Toxicon最新文献

{"title":"Integrating postsynaptic morphology and dynamics to evaluate neuromuscular synapse status: Insights from α-bungarotoxin","authors":"Juan Pablo Henríquez ,&nbsp;Francisca Bermedo-García ,&nbsp;Diego Zelada ,&nbsp;Jessica Mella","doi":"10.1016/j.toxicon.2025.108404","DOIUrl":"10.1016/j.toxicon.2025.108404","url":null,"abstract":"<div><div>The neuromuscular junction (NMJ) is a crucial peripheral synapse that controls muscle contraction. It consists of a presynaptic motor terminal, a postsynaptic muscle domain, and associated cells, such as terminal Schwann cells and kranocytes. Its larger size compared to central synapses has allowed detailed analyses of NMJ morphology that have been widely used as a reliable parameter of synaptic formation, maturation, function, and decline. Due to its high affinity for postsynaptic acetylcholine receptors (AChRs), the snake venom-derived α-bungarotoxin (BTX) has been pivotal in advancing our understanding of NMJ organization, enabling a detailed mapping of postsynaptic morphologies associated to distinct functional outcomes. Although certain morphological features are often associated with NMJ worsening, some of these cellular changes also occur in biological contexts where synaptic function remains intact. In this review, we draw on previous studies and our recent findings using BTX-based pulse-chase assays to suggest that combining morphological analyses with assessments of postsynaptic stability offers a more comprehensive understanding of NMJ function and regenerative potential. We propose that integrating diverse BTX-based tools into studies of NMJ morphology and stability will provide particularly valuable insights in contexts such as aging, injury, and neuromuscular diseases, where these combined parameters may serve as robust predictors of functional outcomes.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108404"},"PeriodicalIF":2.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of natural diphtheria toxin as a potential anticancer agent in colorectal cancer: An in vitro analysis on HT-29 cells","authors":"Tugba Yalcinkaya ,&nbsp;Ahmet Carhan","doi":"10.1016/j.toxicon.2025.108386","DOIUrl":"10.1016/j.toxicon.2025.108386","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the fourth most common cancer worldwide and the second leading cause of cancer-related deaths. The limited efficacy of conventional treatments underscores the need for alternative strategies. Among emerging candidates, diphtheria toxin (DT) has gained attention for its selective cytotoxicity, apoptosis induction, and inhibition of cancer cell proliferation with minimal harm to healthy cells. However, studies on DT's anticancer effects in CRC remain scarce. This study evaluated the cytotoxic and apoptotic effects of DT on HT-29 colorectal cancer cells. MTT assays confirmed DT's selective cytotoxicity, showing stronger effects on HT-29 cells than on normal Vero cells. Flow cytometry revealed DT-induced G1-phase cell cycle arrest. DNA fragmentation and qRT-PCR analyses demonstrated apoptosis activation, with upregulation of pro-apoptotic genes (Bax, FasL) and downregulation of Bcl-2. Additionally, qRT-PCR assessed key molecules in apoptosis, cell cycle regulation, and DNA damage response, including GADD45α, PARP1, p38α, p53, FoxO3a, and RbL2. Our findings suggest that DT inhibits HT-29 cell proliferation, induces apoptosis, and impacts DNA damage response, highlighting its potential as a therapeutic agent requiring further investigations.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108386"},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting oxidative folding of conotoxins using 3D structures of cysteine mutants predicted by AlphaFold 3: A case study of α-conotoxin RgIA, χ-conotoxin CMrVIA and ω-conotoxin MVIIA-Gly","authors":"K. Radhakrishna ,&nbsp;Patil Kanchan Rajshekhar ,&nbsp;R. Arshitha ,&nbsp;Kashibai Patil,&nbsp;Shweta Dhannura,&nbsp;Konkallu Hanumae Gowd","doi":"10.1016/j.toxicon.2025.108402","DOIUrl":"10.1016/j.toxicon.2025.108402","url":null,"abstract":"<div><div>The ability of AlphaFold 3 to accurately predict the 3D structure of polypeptides has been explored to investigate the oxidative folding steps of conotoxins. The peptides α-conotoxin RgIA (α-RgIA) and χ-conotoxin CMrVIA (χ-CMrVIA) share a similar cysteine pattern but differ in their native disulfide connectivity. These short peptides, containing two intramolecular disulfides, may undergo sequential steps of disulfide formation during the oxidative folding process. The current report computed all six possible single disulfide alanine mutants of the peptides and predicted their 3D structures using the AlphaFold 3 server. The potential energy of the conformers derived from the five predicted model structures of the peptides was calculated using the OPLS4 force field in Schrödinger's MacroModel software. The relative potential energy of the single disulfide mutant peptides was computed using the Boltzmann-weighted average energy of the conformers of the corresponding peptides. [C2A,C8A]α-RgIA and [C2A,C11A]χ-CMrVIA are the most stable forms, corresponding to the native single disulfide intermediate analogues. Accordingly, the folding events for α-RgIA are C₃-C₁₂ followed by C₂-C₈, while for χ-CMrVIA, they are C₃-C₈ followed by C₂-C₁₁ connectivity. The current report also explored the native folding steps of an Inhibitory Cystine Knot (ICK) motif peptide ω-conotoxin-MVIIA-Gly using one/two cysteine disulfide alanine mutants. The computation of relative potential energy of the mutant peptides indicates the formation of C₁₅-C₂₅ followed by C₈-C₂₀ and C₁-C₁₆ disulfide bonds. The newly proposed technique that combines AlphaFold 3 with MacroModel conformational sampling tool is allowing to identify the oxidative folding steps of disulfide-rich peptides.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108402"},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venom composition of Tityus cerroazul (Scorpiones: Buthidae) reveals similarities with venoms of other scorpion species from northern South America","authors":"Cecilia Díaz ,&nbsp;Marcelo Mack-Prado ,&nbsp;Eleodoro Bonilla ,&nbsp;Arturo Chang-Castillo ,&nbsp;Fabián Bonilla ,&nbsp;Natalia Ortiz ,&nbsp;Diego Angulo ,&nbsp;Mahmood Sasa","doi":"10.1016/j.toxicon.2025.108385","DOIUrl":"10.1016/j.toxicon.2025.108385","url":null,"abstract":"<div><div>Several buthid scorpions from Costa Rica and Panama have been extensively characterized for their venom components. One exception is <em>Tityus cerroazul</em>, a peculiar species classified in the subgenus <em>Tityus</em>, separated from the rest of the members of the genus that inhabit this geographic region. Although it has been described as a species that prefers natural areas with low human impact, which could explain the few reported envenomation cases, pre-clinical studies indicate that its venom may be toxic to mammals.</div><div>This analysis describes the venom composition and enzymatic activities of <em>T. cerroazul</em> specimens from Panama. Among the identified venom components, we report the presence of NaTxs TdNa5 and bactridin-1 from <em>T. discrepans</em> from Venezuela, as well as partial sequences corresponding to other putative Na+ and K+ toxins, antimicrobial peptides, protease inhibitors, and secreted proteins, mostly found in the venoms of the <em>T.</em> (<em>Atreus</em>) species. We also confirmed the presence of the four peptides (Tce1-Tce4) identified by previous molecular analyses.</div><div>In conclusion, our study suggests that <em>T. cerroazul</em> does not align closely with the venom of species currently assigned to the subgenus <em>Tityus</em>. Instead, it shows a greater similarity to the venom of the <em>Atreus</em> subgenus, which includes most of the <em>Tityus</em> species that inhabit the region. This finding underscores the need to revise its taxonomic classification based on molecular phylogenetic characters.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108385"},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shining a light on the photochemical stability of peptidic bioinsecticides","authors":"Volker Herzig ,&nbsp;Andrew Ahabh ,&nbsp;Alun Jones ,&nbsp;Glenn F. King","doi":"10.1016/j.toxicon.2025.108381","DOIUrl":"10.1016/j.toxicon.2025.108381","url":null,"abstract":"<div><div>Peptide toxins from spider venoms are being increasingly hailed as environmentally friendly alternatives to market-dominating small-molecule chemical insecticides. While the stability of knotted spider-venom peptides towards enzymatic degradation, temperature changes and varying pH conditions has already been examined, their susceptibility to sunlight remains unclear. Field applications of insecticides demand that the insecticidal component is active for at least a few days to ensure sufficient eradication of the targeted insect pests. We therefore exposed four insecticidal spider-venom peptides (ω-Hv1a, ω/κ-Hv1a, Ta1a and Dc1a) to continuous artificial sunlight for up to 7 days. After certain incubation periods, we quantified the percentage of intact peptide and identified sites of peptide cleavage. We found that after 3 days of continuous exposure (=6 days of 12 h/d sunlight), the amount of remaining intact peptide was 16 % (Ta1a), 21 % (Dc1a), 55 % (ω-Hv1a), and 67 % (ω/κ-Hv1a), whereas bovine serum albumin was completely degraded. Even after 7 days (=14 days of 12 h/d sunlight) exposure, more than 50 % of ω/κ-Hv1a and ω-Hv1a remained intact. Peptides with lower molecular mass tended to be less susceptible to sunlight, while cleavage of peptide bonds involving proline or cysteine were most susceptible to photochemical degradation. The photochemical changes detected by mass spectrometry mainly comprised oxidations, deamidations, and cysteine-targeted modifications.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108381"},"PeriodicalIF":2.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory role of arecaidine on PPARγ signaling in oral mucosa: Mechanistic insights from transcriptome and experimental analysis","authors":"Fanzuo Zeng ,&nbsp;Zhenkui Liu ,&nbsp;Jian Yi ,&nbsp;Bowei Chen ,&nbsp;Yin Ouyang ,&nbsp;Wanling Ning ,&nbsp;Jiongwei Tang ,&nbsp;Baiyan Liu","doi":"10.1016/j.toxicon.2025.108403","DOIUrl":"10.1016/j.toxicon.2025.108403","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to elucidate the effects of arecaidine on oral mucosa through RNA sequencing (RNA-Seq) combined with in vivo and in vitro experimental validation.</div></div><div><h3>Methods</h3><div>Based on transcriptomic analysis, we preliminarily explored the molecular targets and mechanisms by which arecaidine influences oral mucosa. Subsequent validation was performed using arecaidine-treated human primary oral mucosal fibroblasts.</div></div><div><h3>Results</h3><div>In vivo experiments revealed that the arecaidine-treated group exhibited significantly restricted oral cavity opening compared to the control group, with markedly reduced mouth-opening values. Histopathological analysis via HE staining and Masson staining demonstrated fibrotic lesions in the arecaidine-treated group. RNA-Seq libraries constructed from oral mucosal tissues identified 100 significantly differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that arecaidine influenced multiple pathways, including autoimmune thyroid disease, allograft rejection, type I diabetes, graft-versus-host disease, and the PPAR-γ signaling pathway. Notably, arecaidine significantly downregulated PPAR-γ, PCK1, pdk4, plin5, Hmgcs2, UCP3, and Angptl4, while upregulating TGF-β1, FOS, and other genes associated with the PPAR pathway. In vitro experiments confirmed that arecaidine induced substantial damage to fibroblasts, suppressing proliferation and promoting the secretion of inflammatory cytokines (e.g., IL-6, TGF-β, TNF-α) after 48 h exposure to high concentrations. Furthermore, arecaidine significantly altered the expression of molecules linked to the PPAR-γ signaling pathway.</div></div><div><h3>Conclusion</h3><div>This study delineates the transcriptomic response of oral mucosa to arecaidine through integrated in vivo and in vitro experiments, confirming its role in inducing submucosal fibrosis. The underlying mechanism is associated with dysregulation of the PPAR-γ signaling pathway.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108403"},"PeriodicalIF":2.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The tongue muscles: Clinical applications in lingual dystonia","authors":"Raymond L. Rosales ,&nbsp;Nadine J. Endaya","doi":"10.1016/j.toxicon.2025.108382","DOIUrl":"10.1016/j.toxicon.2025.108382","url":null,"abstract":"<div><div>Lingual dystonia, a type of oromandibular focal dystonia, involves sustained tongue contractions, often causing protrusion during actions such as speaking or chewing. It is classified as either primary or secondary, depending on the underlying cause. Botulinum neurotoxin (BoNT) is a recognized treatment for focal dystonias, including lingual dystonia. However, precise administration of BoNT can be challenging, limiting its efficacy and potentially causing adverse effects. This review focuses on selecting target muscles and using ultrasound guidance for accurate BoNT administration.</div><div>Using ultrasound, with or without electromyography, a submental injection approach is employed to target the genioglossus and hyoglossus muscles, which are most affected in lingual dystonia. The suprahyoid muscles are critical anatomical considerations during submental injections to avoid aspiration. Additionally, as drooling is a common symptom of lingual dystonia, BoNT injections into the submandibular glands are also discussed. A case series with X-linked dystonia-parkinsonism was our way to clinically demonstrate BoNT injections in those with severe lingual dystonias.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108382"},"PeriodicalIF":2.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Botulinum neurotoxin therapy in dystonic head flexion: Anterior injection approaches to the longus colli and longus capitis muscles","authors":"Lucy Hicklin,&nbsp;Winnie Yeung","doi":"10.1016/j.toxicon.2025.108401","DOIUrl":"10.1016/j.toxicon.2025.108401","url":null,"abstract":"<div><div>Cervical dystonia with anterocollis is challenging to treat due to involvement of the deep neck muscles, longus colli and longus capitis. Without botulinum neurotoxin injections into these muscles, patient outcomes are often poor. This article outlines two innovative injection techniques developed over many years in our multidisciplinary Neuro-ENT clinic. These have proven to be safe, effective and well-tolerated procedures which can be easily performed in the office with readily available equipment.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108401"},"PeriodicalIF":2.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geographic variation in ichthyocrinotoxin from the Estuarine Stonefish (Synanceia horrida)","authors":"Danica Lennox-Bulow,&nbsp;Robert Courtney,&nbsp;Jamie Seymour","doi":"10.1016/j.toxicon.2025.108383","DOIUrl":"10.1016/j.toxicon.2025.108383","url":null,"abstract":"<div><div>Geographic variation in the composition of animal toxins is well documented for venomous taxa, and to a lesser degree, for some poisonous taxa that secrete toxins obtained from their diet. However, very little is known about animals that synthesise their poisons <em>de novo</em>, such as stonefish and their secreted ichthyocrinotoxins. Stonefish are widely distributed throughout the Indo-Pacific, however, the effect of location on the composition of their ichthyocrinotoxin is currently unknown. This study aimed to determine whether the composition of ichthyocrinotoxins from <em>Synanceia horrida</em> (Estuarine Stonefish) varied between three geographically isolated Australian populations including Cairns in far north Queensland, Caloundra in southeast Queensland, and Exmouth in Western Australia. The composition of ichthyocrinotoxins from <em>S. horrida</em> were largely conserved across the three locations, with the size of most of the components falling between 14 and 25 kDa. However, unique components were identified in <em>S. horrida</em> ichthyocrinotoxins from Caloundra and Exmouth populations. Caloundra populations contained unique smaller components (8 and 12 kDa) that were hydrophobic. In contrast, Exmouth populations contained unique larger components (60 and 150 kDa) with no difference in hydrophobicity. We speculate that the composition of ichthyocrinotoxins produced by <em>S. horrida</em> are likely influenced by benthic flora and fauna communities, particularly those that are likely to interact with the animal's skin, such as fouling flora and fauna, as well as parasites. These findings further add to the growing body of evidence underscoring the complexity and compositional diversity of ichthyocrinotoxins produced by stonefish.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108383"},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing time in lethality assay (LD50) for Bothrops jararaca and Crotalus durissus terrificus venoms and lethality neutralizing assay (ED50) for their respective antivenoms: A 3Rs-based retrospective data validation","authors":"Antonio Alves Pereira-Júnior,&nbsp;Fábio Henrique Dias Martins Lima,&nbsp;Isadora Florentino Martins,&nbsp;Renan de Souza Fructuoso da Silva,&nbsp;Elizabeth Porto Reis Lucas","doi":"10.1016/j.toxicon.2025.108358","DOIUrl":"10.1016/j.toxicon.2025.108358","url":null,"abstract":"<div><div>Mouse lethality assays (MLA) remain the gold standard for evaluating antivenom potency despite ethical concerns regarding animal welfare. This study assessed whether reducing observation periods from 48 to 24 h in MLA for determining median lethal dose (LD₅₀) and median effective dose (ED₅₀) of <em>Bothrops jararaca</em> and <em>Crotalus durissus terrificus</em> venoms and antivenoms maintains scientific validity while improving animal welfare. Through retrospective analysis of 518 quality control assays conducted between 2009–2023 at INCQS, including 334 potency assays and 27 median lethal dose assays for <em>B. jararaca</em>, and 134 ED₅₀ assays and 23 LD₅₀ assays for <em>C. d. terrificus</em>, we found that over 98% of deaths occurred within the first 24 h post-injection for all LD₅₀ determinations on venoms and all ED₅₀ determinations on antivenoms for both species. Statistical analyses demonstrated exceptional agreement between 24-hour and 48-hour endpoints, with concordance correlation coefficients exceeding 0.96 for all assays. Bland–Altman analysis revealed narrow limits of agreement with minimal systematic bias, particularly for antivenom potency measurements. Classification performance metrics showed excellent accuracy (98.5%–100%) in identifying satisfactory antivenoms at 24 h compared to the standard 48-hour protocol, with weighted kappa coefficients exceeding 0.98, indicating near-perfect agreement. For <em>C. d. terrificus</em> antivenom, the 24-hour assay demonstrated 100% concordance with the 48-hour classification, while <em>B. jararaca</em> antivenom showed 98.5% accuracy with only 6 discordant results among 334 assays. Kaplan–Meier survival analysis confirmed statistically equivalent survival probabilities between both time points. These findings provide robust evidence supporting the adoption of a 24-hour observation period as an ethically superior refinement that maintains scientific integrity while significantly reducing animal distress. This refinement aligns with the 3Rs principles and could enhance testing efficiency in antivenom quality control, establishing a precedent for similar refinements in other biological assays and supporting the revision of regulatory guidelines to incorporate more humane testing protocols.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108358"},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}