Journal of Bioenergetics and Biomembranes最新文献

{"title":"PRKN-mediated the ubiquitination of IQGAP3 regulates cell growth, metastasis and ferroptosis in early-onset colorectal cancer.","authors":"Gun Chen, Linghua Cong, Chijiang Gu, Ping Li","doi":"10.1007/s10863-024-10039-6","DOIUrl":"https://doi.org/10.1007/s10863-024-10039-6","url":null,"abstract":"<p><p>High IQ motif-containing GTPase activating protein 3 (IQGAP3) expression is considered to be associated with poor prognosis of colorectal cancer (CRC). However, its role in early-onset CRC (EOCRC) progress is unclear. The mRNA and protein levels of IQGAP3 and Parkin (PRKN) were examined by qRT-PCR and western blot. Cell proliferation, apoptosis and metastasis were determined by CCK8 assay, EdU assay, flow cytometry and transwell assay. ROS, MDA, GSH, Fe²⁺, ACSL4 and SLC7A11 levels were detected to assess cell ferroptosis. The interaction between PRKN and IQGAP3 was assessed by Co-IP assay and ubiquitination assay. Xenograft tumor models were constructed to explore the effect of PRKN and IQGAP3 on the tumorigenesis in vivo. IQGAP3 was upregulated, while PRKN was downregulated in EOCRC tissues and cells. IQGAP3 knockdown inhibited CRC cell proliferation, migration and invasion, while enhanced apoptosis and ferroptosis. PRKN ubiquitinated IQGAP3 to promote its degradation. PRKN overexpression suppressed CRC cell growth, metastasis and promoted ferroptosis, while these effects were reversed by upregulating IQGAP3. In animal study, upregulation of PRKN reduced CRC tumorigenesis by decreasing IQGAP3 expression in vivo. IQGAP3, ubiquitinated by PRKN, promoted EOCRC progression by enhancing cell proliferation, metastasis, repressing apoptosis and ferroptosis, which provided a novel target for EOCRC treatment.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction in mitochondrial ATP synthesis mimics the effect of low glucose in depolarizing neurons from the subpostremal nucleus of the solitary tract of rats","authors":"Patrik S. Zarpellon, Cahuê Murat, Ricardo M. Leão","doi":"10.1007/s10863-024-10037-8","DOIUrl":"https://doi.org/10.1007/s10863-024-10037-8","url":null,"abstract":"<p>Neurons of the subpostremal nucleus of the solitary tract (NTS) respond to changes in extracellular glucose with alterations in membrane potential with both depolarization and hyperpolarization. From 5 mM glucose, a rapid shift to 0.5 mM glucose produces a membrane depolarization by an unknown mechanism in most neurons. However, the mechanism involved in this response needs to be known. Here, we investigated if the low glucose-induced depolarization could be mimicked by reducing ATP synthesis and possible mediators of this effect. We showed that applying the mitochondrial uncoupler CCCP (1 µM) reproduced the effects of low glucose depolarizing the membrane, generating an inward current, and decreasing membrane resistance. On the other hand, activation of AMPK did not alter these parameters. To test if low glucose and CCCP could depolarize the membrane by affecting the ionic gradient, we inhibited the electrogenic Na/K pump with 10 µM of ouabain. We observed a similar membrane depolarization but not a decrease in membrane resistance. We conclude that perfusion of neurons of the subpostremal NTS with a low glucose solution depolarizes the membrane by probably reducing intracellular ATP, but not by activating AMPK or decreasing the ionic gradient across the membrane.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NFS1 inhibits ferroptosis in gastric cancer by regulating the STAT3 pathway","authors":"You Jiang, Liqiang Li, Wenbo Li, Kun Liu, Yuee Wu, Zhengguang Wang","doi":"10.1007/s10863-024-10038-7","DOIUrl":"https://doi.org/10.1007/s10863-024-10038-7","url":null,"abstract":"<p>Cysteine desulfurase (NFS1) is highly expressed in a variety of tumors, which is closely related to ferroptosis of tumor cells and affects prognosis. The relationship between NFS1 and the development of gastric cancer (GC) remains unknown. Here we showed that NFS1 expression was significantly higher in GC tissues compared to adjacent normal tissues. Patients with high expression of NFS1 in GC tissues had a lower overall survival rate than those with low expression. NFS1 was highly expressed in cultured GC cells compared to normal gastric cells. Knockdown of NFS1 expression reduced the viability, migration and invasion of GC cells. In cultured GC cells, NFS1 deficiency promoted ferroptosis. Mechanistically, NFS1 inhibited ferroptosis by upregulating the signal transduction and activator of transcription 3 (STAT3) signaling pathway in cultured GC cells. NFS1 knockdown using siRNA inhibited the STAT3 pathway, reduced the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and elevated intracellular levels of reactive oxygen species (ROS), ferrous ion (Fe²⁺), and malondialdehyde (MDA) in cultured GC cells. A specific STAT3 activator significantly reversed the inhibitory effect of NFS1 deficiency on ferroptosis in cultured GC cells. These in vitro results were further confirmed by experiments in vivo using a mouse xenograft tumor model. Collectively, <span>these results indicate that</span> NFS1 is overexpressed in human GC tissues and correlated with prognosis. NFS1 inhibits ferroptosis by activating the STAT3 pathway in GC cells. These results suggest that NFS1 may be a potential prognostic biomarker and therapeutic target to treat GC.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142207583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vesicle-associated membrane protein 8 knockdown exerts anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on colorectal cancer cells by inhibition of the JAK/STAT3 pathway.","authors":"Yi Xu, Tianyao Yang, Qiu Xu, Yan Tang, Qiong Yang","doi":"10.1007/s10863-024-10019-w","DOIUrl":"10.1007/s10863-024-10019-w","url":null,"abstract":"<p><p>Vesicle-associated membrane protein 8 (VAMP8), a soluble n-ethylmaleimide-sensitive factor receptor protein, acts as an oncogenic gene in the progression of several malignancies. Nevertheless, the roles and mechanisms of VAMP8 in colorectal cancer (CRC) progression remain unknown. The expression and prognostic significance of VAMP8 in CRC samples were analyzed through bioinformatics analyses. Cell proliferation was detected using CCK-8 and EdU incorporation assays and apoptosis was evaluated via flow cytometry. Western blot analysis was conducted to examine the protein expression. Ferroptosis was evaluated by measurement of iron metabolism, lipid peroxidation, and glutathione (GSH) content. VAMP8 was increased in CRC samples relative to normal samples on the basis of GEPIA and HPA databases. CRC patients with high level of VAMP8 had a worse overall survival. VAMP8 depletion led to a suppression of proliferation and promotion of apoptosis in CRC cells. Additionally, VAMP8 knockdown suppressed beclin1 expression and LC3-II/LC3-I ratio, elevated p62 expression, increased Fe²⁺, labile iron pool, lipid reactive oxygen species, and malondialdehyde levels, and repressed GSH content and glutathione peroxidase activity. Moreover, VAMP8 knockdown inhibited the activation of janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway in CRC cells. Mechanistically, activation of the JAK/STAT3 pathway by JAK1 or JAK2 overexpression attenuated VAMP8 silencing-mediated anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on CRC cells. In conclusion, VAMP8 knockdown affects the proliferation, apoptosis, autophagy, and ferroptosis by the JAK/STAT3 pathway in CRC cells.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-modified lncRNA DSCAM-AS1 promotes breast cancer progression through inhibiting ferroptosis.","authors":"Zeming Yan, Zhongzeng Liang, Kangwei Luo, Liyan Yu, Chunyan Chen, Miao Yu, Xiaojing Guo, Mingyi Li","doi":"10.1007/s10863-024-10024-z","DOIUrl":"10.1007/s10863-024-10024-z","url":null,"abstract":"<p><p>Numerous studies have indicated that N⁶-methyladenosine (m⁶A) and lncRNAs play pivotal roles in human cancer. However, the underlying functions and mechanisms of m⁶A-lncRNA in the physiological processes of breast cancer remain unclear. Here, we found that DSCAM-AS1 is an m⁶A-modified lncRNA that was overexpressed in breast cancer tissues and cells, indicating poor clinical prognosis. Gain/loss functional assays suggested that DSCAM-AS1 inhibited erastin-induced ferroptosis in breast cancer cells. Mechanistically, there were remarkable m⁶A modification sites on both the 3'-UTR of DSCAM-AS1 and the endogenous antioxidant factor SLC7A11. M⁶A methyltransferase methyltransferase-like 3 (METTL3) methylated both SLC7A11 and DSCAM-AS1. Moreover, DSCAM-AS1 recognized m⁶A sites on the SLC7A11 mRNA, thereby enhancing its stability. Taken together, these findings indicated a potential therapeutic strategy for breast cancer ferroptosis in an m⁶A-dependent manner.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of lysophosphatidic acid (LPA) receptor-mediated signaling in cancer cell biology.","authors":"Miwa Takai, Shiori Mori, Kanya Honoki, Toshifumi Tsujiuchi","doi":"10.1007/s10863-024-10028-9","DOIUrl":"10.1007/s10863-024-10028-9","url":null,"abstract":"<p><p>Lysophosphatidic acid (LPA) is a simple lipid which is endogenously synthesized from lysophosphatidylcholine (LPC) by autotaxin (ATX). LPA mediates a variety of cellular responses through the binding of G protein-coupled LPA receptors (LPA₁ to LPA₆). It is considered that LPA receptor-mediated signaling plays an important role in the pathogenesis of human malignancy. Genetic alterations and epigenetic changes of LPA receptors have been detected in some cancer cells as well as LPA per se. Moreover, LPA receptors contribute to the promotion of tumor progression, including cell proliferation, invasion, metastasis, tumorigenicity, and angiogenesis. In recent studies, the activation of LPA receptor-mediated signaling regulates chemoresistance and radiosensitivity in cancer cells. This review provides an updated overview on the roles of LPA receptor-mediated signaling in the regulation of cancer cell functions and its potential utility as a molecular target for novel therapies in clinical cancer approaches.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of miltefosine-model membranes interactions at the molecular level for two different PS levels modeling cancer cells.","authors":"Züleyha Özçelik Çetinel, Duygu Bilge","doi":"10.1007/s10863-024-10025-y","DOIUrl":"10.1007/s10863-024-10025-y","url":null,"abstract":"<p><p>Miltefosine (MLT) is a broad-spectrum drug included in the alkylphospholipids (APL) used against leishmania and various types of cancer. The most crucial feature of APLs is that they are thought to only kill cancerous cells without harming normal cells. However, the molecular mechanism of action of APLs is not completely understood. The increase in the phosphatidylserine (PS) ratio is a marker showing the stage of cancer and even metastasis. The goal of this research was to investigate the molecular effects of miltefosine at the molecular level in different PS ratios. The effects of MLT on membrane phase transition, membrane orders, and dynamics were studied using DPPC/DPPS (3:1) and DPPC/DPPS (1:1) multilayer (MLV) vesicles mimicking DPPS ratio variation, Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared spectroscopy (FTIR). Our findings indicate that miltefosine is evidence at the molecular level that it is directed towards the tumor cell and that the drug's effect increases with the increase of anionic lipids in the membrane depending on the stage of cancer.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<ArticleTitle xmlns:ns0=\"http://www.w3.org/1998/Math/MathML\">Modelling spatio-temporal interactions between second messengers Ca <ns0:math><ns0:msup><ns0:mrow /> <ns0:mrow><ns0:mn>2</ns0:mn> <ns0:mo>+</ns0:mo></ns0:mrow> </ns0:msup> </ns0:math> and cAMP in a pancreatic <ns0:math><ns0:mi>β</ns0:mi></ns0:math> -cell.","authors":"Vaishali, Neeru Adlakha","doi":"10.1007/s10863-024-10021-2","DOIUrl":"10.1007/s10863-024-10021-2","url":null,"abstract":"<p><p>Calcium serves as a widespread second messenger in almost every human and animal cell. The regulation of various cellular processes, such as transcriptional control and the kinetics of membrane channels, is significantly influenced by intracellular calcium ions (Ca <math><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> ), and linkages between Ca <math><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> and other second messengers should activate signaling networks. The passage of ions across the cell membrane regulates Ca <math><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> levels in pancreatic <math><mi>β</mi></math> -cells and requires the coordinated interaction of various ion transport mechanisms and organelles. The signaling of Ca <math><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> in <math><mi>β</mi></math> -cells and its interactions with the intracellular dynamics of cyclic adenosine monophosphate (cAMP) is poorly understood. Therefore, the current investigation proposes a mathematical model to illustrate the spatiotemporal dynamical interaction between Ca <math><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> and cAMP. In order to construct a one-dimensional mathematical model, the fundamental initial and boundary conditions derived from the physiological characteristics of the <math><mi>β</mi></math> -cell are incorporated. The numerical results were obtained by MATLAB simulations using the finite element method and the Crank-Nicolson method. The current study aims to offer an update on regulation between Ca <math><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> and cAMP signaling circuits, with a focus on interactions that occur in localized areas of the <math><mi>β</mi></math> -cell. The model gives the individual effect of each parameter on the regulation of Ca <math><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> and cAMP profiles in a <math><mi>β</mi></math> -cell. Evidently, impairments in the regulation of messenger pathways contribute to the pathological conditions, as demonstrated by the results obtained.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrocontractile remodeling of isolated cardiomyocytes induced during early-stage hypercholesterolemia.","authors":"Artur Santos-Miranda, Julliane V Joviano-Santos, Ivan Lobo Sousa Marques, Stefany Cau, Fabrício A Carvalho, Júlia R Fraga, Jacqueline I Alvarez-Leite, Danilo Roman-Campos, Jader S Cruz","doi":"10.1007/s10863-024-10026-x","DOIUrl":"10.1007/s10863-024-10026-x","url":null,"abstract":"<p><p>Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases. However, it is mostly associated with vascular dysfunction and atherosclerotic lesions, while evidence of direct effects of hypercholesterolemia on cardiomyocytes and heart function is still incomplete and controversial. In this study, we assessed the direct effects of hypercholesterolemia on heart function and the electro-contractile properties of isolated cardiomyocytes. After 5 weeks, male Swiss mice fed with AIN-93 diet added with 1.25% cholesterol (CHO), developed an increase in total serum cholesterol levels and cardiomyocytes cholesterol content. These changes led to altered electrocardiographic records, with a shortening of the QT interval. Isolated cardiomyocytes displayed a shortening of the action potential duration with increased rate of depolarization, which was explained by increased I_K, reduced I_Ca.L and altered I_Na voltage-dependent inactivation. Also, reduced diastolic [Ca²⁺]_i was found with preserved adrenergic response and cellular contraction function. However, contraction of isolated hearts is impaired in isolated CHO hearts, before and after ischemia/reperfusion, although CHO heart was less susceptible to arrhythmic contractions. Overall, our results demonstrate that early hypercholesterolemia-driven increase in cellular cholesterol content is associated with direct modulation of the heart and cardiomyocytes' excitability, Ca²⁺ handling, and contraction.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin attenuates LPS-induced myocardial injury by reducing ferroptosis.","authors":"Ke Hu, Pin Jiang, Jiaxin Hu, Bing Song, Ya Hou, Jinxuan Zhao, Haiting Chen, Jun Xie","doi":"10.1007/s10863-024-10020-3","DOIUrl":"10.1007/s10863-024-10020-3","url":null,"abstract":"<p><p>Septic cardiomyopathy is a severe cardiovascular disease with a poor prognosis. Previous studies have reported the involvement of ferroptosis in the pathogenesis of septic cardiomyopathy. SGLT2 inhibitors such as dapagliflozin have been demonstrated to improve ischemia-reperfusion injury by alleviating ferroptosis in cardiomyocyte. However, the role of dapagliflozin in sepsis remains unclear. Therefore, our study aims to investigate the therapeutic effects of dapagliflozin on LPS-induced septic cardiomyopathy. Our results indicate that dapagliflozin improved cardiac function in septic cardiomyopathy experimental mice. Mechanistically, dapagliflozin works by inhibiting the translation of key proteins involved in ferroptosis, such as GPX4, FTH1, and SLC7A11. It also reduces the transcription of lipid peroxidation-related mRNAs, including PTGS2 and ACSL4, as well as iron metabolism genes TFRC and HMOX1.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}