Toxicon最新文献

{"title":"Block of Kv1 potassium channels and NMR structure of recombinant conotoxin κ-SrXIA","authors":"Laura I. Escobar ,&nbsp;Carlos Daniel Quezada Suaste ,&nbsp;Carolina Salvador ,&nbsp;Daniel León Aparicio ,&nbsp;Carolina Monserrath Melchor-Meneses ,&nbsp;Jorge Bravo-Martínez ,&nbsp;Víctor de la Rosa ,&nbsp;Zinaeli López-González ,&nbsp;Federico del Río-Portilla","doi":"10.1016/j.toxicon.2025.108384","DOIUrl":"10.1016/j.toxicon.2025.108384","url":null,"abstract":"<div><div>The biologically active components of <em>Conus</em> venoms are mainly small peptides with disulfide-bonded structures. Some conotoxins contain post-translational modifications as an evolutionary strategy to enhance their potency and selectivity towards ion channels and receptors. Few conotoxins are known to target mammalian Kv1 channels. κ-SrXIA from the venom of <em>Conus spurius</em> inhibits the voltage-gated potassium Kv1.2 and Kv1.6 channels through a basic ring of Arg. The 32 amino acid κ-SrXIA has eight Cys residues arranged in the pattern that defines the I-superfamily with four disulfide bridges, two gamma-carboxy-glutamates (Gla), and a Pro-amidated C-terminus (X). In this study, we obtained and determined the biological activity and NMR structure of recombinant κ-SrXIA without Gla and X. The conotoxin cDNA was expressed in <em>E. coli</em> CD41 and purified by GST-affinity chromatography and RP-HPLC. Pharmacological assays were performed by two-electrode voltage-clamp recordings in <em>Xenopus laevis</em> oocytes expressing recombinant Kv1.1, Kv1.2, Kv1.3, Kv1.4 and Kv1.6 channels. Except for Kv1.3, κ-Sr-XIA irreversibly blocked Kv1 channels displaying a lower affinity and a slower inhibition kinetics than native conotoxin. Even when κ-SrXIA displayed a high structural similarity to GXIA from the I₃-superfamily, the resultant disulfide connectivity forming an ICK+1 motif showed two antiparallel β-strands as ι-RXIA from the I₁-superfamily. This study represents the first 3D NMR structure for a member of the I₂-superfamily.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108384"},"PeriodicalIF":2.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917986","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":"LCA, a bacterial metabolite, induces ferroptosis and senescence in triple-negative breast cancer","authors":"Xiayun Jin ,&nbsp;Xiangyu Jin ,&nbsp;Xia Zhang ,&nbsp;Shishi Zhou ,&nbsp;Hua Chai","doi":"10.1016/j.toxicon.2025.108373","DOIUrl":"10.1016/j.toxicon.2025.108373","url":null,"abstract":"<div><div>Lithocholic Acid (LCA) is a secondary bile acid generated through the microbial metabolism of primary bile acids in the gut. In recent years, it has been found to have potential anti-tumor effects. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. Chemotherapy remains the primary treatment, but it has significant side effects and often leads to drug resistance. Therefore, exploring new treatment strategies is of great importance. This research seeks to elucidate the mechanism of LCA in TNBC and establish a theoretical foundation for its clinical use. Through cell proliferation assays, iron metabolism detection, oxidative stress analysis, ferroptosis marker detection, and autophagy-related experiments, we systematically investigated the effects of LCA on TNBC cells. The findings indicated that LCA effectively suppressed TNBC cell proliferation and triggered mitochondrial iron overload and oxidative stress, resulting in ferroptosis via ferritinophagy. Molecular mechanism studies revealed that after LCA treatment, the expression of ferroptosis-related markers GPX4 and FTH was downregulated, while NCOA4 expression was upregulated. Autophagy inhibitors or AMPK inhibitors significantly reversed LCA-induced ferroptosis, indicating that LCA induces ferroptosis by promoting ferritinophagy and releasing iron ions. This study elucidates the molecular mechanism by which LCA induces ferroptosis in TNBC cells via regulation of iron metabolism, oxidative stress, and autophagy. It provides crucial experimental evidence and theoretical support for LCA as a potential anti-breast cancer drug, offering novel insights and targets for TNBC treatment.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108373"},"PeriodicalIF":2.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999259","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":"Muscle physiology in spasticity and muscle stiffness","authors":"Preeti Raghavan","doi":"10.1016/j.toxicon.2025.108350","DOIUrl":"10.1016/j.toxicon.2025.108350","url":null,"abstract":"<div><div>This paper examines the physiological changes in spastic muscles contributing to spasticity and muscle stiffness, focusing on the underlying mechanisms and their clinical implications. Spasticity, which is prevalent in neurological conditions such as multiple sclerosis, cerebral palsy, spinal cord injury, stroke, and traumatic brain injury, is characterized by disordered sensorimotor control and often results in increased muscle stiffness and resistance to movement. Recent developments in the understanding of spasticity suggest the importance of architectural changes in muscles that may contribute to increased passive resistance, potentiate reflex mechanisms, and progression to fibrosis, with hyaluronan (HA), a glycosaminoglycan, playing a pivotal in modulating the properties of the muscle extracellular matrix (ECM). The hyaluronan hypothesis of muscle stiffness postulates that the accumulation and biophysical alteration of HA in the ECM of muscle increases its viscosity, resulting in increased passive mechanical resistance. This is turn mayincrease muscle sensitivity to stretch, potentiating spasticity, and lead to cellular differentiation of myofibroblasts to fibroblasts ultimately leading to fibrosis and contracture. A deeper understanding of HA's role in ECM dynamics offers promising avenues for novel treatments aimed at mitigating stiffness and preventing long-term disability in patients with spasticity.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"259 ","pages":"Article 108350"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891394","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":"Disparity among venom components, and morphometrics in Centruroides baergi Hoffmann, 1932, a medically relevant scorpion species from Mexico","authors":"Fernando O. Bejarano-Mendoza ,&nbsp;Ilse Viridiana Gómez-Ramírez ,&nbsp;Antonio Juan Cortés Guzmán ,&nbsp;Baltazar Becerril ,&nbsp;Lourival D. Possani ,&nbsp;Jimena I. Cid-Uribe ,&nbsp;Edmundo González-Santillán","doi":"10.1016/j.toxicon.2025.108370","DOIUrl":"10.1016/j.toxicon.2025.108370","url":null,"abstract":"<div><div><em>Centruroides baergi</em> is a scorpion species distributed in the biogeographical province of the Balsas Basin in Mexico. Health officials have reported acute envenomation in human populations living on the western side of this scorpion's range, but none in the eastern region. This disparity in toxicity suggested that there may be two distinct species. We used two different approaches, including venom analysis and morphometric specimens from both regions, to test our hypothesis. We performed chromatographic, electrophoretic, and mass spectrometry analysis to identify the known β-toxins involved in the intoxication. The most remarkable finding was the absence of Cb3 β-toxin in the eastern population. Consequently, the LD₅₀ of the eastern population was lower than that of the western population. We analyzed linear and ratio body measurements with parametric and nonparametric statistics to test species limits. These analyses indicated that all putative populations of <em>C. baergi</em> are significantly similar, suggesting that they may represent a single species. Unexpectedly, the population of scorpions in the center of the study area, Suchixtlahuaca, previously identified as <em>C. baergi</em>, showed significant morphological and venom composition differences. We provided empirical evidence of an abrupt change of highly toxic peptides around the 98th meridian that limits populations of <em>Centruroides baergi</em> to the east of Mexico.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"259 ","pages":"Article 108370"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942353","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":"Regional differences in intra-body distribution of saxitoxins in freshwater pufferfish Pao sp. A from Cambodia","authors":"Hongchen Zhu ,&nbsp;Junji Takeoka ,&nbsp;In Sokra ,&nbsp;Linan Horn ,&nbsp;Laymithuna Ngy ,&nbsp;Kei'ichiro Iguchi ,&nbsp;Yuzuru Utsunomiya ,&nbsp;Minoru Wada ,&nbsp;Akinori Yamada ,&nbsp;Naoki Yagishita ,&nbsp;Tomohiro Takatani ,&nbsp;Osamu Arakawa","doi":"10.1016/j.toxicon.2025.108363","DOIUrl":"10.1016/j.toxicon.2025.108363","url":null,"abstract":"<div><div>The Mekong River in Cambodia is inhabited by approximately ten species of freshwater pufferfish of the family Tetraodontidae. However, limited information is available regarding the toxin profile of these fish. In this study, to obtain sufficient information on the intra-body distribution of toxins in Cambodian freshwater pufferfish, one species of <em>Pao</em> freshwater pufferfish (<em>Pao</em> sp. A) were collected from Phnom Penh (PNH) in November 2019 (n = 23) and from Kratie (KTI) in March 2023 (n = 21). Toxin analyses of these samples revealed that individuals from both regions possessed saxitoxins (STXs) and contained no tetrodotoxin. <em>Pao</em> sp. A specimens from PNH possessed high STXs levels in the skin, muscle, liver, and gonads, whereas those from KTI showed relatively low levels of STXs concentrated in the skin. STXs amount in the ovaries in PNH individuals increased exponentially with increasing the gonadosomatic index (GSI). We also clarified that STXs concentration in the skin became increasingly higher as KTI individuals grew. These results suggest that differences in living regions may affect the intra-body distribution of STXs in <em>Pao</em> freshwater pufferfish, with maturation and/or growth contributing as well.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"259 ","pages":"Article 108363"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891393","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":"Unique physiological and regulatory activity drives divergent toxin and non-toxin gene expression in rattlesnake accessory venom glands","authors":"Claire Kim ,&nbsp;Sierra N. Smith ,&nbsp;Siddharth S. Gopalan ,&nbsp;Samuel R. Kerwin ,&nbsp;Kaas Ballard ,&nbsp;Blair W. Perry ,&nbsp;Cara F. Smith ,&nbsp;Anthony J. Saviola ,&nbsp;Richard H. Adams ,&nbsp;Stephen P. Mackessy ,&nbsp;Todd A. Castoe","doi":"10.1016/j.toxicon.2025.108376","DOIUrl":"10.1016/j.toxicon.2025.108376","url":null,"abstract":"<div><div>Understanding the mechanisms by which organs and tissues evolve new physiological functions is central to understanding the evolution of novelty. This is particularly interesting in the context of related tissues that evolve specialized, yet complementary, functions. Snake venom glands are an attractive system to test hypotheses related to the evolution and specialization of novel physiological function, as these modified salivary glands have evolved over ∼60 MY to synthesize and store venom. Front-fanged venomous snakes (elapids and viperids) possess two types of venom glands: the main and accessory glands. The larger main gland produces greater quantities of venom toxins and has been studied extensively, while the smaller accessory gland has received less attention. Here, we explore gene expression differences between main and accessory venom glands across three rattlesnake species (<em>Crotalus cerberus</em>, <em>C. oreganus concolor</em> and <em>C. viridis</em>). Our findings indicate that accessory glands express most venom genes at significantly lower levels than the main gland, with a few exceptions that may represent biologically relevant contributions of accessory glands to venom. The two glands also exhibit distinct trans-regulatory environments that we link to key differences in their underlying physiology and secretory roles. Our results further suggest that two signaling pathways that regulate venom, the unfolded protein response (UPR) and extracellular signal-regulated kinase (ERK), show significantly lower activation in the accessory gland. These findings provide insight into the physiological and functional diversification of snake venom systems, highlighting how distinct glandular systems have evolved contrasting and complementary roles driven by distinct physiological and regulatory mechanisms.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"259 ","pages":"Article 108376"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942354","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":"Seasonal variation in tetramine content in Korean marine gastropods Neptunea arthritica and Neptunea eulimata","authors":"Hyunjun Lee ,&nbsp;Bong Ki Park ,&nbsp;Kwang-Sik Choi ,&nbsp;Nobuhisa Kajino ,&nbsp;Wan-Ok Lee ,&nbsp;Changsun Choi ,&nbsp;Hyang Sook Chun ,&nbsp;Jihyun Lee","doi":"10.1016/j.toxicon.2025.108379","DOIUrl":"10.1016/j.toxicon.2025.108379","url":null,"abstract":"<div><div>Tetramine is a toxin that is primarily found in the salivary glands of carnivorous marine gastropods. Countries, such as South Korea and Japan, where marine gastropods are commonly consumed, continue to report annual cases of tetramine poisoning. Therefore, it is crucial to investigate the seasonal variations in tetramine content in these species. In this study, liquid chromatography–tandem mass spectrometry (LC–MS/MS) was employed to analyze the monthly variations in tetramine content across various tissues of <em>Neptunea arthritica</em> and <em>Neptunea eulimata</em> collected over a one-year period (September 2023 to August 2024) from the East Coast of Korea. The condition indices of both species were calculated to estimate their spawning seasons. Compared to other tissues (i.e., the foot and midgut gland), the highest tetramine content was consistently found in the salivary glands across all seasons and species. The tetramine content in the salivary glands peaked in November 2023 (4580.05 mg/kg for <em>N. arthritica</em> and 7762.16 mg/kg for <em>N. eulimata</em>) and declined to the lowest value in February 2024 (568.10 mg/kg for <em>N. arthritica</em> and 679.35 mg/kg for <em>N. eulimata</em>). After the spawning season, the increased feeding activity may result in elevated tetramine levels, potentially contributing to prey capture. Therefore, removing the salivary glands of these species, particularly in November, is critical to mitigate the risk of tetramine poisoning.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108379"},"PeriodicalIF":2.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906455","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":"Prevention and management of adverse effects following botulinum neurotoxin injection therapy in the larynx and tongue","authors":"Lucy Hicklin,&nbsp;Winnie Yeung","doi":"10.1016/j.toxicon.2025.108380","DOIUrl":"10.1016/j.toxicon.2025.108380","url":null,"abstract":"<div><div>Botulinum neurotoxin therapy is the gold standard for managing focal dystonias affecting the larynx and tongue. However, the region's complex anatomy and vital functions pose unique challenges for the injector. This article provides an overview of the pre-treatment evaluations and injection techniques to minimise the adverse effects commonly linked to botulinum neurotoxin therapy for conditions including laryngeal dystonia, cricopharyngeal dysfunction and lingual dystonia, to achieve safe and effective patient outcomes.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108380"},"PeriodicalIF":2.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906040","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":"Anti-insect activity of benzylacetone and its structural analogues against Tribolium castaneum (Coleoptera: Tenebrionidae)","authors":"Yueqiang Xin ,&nbsp;Zexu Pan ,&nbsp;Yangshan Liu ,&nbsp;Xiang Ji ,&nbsp;Yanjun Hao ,&nbsp;Hongyan Cao ,&nbsp;Yuli Sang","doi":"10.1016/j.toxicon.2025.108378","DOIUrl":"10.1016/j.toxicon.2025.108378","url":null,"abstract":"<div><div>Several studies have confirmed that the volatile oil of <em>Rhododendron anthopogonoides</em> Maxim has good anti-insect activity and is expected to become an environmentally friendly botanical insecticide, with benzylacetone as its main active component. Benzylacetone has a simple chemical structure, containing only three elements of carbon, hydrogen and oxygen, low toxicity, and easy degradation. Therefore, in this study, benzylacetone and its seven structural analogues were selected for testing their anti-insect activity to <em>Tribolium castaneum</em> Herbst (Coleoptera: Tenebrionidae), in order to explore the key structural sites where benzylacetone plays a role in combating <em>T. castaneum</em>. Benzylacetone demonstrated better repellent activity compared to the positive control pyrethroid, and when the single bonds at positions 3 and 4 were transformed into double bonds, the percent repellency increased. Additionally, the fumigation activity of benzylacetone exhibited a concentration-dependent trend and was significantly higher than that of the positive control pyrethroid. After losing two methylene groups at positions 3 and 4, the LC50 decreased to 13.10 mg/L air, which was approximately 9.4 times lower than that of benzylacetone. In terms of contact activity against <em>T. castaneum</em>, benzylacetone was about 2 times more effective than pyrethroids. Moreover, when the single bond at positions 3 and 4 became a double bond, the contact mortality was 2.5 times higher than that of benzylacetone, and the LD50 reached 10.47 μg/adult. Based on the results of repellent, fumigation, and contact toxicity experiments, it was found that the side chains of benzylacetone, carbonyl groups on the side chains, and benzene ring unsubstituted were the key structures for its prevention and control against <em>T. castaneum</em>. This study is an exploration of the structure-activity relationship of benzylacetone in the anti-insect of <em>T. castaneum</em>, providing ideas for its structural modification.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"261 ","pages":"Article 108378"},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918121","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":"Molecular and fluorometric based approach for the detection and isolation of aflatoxin producing Aspergillus sp. in chewing or smokeless tobacco","authors":"Adeena Siddiqui,&nbsp;Saira Yahya,&nbsp;Shaista Fatima,&nbsp;Misbah Khadim","doi":"10.1016/j.toxicon.2025.108377","DOIUrl":"10.1016/j.toxicon.2025.108377","url":null,"abstract":"<div><div>Tobacco contains many harmful chemicals, toxins, and carcinogens that can cause serious health hazards. Mycotoxins are present in all forms of tobacco, including smokeless tobacco (SLT) which are harmful for human health and associated with different types of cancer. Using microbial and molecular techniques, we identified aflatoxigenic <em>Aspergillus</em> species in SLT. Fifty samples of chewing tobacco were collected randomly from different locations of Karachi. Fungi were grown on Sabouraud Dextrose agar (SDA) by spread plate method and <em>A. flavus</em> was identified macroscopically, microscopically and by amplifying the ITS region. Confirmed isolates of <em>A. flavus</em> were analyzed for aflatoxin production by Ammonia vapor test and by UV on coconut agar medium (CAM). The regulatory genes (<em>aflR and aflS</em>) associated with aflatoxins in <em>A. flavus</em> were also amplified. Different fungal species were identified from SLT samples in which <em>A. flavus</em> was the most dominant. Aflatoxin production analysis by ammonia vapor test revealed that 64 % isolates were aflatoxigenic while on Coconut agar medium (CAM) 43 % isolates were aflatoxigenic. Aflatoxins were quantified in only <em>A. flavus</em> positive samples which were in the range of 10–47 μg/kg. Aflatoxin concentration detected in SLT was above the recommended level of FDA standard in majority of the samples.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"261 ","pages":"Article 108377"},"PeriodicalIF":2.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881710","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}