{"title":"Construction of a novel lncRNA-miRNA-mRNA competing endogenous RNA network in muscle in response to exercise training.","authors":"Mingkun Nie, Qingling Liu, Cheng Yan","doi":"10.4149/gpb_2022062","DOIUrl":"https://doi.org/10.4149/gpb_2022062","url":null,"abstract":"<p><p>Physical inactivity has evidently been a hazard factor for many diseases, including cardiovascular disease, diabetes, cancer, etc. Rising evidence indicates that RNA, as competitive endogenous RNA (ceRNA), plays an important role in adaptive changes in skeletal muscle in response to exercise training. Although the effects of exercise-induced fitness on skeletal muscle have been well established, the mechanisms underlying are not fully understood. The purpose of this study is to construct a novel ceRNA network in skeletal muscle in response to exercise training. Skeletal muscle gene expression profiles were downloaded from the GEO database. Then, we identified differentially expressed lncRNAs, miRNAs, and mRNAs between the pre-exercise and post-exercise samples. Subsequently, we constructed lncRNA-miRNA-mRNA regulatory networks based on the ceRNA theory. 1153 mRNAs (687 upregulated and 466 downregulated), 7 miRNAs (3 upregulated and 4 downregulated), and 5 lncRNAs (3 upregulated and 2 downregulated) were identified as differentially expressed genes. 3 lncRNAs, 5 miRNAs and 227 mRNAs were obtained to build miRNA-mediated ceRNA networks. We constructed a novel ceRNA regulatory network in muscle in response to exercise training, which provides insights into molecular mechanisms underlying the health benefits brought by physical activity.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089300","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}
Tomas Baka, Peter Stanko, Kristina Repova, Silvia Aziriova, Kristina Krajcirovicova, Andrej Barta, Stefan Zorad, Fedor Simko
{"title":"Ivabradine curbs isoproterenol-induced kidney fibrosis.","authors":"Tomas Baka, Peter Stanko, Kristina Repova, Silvia Aziriova, Kristina Krajcirovicova, Andrej Barta, Stefan Zorad, Fedor Simko","doi":"10.4149/gpb_2022057","DOIUrl":"https://doi.org/10.4149/gpb_2022057","url":null,"abstract":"<p><p>This study investigated whether chronic isoproterenol administration could induce kidney alterations and whether ivabradine, a heart rate (HR)-reducing substance exerting cardiovascular protection, is able to attenuate potential kidney damage. Twenty-eight Wistar rats were divided into non-diseased controls, rats treated with ivabradine, rats treated with isoproterenol, and rats treated with isoproterenol plus ivabradine. Six weeks of isoproterenol administration was associated with decreased systolic blood pressure (SBP) (by 25%) and glomerular, tubulointerstitial and vascular/perivascular fibrosis due to enhanced type I collagen volume (7-, 8-, and 4-fold, respectively). Ivabradine reduced HR (by 15%), partly prevented SBP decline (by 10%) and site-specifically mitigated kidney fibrosis by decreasing type I collagen volume in all three sites investigated (by 69, 58, and 67%, respectively) and the ratio of type I collagen-to-type III collagen in glomerular and vascular/perivascular sites (by 79 and 73%, respectively). We conclude that ivabradine exerts protection against kidney remodelling in isoproterenol-induced kidney damage.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9458852","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}
Alparslan Koç, Mustafa Gazi, Ali Caner Sayar, Didem Onk, Muhammet Ali Arı, Bahadır Süleyman, Ahmet Gökhan Ağgül, Fikret Altındağ, Durdu Altuner, Halis Süleyman
{"title":"Molecular mechanism of the protective effect of adenosine triphosphate against paracetamol-induced liver toxicity in rats.","authors":"Alparslan Koç, Mustafa Gazi, Ali Caner Sayar, Didem Onk, Muhammet Ali Arı, Bahadır Süleyman, Ahmet Gökhan Ağgül, Fikret Altındağ, Durdu Altuner, Halis Süleyman","doi":"10.4149/gpb_2022055","DOIUrl":"https://doi.org/10.4149/gpb_2022055","url":null,"abstract":"<p><p>Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxidative liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9458853","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}
Elshymaa A Abdel-Hakeem, Nagwa M Zenhom, Sahar A Mokhemer
{"title":"Testicular cytoprotective effect of glucagon like peptide-1 in diabetic rats involves inhibition of apoptosis, endoplasmic reticulum stress and activation of autophagy.","authors":"Elshymaa A Abdel-Hakeem, Nagwa M Zenhom, Sahar A Mokhemer","doi":"10.4149/gpb_2022064","DOIUrl":"https://doi.org/10.4149/gpb_2022064","url":null,"abstract":"<p><p>This study aimed to explore the possible cytoprotective effects of exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the testicles of diabetic rats. Exenatide has numerous advantageous properties in addition to its hypoglycemic effect. However, its impact on testicular tissue in diabetes needs more clarification. Therefore, rats were divided into control, exenatide-treated, diabetic and exenatide-treated diabetic groups. Blood glucose and serum levels of insulin, testosterone, pituitary gonadotropins and kisspeptin-1 were measured. Real-time PCR for beclin-1, p62, mammalian target of rapamycin (mTOR), and AMP-activated protein kinase (AMPK), were estimated in testicular tissue in addition to markers of oxidative stress, inflammation, and endoplasmic reticulum stress. Also, immuno-expression of protein P53, nuclear erythroid factor2 (Nrf2) and vimentin was conducted. Exenatide was able to attenuate diabetic toxic changes and enhance autophagy in testicular tissue. These results indicate the protective effect of exenatide against diabetic testicular dysfunction.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10311818","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":"Circ_0001498 contributes to lipopolysaccharide-induced lung cell apoptosis and inflammation in sepsis-related acute lung injury via upregulating SOX6 by interacting with miR-574-5p.","authors":"Wei Hu, Qin Wang, Zhichun Luo, Yaqiong Shi, Liangping Zhang, Zhijun Zhang, Jianlin Liu, Kelan Liu","doi":"10.4149/gpb_2022054","DOIUrl":"https://doi.org/10.4149/gpb_2022054","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) have important regulation in in sepsis-related acute lung injury (ALI). Circ_0001498 was significantly overexpressed in sepsis-induced acute respiratory distress syndrome. The aims of this study were to explore role and mechanism of circ_0001498 in lipopolysaccharide (LPS)-treated WI-38 cells. Human samples were collected from 56 sepsis patients and 46 healthy volunteers at Liyang People's Hospital. Circ_0001498, microRNA-574-5p (miR-574-5p) or sex-determining region Y-related high-mobility-group box 6 (SOX6) levels were detected via reverse transcription-quantitative polymerase chain reaction assay. Cell viability was determined through Cell Counting Kit-8 assay. Apoptosis rate was examined by flow cytometry. Western blot was used for measurement of proteins. Inflammatory cytokines were detected via enzyme-linked immunosorbent assay. Target relation was analyzed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Circ_0001498 was overexpressed in sepsisrelated ALI patients and LPS-treated WI-38 cells. Silencing circ_0001498 reduced LPS-induced cell apoptosis and inflammation. Circ_0001498 interacted with miR-574-5p. The regulation of circ_0001498 knockdown was abolished by miR-574-5p inhibitor. Furthermore, miR-574-5p directly targeted SOX6 and circ_0001498 upregulated SOX6 via targeting miR-574-5p. Overexpression of miR-574-5p alleviated LPS-induced cell injury by downregulating SOX6. This research identified that circ_0001498 facilitated sepsis-related ALI progression by targeting miR-574-5p to upregulate SOX6.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10601774","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":"Celastrol attenuates Guillain-Barré syndrome by inhibiting TLR4/NF-κB/STAT3 pathway-mediated Th1/Th17 cell differentiation.","authors":"Hefang Shao, Weijiao Fan, Yang Tang","doi":"10.4149/gpb_2022048","DOIUrl":"https://doi.org/10.4149/gpb_2022048","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) is an acute immune-mediated paralytic neuropathy with variable disease course and outcome. In this study, we aimed to investigate the therapeutic effects of celastrol on GBS and uncover its underlying mechanisms. Experimental autoimmune neuritis (EAN) is a typical animal model for GBS, and thus an EAN rat model was established with the injection of celastrol or/and LPS. We assessed the body weights and EAN clinical scores of rats. HE staining, flow cytometry, RT-qPCR, and Western blotting were respectively employed to measure pathological damage, proportions of cells (Th1, Th17, and Treg), Th1/Th17 cell differentiation-related mRNAs (IFN-γ, TBX21, IL-18, RORγT, IL-17, and IL-23) and TLR4/NF-κB/STAT3 pathway-related proteins (TLR4, NF-κB, p-NF-κB, STAT3, and p-STAT3). We found that celastrol attenuated clinical symptoms and pathological damage of GBS in EAN rats. Moreover, celastrol down-regulated Th1 and Th17 cell proportions, and the levels of IFN-γ, TBX21, IL-18, RORγT, IL-17, and IL-23 in EAN rats. Meanwhile, the levels of TLR4, p-NF-κB, and p-STAT3 were decreased by celastrol. Taken together, celastrol could restrain Th1/Th17 cell differentiation through inhibition of the TLR4/NF-κB/STAT3 pathway in EAN rats. Our findings suggest that celastrol may exert therapeutic effects on GBS by suppressing TLR4/NF-κB/STAT3 pathway-mediated Th1/Th17 cell differentiation.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10639611","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}
Çiğdem Yazici-Mutlu, Arzu Keskin-Aktan, Kazime G Akbulut
{"title":"Effects of curcumin and melatonin treatment in the cerebral cortex of adult rats.","authors":"Çiğdem Yazici-Mutlu, Arzu Keskin-Aktan, Kazime G Akbulut","doi":"10.4149/gpb_2022047","DOIUrl":"https://doi.org/10.4149/gpb_2022047","url":null,"abstract":"The study investigated the effect of exogenous melatonin and (or) curcumin treatment on the cerebral cortex of adult rats. In this context, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), superoxide dismutase (SOD), nuclear factor E2-related factor 2 (Nrf2) and SIRT2 protein expression were examined. A total of 30 Wistar albino rats involved in the study were randomly divided into five groups. Over 30 days, the control groups received phosphate-buffered saline or dimethyl sulfoxide injections, and the treatment groups received melatonin, curcumin, or a combination of melatonin and curcumin injections. In the cerebral cortex homogenates, the MDA, GSH, and sum of NO were respectively determined by the thiobarbituric acid, modified Ellman and Griess test methods. The SOD and Nrf2 levels were examined using the ELISA method and SIRT2 protein expression using the Western blot technique. The study found that both melatonin and curcumin treatments significantly reduced lipid peroxidation and SIRT2 protein expression levels (p < 0.05) and increased the Nrf2 level in the cytoplasm (p < 0.05). The study revealed that curcumin and melatonin treatments reduced MDA and SIRT2 protein expression level and increased intracellular Nrf2, GSH, and SOD in the cortex tissue. We also found that the combined melatonin and curcumin treatment produced no synergistic effect.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10640050","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}
Maria Komelkova, Boris Yushkov, Stanislav Fedorov, Roman Ibragimov, Pavel Platkovskiy, Desheng Hu, Shanshan Luo, Alexey Sarapultsev
{"title":"Early-life maternal deprivation in rats increases sensitivity to the subsequent stressors: a pilot study","authors":"Maria Komelkova, Boris Yushkov, Stanislav Fedorov, Roman Ibragimov, Pavel Platkovskiy, Desheng Hu, Shanshan Luo, Alexey Sarapultsev","doi":"10.4149/gpb_2023022","DOIUrl":"https://doi.org/10.4149/gpb_2023022","url":null,"abstract":"Early life experiences, particularly maternal deprivation (MD), have long-lasting implications on emotional and cognitive development. Using Wistar rats as a model, this study explores the impact of MD followed by predator stress exposure (PSS) to simulate aspects of post-traumatic stress disorder (PTSD). A cohort of 41 male rat pups underwent MD from postnatal days 2 to 14, followed by PSS at day 90. Female rat pups were not included in the experiment. Behavior was subsequently assessed using the Elevated Plus Maze test 14 days post-PSS. While MD led to subtle changes such as decreased activity and increased anxiety-like behavior, PSS induced pronounced anxiogenic effects. Notably, PSS after MD resulted in decreased basal corticosterone levels, mirroring conditions observed in PTSD. The findings suggest that although MD itself does not induce significant behavioral changes, it predisposes individuals to heightened sensitivity to subsequent stressors. This study underscores the utility of a two-stage PSS model for more accurately reflecting the complexities inherent in stress-related disorders, including PTSD.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135704116","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":"Effects of percutaneous coronary intervention via transradial artery access combined with metoprolol on cardiac function and vascular endothelial function in elderly patients with coronary heart disease","authors":"Feng Cheng, Juan Xu","doi":"10.4149/gpb_2023028","DOIUrl":"https://doi.org/10.4149/gpb_2023028","url":null,"abstract":"This research was designed to unveil the impacts of percutaneous coronary intervention via transradial artery access (TRA-PCI) combined with metoprolol on cardiac function and vascular endothelial function in elderly patients with coronary heart disease (CHD). Collectively, 112 CHD patients were enrolled and allocated into a control group (patients treated with TRA-PCI) and an observation group (patients treated with TRA-PCI and metoprolol) following the random number table method (n = 56 patients). The treatment outcome, cardiac function indicators, serum inflammatory factor indicators, vascular endothelial function indicators, and the occurrence of coronary restenosis were compared between the two groups. After treatment, elevated total effective rate was noted in CHD patients treated with TRA-PCI and metoprolol in contrast to TRA-PCI treatment alone. CHD patients treated with TRA-PCI and metoprolol alleviated cardiac function and vascular endothelial function and reduced inflammatory response and the occurrence of coronary restenosis in comparison to TRA-PCI treatment alone. TRA-PCI combined with metoprolol is effective in improving cardiac function and endothelial function, and reducing the degree of inflammation in the body and the occurrence of coronary restenosis in CHD patients.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135667823","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}
Alparslan Koç, Ufuk Kuyrukluyildiz, Mustafa Gazi, Ali Caner Sayar, Durdu Altuner, Halis Süleyman, Bülent Yavuzer, Taha Abdulkadir Çoban, Zeynep Süleyman, Gülce Naz Yazici
{"title":"The effects of sugammadex on gastric ischemia-reperfusion injury in rats: Biochemical and histopathological evaluation.","authors":"Alparslan Koç, Ufuk Kuyrukluyildiz, Mustafa Gazi, Ali Caner Sayar, Durdu Altuner, Halis Süleyman, Bülent Yavuzer, Taha Abdulkadir Çoban, Zeynep Süleyman, Gülce Naz Yazici","doi":"10.4149/gpb_2022049","DOIUrl":"https://doi.org/10.4149/gpb_2022049","url":null,"abstract":"<p><p>The primary sources of reactive oxygen species (ROS) that cause ischemia-reperfusion (I/R) injuries are enzymes xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in the literature, whereby one of the main ROS producing cells via NOX activity are polymophonuclear leukocytes (PNL). Sugammadex, the effect of which we plan to research against gastric I/R damage, is a modified gamma-cyclodextrin that antagonizes the action of steroidal neuromuscular blocking drugs. Previous studies have reported that sugammadex inhibits PNL infiltration. However, it is unknown whether an inhibitory effect on XO is present. We aimed to biochemically and histopathologically investigate the effects of sugammadex on I/R-induced stomach damage in rats. The animals were divided into groups that underwent gastric ischemia-reperfusion (GIR), 4 mg/kg sugammadex + gastric ischemia-reperfusion (SGIR), and a sham operation group (SG). The effect of sugammadex was evaluated by measuring oxidant-antioxidant and PNL parameters. There was no significant difference in XO levels between the SGIR and GIR groups. In the SGIR group, sugammadex inhibited the increase in myeloperoxidase (MPO) and malondialdehyde (MDA) levels (p < 0.001). The amount of MDA and MPO in the SGIR group was similar as in the SG group. Sugammadex significantly suppressed the decrease in tGSH levels in the SGIR group (p < 0.001). The difference between tGSH levels in the SG and SGIR groups was slight. In the SGIR group, sugammadex significantly suppressed the increase in tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL1-β) levels compared to the GIR group (p < 0.001). Additionally, sugammadex corrected histopathological modifications as much as sham group. In conclusion, sugammadex may be beneficial in preventing oxidative stress.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10640053","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}