Toxicon最新文献

{"title":"Crotoxin modulates Encephalitozoon cuniculi-infected macrophages toward the M1 microbicidal profile","authors":"Cristina Gabriela Nascimento de Oliveira ,&nbsp;Anuska Marcelino Alvares-Saraiva ,&nbsp;Elizabeth Cristina Perez ,&nbsp;Sandra Coccuzzo Sampaio ,&nbsp;Maria Anete Lallo","doi":"10.1016/j.toxicon.2025.108348","DOIUrl":"10.1016/j.toxicon.2025.108348","url":null,"abstract":"<div><div>Crotoxin (CTX), a bioactive extract from the snake <em>Crotalus durissus terrificus</em>, has antibacterial, antitumor, and anti-inflammatory properties. Microsporidia are opportunistic, obligate intracellular fungi that infect vertebrates and invertebrates and are highly resistant to conventional drugs. They can also subvert the microbicidal activity of M1 macrophages to an M2 profile, which is more favorable for the pathogen. Thus, in this study, we evaluated the effects of CTX on the viability of spores of the microsporidium <em>Encephalitozoon cuniculi</em>, as well as on the microbicidal activity of macrophages in vitro. <em>E. cuniculi</em> spores were treated with two concentrations of CTX (2.4 and 4.8 μg/mL) and cultivated in RK-13 cells for viability analysis. Additionally, peritoneal adherent cells (APerC), obtained from peritoneal washes of BALB/c mice, were infected with spores of <em>E. cuniculi</em> for 1 h and treated with CTX for 3 h. The profile of macrophages, cytokine production, viability of macrophages, and proliferative capacity of spores were subsequently evaluated. Treatment of <em>E. cuniculi</em> spores with CTX had no fungicidal or fungistatic effects. Compared to the macrophages in the control group, macrophages infected with <em>E. cuniculi</em> and treated with 2.4 μg/mL CTX presented an increase in the M1 profile, more necrosis, and greater production of the cytokines TNF-α and IL-6, and the spores obtained from these macrophages presented a reduction in proliferative capacity. These results indicated that CTX modulated the M1 profile of macrophages infected with <em>E. cuniculi</em>, resulting in greater production of proinflammatory cytokines and stronger microbicidal activity.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"259 ","pages":"Article 108348"},"PeriodicalIF":2.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824487","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":"Toxicon and Toxicon: X - Editorial transitions and future directions in 2025","authors":"Raymond S. Norton ,&nbsp;Denise V. Tambourgi","doi":"10.1016/j.toxicon.2025.108347","DOIUrl":"10.1016/j.toxicon.2025.108347","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"260 ","pages":"Article 108347"},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844671","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":"Plant-derived secondary metabolites against Bothrops envenomation: A review","authors":"Mayara A. Romanelli ,&nbsp;Taissa N. Guerrero ,&nbsp;Ellen Brito ,&nbsp;Lucas Albernaz ,&nbsp;Ana Laura M. Brand ,&nbsp;Dayene S. Gomes ,&nbsp;Humberto Muzi-Filho","doi":"10.1016/j.toxicon.2025.108340","DOIUrl":"10.1016/j.toxicon.2025.108340","url":null,"abstract":"<div><div>Snakebites from the <em>Bothrops</em> genus are a public health issue in Brazil, particularly in the most affected rural areas. Traditional medicinal plants offer potential complementary therapies for mitigating the damages caused by <em>Bothrops</em> envenomation. This review summarizes current research on the antiophidic potential in medicinal plants and its secondary metabolites to neutralize <em>Bothrops</em> venom effects. A comprehensive literature search was conducted to identify studies detailing the biochemical mechanisms and pharmacological effects of plant-based secondary metabolites, including polyphenols, saponins, quinones, sulfated polysaccharides, steroids, coumarins, alkaloids, and coumestans, on venom-induced pathologies. Polyphenols, particularly flavonoids, exhibit significant inhibitory activity against the proteolytic, hemorrhagic, and myotoxic effects of <em>Bothrops</em> venom by binding to active sites of metalloproteinases and phospholipase A₂ (PLA₂) Saponins and quinones demonstrated anti-inflammatory and anti-myotoxic effects through protein precipitation and ion chelation. Sulfated polysaccharides from marine algae showed anticoagulant and anti-edematous properties. Additionally, plant-derived steroids and coumarins inhibited venom-induced coagulation and tissue necrosis. Alkaloids and coumestans, such as wedelolactone, effectively reduced hemorrhagic and neurotoxic damage. Medicinal plants and their secondary metabolites have substantial potential to neutralize the biological responses of bothropic venom. Further research and clinical validation are needed to establish safety, efficacy, and standardized use in snakebite management protocols.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108340"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783963","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":"Evaluation of some blood chemistry parameters caused by different venom doses of Tityus and Centruroides scorpion species from Panama","authors":"Maricruz Morán-González ,&nbsp;Hildaura Acosta de Patiño ,&nbsp;Gerardo Corzo ,&nbsp;Emilio Romero ,&nbsp;Leandra Gómez-Leija","doi":"10.1016/j.toxicon.2025.108331","DOIUrl":"10.1016/j.toxicon.2025.108331","url":null,"abstract":"<div><div>Medically important scorpions in Panama belong to the <em>Tityus</em> and <em>Centruroides</em> genus, including species such as <em>Tityus (Atreus) sp</em>., <em>T. championi</em>, <em>T. festae</em>, <em>C. bicolor</em>, and <em>C. limbatus</em>, which can cause blood chemistry alterations. Therefore, obtaining data through experimental models is crucial for understanding scorpion envenomation. Five scorpion venoms were individually inoculated intravenously into mice (CD-1 strain; 18–20 g) at doses ranging from 0.5 to 1.5 LD₅₀ for each scorpion venom. The control group received only a 0.9 % sodium chloride solution. Blood samples were obtained by intracardiac puncture and were analyzed at times from 5, 15, 30 min, 1, 3, and 24 h. Serum glucose, amylase, CK, CK-MB, creatinine, urea nitrogen, sodium, and potassium levels were determined. It was found that Panamanian scorpion venoms can cause pancreatic damage, as indicated by an increase in glucose and amylase levels, as well as cardiac and muscle damage, as indicated by an increase in the blood concentration of CK and CK-MB enzymes. The renal function could also be affected by the increase in creatinine and urea nitrogen. Concerning electrolyte levels, only sodium showed an increase compared to the control, but potassium showed a decrease in concentration levels. These findings could contribute to the efficient management of scorpionism in Panama's emergency health services.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108331"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731226","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":"AI models uncover factors influencing scorpionism in Northern Brazil","authors":"Thais de Andrade Moura ,&nbsp;Andrés A. Ojanguren-Affilastro ,&nbsp;Mahmood Sasa ,&nbsp;José María Gutiérrez ,&nbsp;Franciely Fernanda Silva ,&nbsp;Tuany Siqueira-Silva ,&nbsp;Pablo Ariel Martinez","doi":"10.1016/j.toxicon.2025.108342","DOIUrl":"10.1016/j.toxicon.2025.108342","url":null,"abstract":"<div><div>Envenomation by scorpion stings is a serious public health problem in tropical regions of the world. In Brazil's Northern region, there has been a significant increase in cases over the last decade, accompanied by a rise in the fatality rate. Climate change and intensive land use are altering the distribution of species that pose health risks and may be associated with the increased incidence of accidents. We integrated species distribution models (SDMs) of three medically important species (<em>Tityus obscurus</em>, <em>T. metuendus</em>, and <em>T. silvestris</em>), bioclimatic data, and land use to predict scorpionism incidence and quantify the importance of predictors in Northern Brazil. We used these predictors to build a model to predict the incidence of scorpion envenomations using the XGBoost artificial intelligence (AI) algorithm and assessed the importance of the predictor variables with the Shapley method.Our models demonstrated good performance in predicting incidence, with a MAE of 7.17 and an RMSE of 10.62. The analysis identified that climatic factors are the main determinants of incidence but also highlighted the relevance of the distribution of <em>T. obscurus</em> and <em>T. silvestris</em> species, pasture areas, and rural population density. The study showed that integrating SDMs and AI techniques is effective for predicting scorpionism incidence and assisting in the formulation of prevention as well as management strategies.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108342"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785254","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":"Chronic pelvic pain and botulinum toxin","authors":"Barbara Illowsky Karp,&nbsp;Pamela Stratton","doi":"10.1016/j.toxicon.2025.108336","DOIUrl":"10.1016/j.toxicon.2025.108336","url":null,"abstract":"<div><div>Botulinum toxin is being explored as a treatment for chronic pelvic pain, a major cause of suffering and disability in both women and men worldwide. For chronic pelvic pain in women, botulinum toxin may be injected into pelvic floor muscles such as levator ani and obturator internus. For pain associated with genitopelvic penetration disorders (vaginismus, vestibulitis, and vulvar pain, bulbospongioussus and ischiocavernosus may be treated. There have been numerous uncontrolled studies of botulinum toxin for chronic pelvic pain in women showing benefit, however, the few randomized controlled clinical trials published to date have given equivocal results. Chronic pelvic pain in men often implicates the prostate gland, so that the condition is commonly called “chronic prostatitis/chronic pelvic pain syndrome.” There are only a handful of clinical trials for male chronic pelvic pain, each using a different site of injection; some with promising results. This paper discusses the use of botulinum toxin in the treatment of chronic pelvic pain in men and women.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108336"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744041","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":"Changes in regulatory requirements for potency testing of snake antivenom in Korea","authors":"Wonjong Lee ,&nbsp;Hyun Jeong Kim ,&nbsp;Yu Jeong Oh ,&nbsp;Su Kyoung Seong ,&nbsp;Young Hoon Kim ,&nbsp;Youngju Choi ,&nbsp;Sang-Mi Park ,&nbsp;Kiwon Han ,&nbsp;Chan Woong Choi","doi":"10.1016/j.toxicon.2025.108337","DOIUrl":"10.1016/j.toxicon.2025.108337","url":null,"abstract":"<div><div>Snake antivenoms are manufactured under Good Manufacturing Practice, with quality controlled according to Korean regulations. Potency results for anti-lethal and anti-hemorrhagic titers collected since 2017 showed ranges of 6280–15,120 and 6080–10,160 U/vial, respectively. A strong correlation (r = 0.8356–0.9216) was observed between the two tests. These findings support the removal of the anti-hemorrhagic test from Korean regulations, aligning with global efforts to reduce animal testing while ensuring the efficacy of biological products.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108337"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761041","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":"Baicalin alleviates lipid accumulation in adipocytes via inducing metabolic reprogramming and targeting Adenosine A1 receptor","authors":"Zaikuan Zhang ,&nbsp;Runzhi Wang ,&nbsp;Jin Cai ,&nbsp;Xinyi Li ,&nbsp;Xiaosong Feng ,&nbsp;Shengming Xu ,&nbsp;Zhihong Jiang ,&nbsp;Peiyi Lin ,&nbsp;Zengyi Huang ,&nbsp;Yajun Xie","doi":"10.1016/j.toxicon.2025.108339","DOIUrl":"10.1016/j.toxicon.2025.108339","url":null,"abstract":"<div><div>Excessive lipid accumulation can lead to obesity, metabolic-associated fatty liver disease, and type 2 diabetes. However, there are currently few drugs that could effectively and safely inhibit the accumulation of intracellular lipids. In this study, we observed that baicalin significantly altered cellular respiration by reducing mitochondrial oxygen consumption while enhancing glycolytic flux, accompanied by increased phosphorylation of AMPK and ACC, suggesting an adaptation to altered energy availability. Baicalin effectively reduced lipid droplet formation and intracellular triglyceride levels in adipocytes, as marked by downregulating genes and proteins associated with lipid storage, including <em>Cd36</em>, <em>Fabp4</em>, and FASN. Transcriptomic analysis identified 2150 differentially expressed genes in baicalin-treated adipocytes, with significant enrichment in metabolic pathways such as glycolysis, gluconeogenesis, and lipid metabolism. Further analysis revealed that baicalin upregulated glycolytic and fatty acid β-oxidation (FAO) pathways while downregulating pyruvate dehydrogenase, inducing a shift toward glycolysis and FAO for energy production. Molecular docking analysis revealed that Adenosine A1 receptor (ADORA1) was the target of baicalin, which inhibited the maturation of sterol regulatory element binding protein 1 (SREBP1) and finally alleviated lipid deposition. These results demonstrate that baicalin induces metabolic reprogramming of adipocytes by inhibiting glucose aerobic metabolism while enhancing anaerobic glycolysis and FAO. Meanwhile, baicalin targets ADORA1, which subsequently influences the processing of SREBP1 and downregulates lipid biosynthesis, positioning baicalin as a potential therapeutic agent against obesity and related metabolic disorders.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108339"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796462","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":"Lutein and Zeaxanthin abated neurobehavioral, neurochemical and oxido-inflammatory derangement in rats intoxicated with Aflatoxin B1","authors":"Solomon Owumi ,&nbsp;Joseph Chimezie ,&nbsp;Marvellous O. Salami ,&nbsp;Japheth A. Ishaya ,&nbsp;Chidindu Vine Onyemuwa ,&nbsp;Mark Nnamdi ,&nbsp;Olatunde Owoeye","doi":"10.1016/j.toxicon.2025.108345","DOIUrl":"10.1016/j.toxicon.2025.108345","url":null,"abstract":"<div><div>Aflatoxin B₁ (AFB₁), a mycotoxin commonly present in feed, has several toxic effects. AFB₁ seems to have a neurotoxic effect that leads to neurobehavioral impairment. On the other hand, Lutein and Zeaxanthin (LUT/ZEA) have antioxidant and anti-inflammatory effects. Here, we aimed to compare the effects of AFB₁ and the co-treatment with LUT/ZEA on neurobehavioural and biochemical changes <em>viz-a-viz</em> oxido-inflammatory response in male rats' hippocampal and pre-frontal cortexes. Experimental rats of the Wistar strain (n = 40) were randomly grouped into treatment cohorts: Control (corn oil 2 mL/kg), AFB₁ (75 μg/kg), LUT/ZEA only (100 mg/kg), AFB₁ + LUT/ZEA (75 μg/kg + 100 mg/kg), and AFB₁ + LUT/ZEA (75 μg/kg + 200 mg/kg). All groups were administered their respective treatment orally for 28 days, while behavioural tests were conducted using open field tests (OFT), Y-maze, novel object tests (NORT), and forced swim tests (FST) 1 h after treatment on day 26–28. The animals were euthanized on day 29. In the hippocampal and pre-frontal cortex, antioxidant indicators (SOD, CAT, GSH, GST, GPx, TSH), inflammatory mediators (XO, NO, MPO), and acetylcholinesterase activity were measured. Our finding presents the anti-oxidant effect of lutein/Zeaxanthin in the brains of AFB₁-intoxicated rats, indicating better cognitive and spatial memory capacity in Y-maze and NORT, an improvement in locomotive and explorative behaviour in OFT and reduction in anxio-depressive-like behaviour in LUT/ZEA co-treated rats. Acetylcholinesterase activity was enhanced in LUT/ZEA co-treated rats. LUT/ZEA co-treatment dampened oxido-inflammatory mediators by decreasing XO, NO, and MPO levels and increasing antioxidant activities (SOD, CAT, GSH, GST, GPx, TSH) in the prefrontal and hippocampal cortices. We surmise that mechanistically, co-treatment with LUT/ZEA effectively lessened AFB₁ neurotoxicity through anti-inflammatory and antioxidant pathways and essentially improved the experimental rats' neurobehavioural outcomes.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108345"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800501","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":"Alleviation of LPS-induced acute lung injury by propolis-based nanocomposites through the TLR4/NFKB and P2X7/AKT pathways: Randomized-controlled experimental study","authors":"Hilal Üstündağ ,&nbsp;Adem Kara ,&nbsp;Necip Gökhan Taş ,&nbsp;Ferdane Danişman Kalindemi̇rtaş ,&nbsp;Nezahat Kurt ,&nbsp;Elif Erbaş ,&nbsp;Mehmet Tahir Huyut ,&nbsp;Mustafa Gül ,&nbsp;İshak Afşin Kari̇per","doi":"10.1016/j.toxicon.2025.108330","DOIUrl":"10.1016/j.toxicon.2025.108330","url":null,"abstract":"<div><div>Sepsis-associated acute lung injury continues to pose a significant medical challenge with substantial morbidity and mortality rates. In this study, we investigated the therapeutic potential of propolis-based treatments and their nanocomposites in modulating inflammation and apoptosis using a lipopolysaccharide (LPS)-induced rat model of sepsis. Forty-two Sprague-Dawley rats were divided into seven groups (n = 6): control, LPS (5 mg/kg, i.p.), LPS + Propolis (100 mg/kg, i.p.), LPS + NanoPropolis (100 mg/kg, i.p.), LPS + silver nanoparticles propolis (AgNPsPro) (50 mg/kg), and a negative propolis group (100 mg/kg, i.p.). The rats were assessed for inflammatory, oxidative stress, and apoptotic markers through Western blot, histopathological analyses, and biochemical measurements. The LPS group exhibited significantly higher levels of pro-inflammatory cytokines (IL-1β, TNF-α) and the systemic infection marker presepsin (PRSN) in blood, as well as the oxidative stress marker malondialdehyde (MDA) in lung tissue. The treatment groups, particularly LPS + AgNPsPro, showed significant reductions in these markers, with decreased levels of MDA, IL-1β, TNF-α, NF-κB, and TLR4, and increased GSH content in lung tissue (p &lt; 0.05). The anti-apoptotic protein BCL-2 was upregulated, while pro-apoptotic BAX expression was reduced, indicating enhanced cell survival. The P2X7 receptor, a key inflammation regulator, and the AKT signaling pathway, involved in cell survival, were positively modulated by the treatments. Histopathological findings corroborated these results, showing less lung tissue damage. In conclusion<strong>,</strong> propolis-based treatments, especially in combination with nanoparticles, demonstrate therapeutic potential in reducing inflammation, oxidative stress, and apoptosis in sepsis-induced lung injury.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108330"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731168","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}