>Structure flexibility is essential for the biological function of proteins. At the same time, many proteins need to discriminate ligands with subtle differences, with one example being ion selectivity. Investigating the mechanisms by which flexible proteins achieve such precise discrimination is crucial for advancing our understanding of their functions. In this work, we study transporter KCC4, which undergoes continuous conformation changes during ion transport and can realize K<sup>+</sup> over Na<sup>+</sup> selectivity. Our findings reveal that the center of the binding site no longer represents a stable equilibrium for the undesired Na<sup>+</sup>, and its binding mode exhibits bifurcation. Interestingly, protein conformation fluctuation can induce collective behavior throughout the entire binding region, which contributes to this bifurcation. Thus, the symmetry of the binding mode decreases from the inherent <i>T</i> <sub>d</sub> symmetry to a C<sub>2v</sub> symmetry, and the binding stability of Na<sup>+</sup> is largely reduced. A similar phenomenon is observed in a GPCR, β<sub>2</sub>-AR, where a less favored ligand forms a biased binding mode with reduced stability. The mechanism underlying the selectivity in such flexible regions could be interpreted as spontaneous symmetry breaking, which may represent a general mechanism by which flexible proteins achieve efficient ligand discrimination.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 2","pages":"1051-1059"},"PeriodicalIF":8.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525716","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}
JACS AuPub Date : 2025-02-07eCollection Date: 2025-03-24DOI: 10.1021/jacsau.4c00957
Margaret L Berrens, Marcos F Calegari Andrade, John T Fourkas, Tuan Anh Pham, Davide Donadio
{"title":"Molecular Fingerprints of Ice Surfaces in Sum Frequency Generation Spectra: A First-Principles Machine Learning Study.","authors":"Margaret L Berrens, Marcos F Calegari Andrade, John T Fourkas, Tuan Anh Pham, Davide Donadio","doi":"10.1021/jacsau.4c00957","DOIUrl":"10.1021/jacsau.4c00957","url":null,"abstract":"<p><p>Understanding the molecular-level structure and dynamics of ice surfaces is crucial for deciphering several chemical, physical, and atmospheric processes. Vibrational sum-frequency generation (SFG) spectroscopy is the most prominent tool for probing the molecular-level structure of the air-ice interface as it is a surface-specific technique, but the molecular interpretation of SFG spectra is challenging. This study utilizes a machine-learning potential, along with dipole and polarizability models trained on <i>ab initio</i> data, to calculate the SFG spectrum of the air-ice interface. At temperatures below ice surface premelting, our simulations support the presence of a proton-ordered arrangement at the Ice I <sub><i>h</i></sub> surface, similar to that seen in Ice XI. Additionally, our simulations provide insight into the assignment of SFG peaks to specific molecular configurations where possible and assess the contribution of subsurface layers to the overall SFG spectrum. These insights enhance our understanding and interpretation of vibrational studies of environmental chemistry at the ice surface.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1173-1183"},"PeriodicalIF":8.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733785","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}
JACS AuPub Date : 2025-02-07DOI: 10.1021/jacsau.4c0095710.1021/jacsau.4c00957
Margaret L. Berrens, Marcos F. Calegari Andrade, John T. Fourkas, Tuan Anh Pham* and Davide Donadio*,
{"title":"Molecular Fingerprints of Ice Surfaces in Sum Frequency Generation Spectra: A First-Principles Machine Learning Study","authors":"Margaret L. Berrens, Marcos F. Calegari Andrade, John T. Fourkas, Tuan Anh Pham* and Davide Donadio*, ","doi":"10.1021/jacsau.4c0095710.1021/jacsau.4c00957","DOIUrl":"https://doi.org/10.1021/jacsau.4c00957https://doi.org/10.1021/jacsau.4c00957","url":null,"abstract":"<p >Understanding the molecular-level structure and dynamics of ice surfaces is crucial for deciphering several chemical, physical, and atmospheric processes. Vibrational sum-frequency generation (SFG) spectroscopy is the most prominent tool for probing the molecular-level structure of the air–ice interface as it is a surface-specific technique, but the molecular interpretation of SFG spectra is challenging. This study utilizes a machine-learning potential, along with dipole and polarizability models trained on <i>ab initio</i> data, to calculate the SFG spectrum of the air–ice interface. At temperatures below ice surface premelting, our simulations support the presence of a proton-ordered arrangement at the Ice I<sub><i>h</i></sub> surface, similar to that seen in Ice XI. Additionally, our simulations provide insight into the assignment of SFG peaks to specific molecular configurations where possible and assess the contribution of subsurface layers to the overall SFG spectrum. These insights enhance our understanding and interpretation of vibrational studies of environmental chemistry at the ice surface.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1173–1183 1173–1183"},"PeriodicalIF":8.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00957","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675773","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}
JACS AuPub Date : 2025-02-07DOI: 10.1021/jacsau.4c0115810.1021/jacsau.4c01158
Sourav Roy*, and , Tatiana Besset*,
{"title":"New Opportunities to Access Fluorinated Molecules Using Organophotoredox Catalysis via C(sp3)–F Bond Cleavage","authors":"Sourav Roy*, and , Tatiana Besset*, ","doi":"10.1021/jacsau.4c0115810.1021/jacsau.4c01158","DOIUrl":"https://doi.org/10.1021/jacsau.4c01158https://doi.org/10.1021/jacsau.4c01158","url":null,"abstract":"<p >Fluorinated molecules are of paramount importance because of their unique properties. As a result, the search for innovative approaches to the synthesis of this class of compounds has been relentless over the years. Among these, the combination of photocatalysis and organofluorine chemistry turned out to be an effective partnership to access unattainable fluorinated molecules. This Perspective provides an overview of the recent advances in synthesizing fluorinated molecules via an organophotoredox-catalyzed defluorination process from trifluoromethylated compounds. It encompasses the preparation of difluoromethylated (hetero)arenes, amides, and esters as well as <i>gem</i>-difluoroalkene derivatives using C(sp<sup>3</sup>)–F bond activation or β-fragmentation. This Perspective will highlight remaining challenges and discuss future research opportunities.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 2","pages":"466–485 466–485"},"PeriodicalIF":8.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c01158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473661","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}
JACS AuPub Date : 2025-02-07eCollection Date: 2025-02-24DOI: 10.1021/jacsau.4c01158
Sourav Roy, Tatiana Besset
{"title":"New Opportunities to Access Fluorinated Molecules Using Organophotoredox Catalysis via C(sp<sup>3</sup>)-F Bond Cleavage.","authors":"Sourav Roy, Tatiana Besset","doi":"10.1021/jacsau.4c01158","DOIUrl":"10.1021/jacsau.4c01158","url":null,"abstract":"<p><p>Fluorinated molecules are of paramount importance because of their unique properties. As a result, the search for innovative approaches to the synthesis of this class of compounds has been relentless over the years. Among these, the combination of photocatalysis and organofluorine chemistry turned out to be an effective partnership to access unattainable fluorinated molecules. This Perspective provides an overview of the recent advances in synthesizing fluorinated molecules via an organophotoredox-catalyzed defluorination process from trifluoromethylated compounds. It encompasses the preparation of difluoromethylated (hetero)arenes, amides, and esters as well as <i>gem</i>-difluoroalkene derivatives using C(sp<sup>3</sup>)-F bond activation or β-fragmentation. This Perspective will highlight remaining challenges and discuss future research opportunities.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 2","pages":"466-485"},"PeriodicalIF":8.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525726","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}
JACS AuPub Date : 2025-02-06DOI: 10.1021/jacsau.4c0088810.1021/jacsau.4c00888
Xiao Gao, Kai Qiao, David M. Wilson*, Myriam M. Chaumeil* and Jeremy W. Gordon*,
{"title":"Deuterium Metabolic Imaging of the Brain Using 2-Deoxy-2-[2H2]-d-glucose: A Non-ionizing [18F]FDG Alternative","authors":"Xiao Gao, Kai Qiao, David M. Wilson*, Myriam M. Chaumeil* and Jeremy W. Gordon*, ","doi":"10.1021/jacsau.4c0088810.1021/jacsau.4c00888","DOIUrl":"https://doi.org/10.1021/jacsau.4c00888https://doi.org/10.1021/jacsau.4c00888","url":null,"abstract":"<p >The positron emission tomography (PET) tracer 2-deoxy-2-[<sup>18</sup>F]fluoroglucose ([<sup>18</sup>F]FDG) is widely used to study diseases where glucose metabolism is dysregulated, including cancer and neurodegenerative disorders. Here we investigate the hypothesis that the 2-position deuterium-enriched analogue 2-deoxy-2-[<sup>2</sup>H<sub>2</sub>]-<span>d</span>-glucose (2-DG-d2) can also map glucose uptake using deuterium metabolic imaging (DMI) without ionizing radiation. To accomplish this, we used a spectrally selective multiband radiofrequency pulse and balanced steady-state free procession (bSSFP) technique, enabling rapid <sup>2</sup>H imaging with high specificity and sensitivity to 2-DG-d2. Both <i>in vitro</i> and <i>in vivo</i> validations demonstrated the sequence’s ability to suppress endogenous water signal. Mapping of 2-DG-d2 with high spatial resolution was achieved in healthy mouse brains, comparable to what might be obtained using [<sup>18</sup>F]FDG PET. The numerous applications of [<sup>18</sup>F]FDG PET, as well as recent clinical translation of the natural abundance 2-deoxy-<span>d</span>-glucose (2-DG) parent sugar, suggest that DMI using 2-DG-d2 may be applied to patients in the future.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 2","pages":"571–577 571–577"},"PeriodicalIF":8.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00888","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473890","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}
JACS AuPub Date : 2025-02-06eCollection Date: 2025-02-24DOI: 10.1021/jacsau.4c01040
Amal Lakhal, Yves Gimbert, Virginie Mouriès-Mansuy, Cyril Ollivier, Louis Fensterbank
{"title":"Alkynyl Radicals, Myths and Realities.","authors":"Amal Lakhal, Yves Gimbert, Virginie Mouriès-Mansuy, Cyril Ollivier, Louis Fensterbank","doi":"10.1021/jacsau.4c01040","DOIUrl":"10.1021/jacsau.4c01040","url":null,"abstract":"<p><p>This Perspective deals with the organic chemistry of alkynyl radicals, a species that is ultimately still little known in the synthetic community. Starting with the first observations and characterizations of alkynyl radicals generated by various methodologies in the gas phase, we then particularly turned our attention to the implications of these highly reactive intermediates in organic synthesis and materials science. Mechanistic considerations have been provided, in particular, for the key steps of generating alkynyl radicals, which are mainly based on photochemical or thermal activation and single electron transfer processes. This Perspective should serve as a roadmap for the synthetic chemist in order to plan more reliably alkynylation reactions based on alkynyl radicals.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 2","pages":"448-465"},"PeriodicalIF":8.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525146","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}