Journal of World Mitochondria Society最新文献

{"title":"Cytobiochemical biomarkers of the state of mitochondria in humans. I. Great differences in children suffering from leukemia or myopathy as compared with healthy children of similar age.","authors":"N. V. Khunderyakova, T. V. Yachkula, M. Zakharchenko, S. Plyasunova, V. Sukhorukov, Tatiyana Baranich, E. G. Litvinova, N. I. Fedotcheva, Polina Sсhwartsburd, M. N. Kondrashova","doi":"10.18143/JWMS_v2i2_1931","DOIUrl":"https://doi.org/10.18143/JWMS_v2i2_1931","url":null,"abstract":"Quantitative indicators of mitochondria functions and dysfunctions and physiological state of the organism were estimated by the activity of dehydrogenases (DH): succinate DH (SDH), SDH + isocitrate (ISC), lactate DH ( LDH), and LDH/SDH as glycolysis-respiration ratio or Warburg еffect measure proposed by our group. Our advanced cyto-BIO-chemical method was used to detect the state of mitochondria within lymphocytes in a smear of blood [1, 2]. The typical examples for the children examined are shown in the figure below. The pronounced rise of LDH activity and decrease in SDH are observed under leucosis. The dysfunctions are even more manifested in the LDH/SDH ratio. There is little difference between DH activity under myopathy and this in healthy children. However, the LDH/SDH ratio clearly reveals the decrease. The increase in Warburg effect is a beneficial property of cancer cells, which is essential for intensive biosynthesis and proliferation [3]. In contrast, the weakening of the restorative processes is typical for myopathy. Biomarkers of glycolysis ( LDH), respiration (SDH) and Warburg effect (LDH/SDH) in young patients suffering from leucosis (L) n=22 and myopathy (M) n=9, compared with healthy(H) n=25 children of similar age, measured by nitroblue reduction (NBR).","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121264672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of mitochondrial peptidase ClpP leads to upregulation of inflammatory factors in brain and embryonal fibroblasts of mice","authors":"S. Gispert, S. Torres-Odio, G. Auburger, J. Heidler, I. Wittig, M. Kössl","doi":"10.18143/JWMS_V2I2_1914","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1914","url":null,"abstract":"The combination of premature ovarian failure and age-associated hearing deafness, inherited in autosomal recessive manner, was named Perrault syndrome. It may be caused by mutations in HSD17B4, HARS2, LARS2, PSMC3IP, C10orf2, CLPP and in un-identified genes. CLPP is a mitochondrial matrix peptidase that is crucial for the unfolded protein response of mitochondria (mtUPR). In a study of Clpp-/- mice we found the Perrault phenotype, but also loss of spermatids, growth retardation and anti-microbial protection. An accumulation of CLPX protein and mitochondrial DNA was accompanied by widespread induction of inflammatory mRNAs in several tissues (Gispert 2013 HMG). Now we tried to elucidate the age-associated hearing loss. Preliminary analyses of DPOAE (distortion product optoacoustic emissions) showed no response above 20000 Hz. Preliminary studies of acoustic startle responses showed a maximal deficit already at an age of 12 months. To understand mtUPR-triggered neurotoxicity at molecular level, we analyzed brain tissue with global proteomics. Elevated levels of inflammatory factors downstream the transcription factor STAT1 were prominent. STAT1 induction was also documented in murine embryonal fibroblasts. Thus, the innate immune system is triggered by the mitochondrial matrix protein degradation deficit due to CLPP deletion.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131258185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Control of Electron Transport Chain Flux by Cytochrome c Threonine 28 phosphorylation in Kidney: Implications for AMP Kinase","authors":"M. Hüttemann, G. Mahapatra, Icksoo Lee, L. Grossman, Asmita Vaishnav, Qinqin Ji, A. Salomon, B. Edwards","doi":"10.18143/JWMS_V2I2_1922","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1922","url":null,"abstract":"Mammalian cytochrome c (Cytc) transfers electrons in the electron transport chain (ETC) but also executes apoptosis and should thus be tightly regulated. We recently showed that heart and liver Cytc is tyrosine phosphorylated. Here we show that Cytc from kidney is phosphorylated on Thr28, likely mediated by AMP kinase, indicating tissue-specific adaptations in metabolic control. In vivo phosphorylated and Thr28Glu phosphomimetic Cytc cause partial inhibition in the reaction with Cytc oxidase, thus helping to control respiration. In Cytc knockout cells expressing Thr28Glu phosphomimetic Cytc we found reduction of intact cellular respiration, mitochondrial membrane potential (DYm), and ROS. High resolution crystal structure analyses and molecular dynamics simulations suggest that the Thr28-containing epitope is the most flexible internal part of Cytc, which is in close proximity to key residues on Cytc oxidase and thus suggests a mechanism for the altered enzyme kinetics. We proposes that under healthy conditions Cytc is phosphorylated to partially inhibit ETC electron flux, preventing DYm hyperpolarization, a known cause of ROS production and trigger of apoptosis. Our data suggest, for the first time, that ETC flux can be controlled at the level of Cytc, making it an attractive target for therapeutic intervention in conditions of mitochondrial dysfunction.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126303211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LANDSCAPING OF THE HUMAN MITOCHONDRIAL RNOME BY COLOC-SEQ","authors":"Damien Jeandard, N. Entelis, I. Tarassov, A. Smirnov","doi":"10.18143/JWMS_V2I2_1926","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1926","url":null,"abstract":"Mitochondria possess their own genome but critically depend on the import of many nuclear-encoded macromolecules to ensure its expression. Beside ~1,500 proteins, in apparently all eukaryotes, from protists to humans, some RNAs (tRNAs, 5S rRNA, miRNAs...) are partially redirected into mitochondria where they participate in gene expression processes(1). Therefore, the mitochondrial RNome represents an intricate mixture of transcriptome and importome. While studies of the mitochondrial transcriptome have now been facilitated by such techniques as RNA-seq(2,3), robust identification of nuclear-encoded transcripts imported into the organelles is still challenging since cytosolic contamination remains even after most thorough purification of mitochondria. Our laboratory is currently developing a conceptually novel experimental approach, Controlled Level of Contamination (CoLoC) which allows, by following RNase-mediated depletion dynamics of each transcript, to unequivocally distinguish between RNAs genuinely present inside mitochondria and mere contaminants. Coupled with deep sequencing (CoLoC-seq), this methodology will provide the first global view of the human mitochondrial RNA importome in diverse cell types and conditions. This knowledge will help a better understanding of nuclear-mitochondrial communication and will open ways to exploit RNA targeting pathways for manipulation of the mitochondrial genetic system and development of therapeutic approaches to currently incurable mitochondrial diseases(4).","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"111 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125643902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial chaperone TRAP1 as a therapeutic target in Parkinson disease","authors":"Lian Li, L. Chin","doi":"10.18143/JWMS_V2I2_1910","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1910","url":null,"abstract":"Parkinson disease (PD) is a major neurodegenerative disease that involves mitochondrial dysfunction. The lack of disease-modifying medications to stop neurodegeneration in PD highlights the need to identify new molecular targets for therapeutic intervention. TNF receptor-associated protein 1 (TRAP1) is a mitochondrial chaperone of the Hsp90 family that was identified in our proteomic screen as a substrate for PD-linked kinase PINK1. By using subcellular fractionation and dual-color 3D-SIM super-resolution imaging analyses, we have shown that TRAP1 primarily resides in the cristae membrane and intracristae space of mitochondria; and our results support a critical role of TRAP1 in these submitochondrial compartments to regulate protein folding and maintain mitochondrial homeostasis. Furthermore, our studies reveal that TRAP1 colocalizes with PINK1 in mitochondrial cristae membrane and intracristae space and functions downstream of PINK1 in cytoprotection against mitochondrial dysfunction and oxidative stress-induced apoptosis. Our findings are further supported by recent Drosophila genetic studies showing that overexpression of TRAP1 is able to ameliorate mitochondrial and motor behavioral defects in PINK1-deficient flies and to restore mitochondrial function in flies with impaired mitochondrial complex I. Together, these results indicate that TRAP1 is a viable target for development of new therapeutics to treat PD and other mitochondrial diseases.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128849882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial GWA analysis in several complex diseases using the KORA population","authors":"A. Flaquer, K. Ladwig, M. Waldenberger, H. Grallert, C. Meisinger, T. Meitinger, A. Peters, K. Strauch","doi":"10.18143/JWMS_V2I2_1911","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1911","url":null,"abstract":"Objectives: Our main goal is to identify mitochondrial susceptibility genes for human complex diseases. Methodology: Using different genotyping platforms and New Generation Sequencing we performed mtGWA analysis in the KORA population (3,080 individuals) with several phenotypes (BMI, cholesterol, post-traumatic stress disorder, thyroid diseases, depression, among others) as well as with life styles (smoking cigarettes, alcohol consumption, and physical activity). Results: we report several mitochondrial genetic variants associated with post-traumatic stress disorders and metabolic syndrome. BMI, HDL cholesterol and TG levels were also associated to mitochondrial variants, indicating that the presence of heteroplasmy in these variants may influence the balance of HDL cholesterol and TG levels. We also observed that no physical activity, alcohol abuse, and smoke cigarettes may increase the heteroplasmy levels of mitochondrial genetic variants. Conclusions: As fluctuations in mtDNA heteroplasmy may signify alterations in cellular activity, our findings highlight the important role of the mtDNA as a biomarker for aging-related diseases and metabolic syndromes.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"96 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115659009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of mitochondrial dynamics on metabolic disease and inflammation","authors":"Lixiang Wang, Yuki Hanada, Yuta Ibayashi, Yukina Takeichi, S. Sakamoto, Kenji Ashida, M. Nomura","doi":"10.18143/JWMS_V2I2_1908","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1908","url":null,"abstract":"Mitochondria are highly dynamic organelles that frequently fuse and divide in response to cellular energy demands, differentiation or pathological conditions. In vertebrates, mitofusin-1 and -2  are involved in mitochondrial fusion while dynamin-related protein 1 (DRP1) and mitochondrial fission factor control mitochondrial fission. In our previous study, by using liver specific DRP1 knockout (Drp1LiKO) mice, we reported that mitochondrial dynamics play a protective role against metabolic disorders such as diabetes and obesity through induction of fibroblast growth factor 21. On the other hand, histological analysis revealed that Drp1LiKO liver exhibited severe inflammation and fibrosis, reminiscences of nonalcoholic steatohepatitis. In this study, the role of mitochondrial dynamics on inflammasome signaling was explored. Here, we found that NLRP3 dependent caspase-1 activation and interleukin-1 beta secretion were markedly increased in Drp1LiKO liver, possibly associated with the defective autophagic degradation and increased reactive oxygen species (ROS) generation. Thus, our results provide new insight into the role of mitochondrial dynamics in inflammasome activation.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128214420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Over-expression of mitochondria-targeted calpain-1 induces dilated heart failure in transgenic mice: an important role of mitochondrial reactive oxygen species","authors":"T. Cao, T. Peng, Z. Dong, Lulu Zhang, R. Ni","doi":"10.18143/JWMS_V2I2_1905","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1905","url":null,"abstract":"Ting Cao*, Dong Zheng, Lulu Zhang, Rui Ni, Tianqing Peng  Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China. Lawson Health Research Institute, Departments of Medicine and Pathology and Laboratory Medicine, Western University, London, Ontario, Canada Background: Calpain-1 has been shown to increase in mitochondria of the heart under certain pathological conditions. Increased calpain-1 in mitochondria is associated with myocardial dysfunction.  Aims: This study was to investigate forced up-regulation of calpain-1 in mitochondria induces myocardial injury and heart failure. Methods and Results: A novel line of transgenic mice over-expressing cardiomyocyte-specific and mitochondria-targeted calpain-1 was generated. Over-expression of mitochondria-targeted calpain-1 increased mitochondrial superoxide generation in hearts and induced cardiac hypertrophy, fibrosis and ventricular chamber dilation, leading to myocardial dysfunction and early death in transgenic mice. These effects of mitochondrial calpain-1 up-regulation were attenuated by administration of mitochondria-targeted antioxidant mito-TEMPO. Increased mitochondrial calpain-1 also correlated with mitochondrial dysfunction in transgenic mouse hearts.  Conclusions: Mitochondrial calpain-1 induces myocardial injury and dysfunction likely by promoting mitochondrial superoxide generation. Thus, mitochondrial calpain-1 may represent a novel mechanism underlying heart failure.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125422905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MITOCHONDRIA-TARGETED THERAPY:CHALLENGES AND HURDLES OF DRUG DISCOVERY PROCESS","authors":"F. Borges","doi":"10.18143/JWMS_V2I2_2052","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_2052","url":null,"abstract":"Mitochondria play a central role in cell life and death. Impairment of mitochondrial functions is observed in a diversity of pathological states such as cancer, diabetes, metabolic disorders and age-related neurodegenerative diseases. The wide-ranging impact of mitochondria highlights those organelles as prime targets for drug discovery. However, the development of mitochondrial-targeted drugs has been hampered by a number of challenges, and there are, at present, no approved therapies. Classically, drug design based on one drug-one target approach has been used in drug discovery projects. However, for some time, drug discovery players have been questioning the success of the reductionist philosophy to ameliorate disease states with multifactorial and polygenic nature. Consequently, the multi-target approach, where a single chemical entity may be able to modulate simultaneously multiple targets, seems to be of particular interest. One of the main limitations with this approach is related to the ability to define the set of targets that are causative of a particular disease state and design compounds that will hit the key targets with a desirable ratio of potencies. This is certainly a daunting challenge but given the current unmet medical needs, and the advantages if the approach is successful, such a venture is worthwhile. Yet, the collaboration among all the stakeholders, like research foundations, academic institutions, physicians, and pharmaceutical industry, are paramount for the success (see COST Action CA15135).","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"280 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116071819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of eNOS and nNOS in fatty acid-dependent Cardiac Inotropy and Calcium Handling in Healthy and Hypertensive Rats","authors":"C. Jin, Yinhua Zhang","doi":"10.18143/JWMS_V2I2_1902","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1902","url":null,"abstract":"Background: Fatty acids (FAs) are the predominant metabolic substrates for myocardial ATP. So far, the effects of FAs on myocyte contraction in normal and hypertensive hearts are unclear. Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS) has been implicated to be essential in FA oxidation in mitochondria. Recently, we have shown that neuronal nitric oxide synthase (nNOS) is up-regulated in left ventricular (LV) myocytes from hypertensive hearts, whereas eNOS protein expression was reduced. Purpose: We aim to analyze palmitic acid (PA)-regulation of myocyte contraction and the roles of eNOS and nNOS in LV myocytes from sham and angiotensin II (Ang II)-induced hypertensive rats. Methods: Sarcomere length and Fura-2 ratio (Fura-2AM, 2 μM) were measured (field stimulation, 2Hz, IonOptix Corp, 37°C). Oxygen consumption rate (OCR) was measured (Instech). NO (nitrite content) was measured by NO assay kit (Griess Reagent System). Used whole cell patch clamp technique, was recording L-type Ca2+ current (ICa) and Na+ - Ca2+ exchanger activity (INCX). Results: Our results showed that PA (100 μM) increased the amplitude of sarcomere shortening and Ca2+ transients in LV myocytes from sham but not in hypertension. Etomoxir (10 μM), a selective carnitine palmitoyl transferase I inhibitor, blunted the inotropic effect of PA in sham, but not effect hypertension, suggesting the contribution of beta-oxidation to in PA-regulation of cardiac inotropy. PA increased basal oxygen consumption and mitochondrial OC capacity in cardiomyocytes from sham and HTN rats. Etomoxir was reversed PA induced basal OC and mitochondrial OC capacity in sham and HTN. Inhibition of eNOS and nNOS with Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 mM, 30 min – 1hr) prevented PA-induced myocyte contraction and Ca2+ transients in sham; such an effect was not observed with nNOS inhibitor, S-methyl-l-thiocitrulline (SMTC, 100 nM, 30 min – 1hr). Similarly, PA failed to increase myocyte contraction in LV myocytes from eNOS-/- mice, suggesting the critical role of eNOS in PA-induced myocyte contraction in sham. In hypertension, both L-NAME and SMTC restored PA-enhancement of myocyte contraction, suggesting the modulatory role of nNOS. PA tended to reduce eNOS-derived NO in sham but significantly increased nNOS-derived NO in hypertension. Indeed, PA increased OCR in sham and L-NAME but not SMTC reduced PA-induced DOCR. In hypertension, PA increased OCR. Importantly, L-NAME and SMTC abolished both basal and PA-induced DOCR. PA maintained Ca2+ influx via L-type Ca2+ channels, and nNOS inhibitor increased Ca2+ influx, in LV cardiomyocyte from sham. PA reduced Ca2+ influx, but nNOS inhibitor significantly increased Ca2+ influx via L-type Ca2+ channels in LV cardiomyocyte from hypertensive rats. Further experiments have shown that SMTC increased the amplitude of Ca2+ transients in hypertension. Conclusion: PA increases Ca2+ transients and myocyte contraction in normal ","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115285437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}