Molecular and Cellular Neuroscience最新文献

{"title":"Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control","authors":"Ellen M. Armour,&nbsp;Christina M. Thomas,&nbsp;Gabrielle Greco,&nbsp;Akanksha Bhatnagar,&nbsp;Felice Elefant","doi":"10.1016/j.mcn.2023.103888","DOIUrl":"10.1016/j.mcn.2023.103888","url":null,"abstract":"<div><p><span><span><span>Nucleocytoplasmic transport (NCT) in neurons is critical for enabling proteins to enter the nucleus and regulate plasticity genes in response to environmental cues. Such experience-dependent (ED) neural plasticity is central for establishing memory formation and cognitive function and can influence the severity of neurodegenerative disorders like </span>Alzheimer's disease (AD). ED neural plasticity is driven by </span>histone acetylation<span><span> (HA) mediated epigenetic mechanisms that regulate dynamic activity-dependent </span>gene transcription<span> profiles in response to neuronal stimulation. Yet, how histone acetyltransferases (HATs) respond to extracellular cues in the </span></span></span><em>in vivo</em> brain to drive HA-mediated activity-dependent gene control remains unclear. We previously demonstrated that extracellular stimulation of rat hippocampal neurons <em>in vitro</em><span><span> triggers Tip60 HAT nuclear import with concomitant synaptic gene induction. Here, we focus on investigating Tip60 HAT subcellular localization and NCT specifically in neuronal activity-dependent gene control by using the learning and memory </span>mushroom body (MB) region of the </span><em>Drosophila</em> brain as a powerful <em>in vivo</em><span> cognitive model system. We used immunohistochemistry (IHC) to compare the subcellular localization of Tip60 HAT in the </span><em>Drosophila</em> brain under normal conditions and in response to stimulation of fly brain neurons <em>in vivo</em><span> either by genetically inducing potassium channels activation or by exposure to natural positive ED conditions. Furthermore, we found that both inducible and ED condition-mediated neural induction triggered Tip60 nuclear import with concomitant induction of previously identified Tip60 target genes and that Tip60 levels in both the nucleus and cytoplasm were significantly decreased in our well-characterized </span><em>Drosophila</em><span> AD model. Mutagenesis<span> of a putative nuclear localization signal<span> (NLS) sequence and nuclear export signal (NES) sequence that we identified in the </span></span></span><em>Drosophila</em> Tip60 protein revealed that both are functionally required for appropriate Tip60 subcellular localization. Our results support a model by which neuronal stimulation triggers Tip60 NCT <em>via</em><span> its NLS and NES sequences to promote induction of activity-dependent neuroplasticity gene transcription and that this process may be disrupted in AD.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"127 ","pages":"Article 103888"},"PeriodicalIF":3.5,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special issue: Synaptic logistics — Maintenance of synaptic composition, properties and function","authors":"Noam E. Ziv ,&nbsp;Antoine Triller","doi":"10.1016/j.mcn.2023.103885","DOIUrl":"10.1016/j.mcn.2023.103885","url":null,"abstract":"","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"127 ","pages":"Article 103885"},"PeriodicalIF":3.5,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10481269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of cytoskeletal proteins as binding partners of Bri2 BRICHOS domain","authors":"Makoto Shimozawa ,&nbsp;Helene Tigro ,&nbsp;Henrik Biverstål ,&nbsp;Ganna Shevchenko ,&nbsp;Jonas Bergquist ,&nbsp;Ruin Moaddel ,&nbsp;Jan Johansson ,&nbsp;Per Nilsson","doi":"10.1016/j.mcn.2023.103843","DOIUrl":"10.1016/j.mcn.2023.103843","url":null,"abstract":"<div><p>Proteins must fold into three-dimensional structures to execute their biological functions. Therefore, maintenance of protein homeostasis, proteostasis, including prevention of protein misfolding is essential for cellular activity and health. Molecular chaperones are key actors in proteostasis. BRICHOS domain is an intramolecular chaperone that also interferes with several aggregation-prone proteins including amyloid β (Aβ), involved in Alzheimer's disease (AD). To extend the knowledge about Bri2 BRICHOS interactome we here used recombinant human (rh) Bri2 BRICHOS-mCherry fusion protein to probe for potential binding partners. Firstly, exogenously added Bri2 BRICHOS-mCherry was used to stain brain sections of wildtype and amyloid precursor protein (<em>App</em>) knock-in AD mice exhibiting robust Aβ pathology. Unexpectedly, we found that rh Bri2 BRICHOS-mCherry stained the cytoplasm of neurons which are devoid of Aβ deposits. To identify these intraneuronal proteins that bind to the rh Bri2 BRICHOS domain, we performed co-immunoprecipitation (co-IP) of mouse brain hippocampi homogenates using the Bri2 BRICHOS-mCherry probe and analyzed co-IP proteins by LC-MS/MS. This identified several cytoskeletal proteins including spectrin alpha and beta chain, drebrin, tubulin β3, and β-actin as binding partners. The interactions were confirmed by a second round of pulldown experiments using rh Bri2 BRICHOS linked to magnetic beads. The interaction of rh Bri2 BRICHOS and tubulin β3 was further investigated by staining both mouse brain sections and SH-SY5Y neuroblastoma cells with rh Bri2 BRICHOS-mCherry and tubulin β3 immunostaining, which revealed partial co-localization. These data suggest a possible interplay of extracellular chaperone Bri2 BRICHOS domain in the intracellular space including the cytoskeleton.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103843"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilirubin induces microglial NLRP3 inflammasome activation in vitro and in vivo","authors":"Ilkcan Ercan ,&nbsp;Serap Cilaker Micili ,&nbsp;Sila Soy ,&nbsp;Defne Engur ,&nbsp;Kemal Ugur Tufekci ,&nbsp;Abdullah Kumral ,&nbsp;Sermin Genc","doi":"10.1016/j.mcn.2023.103850","DOIUrl":"10.1016/j.mcn.2023.103850","url":null,"abstract":"<div><p><span><span>Despite current advancements in neonatal care, hyperbilirubinemia resulting in bilirubin-induced neurological dysfunction (BIND) continues to be one of the major reasons of mortality or lifelong disability. Although the exact mechanisms underlying brain injury upon bilirubin exposure remains unelucidated, inflammation is considered to be one of the major contributors to BIND. This study investigates the role of the </span>NLRP3<span> inflammasome in bilirubin-induced injury using </span></span><em>in vitro</em> and <em>in vivo</em> models. We successfully demonstrated that the upregulation of NLRP3 expression is significantly associated with the release of active caspase-1 and IL-1β in N9 microglial cells exposed to bilirubin. Functional <em>in vitro</em><span> experiments with NLRP3 siRNA confirms that bilirubin-induced inflammasome activation and cell death are mediated by the NLRP3 inflammasome. Following injection of bilirubin into the </span><span><em>cisterna magna</em></span><span> of a neonatal mouse, activation of the NLRP3 inflammasome and microglia<span> were determined by double staining with Iba1-NLRP3 and Iba1-Caspase-1. Upon injection of bilirubin into the </span></span><em>cisterna magna</em>, neuronal loss was significantly higher in the wild-type mouse compared to <em>Nlrp3</em>^{<em>−/−</em>} and <em>Caspase-1</em>^{<em>−/−</em>} strains. Collectively, these data indicate that NLRP3 inflammasome has a crucial role in microglial activation and bilirubin-induced neuronal damage.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103850"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9579628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone H3 dopaminylation in nucleus accumbens, but not medial prefrontal cortex, contributes to cocaine-seeking following prolonged abstinence","authors":"Andrew F. Stewart ,&nbsp;Ashley E. Lepack ,&nbsp;Sasha L. Fulton ,&nbsp;Polina Safovich ,&nbsp;Ian Maze","doi":"10.1016/j.mcn.2023.103824","DOIUrl":"10.1016/j.mcn.2023.103824","url":null,"abstract":"<div><p>Enduring patterns of epigenomic and transcriptional plasticity within the mesolimbic dopamine system contribute importantly to persistent behavioral adaptations that characterize substance use disorders (SUD). While drug addiction has long been thought of as a disorder of dopamine (DA) neurotransmission, therapeutic interventions targeting receptor mediated DA-signaling have not yet resulted in efficacious treatments. Our laboratory recently identified a non-canonical, neurotransmission-independent signaling moiety for DA in brain, termed dopaminylation, whereby DA itself acts as a donor source for the establishment of post-translational modifications (PTM) on substrate proteins (e.g., histone H3 at glutamine 5; H3Q5dop). In our previous studies, we demonstrated that H3Q5dop plays a critical role in the regulation of neuronal transcription and, when perturbed within monoaminergic neurons of the ventral tegmental area (VTA), critically contributes to pathological states, including relapse vulnerability to both psychostimulants (e.g., cocaine) and opiates (e.g., heroin). Importantly, H3Q5dop is also observed throughout the mesolimbic DA reward pathway (e.g., in nucleus accumbens/NAc and medial prefrontal cortex/mPFC, which receive DA input from VTA). As such, we investigated whether H3Q5dop may similarly be altered in its expression in response to drugs of abuse in these non-dopamine-producing regions. In rats undergoing extended abstinence from cocaine self-administration (SA), we observed both acute and prolonged accumulation of H3Q5dop in NAc, but not mPFC. Attenuation of H3Q5dop in NAc during drug abstinence reduced cocaine-seeking and affected cocaine-induced gene expression programs associated with altered dopamine signaling and neuronal function. These findings thus establish H3Q5dop in NAc, but not mPFC, as an important mediator of cocaine-induced behavioral and transcriptional plasticity during extended cocaine abstinence.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103824"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9952957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “wild type and P301L mutant Tau promote neuro-inflammation and α-Synuclein accumulation in lentiviral gene delivery models” [Mol. Cell. Neurosci. 49 (1) (2012), 44–53]","authors":"Preeti J. Khandelwal ,&nbsp;Sonya B. Dumanis ,&nbsp;Alexander M. Herman ,&nbsp;G. William Rebeck ,&nbsp;Charbel E.-H. Moussa","doi":"10.1016/j.mcn.2023.103844","DOIUrl":"10.1016/j.mcn.2023.103844","url":null,"abstract":"","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103844"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9557634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte-associated fibronectin promotes the proinflammatory phenotype of astrocytes through β1 integrin activation","authors":"Pao-Hsien Chu ,&nbsp;Shao-Chi Chen ,&nbsp;Hsin-Yung Chen ,&nbsp;Cheng-Bei Wu ,&nbsp;Wei-Ting Huang ,&nbsp;Hou-Yu Chiang","doi":"10.1016/j.mcn.2023.103848","DOIUrl":"10.1016/j.mcn.2023.103848","url":null,"abstract":"<div><p><span>Astrocytes are key players in neuroinflammation. In response to central nervous system<span><span> (CNS) injury or disease, astrocytes undergo reactive astrogliosis<span>, which is characterized by increased proliferation, migration, and glial fibrillary acidic protein<span> (GFAP) expression. Activation of the transcription factor nuclear factor-κB (NF-κB) and upregulation of downstream proinflammatory mediators in reactive astrocytes induce a proinflammatory phenotype in astrocytes, thereby exacerbating neuroinflammation by establishing an inflammatory loop. In this study, we hypothesized that excessive fibronectin<span> (FN) derived from reactive astrocytes would induce this proinflammatory phenotype in astrocytes in an autocrine manner. We exogenously treated astrocytes with monomer FN, which can be incorporated into the </span></span></span></span>extracellular matrix<span> (ECM), to mimic plasma FN extravasated through a compromised blood–brain barrier in neuroinflammation. We also induced de novo synthesis and accumulation of astrocyte-derived FN through tumor necrosis factor-α (TNF-α) stimulation. The excessive FN deposition resulting from both treatments initiated reactive astrogliosis and triggered NF-κB signaling in the cultured astrocytes. In addition, inhibition of FN accumulation in the ECM by the FN inhibitor pUR4 strongly attenuated the FN- and TNF-α-induced GFAP expression, NF-κB activation, and proinflammatory mediator production of astrocytes by interrupting FN–β1 integrin coupling and thus the inflammatory loop. In an in vivo experiment, </span></span></span>intrathecal injection of pUR4 considerably ameliorated FN deposition, GFAP expression, and NF-κB activation in inflamed spinal cord, suggesting the therapeutic potential of pUR4 for attenuating neuroinflammation and promoting neuronal function restoration.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103848"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9567559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA regulation and function in drug seeking phenotypes","authors":"Stephanie E. Sillivan,&nbsp;Aria Gillespie","doi":"10.1016/j.mcn.2023.103841","DOIUrl":"10.1016/j.mcn.2023.103841","url":null,"abstract":"<div><p><span><span>Drug overdoses have increased dramatically in the United States over the last decade where they are now the leading cause of accidental death. To develop efficient therapeutic options for decreasing drug consumption and overdose risk, it is critical to understand the neurobiological changes induced by drug exposure. Chronic systemic exposure to all drug classes, including opioids, </span>psychostimulants<span>, nicotine, cannabis, and alcohol, induces profound molecular neuroadaptations within the central nervous system that may reveal crucial information about the lasting effects that these substances impart on brain cells. </span></span>Transcriptome<span><span><span><span><span> analyses of messenger RNAs (mRNAs) have identified gene patterns in the brain that result from exposure to various classes of drugs. However, mRNAs represent only a small fraction of the RNA within the cell, and drug exposure also impacts other classes of RNA that are largely understudied, especially </span>circular RNAs. Circular RNAs (circRNAs) are a naturally occurring RNA species formed from back-splicing events during </span>mRNA processing<span> and are enriched in the nervous system. circRNAs are a pleiotropic class of RNAs and have a diverse impact on cellular function, with putative functions including regulation of </span></span>mRNA transcription, </span>protein translation<span><span><span>, microRNA sponging, and sequestration of RNA-binding proteins. Recent studies have demonstrated that circRNAs can modulate cognition and are regulated in the brain in response to drug exposure, yet very few studies have explored the contribution of circRNAs to drug seeking phenotypes. In this review, we will provide an overview of the mechanisms of circRNA function in the cell to highlight how drug-induced circRNA dysregulation may impact the molecular substrates that mediate </span>drug seeking behavior and the current studies that have reported drug-induced dysregulation of circRNAs in the brain. Furthermore, we will discuss how principles of circRNA biology can be adapted to study circRNAs in models of drug exposure and seek to provide further insight into the </span>neurobiology of addiction.</span></span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103841"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational insights into mRNA and protein dynamics underlying synaptic plasticity rules","authors":"Surbhit Wagle ,&nbsp;Nataliya Kraynyukova ,&nbsp;Anne-Sophie Hafner ,&nbsp;Tatjana Tchumatchenko","doi":"10.1016/j.mcn.2023.103846","DOIUrl":"10.1016/j.mcn.2023.103846","url":null,"abstract":"<div><p>Recent advances in experimental techniques provide an unprecedented peek into the intricate molecular dynamics inside synapses and dendrites. The experimental insights into the molecular turnover revealed that such processes as diffusion, active transport, spine uptake, and local protein synthesis could dynamically modulate the copy numbers of plasticity-related molecules in synapses. Subsequently, theoretical models were designed to understand the interaction of these processes better and to explain how local synaptic plasticity cues can up or down-regulate the molecular copy numbers across synapses. In this review, we discuss the recent advances in experimental techniques and computational models to highlight how these complementary approaches can provide insight into molecular cross-talk across synapses, ultimately allowing us to develop biologically-inspired neural network models to understand brain function.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103846"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transcriptional response to acute cocaine is inverted in male mice with a history of cocaine self-administration and withdrawal throughout the mesocorticolimbic system","authors":"Soren D. Emerson ,&nbsp;Maxime Chevée ,&nbsp;Philipp Mews ,&nbsp;Erin S. Calipari","doi":"10.1016/j.mcn.2023.103823","DOIUrl":"10.1016/j.mcn.2023.103823","url":null,"abstract":"<div><p>A large body of work has demonstrated that cocaine-induced changes in transcriptional regulation play a central role in the onset and maintenance of cocaine use disorder. An underappreciated aspect of this area of research, however, is that the pharmacodynamic<span> properties of cocaine can change depending on an organism's previous drug-exposure history. In this study, we utilized RNA sequencing<span> to characterize how the transcriptome-wide effects of acute cocaine exposure were altered by a history of cocaine self-administration and long-term withdrawal (30 days) in the ventral tegmental area<span> (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC) in male mice. First, we found that the gene expression patterns induced by a single cocaine injection (10 mg/kg) were discordant between cocaine-naïve mice and mice in withdrawal from cocaine self-administration. Specifically, the same genes that were upregulated by acute cocaine in cocaine-naïve mice were downregulated by the same dose of cocaine in mice undergoing long-term withdrawal; the same pattern of opposite regulation was observed for the genes downregulated by initial acute cocaine exposure. When we analyzed this dataset further, we found that the gene expression patterns that were induced by long-term withdrawal from cocaine self-administration showed a high degree of overlap with the gene expression patterns of acute cocaine exposure - even though animals had not consumed cocaine in 30 days. Interestingly, cocaine re-exposure at this withdrawal time point reversed this expression pattern. Finally, we found that this pattern was similar across the VTA, PFC, NAc, and within each brain region the same genes were induced by acute cocaine, re-induced during long-term withdrawal, and reversed by cocaine re-exposure. Together, we identified a longitudinal pattern of gene regulation that is conserved across the VTA, PFC, and NAc, and characterized the genes constituting this pattern in each brain region.</span></span></span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103823"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}