Journal of Muscle Research and Cell Motility最新文献

{"title":"Xenogeneic transplantation of mitochondria induces muscle regeneration in an in vivo rat model of dexamethasone-induced atrophy.","authors":"Mi Jin Kim, Ji Min Lee, Kyunghoon Min, Yong-Soo Choi","doi":"10.1007/s10974-023-09643-7","DOIUrl":"10.1007/s10974-023-09643-7","url":null,"abstract":"<p><p>Muscle atrophy significantly impairs health and quality of life; however, there is still no cure. Recently, the possibility of regeneration in muscle atrophic cells was suggested through mitochondrial transfer. Therefore, we attempted to prove the efficacy of mitochondrial transplantation in animal models. To this end, we prepared intact mitochondria from umbilical cord-derived mesenchymal stem cells maintaining their membrane potential. To examine the efficacy of mitochondrial transplantation on muscle regeneration, we measured muscle mass, cross-sectional area of muscle fiber, and changes in muscle-specific protein. In addition, changes in the signaling mechanisms related to muscle atrophy were evaluated. As a result, in mitochondrial transplantation, the muscle mass increased by 1.5-fold and the lactate concentration decreased by 2.5-fold at 1 week in dexamethasone-induced atrophic muscles. In addition, a 2.3-fold increase in the expression of desmin protein, a muscle regeneration marker, showed a significant recovery in MT 5 µg group. Importantly, the muscle-specific ubiquitin E3-ligases MAFbx and MuRF-1 were significantly decreased through AMPK-mediated Akt-FoxO signaling pathway by mitochondrial transplantation compared with the saline group, reaching a level similar to that in the control. Based on these results, mitochondrial transplantation may have therapeutic applications in the treatment of atrophic muscle disorders.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"53-68"},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10748928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANKRD1 expression is aberrantly upregulated in the mdm mouse model of muscular dystrophy and induced by stretch through NFκB","authors":"Michael A. Lopez, Patricia S. Pardo, Junaith S. Mohamed, Aladin M. Boriek","doi":"10.1007/s10974-024-09671-x","DOIUrl":"https://doi.org/10.1007/s10974-024-09671-x","url":null,"abstract":"<p>The muscular dystrophy with myositis (<i>mdm)</i> mouse model results in a severe muscular dystrophy due to an 83-amino-acid deletion in the N2A region of titin, an expanded sarcomeric protein that functions as a molecular spring which senses and modulates the response to mechanical forces in cardiac and skeletal muscles. ANKRD1 is one of the muscle ankyrin repeat domain proteins (MARPs) a family of titin-associated, stress-response molecules and putative transducers of stretch-induced signaling in skeletal muscle. The aberrant over-activation of Nuclear factor Kappa B (NF-κB) and the Ankyrin-repeat domain containing protein 1 (ANKRD1) occurs in several models of progressive muscle disease including Duchenne muscular dystrophy. We hypothesized that mechanical regulation of ANKRD1 is mediated by NF-κB activation in skeletal muscles and that this mechanism is perturbed by small deletion of the stretch-sensing titin N2A region in the <i>mdm</i> mouse. We applied static mechanical stretch of the <i>mdm</i> mouse diaphragm and cyclic mechanical stretch of C₂C₁₂ myotubes to examine the interaction between NF−κΒ and ANKRD1 expression utilizing Western blot and qRTPCR. As seen in skeletal muscles of other severe muscular dystrophies, an aberrant increased basal expression of NF-κB and ANKRD1 were observed in the diaphragm muscles of the <i>mdm</i> mice. Our data show that in the <i>mdm</i> diaphragm, basal levels of NF-κB are increased, and pharmacological inhibition of NF-κB does not alter basal levels of ANKRD1. Alternatively, NF-κB inhibition did alter stretch-induced ANKRD1 upregulation. These data show that NF-κB activity is at least partially responsible for the stretch-induced expression of ANKRD1.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"10 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arginine ingestion inhibits phagocyte invasion in eccentrically contracted rat fast-twitch muscle","authors":"Keita Kanzaki, Masanobu Wada","doi":"10.1007/s10974-024-09672-w","DOIUrl":"https://doi.org/10.1007/s10974-024-09672-w","url":null,"abstract":"<p>Eccentric contraction (ECC) has been shown to induce leukocyte invasion into skeletal muscle, resulting in muscle inflammation. This study aimed to investigate whether prior ingestion of <span>L</span>-arginine (ARG), a nitric oxide precursor, inhibits ECC-induced macrophage invasion. Male Wistar rats received ARG in water for 7 days, beginning 3 days prior to ECC. ECCs were induced in the anterior crural muscles for 200 cycles. Three days later, the tibialis anterior and extensor digitorum longus muscles were excised for biochemical analysis and force measurement, respectively. ARG ingestion increased nitrite and nitrate levels in plasma and muscle, inhibiting force depression and reducing CD68 content in muscles subjected to ECC. ARG ingestion also ameliorated an ECC-induced increase in protein nitration, although neither ARG ingestion nor ECC induction affected protein carbonyl levels. The present results suggest that ingestion of ARG or ARG-rich foods may alleviate inflammation by attenuating phagocyte invasion in eccentrically contracted skeletal muscles.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"213 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a novel western blot assay to monitor patterns and levels of alpha dystroglycan in skeletal muscle of patients with limb girdle muscular dystrophies","authors":"Thulashitha Rajasingham, Hector M. Rodriguez, Andreas Betz, Douglas M. Sproule, Uma Sinha","doi":"10.1007/s10974-024-09670-y","DOIUrl":"https://doi.org/10.1007/s10974-024-09670-y","url":null,"abstract":"<p>The cell membrane protein, dystroglycan, plays a crucial role in connecting the cytoskeleton of a variety of mammalian cells to the extracellular matrix. The α-subunit of dystroglycan (αDG) is characterized by a high level of glycosylation, including a unique O-mannosyl matriglycan. This specific glycosylation is essential for binding of αDG to extracellular matrix ligands effectively. A subset of muscular dystrophies, called dystroglycanopathies, are associated with aberrant, dysfunctional glycosylation of αDG. This defect prevents myocytes from attaching to the basal membrane, leading to contraction-induced injury. Here, we describe a novel Western blot (WB) assay for determining levels of αDG glycosylation in skeletal muscle tissue. The assay described involves extracting proteins from fine needle tibialis anterior (TA) biopsies and separation using SDS-PAGE followed by WB. Glycosylated and core αDG are then detected in a multiplexed format using fluorescent antibodies. A practical application of this assay is demonstrated with samples from normal donors and patients diagnosed with LGMD2I/R9. Quantitative analysis of the WB, which employed the use of a normal TA derived calibration curve, revealed significantly reduced levels of αDG in patient biopsies relative to unaffected TA. Importantly, the assay was able to distinguish between the L276I homozygous patients and a more severe form of clinical disease observed with other <i>FKRP</i> variants. Data demonstrating the accuracy and reliability of the assay are also presented, which further supports the potential utility of this novel assay to monitor changes in ⍺DG of TA muscle biopsies in the evaluation of potential therapeutics.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"53 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomechanical evaluation of flash-frozen and cryo-sectioned papillary muscle samples by using sinusoidal analysis: cross-bridge kinetics and the effect of partial Ca2+ activation","authors":"Jing Xi, Han-Zhong Feng, Jian-Ping Jin, Jinxiang Yuan, Masataka Kawai","doi":"10.1007/s10974-024-09667-7","DOIUrl":"https://doi.org/10.1007/s10974-024-09667-7","url":null,"abstract":"<p>We examined the integrity of flash-frozen and cryo-sectioned cardiac muscle preparations (introduced by Feng and Jin, 2020) by assessing tension transients in response to sinusoidal length changes at varying frequencies (1–100 Hz) at 25 °C. Using 70-μm-thick sections, we isolated fiber preparations to study cross-bridge (CB) kinetics: preparations were activated by saturating Ca²⁺ as well as varying concentrations of ATP and phosphate (Pi). Our results showed that, compared to ordinary skinned fibers, in-series stiffness decreased to 1/2, which resulted in a decrease of isometric tension to 62%, but CB kinetics and Ca²⁺ sensitivity were little affected. The pCa study demonstrated that the rate constant of the force generation step (2π<i>b</i>) is proportionate to [Ca²⁺] at &lt; 5 μM, suggesting that the activation mechanism can be described by a simple second order reaction. We also found that tension, stiffness, and magnitude parameters are related to [Ca²⁺] by the Hill equation, with a cooperativity coefficient of 4–5, which is consistent with the fact that Ca²⁺ activation mechanisms involve cooperative multimolecular interactions. Our results support the long-held hypothesis that Process C (Phase 2) represents the CB detachment step, and Process B (Phase 3) represents the force generation step. Moreover, we discovered that constant <i>H</i> may represent the work-performing step in cardiac preparations. Our experiments demonstrate excellent CB kinetics with two well-defined exponentials that can be more distinguished than those found using ordinary skinned fibers. Flash-frozen and cryo-sectioned preparations are especially suitable for multi-institutional collaborations nationally and internationally because of their ease of transportation.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140600753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle of young females under resistance exercise exhibits a unique innate immune cell infiltration profile compared to males and elderly individuals","authors":"Paola Castrogiovanni, Cristina Sanfilippo, Rosa Imbesi, Giacomo Lazzarino, Giovanni Li Volti, Daniele Tibullo, Nunzio Vicario, Rosalba Parenti, Lazzarino Giuseppe, Ignazio Barbagallo, Amer M. Alanazi, Michele Vecchio, Francesco Cappello, Giuseppe Musumeci, Michelino Di Rosa","doi":"10.1007/s10974-024-09668-6","DOIUrl":"https://doi.org/10.1007/s10974-024-09668-6","url":null,"abstract":"<p>Muscle damage resulting from physical activities such as exercise triggers an immune response crucial for tissue repair and recovery. This study investigates the immune cell profiles in muscle biopsies of individuals engaged in resistance exercise (RE) and explores the impact of age and sex on the immune response following exercise-induced muscle damage. Microarray datasets from muscle biopsies of young and old subjects were analyzed, focusing on the gene expression patterns associated with immune cell activation. Genes were compared with immune cell signatures to reveal the cellular landscape during exercise. Results show that the most significant modulated gene after RE was Folliculin Interacting Protein 2 (FNIP2) a crucial regulator in cellular homeostasis. Moreover, the transcriptome was stratified based on the expression of <i>FNIP2</i> and the 203 genes common to the groups obtained based on sex and age. Gene ontology analysis highlighted the <i>FLCN-FNIP1-FNIP2</i> complex, which exerts as a negative feedback loop to Pi3k-Akt-mTORC1 pathway. Furthermore, we highlighted that the young females exhibit a distinct innate immune cell activation signature compared to males after a RE session. Specifically, young females demonstrate a notable overlap with dendritic cells (DCs), M1 macrophages, M2 macrophages, and neutrophils, while young males overlap with M1 macrophages, M2 macrophages, and motor neurons. Interestingly, in elderly subjects, both sexes display M1 macrophage activation signatures. Comparison of young and elderly signatures reveals an increased M1 macrophage percentage in young subjects. Additionally, common genes were identified in both sexes across different age groups, elucidating biological functions related to cell remodeling and immune activation. This study underscores the intricate interplay between sex, age, and the immune response in muscle tissue following RE, offering potential directions for future research. Nevertheless, there is a need for further studies to delve deeper and confirm the dynamics of immune cells in response to exercise-induced muscle damage.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"38 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140601064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of Luffa cylindrica Roemer against dexamethasone-induced muscle atrophy in primary rat skeletal muscle cells.","authors":"Changhwan Yeo, Hyunseong Kim, Wan-Jin Jeon, Junseon Lee, Jin Young Hong, Hyun Kim, Yoon Jae Lee, Seung Ho Baek, In-Hyuk Ha","doi":"10.1007/s10974-023-09661-5","DOIUrl":"10.1007/s10974-023-09661-5","url":null,"abstract":"<p><p>Glucocorticoids (GCs) are commonly used in the treatment of chronic inflammatory conditions. However, the administration of high doses and long-term use of GCs can induce muscle atrophy (MA) in patients, leading to a decline in quality of life and increased mortality. MA leads to protein degradation in skeletal muscle, resulting in a reduction of muscle mass. This process is triggered by GCs like dexamethasone (DEX), which induce the expression of E3 ubiquitin ligases, namely Atrogin-1 and muscle RING-finger protein-1 (MuRF1). In this study, we examined the anti-MA potential of Luffa cylindrica Roemer (LCR) on DEX-treated primary skeletal myotubes. Primary skeletal myotubes stimulated with LCR alone resulted in a significant upregulation of myotube development, characterized by an increase in both the number and diameter of myotubes. Contrastingly, combined treatment with LCR and DEX reduced the expression of Atrogin-1, while treatment with DEX alone induced the expression of MuRF1. Furthermore, LCR treatment successfully restored the number and diameter of myotubes that had been diminished by DEX treatment. These findings suggest that LCR holds potential for treating MA, as an accelerating effect on muscle development and anti-MA effects on primary skeletal muscle cells were observed.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10844154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-transcriptional regulation of myogenic transcription factors during muscle development and pathogenesis.","authors":"Shen-Liang Chen, Chuan-Che Wu, Ning Li, Tzu-Han Weng","doi":"10.1007/s10974-023-09663-3","DOIUrl":"10.1007/s10974-023-09663-3","url":null,"abstract":"<p><p>The transcriptional regulation of skeletal muscle (SKM) development (myogenesis) has been documented for over 3 decades and served as a paradigm for tissue-specific cell type determination and differentiation. Myogenic stem cells (MuSC) in embryos and adult SKM are regulated by the transcription factors Pax3 and Pax7 for their stem cell characteristics, while their lineage determination and terminal differentiation are both dictated by the myogenic regulatory factors (MRF) that comprise Mrf4, Myf5, Myogenin, and MyoD. The myocyte enhancer factor Mef2c is activated by MRF during terminal differentiation and collaborates with them to promote myoblast fusion and differentiation. Recent studies have found critical regulation of these myogenic transcription factors at mRNA level, including subcellular localization, stability, and translational regulation. Therefore, the regulation of Pax3/7, MRFs and Mef2c mRNAs by RNA-binding factors and non-coding RNAs (ncRNA), including microRNAs and long non-coding RNAs (lncRNA), will be the focus of this review and the impact of this regulation on myogenesis will be further addressed. Interestingly, the stem cell characteristics of MuSC has been found to be critically regulated by ncRNAs, implying the involvement of ncRNAs in SKM homeostasis and regeneration. Current studies have further identified that some ncRNAs are implicated in the etiology of some SKM diseases and can serve as valuable tools/indicators for prediction of prognosis. The roles of ncRNAs in the MuSC biology and SKM disease etiology will also be discussed in this review.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"21-39"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide and ion channels mediate L-cysteine-induced inhibition of colonic smooth muscle contraction.","authors":"Xiaojing Quan, Min Zhang, Zhaojun Qiao, Xuan Kou, Qiong Xue, Jinhai Wang, Lu Li","doi":"10.1007/s10974-023-09664-2","DOIUrl":"10.1007/s10974-023-09664-2","url":null,"abstract":"<p><p>Previous studies have suggested that L-cysteine regulates gut motility through hydrogen sulfide. However, the mechanisms involved in the L-cysteine-induced response have not been extensively studied. This study aimed to investigate the underlying mechanisms of action of L-cysteine on spontaneous contraction of rat colon. Longitudinal and circular muscle strips from rat middle colon were prepared to measure the spontaneous contractile activities of colon in an organ bath system. Whole-cell voltage-clamp techniques were applied to record the currents of L-type voltage-dependent Ca²⁺ channels (VDCCs) and voltage-gated K⁺ channels (Kv) in isolated smooth muscle cells (SMCs) from colon. L-cysteine inhibited the spontaneous contraction of longitudinal and circular muscle strips from the rat colon in a concentration-dependent manner. The inhibition induced by L-cysteine was significantly decreased by inhibitors of H₂S synthesis (p < 0.05). Furthermore, the suppression induced by L-cysteine was partially attenuated by tetrodotoxin, L-NNA and glibenclamide (p < 0.05). Whole-cell voltage-clamp recordings showed that L-cysteine caused a remarkable reduction in the peak currents of VDCCs and significantly increased the membrane currents of Kv channels in isolated SMCs (p < 0.05). We concluded that L-cysteine inhibits the contractile activities of smooth muscle strips from the rat colon. The relaxation in response to L-cysteine may be in part mediated by a nitrergic pathway and by inhibiting the VDCCs in combination with a direct activation of the K_V channels and K_ATP channels.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"11-20"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138885132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic innervation in skeletal muscle and its role at the neuromuscular junction","authors":"Rüdiger Rudolf, Isis C. Kettelhut, Luiz Carlos C. Navegantes","doi":"10.1007/s10974-024-09665-9","DOIUrl":"https://doi.org/10.1007/s10974-024-09665-9","url":null,"abstract":"<p>Neuromuscular junctions are the synapses between motor neurons and skeletal muscle fibers, which mediate voluntary muscle movement. Since neuromuscular junctions are also tightly associated with the capping function of terminal Schwann cells, these synapses have been classically regarded as tripartite chemical synapses. Although evidences from sympathetic innervation of neuromuscular junctions was described approximately a century ago, the essential presence and functional relevance of sympathetic contribution to the maintenance and modulation of neuromuscular junctions was demonstrated only recently. These findings shed light on the pathophysiology of different clinical conditions and can optimize surgical and clinical treatment modalities for skeletal muscle disorders.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"218 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139771518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}