Journal of Cellular Physiology最新文献

{"title":"In Old Mice, Exercise Induces Inflammation and Fibrosis Unless Alk5-Inhibitor and Oxytocin Are Used","authors":"Joana Marie C. Cruz,&nbsp;Hayden Yeung,&nbsp;Rana Alzalzalee,&nbsp;Qile Yang,&nbsp;Hannaneh Kabir,&nbsp;Samantha Annaliese McDonough,&nbsp;Xiaoyue Mei,&nbsp;Michael J. Conboy,&nbsp;Irina M. Conboy","doi":"10.1002/jcp.70054","DOIUrl":"https://doi.org/10.1002/jcp.70054","url":null,"abstract":"<p>Exercise and diet are the best-known methods for attenuating aging-related health decline. However, exercise in older age has diminished gains of strength and agility, and a danger of unrepaired muscle damage. Improving the understanding of age-related differences in response to exercise, our results demonstrate that in old mice, downhill treadmill (eccentric) exercise causes increased influx of CD45+ cells (inflammation) and fibrotic index (fibrosis) in the heart and skeletal muscles. To explain these changes, we identified newly synthesized proteins through bio-orthogonal noncanonical amino acid tagging (BONCAT) and established that exercise exacerbated age-associated protein patterns through a dysregulated transforming growth factor (TGF)-β, Ras/MAPK/PI3Akt, and JAK/STAT pathways. Testing causality, we found that an inhibitor of TGF-β (Alk5 inhibitor, A5i) in combination with the age-diminished peptide oxytocin, previously shown to rejuvenate muscle and brain in sedentary animals, allowed aged mice to exercise without pathologies of skeletal and heart muscles and youthfully restored their de novo proteomes.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315168","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":"The Potential Dual Roles of Metallothionein-1/-2 in Diabetic Osteoarthritis","authors":"Yu-Ping Su,&nbsp;Rong-Ze Hsieh,&nbsp;Kuo-Ti Peng,&nbsp;Chung-Sheng Shi,&nbsp;Kuo-Chin Huang,&nbsp;Shun-Fu Chang","doi":"10.1002/jcp.70056","DOIUrl":"https://doi.org/10.1002/jcp.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteoarthritis (OA) is increasingly recognized as a chronic inflammatory degenerative joint disease. Recent evidence exhibits a higher prevalence of OA among patients with type II diabetes mellitus (T2DM). Metallothioneins (MTs) are important proteins involved in controlling physiology and pathophysiology. MT-1/MT-2 have been further found their positive correlation with OA progression, but their precise roles need more examination. This study aimed to investigate the role of MT-1/MT-2 in the development of diabetic OA and the underlying mechanisms. Cartilage was collected from patients with OA-only and T2DM-OA, and from rats classified as healthy, T2DM, and T2DM with destabilization of medial meniscus (DMM) surgery. Additionally, a cell model treated with high glucose (HG) or advanced glycation end products (AGEs) was used to investigate underlying mechanisms. Our results revealed that MT-1/MT-2 levels were elevated in cartilage from T2DM-OA patients and rats, as well as in T2DM rats subjected to DMM surgery. Similarly, primary chondrocytes treated with HG and AGE showed increased expression of MT-1/MT-2, with distinct distributions and regulatory mechanisms: (a) MT-1 enhanced MMP and transcription factor activity without affecting their expressions, whereas MT-2 increased both the activity and expression of MMPs and transcription factors; (b) MT-1 reduced IL6/IL8 expression, while MT-2 promoted it. Furthermore, this differential regulation appears to be mediated by BMP2 autocrine stimulation. These findings underscore the dual role of MT-1/MT-2 in simultaneously activating self-repair and degenerative processes, potentially influencing diabetic cartilage pathogenesis. Our study suggests that MT-1/MT-2 may serve as valuable theranostic targets for diabetic OA in future clinical applications.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292701","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":"Targeting Heparanase Attenuates Podocyte Injury Induced by Puromycin Aminonucleoside","authors":"Xing-Yun Huang,&nbsp;Yu-Hsien Lu,&nbsp;Hsiao-Hui Lee","doi":"10.1002/jcp.70053","DOIUrl":"https://doi.org/10.1002/jcp.70053","url":null,"abstract":"<p>Podocytes are highly specialized glomerular visceral epithelial cells critical for maintaining the structure and function of the glomerular filtration barrier. These cells adhere to the glomerular basement membrane (GBM) and envelop the outer surfaces of the glomerular capillaries to prevent protein leakage during blood ultrafiltration. The GBM is a dense network of extracellular matrix composed of type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans. In this study, we investigated the protective effect of a heparanase inhibitor on puromycin aminonucleoside (PAN)-induced podocyte injury. Our results demonstrate that PAN treatment significantly disrupted the cytoskeletal architecture of cultured podocytes, reducing the formation of focal adhesions and stress fibers. Interdigitating intercellular junctions were replaced by dot-like structures with accumulated filamentous actin. Co-treatment with the heparanase inhibitor PI-88 effectively prevented these PAN-induced cytoskeletal abnormalities. Furthermore, a BSA filtration assay revealed that PI-88 attenuated PAN-induced increases in podocyte monolayer permeability. Taken together, our findings suggest that heparanase inhibition protects against podocyte injury and may represent a potential therapeutic strategy for glomerular diseases.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255810","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":"RETRACTION: Evaluation of Anticancer Effects of Cerium Oxide Nanoparticles on Mouse Fibrosarcoma Cell Line","authors":"","doi":"10.1002/jcp.70051","DOIUrl":"https://doi.org/10.1002/jcp.70051","url":null,"abstract":"<p><b>RETRACTION</b>: E. Nourmohammadi, H. Khoshdel–Sarkarizi, R. Nedaeinia, H. R. Sadeghnia, L. Hasanzadeh, M. Darroudi and R. K. Oskuee, “Evaluation of Anticancer Effects of Cerium Oxide Nanoparticles on Mouse Fibrosarcoma Cell Line,” <i>Journal of Cellular Physiology</i> 234, no. 4 (2019): 4987–4996, https://doi.org/10.1002/jcp.27303.</p><p>The above article, published online on 06 September 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed upon following an investigation into concerns raised by a third party. The investigation revealed duplication between the L929-Control flow cytometry plot and the L929-Conc30 plot shown in Figure 7b. Furthermore, duplications were identified between the Conc 30 BAX western blot band presented in Figures 9a and the Control BAX western blot band in Figure 9b. These two figures represent different cell lines. An additional duplication was observed between the Control BCL2 band and the Conc 60 BAX band in Figure 9a. The authors provided an explanation and some data, but this was not deemed sufficient. The editors consider the results and conclusions from this study to be substantially compromised. The authors disagree with the retraction.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140598","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":"RETRACTION: Nanos2 Promotes Differentiation of Male Germ Cells Basing on the Negative Regulation of Foxd3 and the Treatment of 5-Azadc and TSA","authors":"","doi":"10.1002/jcp.70022","DOIUrl":"https://doi.org/10.1002/jcp.70022","url":null,"abstract":"<p><b>RETRACTION:</b> W. Zhang, Y. Bi, Y. Wang, M. Wang, D. Li, S. Cheng, J. Jin, T. Li, B. Li, and Y. Zhang, “<i>Nanos2</i> Promotes Differentiation of Male Germ Cells Basing on the Negative Regulation of Foxd3 and the Treatment of 5-Azadc and TSA,” <i>Journal of Cellular Physiology</i>, 234, no. 4 (2019): 3762–3774, https://doi.org/10.1002/jcp.27139.</p><p>The above article, published online on 26 August 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, it was brought to the journal's attention that <i>Nanos2</i> has not been identified in <i>Gallus gallus</i>. Further investigation confirmed that the gene examined in the article was actually <i>Nos2</i>, which encodes nitric oxide synthase 2 (NOS2), a protein with different and unrelated functions from those proposed in the study. Author B. Li stated that she did not directly participate in the experiments conducted for the study and was unaware of its submission. The corresponding author Y. Zhang, on behalf of the remaining co-authors, stated that they mistakenly assumed <i>Nos2</i>, which serves as an alias for <i>Nanos2</i> in other species, to be homologous to <i>Nanos2</i> in chickens. This misidentification undermines the study's rationale, methodology, and conclusions. Accordingly, the article is retracted.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135684","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":"RETRACTION: MiR-330 Suppresses EMT and Induces Apoptosis by Downregulating HMGA2 in Human Colorectal Cancer","authors":"","doi":"10.1002/jcp.70048","DOIUrl":"https://doi.org/10.1002/jcp.70048","url":null,"abstract":"<p><b>RETRACTION:</b> Mansoori, B., A. Mohammadi, S. Naghizadeh, et al. 2020. “MiR-330 Suppresses EMT and Induces Apoptosis by Downregulating HMGA2 in Human Colorectal Cancer,” <i>Journal of Cellular Physiology</i> 235, no. 2: 920–931. https://doi.org/10.1002/jcp.29007.</p><p>The above article, published online on June 26, 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed upon following an investigation by the publisher in response to concerns raised by third parties. Several flaws and inconsistencies have been identified between the described methodology and the presented results. Furthermore, the study's rationale and conclusions drawn are not supported by either the existing literature or the data extracted from The Cancer Genome Atlas (TCGA). Accordingly, the article is retracted as the editors consider its conclusions to be invalid. The authors have been informed of the decision of retraction but not available for a final confirmation.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108750","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":"RETRACTION: Molecular Insights Into Development of Trichoderma Interfusants for Multistress Tolerance Enhancing Antagonism Against Sclerotium rolfsii Sacc","authors":"","doi":"10.1002/jcp.70050","DOIUrl":"https://doi.org/10.1002/jcp.70050","url":null,"abstract":"<p><b>RETRACTION</b>: Hirpara, D. G., H. P. Gajera, A. K. Patel, Z. A. Katakpara, and B. A. Golakiya, “Molecular Insights Into Development of Trichoderma Interfusants for Multistress Tolerance Enhancing Antagonism Against <i>Sclerotium rolfsii</i> Sacc.” <i>Journal of Cellular Physiology</i> 234, no. 5 (2019): 7368–7383. https://doi.org/10.1002/jcp.27496.</p><p>The above article, published online on 28 October 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath, and Wiley Periodicals LLC. A third party notified the journal of image duplications within Figure 2 of this article: Fu 9(a) had been re-used as Fu 21(a) and Fu 22 (12 DAI) had been re-used as Fu 23 (12 DAI). The third party also indicated that the Fu 21(a)/Fu 21(a) image had been re-used in another article by some of the same authors (Hirpara and Gajera [2018]; https://doi.org/10.1016/j.meegid.2018.09.005) and that all images describe different experimental conditions. Lastly, the third party also found evidence of duplicated datapoints within Table 1. An investigation by the publisher confirmed the duplication of images within Figure 8 and also found evidence of duplication and resizing of cellular sections between the Fu 21 and Fu 28 images in Figure S1.</p><p>The authors responded to an inquiry by the publisher and provided what was labeled as original data. The authors confirmed that the FU 21 image in Figure 2 had been reused in another article but stated that the image was intended to provide background information on the purity of the fusant culture and that the duplication does not influence the results. The authors also confirmed the duplications of images in Figure 2 as well as the duplication in Figure S1, but they did not provide the original images for these experiments for verification by the publisher. A review of the original data found several duplicated datapoints that were not adequately explained and that some values reported in the original data did not match those in the published article.</p><p>The retraction has been agreed to because of discrepancies between the published data and the original data, as well as the duplication of images within this article and with another published article, which fundamentally compromises the editors’ confidence in the conclusions presented in the article. The authors disagree with the retraction.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100619","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":"Cardiolipin Dysregulation in Glioblastoma—Effects on Mitochondrial Function Tumor Cell Death and Sensitivity to Mitochondria-Targeting Drugs","authors":"Jean-Jacques Hunter,&nbsp;Luis Del Valle,&nbsp;Francesca Peruzzi,&nbsp;Krzysztof Reiss","doi":"10.1002/jcp.70045","DOIUrl":"https://doi.org/10.1002/jcp.70045","url":null,"abstract":"<div>\u0000 \u0000 <p>Biological systems do not exist in isolation. Analogous to the intricate design of a spider web, the metabolic adaptations propagated by glioblastoma cells are interlaced, creating a “defense mechanism” that increases the likelihood of mutagenesis and proliferation, while mitigating stress-induced tumor cell death and immune evasion. Previous studies have observed the role of cardiolipin (CL) in the electron transport chain (ETC) function and several other intracellular signaling pathways. Our review provides a synopsis of the existing knowledge about CL in glioblastoma and its complex relationship with metabolic reprogramming at the subcellular level. Through a meticulous examination of CL defects due to its biogenesis and stress-induced modifications, we seek to elucidate the multifaceted connections between aberrant CL variants and the metabolic alterations that underlie glioblastoma progression. A comprehensive grasp of these mechanisms could provide future direction in designing chemotherapeutic agents that selectively target glioblastoma, are less harmful to normal cells, and therefore, may extend patient survival.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074693","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":"De Novo Protein Synthesis Occurs Through the Cytoplasmic Translation Machinery in Mammalian Spermatozoa","authors":"Pedro O. Corda,&nbsp;Joana Vieira Silva,&nbsp;Catarina R. Almeida,&nbsp;Philippe Pierre,&nbsp;Margarida Fardilha","doi":"10.1002/jcp.70038","DOIUrl":"https://doi.org/10.1002/jcp.70038","url":null,"abstract":"<div>\u0000 \u0000 <p>The current hypothesis suggests that translation occurs in capacitated spermatozoa through mitochondrial ribosomes. Mitochondrial translation has several particularities, which rise some questions about how mitochondrial ribosomes can ensure sperm translation activity. Here, we aimed to elucidate if cytoplasmic translation occurs in mammalian spermatozoa. A bioinformatic workflow was performed to identify translation-related proteins in human spermatozoa and their association with cytoplasmic translation. The surface sensing of translation (SUnSET) method was used to measure translation activity in capacitated human and bovine spermatozoa. Two translation inhibitors, cycloheximide (CHX, cytoplasmic) and <span>D</span>-chloramphenicol (<span>D</span>-CP, mitochondrial) were used to identify which ribosomes were active in sperm. To spot newly synthesized proteins, puromycin-peptides were immunoprecipitated and analysed by mass spectrometry. A second approach was performed using translation inhibitors and analysing the sperm proteome by mass spectrometry. Bioinformatic analysis revealed that human spermatozoa possess 510 translation proteins, which were enriched for cytoplasmic mRNA translation. CHX decreased translation activity in mammalian sperm, whereas no effect was observed after D-CP treatment. Nine proteins were immunoprecipitated and identified as newly synthesized in capacitated bovine spermatozoa. CHX and <span>D</span>-CP decreased the level of 22 proteins that were replaced, or de novo translated during capacitation. New proteins were associated with relevant processes for sperm physiology. Both translation inhibitors decreased sperm rapid progressive motility and increased sperm immotility. Our results proved sperm translation occurs through cytoplasmic translation machinery in capacitated bovine and human spermatozoa. These results also support that sperm translation is required during capacitation to produce relevant proteins for sperm functions.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074698","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":"RETRACTION: MicroRNA-29a-3p Regulates Abdominal Aortic Aneurysm Development and Progression via Direct Interaction With PTEN","authors":"","doi":"10.1002/jcp.70043","DOIUrl":"https://doi.org/10.1002/jcp.70043","url":null,"abstract":"<p><b>RETRACTION</b>: Zhou, Y., Wang, M., Zhang, J., Xu, P., and Wang, H. 2020. “MicroRNA-29a-3p Regulates Abdominal Aortic Aneurysm Development and Progression via Direct Interaction With PTEN.” <i>Journal of Cellular Physiology</i> 235, no. 12: 9414–9423, https://doi.org/10.1002/jcp.29746.</p><p>The above article, published online on 7 May 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. Following an investigation by the publisher, it was determined that this article was accepted solely on the basis of a compromised peer review process. The editor has therefore decided to retract the article. The authors did not respond to requests for comment.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932285","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}