Steroids最新文献

{"title":"Effect of betulinic acid on MepA efflux pump inhibition in Staphylococcus aureus: Antibacterial and molecular study","authors":"Camila Aparecida Pereira da Silva ,&nbsp;Nara juliana Santos Araújo ,&nbsp;Cícera Datiane Morais Oliveira-Tintino ,&nbsp;José Maria Barbosa Filho ,&nbsp;Gabriel Gonçalves Alencar ,&nbsp;José Bezerra de Araújo-Neto ,&nbsp;Josefa Sayonara dos Santos ,&nbsp;Juliete Bezerra Soares ,&nbsp;Carolina Bandeira Domiciano ,&nbsp;Davi Antas e Silva ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Jacqueline Cosmo Andrade-Pinheiro","doi":"10.1016/j.steroids.2025.109572","DOIUrl":"10.1016/j.steroids.2025.109572","url":null,"abstract":"<div><div>Infections caused by pathogenic bacteria have been responsible for a significant number of deaths in recent decades. Invasive infections caused by <em>Staphylococcus aureus</em> are highly prevalent and have high morbidity and mortality rates. Faced with the increase in multidrug-resistant bacteria, a promising strategy is the development of adjuvant molecules that enhance the effects of antibiotics, such as efflux pump inhibitors. Betulinic acid (BA) is a pentacyclic triterpene of the lupane type, found in various plant species, which has shown various pharmacological activities, including antibacterial potential. This study investigated the inhibitory action of BA on the MepA efflux pump in strains of <em>Staphylococcus aureus</em> K2068, as well as carrying out fluorescence and membrane permeability tests. The minimum inhibitory concentrations (MIC) were determined using the broth microdilution method. Subsequently, their effects on efflux pump-mediated antibiotic resistance were evaluated by reducing the MIC of the antibiotic and ethidium bromide (EtBr), while fluorimetry and permeability potential tests were carried out using the SYTOX Green fluorescence method. BA did not show intrinsic antibacterial activity, however it showed synergistic effects when associated with the antibiotics ciprofloxacin and ethidium bromide, inducing a reduction in MIC and indicating inhibitory effects on the MepA efflux pump. BA also induced a significant increase in fluorescence and demonstrated the ability to permeabilize the bacterial membrane. The results obtained show that BA has a high potential to act as an efflux pump inhibitor and could help in the treatment of resistant bacterial infections.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"215 ","pages":"Article 109572"},"PeriodicalIF":2.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415358","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":"Extraction of diosgenin using different techniques from fenugreek seeds- A review","authors":"Sharavan Kumar ,&nbsp;B.M. Praveen ,&nbsp;Aralihalli Sudhakara ,&nbsp;Prajwal Sherugar ,&nbsp;Yashoda Malgar Puttaiahgowda","doi":"10.1016/j.steroids.2024.109543","DOIUrl":"10.1016/j.steroids.2024.109543","url":null,"abstract":"<div><div>Diosgenin, falls under the category of steroidal saponin present in fenugreek seeds (<em>Trigonella foenum-graecum</em>) in the amount of 0.2–09%. This compound possesses certain pharmacological characteristics like anti-inflammatory, anti-cancer, anti-oxidant etc., that render it a desirable component in the medicinal and nutraceutical industries. Various methods such as, conventional solvent extraction, green extraction methods like Soxhlet extraction, microwave-assisted extraction (MAE), maceration methods, ultrasound-assisted extraction (UAE) and supercritical fluid extraction methods are employed to extract diosgenin from fenugreek seeds. Fundamentals such as solvent choice, pre-treatment techniques, and optimization parameters, affect the diosgenin extraction process. Furthermore, the quantification of diosgenin is governed by analytical methods(chromatography and spectroscopy), underscoring the significance of standardizing diosgenin levels to set the stage for upcoming pharmacological research. However there have been very negligible resources which focuses on conventional and novel techniques for extraction of diosgenin from Fenugreek seeds. This review aims to provide combined insights into the diverse methodologies employed for diosgenin extraction from fenugreek seeds and their implications in pharmaceutical research.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109543"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795210","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 effect of resistance training and nandrolone decanoate administration on cardiac tissue in mice","authors":"Yechiel Atias,&nbsp;Tavor Ben-Zeev,&nbsp;Chagai Levi,&nbsp;Lior Binman,&nbsp;Jay R. Hoffman","doi":"10.1016/j.steroids.2024.109559","DOIUrl":"10.1016/j.steroids.2024.109559","url":null,"abstract":"<div><div><strong>Purpose:</strong> This study examined the effect of resistance training (RT) by itself and in combination with supraphysiological administration of nandrolone decanoate (ND) on the inflammatory, apoptotic, and oxidative stress response in cardiac tissue. The effect of the training and androgen intervention on adiponectin expression, a potential cardio protectant was also examined. <strong>Methods:</strong> Forty male C57Bl/6J mice, 3 months of age were randomized into four groups (n = 10 per group). Two groups of animals performed a 3-day per week RT program for 7-weeks, while the other two groups remained sedentary (SED). The RT and SED animals were further randomized into an androgen group (RTA and SEDA, respectively) or a sham group (RTS and SEDS, respectively). Animals in the RTA and SEDA groups received 38-mg·kg⁻¹ injected once per week. Mice from RTS and SEDS received sham injections. <strong>Results:</strong> Main effects for group indicated that RT resulted in significant elevations in NFκβ (p &lt; 0.001), glutamine peroxidase (GPX) (p = 0.007) and adiponectin (p &lt; 0.001). Main effects for treatment indicated that ND administration resulted in greater elevations in NFκβ (p = 0.01) and TNF-α (p = 0.017). In addition, TNF-α expression was greater in RTA compared to RETS (p = 0.006) and the adiponectin response in RTA was greater (p’s &lt; 0.05) than all other groups. A significant correlation was noted between average training volume during the RT program and GPX expression (r = 0.716, p &lt; 0.001). <strong>Conclusion:</strong> Results indicate that RT and ND administration can increase markers of apoptosis and inflammation. Elevations in adiponectin expression suggest that it may act as a compensatory mechanism supporting cardiovascular health.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109559"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915689","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":"Improved synthesis and characterization of bile acid esters: Organogelation and supramolecular properties","authors":"Jair García-Méndez ,&nbsp;Adolfo López-Torres ,&nbsp;María A. Fernández-Herrera","doi":"10.1016/j.steroids.2025.109560","DOIUrl":"10.1016/j.steroids.2025.109560","url":null,"abstract":"<div><div>Bile acid esters and their derivatives hold significant interest due to their applications in fields such as supramolecular chemistry, biomedicine, and nanomaterials. This study revisits the synthesis and characterization of esters derived from cholic, deoxycholic, and lithocholic acids using short-chain alcohols in combination with microwave-assisted heating. The synthesized esters were analyzed for their potential as gel-forming agents, and their organogelation properties were evaluated. Microwave-assisted synthesis offers rapid and efficient esterification, leading to high yields with improved selectivity. The organogels were characterized through techniques such as differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), revealing distinct structural and thermal properties. The study highlights the potential of these bile acid esters in materials science and supramolecular chemistry, contributing to the development of novel functional materials.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109560"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967028","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":"Novel compound heterozygous CYP17A1 mutations identified in a family with two siblings affected by 17α-hydroxylase/17,20-lyase deficiency","authors":"Rongbo He ,&nbsp;Lin Xu ,&nbsp;Nan Yang ,&nbsp;Shaoshi Zhu ,&nbsp;Hongqi Fan ,&nbsp;Jing Zou ,&nbsp;Rourou Chen ,&nbsp;Li Qian ,&nbsp;Yu Liu","doi":"10.1016/j.steroids.2025.109562","DOIUrl":"10.1016/j.steroids.2025.109562","url":null,"abstract":"<div><h3>Background</h3><div>17α-Hydroxylase/17,20-lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH), caused by mutations in the <em>CYP17A1</em> gene. It typically manifests clinically as variable degree of hypertension, hypokalemia, and disorders of sexual development (DSD), which can include abnormal sexual differentiation in males and sexual infantilism in females. Over 100 mutations in <em>CYP17A1</em> have been identified, with most cases involving missense mutations or small deletions.</div></div><div><h3>Method</h3><div>This study examined the clinical features, biochemical profiles, and genetic background of two 46, XY siblings from the same family, both diagnosed with 17OHD—a scenario that is uncommonly seen in clinical practice. We performed a genetic analysis of the <em>CYP17A1</em> gene in two generations of the family to confirm the diagnosis.</div></div><div><h3>Results</h3><div>Both patients are phenotypically female, presenting with hypertension, hypokalemia, primary amenorrhea, and absent secondary sexual characteristics. Genetic analysis revealed two novel compound heterozygous mutations in the <em>CYP17A1</em> gene: R45WfsTer5 (a frameshift mutation) and L361P (a missense mutation). Neither variant is reported in the ClinVar database, and the frameshift mutation (R45WfsTer5) is newly identified.</div></div><div><h3>Conclusions</h3><div>The discovery of these two novel <em>CYP17A1</em> mutations expands the genetic spectrum of 17OHD and provides new insights into the genetic underpinnings of the disease. Personalized treatment plans are necessary, and the choice of glucocorticoids with stronger sodium retention effects may be required to manage hypertension and electrolyte imbalances in select patients.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109562"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060748","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":"Synthesis of novel α-spinasterol derivatives and their inhibitory effects on CCL17 and CCL22 chemokine expression","authors":"Hyejin Moon ,&nbsp;Hongjoon Yoon ,&nbsp;Hana Jung,&nbsp;Tae Hoon Lee,&nbsp;Hakwon Kim","doi":"10.1016/j.steroids.2024.109553","DOIUrl":"10.1016/j.steroids.2024.109553","url":null,"abstract":"<div><div>Natural α-spinasterol is well known for its various biological activities. In this study, we investigated the anti-inflammatory effects of newly synthesized α-spinasterol derivatives by tracking the expression of CCL17 and CCL22 chemokines, which serve as biomarkers for immune cell trafficking in skin inflammation. Initially, the 3-epimer of α-spinasterol, which results from inversion of stereochemistry at the C-3 position of α-spinasterol, was synthesized using the Mitsunobu reaction. Subsequently, new compounds were synthesized by introducing azido, amino, and amide groups at the C-3 position of α-spinasterol or 3-<em>epi</em>-α-spinasterol. The anti-inflammatory activity of these compounds was evaluated by examining their inhibitory effects on the mRNA expression of CCL17 and CCL22. Among these derivatives, 3α-<strong>8</strong>, 3α-<strong>12b</strong>, and 3α-<strong>12c</strong> exhibited potential anti-inflammatory activity <em>in vitro</em>, compared to α-spinasterol. Furthermore, compound 3α-<strong>8</strong> showed even greater activity than 3α-<strong>12b</strong> and 3α-<strong>12c</strong>, underscoring its potential as a highly effective agent. These results suggest that the newly synthesized α-spinasterol derivatives hold promise as candidates for skin inflammation therapeutics.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109553"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812970","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":"Allosteric communications between domains of nuclear receptors","authors":"Fraydoon Rastinejad","doi":"10.1016/j.steroids.2024.109551","DOIUrl":"10.1016/j.steroids.2024.109551","url":null,"abstract":"<div><div>Nuclear receptors (NRs) regulate gene expression in response to hormonal signals, influencing diverse physiological processes and diseases. Structural and dynamics investigations based on X-ray crystallography, cryo-electron microscopy (cryo-EM), hydrogen–deuterium exchange mass spectrometry, and molecular dynamics simulations, have significantly deepened our understanding of the conformational states, dynamics, and interdomain interactions of multi-domain NRs. Structural studies have examined heterodimeric complexes such as peroxisome proliferator-activated receptor gamma (PPAR-γ) with retinoid X receptor alpha (RXRα), liver X receptor beta (LXRβ) with RXRα, and retinoic acid receptor beta (RARβ) with RXRα, as well as homodimers like hepatic nuclear factor 4 alpha (HNF-4α), androgen receptor (AR), and glucocorticoid receptor (GR). These investigations highlight critical allosteric communication between ligand-binding domains (LBDs) and DNA-binding domains (DBDs), emphasizing the roles of flexible hinge regions and <em>N</em>-terminal segments in adapting to diverse DNA configurations. Both non-steroid receptor heterodimers and homodimers exhibit robust interdomain connections that mediate allosteric signaling. For instance, AR demonstrates three distinct conformational states that underscore its dynamic behavior, while GR exhibits unique ligand-dependent domain interactions shaping receptor signaling. The collective findings so far suggest a conserved mechanism of cross-domain communication across the NR family. Supported by complementary biophysical, spectroscopic, mutagenesis, and computational studies, this body of research has elucidated the nature of domain-domain interfaces and their pivotal roles in regulating the transcriptional activity of steroid and non-steroid receptors.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109551"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802309","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":"Patterns of corticosterone exposure affect the subcellular localisation of mineralocorticoid and glucocorticoid receptor complexes and gene expression","authors":"Susana N. Paul ,&nbsp;Anna De Visser ,&nbsp;Federica Motta ,&nbsp;Caroline A. Rivers ,&nbsp;John R. Pooley ,&nbsp;Stafford L. Lightman ,&nbsp;Onno C. Meijer","doi":"10.1016/j.steroids.2024.109524","DOIUrl":"10.1016/j.steroids.2024.109524","url":null,"abstract":"<div><div>Mineralocorticoid (MR) and glucocorticoid receptors (GR) act as transcription factors and major mediators of glucocorticoid signalling, with pivotal roles in regulating the stress response and hormonal signalling, mood, cognition and memory. The MR and GR share many target genes, have a high degree of homology in their DNA binding (DBD) and ligand binding domain (LBD) but differ considerably in the <em>N</em>-terminal domain (NTD). Using Proximity Ligation Assay (PLA) we quantitatively assessed MR-GR complex subcellular localisation and transcriptional regulation in murine neuroblastoma (N2A) cells stimulated by constant or pulsatile corticosterone (CORT) patterns. We observe that continuous receptor activation by CORT caused localisation at the periphery of the cell nucleus. Truncation of the receptor Ligand Binding Domain (LBD) led to a stronger localisation of MR-GR complexes at the periphery of the cell nuclei. This was also observed for GR immunofluorescence (IF), while in cells expressing only MR or GR the mRNA response to pulsatile hormone treatment was substantially attenuated. However, there was no clearcut correlation between the spatial distribution of MR-GR complexes and the mRNA levels of target genes. Overall, our findings suggest that longer presence in the cell nucleus favors more peripheral nuclear localisation.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109524"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569520","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":"Effect of estrogen on myocardial ischemia–reperfusion injury in male and female rats and related mechanism","authors":"Sichong Chen ,&nbsp;Lijuan Yang ,&nbsp;Jiayao Xue ,&nbsp;Xinmiao Tian,&nbsp;Huiyuan Hu,&nbsp;Qinghua Gao,&nbsp;Rui Feng,&nbsp;Liying Hao","doi":"10.1016/j.steroids.2025.109561","DOIUrl":"10.1016/j.steroids.2025.109561","url":null,"abstract":"<div><div>Due to the difference of estrogen levels in different phases of estrous cycle, it is necessary to exclude the influence of endogenous estrogen when studying the cardiovascular effects of estrogen and its analogues. In this study, the ischemia/reperfusion (I/R) injury of isolated heart were investigated in female rats during different phases of estrous cycle with male rats as comparison. The results indicated that the estrogen content in blood of rats during metestrus and diestrus (MD) was lower than those during proestrus and estrous (PE). 17β-Estradiol (E2) at 10⁻⁸ M did not show significant effects on I/R injury in male rats and female rats during PE. However, E2 exerted an obviously protective effects against I/R injury on heart rate (HR), lactate dehydrogenase (LDH) and creatine kinase (CK) release in female rats during MD. Furthermore, E2 relieved I/R injury in female rats during MD by decreasing the infarct size and the expression level of p-CaMKII. The results suggested estrous cycles may influence on the extent of cardiac I/R injury due to the regulation of E2 on CaMKII expression level, providing an idea that the estrus cycle should be considered for animal model preparation and toxicity studies in estrogen and environmental hormone research.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109561"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053643","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":"Nandrolone decanoate induces heart injury via oxidative damage and mitochondrial apoptotic pathway by regulation of TLR4/NF-κB/NLRP3 axis in male rats: The rescue effect of N-acetylcysteine","authors":"Haniyeh Amini ,&nbsp;Alireza Shirpoor ,&nbsp;Roya Naderi","doi":"10.1016/j.steroids.2025.109563","DOIUrl":"10.1016/j.steroids.2025.109563","url":null,"abstract":"<div><div>Myocardial apoptosis is a leading cause of damage in cardiac tissues of nandrolone (ND) treatment. However, its molecular mechanism is not fully understood. This study aims to investigate the effect of ND with or without N −acetylcysteine (NAC) treatment on oxidative damage and TLR4/NF-κB /NLRP3 signaling pathway in the heart of male rats. Eighteen male Wistar rats with a weight range of 220 ± 10 g were selected. They were divided into three groups (n = 6): control (C) group, ND group, NAC + ND group. After six weeks of treatment, the TUNEL staining indicated that ND increased the number of apoptotic cells in the hearts of male rats. The molecular analysis demonstrated that ND exposure resulted in increased protein levels of cytochrome <em>c</em>, c-Caspase-3/p-Caspase-3 ratio, p53, TLR4, NF-κB, NLRP3, and 8-OHdG with a concomitant up-regulation of LDH and CK-MB enzymes activity in the heart tissue compared to the C group. Our findings suggested that ND can cause damage to heart tissue via induction of DNA damage, apoptosis, and probably TLR4/NF-κB/NLRP3 signaling pathway plays a crucial role in this process. It also demonstrates that these negative effects of ND can be reduced by using NAC treatment as an antioxidant and anti-inflammatory agent.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109563"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080910","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}