生物学最新文献

{"title":"Association between the triglyceride glucose index and short-term mortality in septic patients with or without obesity: a retrospective cohort study.","authors":"Zhou Lv, Juntao Wang, Minglu Gu, Liuyan Zhou, Saie Shen, Chunmei Huang","doi":"10.1080/21623945.2024.2379867","DOIUrl":"10.1080/21623945.2024.2379867","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients.</p><p><strong>Methods: </strong>This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis.</p><p><strong>Results: </strong>8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76-9.71) vs. 9.10(8.67-9.54), <i>p</i> < 0.001]. The adjusted multivariate regression model showed that elevated TyGI values were linked to a greater likelihood of death in ICU (odds ratio [OR] range 1.072-1.793, <i>p</i> < 0.001) and hospital (OR range 1.068-1.445, <i>p</i> = 0.005). Restricted Cubic Spline analysis revealed a nonlinear association between TyGI and in-ICU and in-hospital mortality risks within specified ranges. Subgroup analysis revealed interaction effects in the general obesity, abdominal obesity, and impaired fasting glucose subgroups (<i>p</i> = 0.014, 0.016, and < 0.001, respectively).</p><p><strong>Conclusion: </strong>TyGI was associated with an increased sepsis-related short-term mortality risk and adverse outcomes after ICU admission.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618985","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":"Effects of miR-29c on proliferation and adipogenic differentiation of porcine bone marrow mesenchymal stromal cells.","authors":"Anjing Zhang, Lu Lu, Fuxing Yang, Tingting Luo, Shuqi Yang, Peidong Yang, Xuemin Li, Xiaoli Deng, Yang Qiu, Litong Chen, Keren Long, Dengke Pan, Long Jin, Mingzhou Li, Li Chen","doi":"10.1080/21623945.2024.2365211","DOIUrl":"10.1080/21623945.2024.2365211","url":null,"abstract":"<p><p>microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of <i>IGF1</i> inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299745","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":"Dynamics of a stochastic modified Leslie-Gower predator-prey system with hunting cooperation.","authors":"Chao Li, Peilin Shi","doi":"10.1080/17513758.2024.2366495","DOIUrl":"https://doi.org/10.1080/17513758.2024.2366495","url":null,"abstract":"<p><p>In this paper, we consider a stochastic two-species predator-prey system with modified Leslie-Gower. Meanwhile, we assume that hunting cooperation occurs in the predators. By using Itô formula and constructing a proper Lyapunov function, we first show that there is a unique global positive solution for any given positive initial value. Furthermore, based on Chebyshev inequality, the stochastic ultimate boundedness and stochastic permanence are discussed. Then, under some conditions, we prove the persistence in mean and extinction of system. Finally, we verify our results by numerical simulations.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the redox landscape: reactive oxygen species in regulation of cell cycle.","authors":"Viktoria Mackova, Martina Raudenska, Hana Holcova Polanska, Milan Jakubek, Michal Masarik","doi":"10.1080/13510002.2024.2371173","DOIUrl":"https://doi.org/10.1080/13510002.2024.2371173","url":null,"abstract":"<p><p><b>Objectives:</b> To advance our knowledge of disease mechanisms and therapeutic options, understanding cell cycle regulation is critical. Recent research has highlighted the importance of reactive oxygen species (ROS) in cell cycle regulation. Although excessive ROS levels can lead to age-related pathologies, ROS also play an essential role in normal cellular functions. Many cell cycle regulatory proteins are affected by their redox status, but the precise mechanisms and conditions under which ROS promote or inhibit cell proliferation are not fully understood.<b>Methods:</b> This review presents data from the scientific literature and publicly available databases on changes in redox state during the cell cycle and their effects on key regulatory proteins.<b>Results:</b> We identified redox-sensitive targets within the cell cycle machinery and analysed different effects of ROS (type, concentration, duration of exposure) on cell cycle phases. For example, moderate levels of ROS can promote cell proliferation by activating signalling pathways involved in cell cycle progression, whereas excessive ROS levels can induce DNA damage and trigger cell cycle arrest or cell death.<b>Discussion:</b> Our findings encourage future research focused on identifying redox-sensitive targets in the cell cycle machinery, potentially leading to new treatments for diseases with dysregulated cell proliferation.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilirubin regulates cell death type by alleviating macrophage mitochondrial dysfunction caused by cigarette smoke extract.","authors":"Jingjing Wei, Yuan Tian, Jinshu Wei, Meiqi Guan, Xiaoya Yu, Jianing Xie, Guoquan Fan","doi":"10.1080/13510002.2024.2382946","DOIUrl":"10.1080/13510002.2024.2382946","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the effects and mechanisms of bilirubin on mitochondrial function and type of macrophage cell death after exposure to cigarette smoke extract (CSE).</p><p><strong>Methods: </strong>RAW264.7 macrophages were treated with different concentrations of CSE and bilirubin solutions and divided into four groups: control, CSE, bilirubin, and bilirubin + CSE groups. The necrotic and apoptotic states of the macrophages were determined using an Annexin V-fluorescein 5-isothiocyanate/propidium iodide (FITC/PI) staining kit. Cytoplasmic NOD-like receptor family, pyrin domain containing 3 (NLRP3) expression in macrophages was detected by immunofluorescence and the levels of IL-1β and IL-18 in the supernatants of culture medium were detected by enzyme linked immunosorbent assay (ELISA) test. A JC-1 mitochondrial membrane potential detection kit was used to assess mitochondrial membrane damage and the adenosine triphosphate (ATP) assay kit was used to determine intracellular ATP levels. After the macrophages were stained with reactive oxygen species (ROS) specific dye, 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), the fluorescence intensity and proportion of ROS-positive macrophages were measured using flow cytometry.</p><p><strong>Results: </strong>We observed that compared with those of 0 μM (control group), concentrations of 5, 10, or 20 μΜ bilirubin significantly decreased cell viability, which was increased by bilirubin exposure below 1 μM. The effect of CSE on macrophage viability was concentration- and time-dependent. Bilirubin of 0.2 μM could alleviate the inhibition of macrophage viability caused by 5% CSE. In addition, bilirubin intervention could reduce the occurrence of necrosis and pyroptosis to a certain extent.</p><p><strong>Conclusions: </strong>CSE could cause mitochondrial dysfunction in macrophages, as demonstrated by a decrease in mitochondrial membrane potential and intracellular ATP levels and an increase in ROS production, while bilirubin could relieve mitochondrial dysfunction caused by CSE.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide methylation analysis in patients with proximal hypospadias - a pilot study and review of the literature.","authors":"Yolande van Bever, Ruben G Boers, Hennie T Brüggenwirth, Wilfred Fj van IJcken, Frank J Magielsen, Annelies de Klein, Joachim B Boers, Leendert Hj Looijenga, Erwin Brosens, Joost Gribnau, Sabine E Hannema","doi":"10.1080/15592294.2024.2392048","DOIUrl":"10.1080/15592294.2024.2392048","url":null,"abstract":"<p><p>In patients with proximal hypospadias, often no genetic cause is identified despite extensive genetic testing. Many genes involved in sex development encode transcription factors with strict timing and dosing of the gene products. We hypothesised that there might be recurrent differences in DNA methylation in boys with hypospadias and that these might differ between patients born small versus appropriate for gestational age. Genome-wide Methylated DNA sequencing (MeD-seq) was performed on 32bp LpnPI restriction enzyme fragments after RE-digestion in leucocytes from 16 XY boys with unexplained proximal hypospadias, one with an unexplained XX testicular disorder/difference of sex development (DSD) and twelve, healthy, sex- and age-matched controls. Five of seven differentially methylated regions (DMRs) between patients and XY controls were in the Long Intergenic Non-Protein Coding RNA 665 (LINC00665; CpG24525). Three patients showed hypermethylation of MAP3K1. Finally, no DMRs in XX testicular DSD associated genes were identified in the XX boy versus XX controls. In conclusion, we observed no recognizable epigenetic signature in 16 boys with XY proximal hypospadias and no difference between children born small versus appropriate for gestational age. Comparison to previous methylation studies in individuals with hypospadias did not show consistent findings, possibly due to the use of different inclusion criteria, tissues and methods.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992223","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":"Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis <i>via</i> the p62-Keap1-Nrf2 pathway.","authors":"Zhihui Lin, Chang Wu, Dongyan Song, Chenxi Zhu, Bosen Wu, Jie Wang, Yangjing Xue","doi":"10.1080/13510002.2024.2392329","DOIUrl":"10.1080/13510002.2024.2392329","url":null,"abstract":"<p><p>Doxorubicin (Dox) is extensively used as an antitumor agent, but its severe cardiotoxicity significantly limits its clinical use. Current treatments for Dox-induced cardiotoxicity are inadequate, necessitating alternative solutions. This study evaluated the effects of sarmentosin, a compound from Sedum sarmentosum, on Dox-induced cardiotoxicity and dysfunction. Sarmentosin was administered as a pretreatment to both mice and H9c2 cells before Dox exposure. Subsequently, markers of Dox-induced cardiotoxicity and ferroptosis in serum and cell supernatants were measured. Western blot analysis was utilized to detect levels of ferroptosis, oxidative stress, and autophagy proteins. Additionally, echocardiography, hematoxylin-eosin staining, ROS detection, and immunofluorescence techniques were employed to support our findings. Results demonstrated that sarmentosin significantly inhibited iron accumulation, lipid peroxidation, and oxidative stress, thereby reducing Dox-induced ferroptosis and cardiotoxicity in C57BL/6 mice and H9c2 cells. The mechanism involved the activation of autophagy and the Nrf2 signaling pathway. These findings suggest that sarmentosin may prevent Dox-induced cardiotoxicity by mitigating ferroptosis. The study underscores the potential of compounds like sarmentosin in treating Dox-induced cardiotoxicity.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Akkermansia muciniphila</i>: A promising probiotic against inflammation and metabolic disorders.","authors":"Yanqing Zhao, Huijun Yang, Peng Wu, Shuguo Yang, Wenkun Xue, Biao Xu, Sirui Zhang, Bin Tang, Daoxiu Xu","doi":"10.1080/21505594.2024.2375555","DOIUrl":"10.1080/21505594.2024.2375555","url":null,"abstract":"<p><p>Metabolic disease is a worldwide epidemic that has become a public health problem. Gut microbiota is considered to be one of the important factors that maintain human health by regulating host metabolism. As an abundant bacterium in the host gut, <i>A. muciniphila</i> regulates metabolic and immune functions, and protects gut health. Multiple studies have indicated that alterations in the abundance of <i>A. muciniphila</i> are associated with various diseases, including intestinal inflammatory diseases, obesity, type 2 diabetes mellitus, and even parasitic diseases. Beneficial effects were observed not only in live <i>A. muciniphila</i>, but also in pasteurized <i>A. muciniphila, A. muciniphila</i>-derived extracellular vesicles, outer membrane, and secreted proteins. Although numerous studies have only proven the simple correlation between multiple diseases and <i>A. muciniphila</i>, an increasing number of studies in animal models and preclinical models have demonstrated that the beneficial impacts shifted from correlations to in-depth mechanisms. In this review, we provide a comprehensive view of the beneficial effects of <i>A. muciniphila</i> on different diseases and summarize the potential mechanisms of action of <i>A. muciniphila</i> in the treatment of diseases. We provide a comprehensive understanding of <i>A. muciniphila</i> for improving host health and discuss the perspectives of <i>A. muciniphila</i> in the future studies.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of <i>Staphylococcus argenteus</i> in pediatrics: Molecular insights from a hospital in East China.","authors":"Chao Fang, Zheng Zhou, Jianping Li, Mingming Zhou","doi":"10.1080/21505594.2024.2396477","DOIUrl":"10.1080/21505594.2024.2396477","url":null,"abstract":"<p><p><i>Staphylococcus argenteus</i> is a novel species within the <i>Staphylococcus aureus</i> complex and can cause serious bloodstream infections (BSIs) in humans, which have been mainly reported in adults, especially the elderly. In this study, we analyzed the molecular characterization of a strain of <i>S. argenteus</i> (22WJ8192) isolated from the peripheral vein blood sample of a seven-month-old female infant in Eastern China. The 22WJ8192 belonged to sequence type (ST)2250 and harbored six antibiotic-resistance genes and 53 virulence genes and was resistant to penicillin. Additionally, we conducted a comparative analysis of the molecular characteristics of <i>S. argenteus</i> sourced from various origins within the dataset, predominantly from the National Center for Biotechnology Information Collection (NCBI) genome database. Antibiotic-resistance genes <i>blaR1</i>, <i>blaI_of_Z</i>, <i>blaZ</i>, <i>fosB-Saur</i>, <i>tet(L)</i>, <i>aph(3\")-IIIa</i>, <i>mecA</i>, and <i>dfrG</i> were more prevalent among the strains of human origin. Virulence genes <i>lukF-PV</i>, <i>sak</i>, <i>sdrE</i>, <i>scn</i>, <i>sdrC</i>, and <i>sdrD</i> were more prevalent among strains of human origin. The presence of antibiotic-resistance genes <i>blaR1</i>, <i>blaI_of_Z</i>, <i>blaZ</i>, <i>fosB-Saur</i>, and <i>aph(3\")-IIIa</i> in strain 22WJ8192 was also more common among strains of human origin in the dataset. Conversely, the antibiotic-resistance genes <i>tet(L)</i>, <i>mecA</i>, and <i>dfrG</i>, typically found in strains of human origin, were not detected in 22WJ8192. Additionally, virulence genes <i>lukF-PV</i>, <i>sak</i>, <i>sdrE</i>, <i>scn</i>, <i>sdrC</i>, and <i>sdrD</i> present in 22WJ8192 exhibited a higher prevalence among strains of human origin in the dataset. In conclusion, this study emphasizes the potential of <i>S. argenteus</i> ST2250 to induce severe bloodstream infections in infants, shedding light on the molecular characteristics of this strain.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of a battery of investigated genes in lipid droplet pathophysiology and associated comorbidities.","authors":"Sami N Al Harake, Yasamin Abedin, Fatema Hatoum, Nour Zahraa Nassar, Ali Ali, Aline Nassar, Amjad Kanaan, Samer Bazzi, Sami Azar, Frederic Harb, Hilda E Ghadieh","doi":"10.1080/21623945.2024.2403380","DOIUrl":"10.1080/21623945.2024.2403380","url":null,"abstract":"<p><p>Lipid droplets (LDs) are highly specialized energy storage organelles involved in the maintenance of lipid homoeostasis by regulating lipid flux within white adipose tissue (WAT). The physiological function of adipocytes and LDs can be compromised by mutations in several genes, leading to NEFA-induced lipotoxicity, which ultimately manifests as metabolic complications, predominantly in the form of dyslipidemia, ectopic fat accumulation, and insulin resistance. In this review, we delineate the effects of mutations and deficiencies in genes - <i>CIDEC</i>, <i>PPARG</i>, <i>BSCL2</i>, <i>AGPAT2</i>, <i>PLIN1</i>, <i>LIPE</i>, <i>LMNA</i>, <i>CAV1</i>, <i>CEACAM1</i>, and <i>INSR</i> - involved in lipid droplet metabolism and their associated pathophysiological impairments, highlighting their roles in the development of lipodystrophies and metabolic dysfunction.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339134","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}