Purinergic Signalling最新文献

{"title":"Proteasomal-dependent endothelial P2Y₆ receptor downregulation as an adaptive mechanism limiting monocyte adhesion during intestinal schistosomiasis.","authors":"Nathalia F Oliveira, Matheus M L V Monteiro, Leticia D Crepaldi, Robson Coutinho-Silva, Luiz Eduardo B Savio, Claudia L Martins Silva","doi":"10.1007/s11302-026-10141-x","DOIUrl":"10.1007/s11302-026-10141-x","url":null,"abstract":"<p><p>Schistosomiasis, a complex chronic intravascular parasitic disease caused by Schistosoma mansoni, triggers a multifaceted host immune response and drives endothelial cells toward a sustained proinflammatory phenotype. The dysfunctional endothelial cells are a hallmark event that contributes to intestinal and liver damage mainly due to an increased monocyte adhesion, but the elevated morbidity unveils the lack of knowledge about disease pathogenesis. Purinergic P2Y₆ receptor (P2Y₆R) expression is induced in some inflammatory models; therefore, we hypothesized that endothelial P2Y₆R contributes to monocyte adhesion and mesenteric inflammation in S. mansoni-infected mice. Our results show that, unlike control mice, P2Y₆R stimulation failed to enhance monocyte adhesion to endothelial cells from infected animals. Molecular analyses using RT-qPCR and immunocytochemistry revealed significant downregulation of P2Y₆R expression in endothelial cells from the infected group at both transcript and protein levels. Importantly, pretreatment with a proteasome inhibitor restored both P2Y₆R expression and function, implicating proteasomal degradation as a key mechanism underlying receptor loss during infection. Elevated lipid peroxidation in endothelial cells from the infected group further supported a role for reactive oxygen species (ROS)-dependent proteasome activation and receptor degradation. Collectively, these findings suggest that infection selectively modulates P2Y₆R signaling by promoting proteasome-dependent downregulation of P2Y₆R in endothelial cells, which could be an adaptive mechanism to reduce mesenteric inflammation and limit host tissue damage and morbidity during chronic infection.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host-directed therapeutic strategies against apicomplexan parasites: targeting purinergic P2 receptors.","authors":"Mariana M Chaves, Nayara Carvalho-Barbosa, Luiz Eduardo Baggio Savio, Robson Coutinho-Silva","doi":"10.1007/s11302-026-10145-7","DOIUrl":"10.1007/s11302-026-10145-7","url":null,"abstract":"<p><p>Apicomplexan parasites establish intracellular infections that profoundly alter host cell physiology and elicit complex immune responses. The long-standing coevolution between these parasites and vertebrate hosts has resulted in extensive overlap between parasite and host metabolic pathways, limiting the feasibility of conventional parasite-centered therapeutic approaches. Increasing evidence indicates that host-derived signals generated during infection play a decisive role in shaping parasite survival and dissemination. Among these signals, extracellular nucleotides released in response to cellular stress and tissue damage have emerged as key modulators of innate immune responses. These molecules are sensed by purinergic P2 receptors, which integrate danger signals with inflammatory and microbicidal pathways. This review examines how purinergic signaling contributes to host-parasite interactions during apicomplexan infections, with particular emphasis on Toxoplasma gondii and Plasmodium spp. We discuss the dual role of P2 receptors in coordinating immune responses and directly affecting parasite viability, highlighting their potential as targets for host-directed therapeutic strategies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latest advances on the role of P2X Receptors in colorectal inflammation and cancer.","authors":"Luigia Ruo, Federica Fortuna, Marianna Grignolo, Anna Pegoraro, Elena Adinolfi","doi":"10.1007/s11302-026-10146-6","DOIUrl":"10.1007/s11302-026-10146-6","url":null,"abstract":"<p><p>Extracellular adenosine triphosphate (eATP) is a hallmark of inflammatory and tumor-associated microenvironments, where it functions as a key extracellular signalling molecule through activation of purinergic receptors. In the gastrointestinal tract, and particularly in the colon, eATP-mediated signalling regulates epithelial barrier function, neuroimmune interactions, and immune responses. P2X receptors, a family of eATP-gated ion channels, are differentially expressed across epithelial, neuronal, and immune cell populations and are increasingly recognized as contributors to colonic pathophysiology. This review summarizes current evidence on the roles of P2X receptors in inflammatory bowel disease and colon carcinoma, highlighting their involvement in intestinal inflammation, visceral hypersensitivity, immune cell activation, and tumor-associated processes. We discuss how dysregulated P2X receptor signalling contributes to chronic inflammation and supports a tumor-promoting microenvironment, while also emphasizing the context- and cell-type-specific nature of these responses. Finally, we outline emerging therapeutic strategies targeting P2X receptors and underscore the importance of personalized approaches based on receptor expression patterns within the colonic tissue.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mixed circuit training as a non-pharmacological strategy to improve platelet function and oxidative balance in type 2 diabetes: role of purinergic signaling.","authors":"Lucas Macedo Chaves, Samantha Nuncio Prestes, André Campos De Lima, Aline Mânica, Daniela Zanini, Sedinei Lopes Copatti, Clodoaldo Antônio De Sá, Andréia Machado Cardoso","doi":"10.1007/s11302-026-10136-8","DOIUrl":"10.1007/s11302-026-10136-8","url":null,"abstract":"<p><p>This study investigates the impact of a 16-week mixed circuit training (MCT) program on purinergic signaling and oxidative stress markers in women with type 2 diabetes mellitus (T2DM), focusing on its potential to modulate platelet-related purinergic signaling and oxidative stress markers that are mechanistically linked to platelet activation. A total of 21 women with T2DM and 23 non-diabetic controls, all sedentary and middle-aged, underwent MCT twice weekly. Biochemical, hemodynamic, and oxidative stress parameters, along with platelet ectonucleotidase activity and extracellular ATP levels, were assessed pre- and post-intervention. MCT significantly decreased ectonucleotidase diphosphohydrolase (E-NTPDase) activity for ADP hydrolysis in platelets, along with a reduction in extracellular ATP levels, indicating a modulation of purinergic signaling. Additionally, exercise enhanced antioxidant defenses, increasing glutathione-S-transferase (GST) activity and vitamin C levels, while reducing myeloperoxidase (MPO) activity, a key pro-oxidant enzyme. These changes suggest a shift toward a biochemical profile that may be relevant to thromboinflammatory pathways; however, no direct measures of platelet aggregation were performed. Mixed circuit training emerges as a valuable non-pharmacological strategy for improving oxidative balance and modulating purinergic markers in women with T2DM, warranting future studies including functional platelet assays and clinical outcomes.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenolic compounds and chemotherapeutic agents differentially regulate P2X receptor subtypes in malignant melanoma.","authors":"Serkan Sen, Sefa Celik","doi":"10.1007/s11302-026-10142-w","DOIUrl":"10.1007/s11302-026-10142-w","url":null,"abstract":"<p><p>Melanoma is an aggressive malignancy characterized by high metastatic potential and resistance to conventional therapies. Emerging evidence suggests that purinergic P2X receptors, particularly P2X7, play critical roles in regulating tumor cell proliferation, apoptosis, and invasion. However, the transcriptional regulation of P2X receptor subtypes in response to therapeutic compounds remains incompletely characterized. This study aimed to investigate the transcriptional modulation of all seven P2X receptor subtypes (P2XR1-7) in G361 melanoma cells following exposure to selected phenolic compounds and chemotherapeutic agents. Cell viability was evaluated by MTT assay, and half-maximal inhibitory concentrations (IC₅₀) were determined using non-linear regression analysis in GraphPad Prism software. Chemotherapeutic agents, including paclitaxel and sunitinib, exhibited strong cytotoxic effects under the experimental conditions employed, whereas phenolic compounds (quercetin, retinoic acid, and resveratrol) demonstrated moderate anti-proliferative activity. Quantitative real-time PCR analyses revealed compound-specific transcriptional response patterns. Quercetin induced upregulation across multiple P2X receptor subtypes, retinoic acid exhibited a partially suppressive profile, and resveratrol showed selective downregulation. In contrast, chemotherapeutic agents generally induced mRNA upregulation, particularly in P2XR4, P2XR5, and P2XR7 subtypes. These findings demonstrate that P2X receptor genes are differentially modulated at the transcriptional level by natural and synthetic compounds. The present work provides a transcriptional framework identifying subtype-specific response patterns and nominates candidate P2X receptors for future protein-level and functional validation studies in melanoma.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The P2X7 receptor/NLRP3 inflammasome signaling axis in sepsis: molecular mechanisms, organ-specific pathophysiology, and emerging therapeutic strategies.","authors":"Hilal Üstündağ","doi":"10.1007/s11302-026-10140-y","DOIUrl":"10.1007/s11302-026-10140-y","url":null,"abstract":"<p><p>Sepsis remains a leading cause of mortality in intensive care units worldwide, representing life-threatening organ dysfunction arising from dysregulated host responses to infection. The purinergic P2X7 receptor (P2X7R) and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome have emerged as critical regulators of inflammatory responses during sepsis pathogenesis. Extracellular adenosine triphosphate (ATP), released as a danger-associated molecular pattern from damaged and dying cells, activates the P2X7R, triggering potassium efflux that serves as the cardinal signal for NLRP3 inflammasome assembly. The activated inflammasome complex mediates caspase-1-dependent proteolytic maturation of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18, while simultaneously inducing gasdermin D (GSDMD)-mediated pyroptotic cell death-an inflammatory form of programmed cell death characterized by membrane pore formation, cellular swelling, and release of intracellular contents. Paradoxically, emerging evidence indicates that excessive P2X7R activation during sepsis progression induces profound mitochondrial dysfunction in circulating monocytes, leading to impaired NLRP3 inflammasome function and a state of immunoparalysis that coincides with an increased mortality. This comprehensive review examines the molecular mechanisms governing P2X7/NLRP3 signaling in sepsis; critically evaluates its dual and seemingly contradictory roles in hyperinflammation versus immunosuppression; delineates organ-specific manifestations across the lung, kidney, heart, brain, liver, and intestine; and systematically evaluates emerging therapeutic strategies including direct NLRP3 inhibitors such as MCC950, selective P2X7R antagonists, IL-1 receptor blockade, GSDMD inhibitors, and natural compounds with inflammasome-modulating properties. Understanding the temporal dynamics of this signaling axis is crucial for developing precision-targeted interventions that appropriately balance pathogen clearance with prevention of excessive inflammatory tissue damage.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The biphasic regulatory effect of adenosine A2B receptor in ischemic brain injury and its therapeutic potential.","authors":"Xu Rui, Wang Xi, Li Mengzhu, Su Peiwei, Liu Mudong, Zhu Chao, Luo Wanyu, Zhao Haijun","doi":"10.1007/s11302-026-10137-7","DOIUrl":"10.1007/s11302-026-10137-7","url":null,"abstract":"<p><p>Ischemic brain injury is the leading cause of neurological disability and death worldwide. Adenosine A2B receptor (A2BR) is a member of the G protein-coupled receptor family, playing a crucial role in regulating excitotoxicity, inflammation, cell apoptosis, and vascular homeostasis. New evidence suggests that adenosine A2BR has a biphasic, time-dependent effect on ischemic brain injury. Its antagonists exhibit neuroprotective effects in the acute phase, while agonists have anti-inflammatory and vascular protective effects in the later stage, providing a new therapeutic direction for improving the long-term prognosis of patients with ischemic brain injury. This article reviews the research progress of A2BR in ischemic brain injury, including its molecular structure, expression kinetics, cell distribution, mechanism of action, pharmacological intervention, and systemic significance. We also discussed the therapeutic prospects of targeting A2BR and provided future prospects for personalized treatment strategies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of adenosinergic pathway and methylxanthines in Parkinson's disease: Blowing in the wind or not.","authors":"Alaa Ismail, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Luay M Alkazmi, Abdullah Faisal Albukhari, Mustafa M Shokr, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha","doi":"10.1007/s11302-025-10114-6","DOIUrl":"10.1007/s11302-025-10114-6","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a systemic neurodegenerative disease, and is mainly related to the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Despite extensive research regarding PD neuropathology, there are no active drugs to avert this disease. It has been described that the adenosine pathway, which is expressed centrally and peripherally, is involved in the pathogenesis of PD and other neurodegenerative diseases. Adenosine acts on adenosine receptors (ARs), including A1R, A2AR, A2BR, and A3R. Both A1R and A3R are neuroprotective, while A2AR and A2BR are neurotoxic for the brain. A2AR, in the SNpc, mediates the neurotoxicity of adenosine in PD. In addition, data from epidemiological studies highlighted controversial findings in PD and other neurodegenerative diseases. Therefore, the present review aims to revise from published articles the potential role of the adenosine pathway in PD neuropathology, and how methylxanthines affect the dopaminergic neurotransmission in the SNpc. This review highlighted that selective A2AR antagonists could be more effective than non-selective AR antagonists in the management of motor and non-motor symptoms of PD.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular ATP induces the proinflammatory phenotype transition of MH7A cells by activating P2X7 receptor.","authors":"Chengxiang Wang, Jiayao Hao, Yan Liu, Haili Shen","doi":"10.1007/s11302-026-10138-6","DOIUrl":"10.1007/s11302-026-10138-6","url":null,"abstract":"<p><p>The transition of fibroblast-like synoviocytes (FLS) toward a proinflammatory phenotype is a hallmark of rheumatoid arthritis (RA), with proinflammatory RA-FLS exacerbating joint destruction via hyperproliferation, enhanced migration/invasion, and excessive inflammatory cytokine secretion. Extracellular ATP (eATP), a key damage-associated molecular pattern, is elevated in RA's inflammatory microenvironment and exerts proinflammatory effects on immune cells via P2X7 receptors (P2X7R), but its role in regulating RA-FLS' proinflammatory phenotype via P2X7R remains unclear. Using MH7A cells (a RA-FLS line), this study investigated eATP's effect on RA-FLS' proinflammatory transition and P2X7R's mediatory role to support FLS-targeted RA therapies. Methods included CCK-8 assays for optimal eATP/antagonist concentrations and metabolic activity, TranswellPlease check if the affiliations are captured correctly. assays for migration/invasion, q-PCR/Western blotting for P2X7R expression, ELISA for IL-1β/IL-6/TNF-α secretion, and Western blotting for NLRP3 (NOD-like receptor protein 3) inflammasome (NLRP3, pro-caspase-1, cleaved-caspase-1) activation. Results showed eATP enhanced MH7A migration/invasion, upregulated P2X7R, increased NLRP3 inflammasome activation, and elevated cytokine secretion, while P2X7R antagonist pretreatment abrogated these changes. Thus, eATP induces MH7A's proinflammatory transition by activating P2X7R, with targeting the eATP-P2X7R pathway representing a promising RA therapeutic target.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of immune responses by opioids through toll-like and P2X receptor signaling in COVID-19.","authors":"Mohammad Abbas Sheikholeslami, Siavash Parvardeh, Shiva Ghafghazi, Malek Zarei","doi":"10.1007/s11302-025-10122-6","DOIUrl":"10.1007/s11302-025-10122-6","url":null,"abstract":"<p><p>The pathogenesis of COVID-19 involves complex interactions between viral replication and host immune dysregulation, mediated by toll-like receptors (TLRs) and P2X receptors (P2XRs). These receptors detect pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), triggering inflammatory cascades. Opioids, beyond their analgesic role, modulate innate and adaptive immune responses via opioid receptors and indirectly through TLR and P2X signaling. This narrative review integrates experimental, clinical, and bioinformatic evidence to explore the mechanistic crosstalk between opioid signaling, TLRs (notably TLR2, TLR4, TLR9), and P2XRs (notably P2X4 and P2X7) in COVID-19 immunopathology. Chronic opioid exposure may either enhance or suppress inflammation depending on dose, duration, and immune context. In COVID-19, the hyperactivation of TLR4, TLR7, and TLR9 drives cytokine storms, while the release of ATP from damaged cells activates P2X7, thereby amplifying the inflammatory response. ATP breakdown into adenosine further modulates immunity via A2A and A2B receptors. Targeting TLR4 and P2X7 offers a promising therapeutic strategy to mitigate hyperinflammation and improve outcomes in COVID-19 and related inflammatory diseases. In addition, we outline how the Contact System, the Kallikrein-Kinin System (KKS), the Renin-Angiotensin System (RAS), and the NLRP3 inflammasome provide the innate inflammatory backdrop through which opioids and P2 receptor signaling may shape immune dysregulation in COVID-19. Notably, direct clinical evidence for opioid-P2 receptor interactions in COVID-19 remains limited, highlighting the need for targeted translational studies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 2","pages":"22"},"PeriodicalIF":2.5,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}