Yan Song, Linda J Fothergill, Kari S Lee, Brandon Y Liu, Ada Koo, Mark Perelis, Shanti Diwakarla, Brid Callaghan, Jie Huang, Jill Wykosky, John B Furness, Gene W Yeo
{"title":"Stratification of enterochromaffin cells by single-cell expression analysis.","authors":"Yan Song, Linda J Fothergill, Kari S Lee, Brandon Y Liu, Ada Koo, Mark Perelis, Shanti Diwakarla, Brid Callaghan, Jie Huang, Jill Wykosky, John B Furness, Gene W Yeo","doi":"10.1101/2023.08.24.554649","DOIUrl":"10.1101/2023.08.24.554649","url":null,"abstract":"<p><p>Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine (5-HT) to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify fourteen EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A <i>Piezo2</i> <sup>+</sup> population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic and pharmacological approaches, we demonstrated <i>Piezo2</i> <sup>+</sup> ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/67/34/nihpp-2023.08.24.554649v1.PMC10473706.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178778","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}
Zhiying Zhang, Thomas C Todeschini, Yi Wu, Roman Kogay, Ameena Naji, Joaquin Cardenas Rodriguez, Rupavidhya Mondi, Daniel Kaganovich, David W Taylor, Jack P K Bravo, Marianna Teplova, Triana Amen, Eugene V Koonin, Dinshaw J Patel, Franklin L Nobrega
{"title":"Kiwa is a bacterial membrane-embedded defence supercomplex activated by phage-induced membrane changes.","authors":"Zhiying Zhang, Thomas C Todeschini, Yi Wu, Roman Kogay, Ameena Naji, Joaquin Cardenas Rodriguez, Rupavidhya Mondi, Daniel Kaganovich, David W Taylor, Jack P K Bravo, Marianna Teplova, Triana Amen, Eugene V Koonin, Dinshaw J Patel, Franklin L Nobrega","doi":"10.1101/2023.02.26.530102","DOIUrl":"10.1101/2023.02.26.530102","url":null,"abstract":"<p><p>Bacteria and archaea deploy diverse, sophisticated defence systems to counter virus infection, yet many immunity mechanisms remain poorly understood. Here, we characterise the Kiwa defence system as a membrane-associated supercomplex that senses changes in the membrane induced by phage infection and plasmid conjugation. This supercomplex, comprising KwaA tetramers bound to KwaB dimers, as its basic repeating unit, detects structural stress via KwaA, activating KwaB, which binds ejected phage DNA through its DUF4868 domain, stalling phage DNA replication forks and thus disrupting replication and late transcription. We show that phage-encoded DNA mimic protein Gam, which inhibits RecBCD, also targets Kiwa through KwaB recognition. However, Gam binding to one defence system precludes its inhibition of the other. These findings reveal a distinct mechanism of bacterial immune coordination, where sensing of membrane disruptions and inhibitor partitioning enhance protection against phages and plasmids.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90459837","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}
Matthew S Price, Elham Rastegari, Richa Gupta, Katie Vo, Travis I Moore, Kartik Venkatachalam
{"title":"Intracellular Lactate Dynamics in <i>Drosophila</i> Glutamatergic Neurons.","authors":"Matthew S Price, Elham Rastegari, Richa Gupta, Katie Vo, Travis I Moore, Kartik Venkatachalam","doi":"10.1101/2024.02.26.582095","DOIUrl":"10.1101/2024.02.26.582095","url":null,"abstract":"<p><p>Rates of lactate production and consumption reflect the metabolic state of many cell types, including neurons. Here, we investigate the effects of nutrient deprivation on lactate dynamics in <i>Drosophila</i> glutamatergic neurons by leveraging the limiting effects of the diffusion barrier surrounding cells in culture. We found that neurons constitutively consume lactate when availability of trehalose, the glucose disaccharide preferred by insects, is limited by the diffusion barrier. Acute mechanical disruption of the barrier reduced this reliance on lactate. Through kinetic modeling and experimental validation, we demonstrate that neuronal lactate consumption rates correlate inversely with their mitochondrial density. Further, we found that lactate levels in neurons exhibited temporal correlations that allowed prediction of cytosolic lactate dynamics after the disruption of the diffusion barrier from pre-perturbation lactate fluctuations. Collectively, our findings reveal the influence of diffusion barriers on neuronal metabolic preferences, and demonstrate the existence of temporal correlations between lactate dynamics under conditions of nutrient deprivation and those evoked by the subsequent restoration of nutrient availability.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095206","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}
Fang Kong, Megha Upadya, Andrew See Weng Wong, Rinkoo Dalan, Ming Dao
{"title":"Isolating Small Extracellular Vesicles from Small Volumes of Blood Plasma using size exclusion chromatography and density gradient ultracentrifugation: A Comparative Study.","authors":"Fang Kong, Megha Upadya, Andrew See Weng Wong, Rinkoo Dalan, Ming Dao","doi":"10.1101/2023.10.30.564707","DOIUrl":"10.1101/2023.10.30.564707","url":null,"abstract":"<p><p>Small extracellular vesicles (sEVs) are heterogeneous biological vesicles released by cells under both physiological and pathological conditions. Due to their potential as valuable diagnostic and prognostic biomarkers in human blood, there is a pressing need to develop effective methods for isolating high-purity sEVs from the complex milieu of blood plasma, which contains abundant plasma proteins and lipoproteins. Size exclusion chromatography (SEC) and density gradient ultracentrifugation (DGUC) are two commonly employed isolation techniques that have shown promise in addressing this challenge. In this study, we aimed to determine the optimal combination and sequence of SEC and DGUC for isolating sEVs from small plasma volumes, in order to enhance both the efficiency and purity of the resulting isolates. To achieve this, we compared sEV isolation using two combinations: SEC-DGUC and DGUC-SEC, from unit volumes of 500 <i>μl</i> plasma. Both protocols successfully isolated high-purity sEVs; however, the SEC-DGUC combination yielded higher sEV protein and RNA content. We further characterized the isolated sEVs obtained from the SEC-DGUC protocol using flow cytometry and mass spectrometry to assess their quality and purity. In conclusion, the optimized SEC-DGUC protocol is efficient, highly reproducible, and well-suited for isolating high-purity sEVs from small blood volumes.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157784","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}
Pravda Quiñones-Labernik, Kelsey L Blocklinger, Matthew R Bruce, Sarah L Ferri
{"title":"Excess neonatal testosterone causes male-specific social and fear memory deficits in wild-type mice.","authors":"Pravda Quiñones-Labernik, Kelsey L Blocklinger, Matthew R Bruce, Sarah L Ferri","doi":"10.1101/2023.10.18.562939","DOIUrl":"10.1101/2023.10.18.562939","url":null,"abstract":"<p><p>Neurodevelopmental disorders disproportionately affect males compared to females. The biological mechanisms of this male susceptibility or female protection have not been identified. There is evidence that fetal/neonatal gonadal hormones, which play a pivotal role in many aspects of development, may contribute. Here, we investigate the effects of excess testosterone during a critical period of sex-specific brain organization on social approach and fear learning behaviors in C57BL/6J wild-type mice. Male, but not female, mice treated with testosterone on the day of birth (PN0) exhibited decreased social approach as juveniles and decreased contextual fear memory as adults, compared to vehicle-treated controls. These deficits were not driven by anxiety-like behavior or changes in locomotion or body weight. Mice treated with the same dose of testosterone on postnatal day 18 (PN18), which is outside of the critical period of brain masculinization, did not demonstrate impairments compared to the vehicle group. These findings indicate that excess testosterone during a critical period of early development, but not shortly after, induces long-term deficits relevant to the male sex bias in neurodevelopmental disorders.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415623","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}
Anthony E Jones, Amy Rios, Neira Ibrahimovic, Carolina Chavez, Nicholas A Bayley, Andréa B Ball, Wei Yuan Hsieh, Alessandro Sammarco, Amber R Bianchi, Angel A Cortez, Thomas G Graeber, Alexander Hoffmann, Steven J Bensinger, Ajit S Divakaruni
{"title":"The metabolic cofactor Coenzyme A enhances alternative macrophage activation via MyD88-linked signaling.","authors":"Anthony E Jones, Amy Rios, Neira Ibrahimovic, Carolina Chavez, Nicholas A Bayley, Andréa B Ball, Wei Yuan Hsieh, Alessandro Sammarco, Amber R Bianchi, Angel A Cortez, Thomas G Graeber, Alexander Hoffmann, Steven J Bensinger, Ajit S Divakaruni","doi":"10.1101/2024.03.28.587096","DOIUrl":"10.1101/2024.03.28.587096","url":null,"abstract":"<p><p>Metabolites and metabolic co-factors can shape the innate immune response, though the pathways by which these molecules adjust inflammation remain incompletely understood. Here we show that the metabolic cofactor Coenzyme A (CoA) enhances IL-4 driven alternative macrophage activation [m(IL-4)] <i>in vitro</i> and <i>in vivo</i>. Unexpectedly, we found that perturbations in intracellular CoA metabolism did not influence m(IL-4) differentiation. Rather, we discovered that exogenous CoA provides a weak TLR4 signal which primes macrophages for increased receptivity to IL-4 signals and resolution of inflammation via MyD88. Mechanistic studies revealed MyD88-linked signals prime for IL-4 responsiveness, in part, by reshaping chromatin accessibility to enhance transcription of IL-4-linked genes. The results identify CoA as a host metabolic co-factor that influences macrophage function through an extrinsic TLR4-dependent mechanism, and suggests that damage-associated molecular patterns (DAMPs) can prime macrophages for alternative activation and resolution of inflammation.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10996702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859283","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}
Tina Tian, Kevin Patel, David Kim, HaoMin SiMa, Alandrea R Harris, Jordan N Owyoung, Patricia J Ward
{"title":"Conditioning electrical stimulation fails to enhance sympathetic axon regeneration.","authors":"Tina Tian, Kevin Patel, David Kim, HaoMin SiMa, Alandrea R Harris, Jordan N Owyoung, Patricia J Ward","doi":"10.1101/2023.02.03.527071","DOIUrl":"10.1101/2023.02.03.527071","url":null,"abstract":"<p><p>Peripheral nerve injuries are common, and there is a critical need for the development of novel treatments to complement surgical repair. Conditioning electrical stimulation (CES) is a novel variation of the well-studied perioperative electrical stimulation treatment paradigm. CES is a clinically attractive alternative because of its ability to be performed at the bedside prior to a scheduled nerve repair surgery. Although 60 minutes of CES has been shown to enhance motor and sensory axon regeneration, the effects of CES on sympathetic regeneration are unknown. We investigated how two clinically relevant CES paradigms (10 minutes and 60 minutes) impact sympathetic axon regeneration and distal target reinnervation. Our results indicate that the growth of sympathetic axons is inhibited by CES at acute time points, and at a longer survival time point post-injury, there is no difference between sham CES and the CES groups. We conclude sympathetic axons may retain some regenerative ability, but no enhancement is exhibited after CES, which may be accounted for by the inability of the electrical stimulation paradigm to recruit the small-caliber sympathetic axons into activity. Furthermore, 10-minute CES did not enhance motor and sensory regeneration with a direct repair, and neither 60-minute nor 10-minute CES enhanced motor and sensory regeneration through a graft. Further studies will be needed to optimize electrical stimulation parameters to enhance the regeneration of all neuron types.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10692145","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}
Alejandra Fernandez, Nick Sarn, Charis Eng, Kevin M Wright
{"title":"Altered primary somatosensory neuron development in a <i>Pten</i> heterozygous model for autism spectrum disorder.","authors":"Alejandra Fernandez, Nick Sarn, Charis Eng, Kevin M Wright","doi":"10.1101/2023.08.04.552039","DOIUrl":"10.1101/2023.08.04.552039","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interactions, repetitive behaviors, and hyper- or hyposensitivity to sensory stimuli. The mechanisms underlying the emergence of sensory features in ASD are not fully understood, but recent studies in rodent models highlight that these may result from differences in primary sensory neurons themselves. We examined sensory behaviors in a <i>Pten</i> haploinsufficient mouse model ( <i>Pten <sup>Het</sup></i> ) for syndromic ASD and identified elevated responses to mechanical stimuli and a higher threshold to thermal responses. Transcriptomic and <i>in vivo</i> anatomical analysis identified alterations in subtype-specific markers of primary somatosensory neurons in <i>Pten <sup>Het</sup></i> dorsal root ganglia (DRG). These defects emerge early during DRG development and involve dysregulation of multiple signaling pathways downstream of <i>Pten</i> . Finally, we show that mice harboring an ASD-associated mutation ( <i>Pten <sup>Y69H</sup></i> ) also show altered expression of somatosensory neuron subtype-specific markers. Together, these results show that precise levels of <i>Pten</i> are required for proper somatosensory development and provide insight into the molecular and cellular basis of sensory abnormalities in a model for syndromic ASD.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175355","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":"Efficient coding in biophysically realistic excitatory-inhibitory spiking networks.","authors":"Veronika Koren, Simone Blanco Malerba, Tilo Schwalger, Stefano Panzeri","doi":"10.1101/2024.04.24.590955","DOIUrl":"10.1101/2024.04.24.590955","url":null,"abstract":"<p><p>The principle of efficient coding posits that sensory cortical networks are designed to encode maximal sensory information with minimal metabolic cost. Despite the major influence of efficient coding in neuroscience, it has remained unclear whether fundamental empirical properties of neural network activity can be explained solely based on this normative principle. Here, we derive the structural, coding, and biophysical properties of excitatory-inhibitory recurrent networks of spiking neurons that emerge directly from imposing that the network minimizes an instantaneous loss function and a time-averaged performance measure enacting efficient coding. We assumed that the network encodes a number of independent stimulus features varying with a time scale equal to the membrane time constant of excitatory and inhibitory neurons. The optimal network has biologically-plausible biophysical features, including realistic integrate-and-fire spiking dynamics, spike-triggered adaptation, and a non-specific excitatory external input. The excitatory-inhibitory recurrent connectivity between neurons with similar stimulus tuning implements feature-specific competition, similar to that recently found in visual cortex. Networks with unstructured connectivity cannot reach comparable levels of coding efficiency. The optimal ratio of excitatory vs inhibitory neurons and the ratio of mean inhibitory-to-inhibitory vs excitatory-to-inhibitory connectivity are comparable to those of cortical sensory networks. The efficient network solution exhibits an instantaneous balance between excitation and inhibition. The network can perform efficient coding even when external stimuli vary over multiple time scales. Together, these results suggest that key properties of biological neural networks may be accounted for by efficient coding.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873208","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}
Abigail L Lind, Nathan A McDonald, Elias R Gerrick, Ami S Bhatt, Katherine S Pollard
{"title":"Contiguous and complete assemblies of <i>Blastocystis</i> gut microbiome-associated protists reveal evolutionary diversification to host ecology.","authors":"Abigail L Lind, Nathan A McDonald, Elias R Gerrick, Ami S Bhatt, Katherine S Pollard","doi":"10.1101/2023.11.20.567959","DOIUrl":"10.1101/2023.11.20.567959","url":null,"abstract":"<p><p><i>Blastocystis</i>, an obligate host-associated protist, is the most common microbial eukaryote in the human gut and is widely distributed across vertebrate hosts. The evolutionary transition of <i>Blastocystis</i> from its free-living stramenopile ancestors to a radiation of host-associated organisms is poorly understood. To explore this, we cultured and sequenced eight strains representing the significant phylogenetic diversity of the genus using long-read, short-read, and Hi-C DNA sequencing, alongside gene annotation and RNA sequencing. Comparative genomic analyses revealed significant variation in gene content and genome structure across <i>Blastocystis</i>. Notably, three strains from herbivorous tortoises, phylogenetically distant from human subtypes, have markedly larger genomes with longer introns and intergenic regions, and retain canonical stop codons absent in the human-associated strains. Despite these genetic differences, all eight isolates exhibit gene losses linked to the reduced cellular complexity of <i>Blastocystis,</i> including losses of cilia and flagella genes, microtubule motor genes, and signal transduction genes. Isolates from herbivorous tortoises contained higher numbers of plant carbohydrate-metabolizing enzymes, suggesting that like gut bacteria, these protists ferment plant material in the host gut. We find evidence that some of these carbohydrate-metabolizing enzymes were horizontally acquired from bacteria, indicating that horizontal gene transfer is an ongoing process in <i>Blastocystis</i> that has contributed to host-related adaptation. Together, these results highlight substantial genetic and metabolic diversity within the <i>Blastocystis</i> genus, indicating different lineages of <i>Blastocystis</i> have varied ecological roles in the host gut.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479573","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}