Bei Li, Yiyue Shi, Wenyu Hou, Haoyuan Guan, Jun Li, Tuo Yi, Wei Li, Donglin Cai, Petra Schwarz, Adriano Aguzzi, Caihong Zhu
{"title":"Ablation of progranulin augments microglial activation and accelerates prion progression.","authors":"Bei Li, Yiyue Shi, Wenyu Hou, Haoyuan Guan, Jun Li, Tuo Yi, Wei Li, Donglin Cai, Petra Schwarz, Adriano Aguzzi, Caihong Zhu","doi":"10.1186/s40478-025-02128-3","DOIUrl":"https://doi.org/10.1186/s40478-025-02128-3","url":null,"abstract":"<p><p>Mutations or polymorphisms in GRN, encoding the CNS glycoprotein progranulin (PGRN), have been linked to several neurodegenerative diseases. In this study, we explored the role of PGRN in prion diseases. We observed that prion infection upregulated microglial PGRN expression. Following intracerebral inoculation with RML6 prions, Grn<sup>-/-</sup> mice exhibited accelerated disease progression compared to Grn<sup>+/-</sup> and Grn<sup>+/+</sup> littermates. Histological analysis revealed augmented microglial activation in Grn<sup>-/-</sup> mice. Temporal analysis revealed enhanced early microglial activation and prion clearance at 120 dpi, followed by excessive complement activation but inadequate clearance by 150 dpi. Additionally, Grn<sup>-/-</sup> brains exhibited exacerbated astrogliosis and vacuolation. RNA-seq analysis indicated that complete PGRN deficiency in prion-infected mice shifted microglia from homeostatic to pro-inflammatory states. Notably, microglia-specific depletion of PGRN did not affect prion pathogenesis, suggesting that PGRN deficiency affects microglial activation and prion progression in a non-cell autonomous manner. These findings suggest that microglia respond to prion infection in a stepwise manner, and PGRN plays a critical role in modulating prion-induced microglial activation. Our results highlight the neuroprotective role of PGRN in prion disease and suggest that supplementation or boosting expression of PGRN could represent a promising therapeutic strategy.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"214"},"PeriodicalIF":5.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristina Benito-Casado, Esther Durán-Mateos, Águeda Ferrer-Donato, Gemma Barroso García, Raúl Domínguez-Rubio, Mónica Povedano, Carmen M Fernandez-Martos
{"title":"White adipose tissue undergoes pathological dysfunction in the TDP-43<sup>A315T</sup> mouse model of amyotrophic lateral sclerosis (ALS).","authors":"Cristina Benito-Casado, Esther Durán-Mateos, Águeda Ferrer-Donato, Gemma Barroso García, Raúl Domínguez-Rubio, Mónica Povedano, Carmen M Fernandez-Martos","doi":"10.1186/s40478-025-02130-9","DOIUrl":"10.1186/s40478-025-02130-9","url":null,"abstract":"<p><p>White adipose tissue (WAT) has a crucial role in maintaining systemic energy homeostasis. Numerous biological pathway studies have highlighted the importance of adipokines in regulating metabolic pathways and contributing to metabolic dysfunction in animal models and patients with ALS. Despite these associations, the specific molecular mechanisms remain poorly understood. Moreover, the direct contribution of WAT to the energy metabolism abnormalities observed in ALS has yet to be clearly defined. The current study sought to identify perturbances in WAT, main source of leptin, during the clinical course of the disease in TDP-43<sup>A315T</sup> mice using histological, proteomic, and molecular biological techniques. We present the first evidence of a significant histological alteration in WAT prior to the symptomatic stage of the disease in TDP-43<sup>A315T</sup> mice, providing novel insights into pathological features earlier in the onset of symptoms, and showing WAT as a target organ for ALS. In human ALS cases, we found that circulating leptin levels at the time of diagnosis were lower in the plasma of men with ALS who were overweight or obese and had rapidly progressive ALS, emphasizing the importance of considering sex-specific approaches when analysing adipokines essential for body weight control.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"213"},"PeriodicalIF":5.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pratyush Suryavanshi, Satya Murthy Tadinada, Samuel Baule, Naisha Jhaveri-Cruz, Ted Abel, Joseph Glykys
{"title":"Dendritic beading during early brain development impairs signal transmission and synaptic plasticity.","authors":"Pratyush Suryavanshi, Satya Murthy Tadinada, Samuel Baule, Naisha Jhaveri-Cruz, Ted Abel, Joseph Glykys","doi":"10.1186/s40478-025-02123-8","DOIUrl":"10.1186/s40478-025-02123-8","url":null,"abstract":"<p><p>Excessive glutamate receptor activation during brain pathologies causes varicose dendritic swelling, also known as \"dendritic beading\", yet its impact on developing brain circuits is poorly understood. Using field electrophysiology and two-photon imaging in awake, behaving mice and acute brain slices (P11-19), we found that severe and recurrent seizure-like activity (induced by NMDA and 4-aminopyridine) resulted in widespread, long-lasting dendritic beading and spine loss in cortical and hippocampal neurons, with localization patterns distinct from those described in adults. Beads showed persistently high calcium levels and stopped the spread of dendritic calcium signals. Dendritic beads suppressed hippocampal evoked field potentials, followed by only partial recovery, and reduced hippocampal long-term potentiation. Clinically used hyperosmotic treatments (mannitol or hypertonic saline) reduced seizure-induced beading and restored dendritic signal propagation. These findings suggest that seizure-induced dendritic beading disrupts circuit function and synaptic plasticity and may contribute to cognitive deficits after early-life seizures.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"212"},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mara Zielinski, Fernanda S Peralta Reyes, Lothar Gremer, Simon Sommerhage, María Pagnon de la Vega, Christine Röder, Thomas V Heidler, Stina Syvänen, Dieter Willbold, Dag Sehlin, Martin Ingelsson, Gunnar F Schröder
{"title":"Cryo-EM studies of amyloid-β fibrils from human and murine brains carrying the Uppsala APP mutation (Δ690-695).","authors":"Mara Zielinski, Fernanda S Peralta Reyes, Lothar Gremer, Simon Sommerhage, María Pagnon de la Vega, Christine Röder, Thomas V Heidler, Stina Syvänen, Dieter Willbold, Dag Sehlin, Martin Ingelsson, Gunnar F Schröder","doi":"10.1186/s40478-025-02120-x","DOIUrl":"10.1186/s40478-025-02120-x","url":null,"abstract":"<p><p>Today, 13 intra-amyloid-β (Aβ) amyloid precursor protein (APP) gene mutations are known to cause familial Alzheimer's disease (AD). Most of them are point mutations causing an increased production or a change in the conformation of Aβ. The Uppsala APP mutation (Δ690-695 in APP, Δ19-24 in Aβ) is the first known multi-codon deletion causing autosomal dominant AD. Here, we applied cryo-electron microscopy (cryo-EM) to investigate the structure of Aβ fibrils with the Uppsala APP mutation from tg-UppSwe mouse brain tissue. Murine AβUpp(1-42)<sub>Δ19-24</sub> are made of two identical S-shaped protofilaments with an ordered fibril core of S8-A42. The murine Aβ fold is almost identical to previously described human type II filaments, although the amino acid sequences differ considerably. In addition, we report the cryo-EM structure of Aβ fibrils from the temporal cortex of a patient with the Uppsala APP mutation. The observed structure of the human Aβ fold closely resembles previously described type I fibrils. Structural modeling suggests that these fibrils are composed of wild-type Aβ, which implies that AβUpp may be less soluble and thus not readily accessible for cryo-EM image processing and structure determination. Additionally, from the human sample we determined the structures of tau paired helical filaments and tau straight filaments, which are identical to those found in sporadic AD cases. Finally, we present the 3D cryo-EM structures of four dominant AβUpp(1-42)<sub>Δ19-24</sub> fibril polymorphs, formed in vitro. All four polymorphs differ from the observed folds of Uppsala Aβ in murine and human brain tissue, respectively.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"209"},"PeriodicalIF":5.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lorenz Dörner, Elisa-Maria Suhm, Vanessa Ries, Vitor Moura Goncalves, Marco Skardelly, Marcos Tatagiba, Jens Schittenhelm, Felix Behling
{"title":"Clinical and inflammatory factors associated with the extent of resection in primary, sporadic vestibular schwannomas: A retrospective study.","authors":"Lorenz Dörner, Elisa-Maria Suhm, Vanessa Ries, Vitor Moura Goncalves, Marco Skardelly, Marcos Tatagiba, Jens Schittenhelm, Felix Behling","doi":"10.1186/s40478-025-02127-4","DOIUrl":"10.1186/s40478-025-02127-4","url":null,"abstract":"<p><strong>Background: </strong>The extent of resection (EOR) is known to impact recurrence free survival in vestibular schwannomas (VS). Identifying predictive factors for complete resection may direct treatment decisions in the future. In recent years there is increasing evidence for the involvement of inflammatory processes in the development and growth of VS. It is currently unclear whether inflammatory changes may also play a role in the extent of resection in VS.</p><p><strong>Methods: </strong>In this retrospective study, we analyzed clinical data, tumor extension, cystic characteristics and immunohistochemical markers for inflammation (CD68, CD163, CD3, CD8) and proliferation (MIB-1) as potential factors influencing the EOR in 1007 surgically treated primary sporadic VS. With CART-determined specific cut-offs for each inflammation marker, a common inflammatory score from 0 to 2 was determined. Univariate and multivariate analyses were performed for the EOR.</p><p><strong>Results: </strong>Total resection was achieved in 86.5% of cases. Incomplete resection was associated with advanced age (p = 0.0002), larger tumor size (p < 0.0001) and cystic characteristics on preoperative imaging (p < 0.0001). Increased expression of CD163, CD68 and CD3 (p < 0.0001, p = 0.0015 and p = 0.0024 respectively) was associated with partial tumor resection (PR). CD8 was significant when its CART-determined cut-off was considered (p = 0.0032). A higher inflammatory score was significantly connected to partial resection (p < 0.0001). In the multivariate analysis, larger size (p < 0.0001), older age (p = 0.0051), cystic characteristics (p = 0.0005) and higher CD68 expression (p = 0.0341) were independently significant factors for partial resection.</p><p><strong>Conclusions: </strong>Advanced age, greater tumor extension, cystic growth and higher infiltration with macrophages are independent factors for a less radical extent of resection.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"211"},"PeriodicalIF":5.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yangyang Huang, Celine Geywitz, Anjalika Bandaru, Ian A Glass, Lucas Schirmer, Hiroko Nobuta, Cheryl F Dreyfus
{"title":"The mGluR5 agonist CHPG enhances human oligodendrocyte differentiation.","authors":"Yangyang Huang, Celine Geywitz, Anjalika Bandaru, Ian A Glass, Lucas Schirmer, Hiroko Nobuta, Cheryl F Dreyfus","doi":"10.1186/s40478-025-02124-7","DOIUrl":"10.1186/s40478-025-02124-7","url":null,"abstract":"<p><p>Previous studies in adult mice indicate that the mGluR5 agonist 2-chloro-5-hydroxyphenyl glycine (CHPG), reduces cuprizone-elicited losses in myelin. This effect is partly mediated by CHPG binding to mGluR5 receptors on reactive astrocytes, triggering the release of brain derived neurotrophic factor (BDNF), which results in an increase in myelin. However, it remains unclear whether CHPG has similar beneficial effects on human oligodendrocytes. To address this issue, we examined effects of CHPG using both cultured human induced pluripotent stem cell (hiPSC)-derived oligodendrocytes and primary human fetal oligodendrocytes. We show that CHPG increases the proportion of MBP<sup>+</sup> mature oligodendrocytes without affecting survival. This effect is mediated by increasing the proliferation of oligodendrocyte precursor cells (OPCs) and enhancing differentiation in young oligodendrocytes. In contrast to observations in mice, mGluR5 expression in humans is localized on PDGFRα<sup>+</sup> OPCs and O4<sup>+</sup> immature oligodendrocytes, but not astrocytes. Using purified human OPC cultures, we show a direct effect of CHPG in increasing the proportion of MBP<sup>+</sup> mature oligodendrocytes. To identify potential cellular targets of CHPG in demyelinating disease, we analyzed postmortem tissue from individuals with chronic active multiple sclerosis (MS) and healthy controls. In contrast to the hiPSCs or primary oligodendrocytes, demyelinated white matter from MS patients shows elevated mGluR5 mRNA expression in astrocytes. Taken together, our findings suggest that CHPG enhances the differentiation of human OPCs through a mechanism distinct from that observed in cuprizone-treated mice. Moreover, astrocytes in MS pathology upregulate mGluR5, suggesting mGluR5 expression changes dynamically under disease conditions.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"210"},"PeriodicalIF":5.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chao Sun, Di Ma, Jacob Hansen, Jeffrey R Tonniges, Hongzhen Hu, Liwen Zhang, Chen Gu
{"title":"Blocking axon-glial mechanotransduction to prevent concussive brain injury.","authors":"Chao Sun, Di Ma, Jacob Hansen, Jeffrey R Tonniges, Hongzhen Hu, Liwen Zhang, Chen Gu","doi":"10.1186/s40478-025-02117-6","DOIUrl":"10.1186/s40478-025-02117-6","url":null,"abstract":"<p><p>All cells in the central nervous system (CNS) are considered mechanosensitive, but how they collectively respond to a concussive head impact and contribute to the transition from the primary to secondary injury remains unknown. Using a mouse model for mild traumatic brain injury (mTBI) or concussion, we report that blocking the activity of TRPV4 transient receptor potential channels inhibits mTBI-induced sequential changes of neurons and glial cells, as well as behavioral disturbances. A concussive head impact immediately induces axonal varicosities, preceding NMDA-receptor-mediated microglial activation and cortical demyelination. Afterward, these changes differentially and partially recover. Blocking TRPV4 channels before or after head impact markedly suppresses axon-glial and behavioral changes or enhances their recovery, respectively. Using knockout mice and AAV-Cre-mediated acute and cell-type-specific deletion, we further show that neuronal TRPV4 channels, as an mTBI target, regulate the homeostasis of axon mechanosensation and their hyperactivation causes axonal varicosity formation followed by axon-to-glia mechanotransduction.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"205"},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Fouka, Iraklis Tsakogias, Elena-Georgia Gialinaki, Athanasios Stavropoulos, Christiane Volbracht, Louis De Muynck, Diederik Moechars, Ronald Melki, George K Tofaris, Leonidas Stefanis, Maria Xilouri
{"title":"In vivo validation of novel non-invasive PHP.eB AAVs as a potential therapeutic approach for alpha-synucleinopathies.","authors":"Maria Fouka, Iraklis Tsakogias, Elena-Georgia Gialinaki, Athanasios Stavropoulos, Christiane Volbracht, Louis De Muynck, Diederik Moechars, Ronald Melki, George K Tofaris, Leonidas Stefanis, Maria Xilouri","doi":"10.1186/s40478-025-02121-w","DOIUrl":"10.1186/s40478-025-02121-w","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by the accumulation of alpha-synuclein (aSyn) aggregates in specific brain regions, which are likely to be the disease-causing entities. Herein, we employed novel, systemically administered, brain-penetrating viral vectors (PHP.eB AAVs) in order to evaluate the potential therapeutic utility of lowering the endogenous aSyn protein burden in the aSyn pre-formed fibril (PFF)-mouse model. Such vectors expressing short hairpin RNAs or micro RNAs targeting the mouse Snca transcript (or respective scrambled control sequences) were intravenously administered in adult wild-type mice and two weeks later human aSyn PFFs were injected into the dorsal striatum. Following the administration of the Snca-targeting PHP.eB AAVs, a successful widespread viral transduction was achieved throughout the brain, accompanied by an efficient reduction of endogenous aSyn protein levels within transduced dopaminergic neurons. Intrastriatal injection of human aSyn PFFs led to the formation of pSer129-aSyn-rich cytoplasmic inclusions in brain regions connected to the PFF-injection site, nigrostriatal degeneration and relevant behavioral motor deficits, at 2.5 months post PFF-injection. Importantly, PHP.eB AAV-mediated down-regulation of endogenous aSyn reduced the accumulation of pSer129-aSyn<sup>+</sup> inclusions, mitigated nigrostriatal degeneration and alleviated motor impairments. Spread of pathology to other brain regions was also attenuated. Overall, such data highlight further the contribution of the intracellular aSyn protein load to the spread of pathology and suggest that this non-invasive delivery strategy holds promise in the research avenues for treating neurodegenerative diseases with widespread pathology, such as Synucleinopathies.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"207"},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Azzurra Cottarelli, Danny Jamoul, Mary Claire Tuohy, Sanjid Shahriar, Michael Glendinning, Grace Prochilo, Aimee L Edinger, Ahmet Arac, Dritan Agalliu
{"title":"Rab7a is required to degrade select blood-brain barrier junctional proteins after ischemic stroke.","authors":"Azzurra Cottarelli, Danny Jamoul, Mary Claire Tuohy, Sanjid Shahriar, Michael Glendinning, Grace Prochilo, Aimee L Edinger, Ahmet Arac, Dritan Agalliu","doi":"10.1186/s40478-025-02125-6","DOIUrl":"10.1186/s40478-025-02125-6","url":null,"abstract":"<p><p>The integrity of adherens and tight junctions is critical for blood-brain barrier (BBB) function in the healthy brain. Disassembly of cell junctions due to degradation of adherens and tight junction-associated proteins leads to acute BBB dysfunction after ischemic stroke, but the mechanisms of this process are not fully understood. Using genetic studies in mice coupled with histopathological analysis of the brains after ischemic stroke, we demonstrate that endothelial cell deletion of Rab7a, a small GTPase crucial for protein degradation through the endolysosomal system, reduces acute BBB leakage and improves neuronal health in mice after ischemic stroke by reducing the degradation of select adherens and tight junction proteins, and preserving the structural morphology of tight junctions at both confocal and electron microscopy level. Two pro-inflammatory cytokines, TNFα and IL1β, that are known to trigger disruption of paracellular barrier properties in primary brain endothelial cells in vitro and are upregulated after ischemic stroke, contribute to Rab7a activation in primary mouse brain endothelial cells (BECs). In contrast, oxygen-glucose deprivation does not activate Rab7a in mouse BECs. Rab7a is, therefore, critical for degradation of select BEC junctional proteins during the acute increase in BBB permeability after ischemic stroke.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"203"},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}