{"title":"Inducing agents and PCOS - A comprehensive analysis.","authors":"Dhanyaa Muthukumaran, Jayalakshmi Kumar, Rajeshkumar Shanmugam","doi":"10.1016/j.jsbmb.2025.106840","DOIUrl":"10.1016/j.jsbmb.2025.106840","url":null,"abstract":"<p><p>Polycystic Ovary Syndrome (PCOS) is a severe and heterogeneous endocrine disorder affecting 6-20 % of women of reproductive age globally. Despite its high prevalence, the underlying etiology and pathophysiology remain unclear, necessitating the use of animal models to study disease mechanisms and therapeutic targets. This review critically evaluates various induction agents used in PCOS animal models and their ability to mimic the clinical, metabolic, and reproductive manifestations of the human condition. Induction agents explored include androgens [Testosterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA)], estrogen (estradiol valerate), aromatase inhibitors (letrozole), endocrine disruptors (bisphenol A), and dietary modifications (high-fat or high-sugar diets). These agents, administered in species such as rats, mice, zebrafish, reproduce hallmark PCOS features, including hyperandrogenism, anovulation, polycystic ovaries, and insulin resistance. The review highlights the mechanisms, symptom profiles, and translational relevance of each model. Comparative analysis is provided to assess the strengths and limitations associated with each agent, considering factors such as hormonal balance, metabolic function, and reproductive outcomes. Animal models serve as essential tools for understanding PCOS and testing therapeutic interventions. Each inducing agent offers unique insights into specific aspects of the disorder, although none fully replicates the human syndrome. The selection of the agent and animal species based on research goals is vital for clinical relevance. Future work should focus on integrating models that reflect both reproductive and metabolic features of PCOS to improve translational value.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106840"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Canine aldo-keto reductase 1C3 (AKR1C3/PGFS) exhibits 17β/20α-hydroxysteroid dehydrogenase activity and is inhibited by trilostane.","authors":"Satoshi Endo, Riri Hayashi, Yutaro Nakada, Yudai Kudo, Yoshifumi Morikawa, Yuji Sakai, Koichi Suenami, Naohito Abe, Toshiyuki Matsunaga, Akira Hara, Hiroshi Ueda","doi":"10.1016/j.jsbmb.2025.106874","DOIUrl":"https://doi.org/10.1016/j.jsbmb.2025.106874","url":null,"abstract":"<p><p>Most members of the aldo-keto reductase (AKR) 1C subfamily are hydroxysteroid dehydrogenases (HSDs), and their numbers are more than four in many individual mammals. In contrast, there is only one gene for the AKR1C protein (AKR1C3) in dogs, which have been used as a preclinical model for human biomedical research. Here, we report that dog AKR1C3 (known as prostaglandin-F synthase) catalyzes the conversion of the 17-keto group of estrone, 4- and 5-androstenes, and 5α-androstanes to their 17β-hydroxy-metabolites with NADPH as a coenzyme. Dog AKR1C3 also exhibited 20α-HSD activity toward 20-keto-C<sub>21</sub>-steroids (deoxycorticosterone, its 5α-dihydro- and 5α-tetrahydro-derivatives, and progesterone), but, notably, did not display 3-ketosteroid reductase activity. Additionally, dog AKR1C3 reduced various nonsteroidal carbonyl compounds including endogenous 4-oxo-2-nonenal, all-trans-retinal, and isatin, of which isatin was the most excellent substrate. In the reverse reaction, the enzyme weakly oxidized 17β- and 20α-hydroxysteroids and some alicyclic alcohols. Further site-directed mutagenesis study revealed that residue M55 is responsible for the lack of 3-ketosteroid reductase activity. The enzyme was inhibited by flavonoids, nonsteroidal anti-inflammatory drugs, bile acids, benzbromarone, abiraterone, and trilostane, of which trilostane inhibited most potently (IC<sub>50</sub> 0.30µM), and its inhibition was uncompetitive and competitive with respect to the substrates in the forward and reverse reactions, respectively. Thus, dog AKR1C3 may play a role in the metabolism of steroid hormones (as a reductive 17β/20α-HSD) and nonsteroidal carbonyl compounds, and is a novel target of trilostane that is used to treat Cushing's disease in dogs.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106874"},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xia Ge, Min Ye, Aihua Fei, Qingping Zhang, Aihong Yuan
{"title":"Advancements in Understanding the Role and Mechanisms of Mitochondria in Diabetes: A Comprehensive Review.","authors":"Xia Ge, Min Ye, Aihua Fei, Qingping Zhang, Aihong Yuan","doi":"10.1016/j.jsbmb.2025.106875","DOIUrl":"https://doi.org/10.1016/j.jsbmb.2025.106875","url":null,"abstract":"<p><p>Diabetes mellitus is a global health crisis with a rising prevalence attributed to complex interactions of genetic, lifestyle, and environmental factors. This comprehensive review delves into the pivotal role of mitochondrial dysfunction in the onset and progression of diabetes. It outlines how defects in mitochondrial oxidative phosphorylation, increased free radical production, and mitochondrial DNA damage contribute to insulin resistance, β-cell apoptosis, and systemic metabolic dysfunctions. The review highlights the critical roles of mitochondria in energy metabolism, oxidative balance, and the interplay of genetic and environmental factors in diabetes. It also emphasizes the association of impaired mitochondrial function with various diabetes-related complications and organ-specific diseases, underscoring the urgent need for innovative therapeutic strategies. Potential interventions discussed include pharmacological agents promoting mitochondrial biogenesis and enhancing mitochondrial dynamics, alongside dietary and lifestyle modifications that support mitochondrial function and overall metabolic health. The review calls for intensified research into mitochondrial mechanisms and their therapeutic targets, advocating for comprehensive clinical trials and support from medical and governmental institutions to advance diabetes management strategies centered on mitochondrial health.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106875"},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingqi Zhao , Xue Liu , Yong Pang , Haoge Luo , Jie Zhang , Chen Shao
{"title":"Androgen receptor inhibitory activity of dihydrocapsaicin: Insights from in vitro, in vivo and in silico studies","authors":"Jingqi Zhao , Xue Liu , Yong Pang , Haoge Luo , Jie Zhang , Chen Shao","doi":"10.1016/j.jsbmb.2025.106872","DOIUrl":"10.1016/j.jsbmb.2025.106872","url":null,"abstract":"<div><div>As a natural capsaicinoid from <em>Capsicum annuum</em> L., dihydrocapsaicin is well known for its anti-obesity property by reducing fat accumulation in adipose tissue. The androgen receptor (AR) is essential for both health and disease in humans and is the main focus for prostate cancer treatment. This study seeks to explore how dihydrocapsaicin inhibits the AR in human prostate cancer cell lines, aiming to offer a new natural product-derived AR inhibitor for the clinical management of prostate-related conditions. At first, it was observed that dihydrocapsaicin can induce proliferation suppression in human prostate cancer cells by hindering the cell cycle at the G0/G1 phase. In addition, dihydrocapsaicin probably inhibited AR activity by blocking its movement from the cytoplasm to the nucleus through binding to the AR-LBD, highlighting its potential as an effective inhibitor. From a mechanistic perspective, dihydrocapsaicin facilitated AR release from a stabilizing chaperone complex and enhanced its ubiquitination by E3 ligases, resulting in AR partial degradation via the ubiquitin-proteasome pathway. Our study on the molecular mechanisms behind dihydrocapsaicin's inhibitory effects on the AR revealed that it not only hindered the growth of prostate cancer cells but also reduced tumor growth <em>in vivo</em>. These results offer both experimental evidence and a theoretical basis for the thorough development of AR inhibitors, emphasizing dihydrocapsaicin's potential for application in functional foods or nutritional supplements targeting prostatic disorders.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106872"},"PeriodicalIF":2.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
André Hadad , Victor L.B. França , Jackson L. Amaral , Hernandes F. Carvalho , Valder N. Freire
{"title":"Quantum biochemistry characterization of representative conformations of the sex hormone-binding globulin monomer bound to estradiol, dihydrotestosterone and testosterone","authors":"André Hadad , Victor L.B. França , Jackson L. Amaral , Hernandes F. Carvalho , Valder N. Freire","doi":"10.1016/j.jsbmb.2025.106873","DOIUrl":"10.1016/j.jsbmb.2025.106873","url":null,"abstract":"<div><div>The transport of sex steroid hormones in the plasma is largely mediated by sex-hormone binding globulin (SHBG). SHBG is a functional homodimer, meaning it can bind two sex hormones with similar affinities. This binding occurs through a complex allosteric mechanism. This globulin plays a pivotal role in regulating the availability of sex hormones within target tissues and cells. Given the established correlation between SHBG and various pathological disorders, there has been increasing interest in characterizing the interactions between SHBG and hormones as well as in identifying potential inhibitors or modulators of the SHBG function. In this regard, the present study aims to provide novel insights into the binding of SHBG with estradiol (EST), dihydrotestosterone (DHT), and testosterone (TES). To this end, molecular docking, molecular dynamics, and quantum mechanics were employed here. The analysis of representative conformations of the highest and lowest interaction energies revealed a high degree of similarity in the binding sites. The SHBG::TES interaction, for which structural data are lacking, exhibited a high degree of structural and energetic similarity to the SHBG::EST and SHBG::DHT complexes. Quantum mechanics calculations demonstrated the following order of theoretical binding affinity, from the highest to lowest: SHBG::DHT > SHBG::EST > SHBG::TES. Furthermore, SER42, PHE67, MET107, and MET139 exhibited the lowest interaction energies, thereby emphasizing the critical role of these residues in SHBG coupling and steroid hormone transport. The energetic description of these complexes contributes to a deeper understanding of steroid hormone transport and provides new insights for targeting SHBG in drug discovery.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106873"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of endogenous steroid sulfates and glucuronides in urine after oral and transdermal administration of testosterone. Part I: Male participants","authors":"Sandra Pfeffer , Günter Gmeiner , Nenad Dikic , Marija Andjelkovic , Guro Forsdahl","doi":"10.1016/j.jsbmb.2025.106870","DOIUrl":"10.1016/j.jsbmb.2025.106870","url":null,"abstract":"<div><div>The detection of the performance-enhancing drug testosterone (T) remains a significant challenge in doping control analysis. Longitudinal monitoring through the steroidal Athlete Biological Passport (ABP) is a valuable tool for T detection, but further research is needed to enhance its efficacy. Phase II metabolites of endogenous anabolic androgenic steroids (EAAS), including glucuronides and sulfates, have gained increasing interest as potential new biomarkers for the steroidal ABP. Notably, sulfate metabolites have demonstrated higher sensitivity to oral, transdermal, and intramuscular T administration, with extended detection windows compared to traditional biomarkers. However, before incorporating these promising biomarkers into urinary steroid profiling, it is essential to address the metabolic variations associated with different T administration methods, as well as differences related to ethnicity and sex. In this part of the study, we investigate the effects of oral and transdermal T administration on conventional biomarkers and phase II EAAS metabolites in male participants. Sulfate ratios indicated higher sensitivity to multiple administrations of testosterone undecanoate (TU) tablets and T gel, significantly prolonging detection times compared to conventional steroid profile biomarkers. Specifically, sulfate ratios such as androsterone sulfate (AS)/testosterone sulfate (TS) and epiandrosterone sulfate (EpiAS)/TS enabled detection for an average of 20 days following the last oral TU dose and at least 16 days after the last transdermal T application. These findings provide further evidence that incorporating sulfate EAAS metabolites into steroid profiling enhances detection capabilities. For advanced T doping detection, sulfate metabolites should be considered essential biomarkers in the steroid profile.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106870"},"PeriodicalIF":2.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kouta Noriyama , Nobuhisa Todo , Nobuyo Tamiya , Masaki Shigeta , Yuki Toda , Shigekuni Hosogi , Eishi Ashihara
{"title":"17β-estradiol (E2) increases ciliary beat frequency via membrane estrogen receptor β","authors":"Kouta Noriyama , Nobuhisa Todo , Nobuyo Tamiya , Masaki Shigeta , Yuki Toda , Shigekuni Hosogi , Eishi Ashihara","doi":"10.1016/j.jsbmb.2025.106871","DOIUrl":"10.1016/j.jsbmb.2025.106871","url":null,"abstract":"<div><div>Estrogen receptors (ER) are expressed in various tissues, including the lungs and other respiratory tissues, independent of sex. However, the role of estrogen in the respiratory tract is not fully understood. Airway ciliated cells are important for mucociliary clearance (MCC), which protects the human airways from foreign substances, and ciliary beat frequency (CBF) is an important indicator of MCC efficiency. Although the function of estrogen in airway smooth muscle cells and goblet cells has been studied, its effects on airway ciliated cells remain unclear. Here, we investigated the effect of 17β-estradiol (E2) on CBF. E2 increased CBF and intracellular cAMP concentration ([cAMP]<sub>i</sub>) in murine airway ciliated cells, whereas it had no effect on intracellular Ca<sup>2 +</sup> concentration and intracellular pH. The selective ERβ inhibitor PHTPP suppressed the E2-induced increase in CBF and [cAMP]<sub>i</sub>. β-Estradiol 6-(O-carboxymethyl)oxime: bovine serum albumin conjugate, which activates membrane ER, also increased CBF and [cAMP]<sub>i</sub> in murine airway ciliated cells, and PHTPP suppressed these effects. The results of this study indicate that E2 increases CBF by increasing [cAMP]<sub>i</sub> via membrane ERβ in murine airway ciliated cells. These results provide new insight into the function of estrogen in airway ciliated cells.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106871"},"PeriodicalIF":2.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of 14–3-3 protein enhances steroid hormone production and oxidative stress in mouse ovary: Implications for apoptosis regulation","authors":"Shatrudhan Upadhyay , Namrata Dubey , Aanya Singh","doi":"10.1016/j.jsbmb.2025.106869","DOIUrl":"10.1016/j.jsbmb.2025.106869","url":null,"abstract":"<div><div>The ovary is a primary reproductive organ where the fine balance between steroidogenesis, oxidative stress, and apoptosis governs female reproductive health. A highly conserved protein, 14–3–3, is known to influence steroid biosynthesis, redox balance, and cell survival; however, its integrative role in ovarian physiology remains poorly defined. This study investigated the consequences of pharmacological inhibition of 14–3–3 protein using BV02 in <em>in vitro</em> cultured mouse ovaries. Immunohistochemical analysis revealed strong expression of 14–3–3 in granulosa cells, with moderate expression in oocytes and theca cells. In the BV02-treated ovary (100 μM), there was significant elevation in the levels of ovarian progesterone, testosterone, and estradiol, indicating enhanced steroidogenesis. However, the treated ovaries showed decreased activity of catalase and superoxide dismutase (SOD), along with increased lipid peroxidation (TBARS), indicating increased oxidative stress. Western blot analysis showed downregulation of the anti-apoptotic protein Bcl-2 together with elevated levels of the pro-apoptotic protein Caspase-3, signifying a molecular shift toward apoptosis. Correlation analysis further established strong associations (p < 0.05) between oxidative stress markers and apoptotic regulators, highlighting a mechanistic link between impaired antioxidant defenses and apoptosis. These findings reveal that 14–3–3 protein acts as a dual regulator of ovarian physiology by restraining steroid hormone production in addition to maintaining redox balance and cell survival. Disruption of this equilibrium may lead to pathological states such as polycystic ovary syndrome (PCOS) and ovarian cancer. Thus, this study provides novel mechanistic insights into the regulatory role of 14–3–3 protein in the ovary and underscores its potential as a therapeutic target in reproductive disorders.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106869"},"PeriodicalIF":2.5,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meriam Messedi, Wassim Guidara, Mohammad Samadi, Fatma Makni-Ayadi, Gérard Lizard
{"title":"Potential contribution of oxysterols and cholestanol in the vascular inflammatory process occurring in patients with Behcet's disease.","authors":"Meriam Messedi, Wassim Guidara, Mohammad Samadi, Fatma Makni-Ayadi, Gérard Lizard","doi":"10.1016/j.jsbmb.2025.106868","DOIUrl":"10.1016/j.jsbmb.2025.106868","url":null,"abstract":"<p><p>Oxysterols, which are cholesterol oxidation products, can be generated by either enzymatic reactions and/or reactive oxygen species (ROS). Oxysterols considered to play key roles in health and diseases, have several physiological and biological activities. They exhibit strong immune-modulatory, pro-inflammatory and pro-oxidant properties supporting that some of them are involved in the pathogenesis of numerous chronic diseases associated with inflammation mainly cardiovascular and neurological diseases. Some oxysterols, especially those oxidized on the lateral chain, can bind to nuclear receptors such as the liver X receptors (LXR) involved in the control of transcriptional programs that regulate cell metabolism. Since Behçet's disease (BD) is an acute systemic vasculitis leading to severe vascular damage, recent studies deem that BD could be considered a chronic immune inflammatory disease. Although BD constitutes a separate disease entity, it is still underdiagnosed, and no treatments are available. Whereas the pathophysiology of BD is not well known, the vasculitis is common to its different etiologies. Therefore, as several oxysterols are known to contribute to vascular damage, these molecules were analyzed in the plasma of BD patients. Noteworthy, altered oxysterol profiles were observed in BD patients from Tunisia. These patients were characterized by abnormal levels of 7-ketocholesterol (7KC), 25-hydroxycholesterol (25-OHC), 27-hydroxycholesterol (27-OHC), and cholestane-3β,5α,6β-triol (CT). Thus, 7KC and 25-OHC were decreased whereas 27-OHC and CT were increased. Cholesterol undergoes a rapid non enzymatic oxidation to form cholesterol-5α,6α-epoxide and cholesterol-5β,6β-epoxide, and these molecules are then converted by cholesterol 5,6 epoxide hydrolase (ChEH) and/or ROS to CT. In addition, cholestanol level was increased. Therefore, there are evidence of altered oxysterol profiles and cholestanol level in BD patients. It is proposed that oxysterols and cholestanol could be used as biomarkers to characterize BD disease i) to distinguish different forms of this disease and of its outcome, and ii) to identify efficient treatments. Based on the abnormal levels of oxysterols and cholestanol observed in the plasma of BD Tunisian patients, current data support that a rupture of oxysterol homeostasis and perturbations of cholesterol metabolism, suggested by increased cholestanol level, could both contribute to the pathophysiology of Behçet's disease.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106868"},"PeriodicalIF":2.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}