Redox Report最新文献

{"title":"Hyperoxia exposure induces ferroptosis and apoptosis by downregulating PLAGL2 and repressing HIF-1α/VEGF signaling pathway in newborn alveolar typeII epithelial cell.","authors":"Yuting Zhu, Hongmei Hou, Yawen Li, Yanyu Zhang, Yuanyuan Fang, Si Chen, Le Zhang, Weilai Jin, Yahui Zhou","doi":"10.1080/13510002.2024.2387465","DOIUrl":"10.1080/13510002.2024.2387465","url":null,"abstract":"<p><strong>Backgroud: </strong>Bronchopulmonary dysplasia (BPD) is one of the most important complications plaguing neonates and can lead to a variety of sequelae. the ability of the HIF-1α/VEGF signaling pathway to promote angiogenesis has an important role in neonatal lung development.</p><p><strong>Method: </strong>Newborn rats were exposed to 85% oxygen. The effects of hyperoxia exposure on Pleomorphic Adenoma Gene like-2 (PLAGL2) and the HIF-1α/VEGF pathway in rats lung tissue were assessed through immunofluorescence and Western Blot analysis. In cell experiments, PLAGL2 was upregulated, and the effects of hyperoxia and PLAGL2 on cell viability were evaluated using scratch assays, CCK-8 assays, and EDU staining. The role of upregulated PLAGL2 in the HIF-1α/VEGF pathway was determined by Western Blot and RT-PCR. Apoptosis and ferroptosis effects were determined through flow cytometry and viability assays.</p><p><strong>Results: </strong>Compared with the control group, the expression levels of PLAGL2, HIF-1α, VEGF, and SPC in lung tissues after 3, 7, and 14 days of hyperoxia exposure were all decreased. Furthermore, hyperoxia also inhibited the proliferation and motility of type II alveolar epithelial cells (AECII) and induced apoptosis in AECII. Upregulation of PLAGL2 restored the proliferation and motility of AECII and suppressed cell apoptosis and ferroptosis, while the HIF-1α/VEGF signaling pathway was also revived.</p><p><strong>Conclusions: </strong>We confirmed the positive role of PLAGL2 and HIF-1α/VEGF signaling pathway in promoting BPD in hyperoxia conditions, and provided a promising therapeutic targets.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"29 1","pages":"2387465"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894144","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":"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":"29 1","pages":"2392329"},"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":"Fluorescent probes for sensing peroxynitrite: biological applications.","authors":"Yan Yang, Jinting Shang, Yiyuan Xia, Yuran Gui","doi":"10.1080/13510002.2024.2430157","DOIUrl":"10.1080/13510002.2024.2430157","url":null,"abstract":"<p><p>Peroxynitrite (ONOO^-) is a quintessential reactive oxygen species (ROS) and reactive nitrogen species (RNS), renowned for its potent oxidizing and nitrifying capabilities. Under normal physiological conditions, a baseline level of ONOO^- is present within the body. However, its production escalates significantly in response to oxidative stress. ONOO^- is highly reactive with various biomolecules <i>in vivo</i>, particularly proteins, lipids, and nucleic acids, thereby playing a role in a spectrum of physiological and pathological processes, such as inflammation, cancer, neurodegenerative diseases, and cardiovascular diseases. Consequently, detecting ONOO^- <i>in vivo</i> is of paramount importance for understanding the etiology of various diseases and facilitating early diagnosis. Fluorescent probes have become a staple in the identification of biomolecules due to their ease of use, convenience, and superior sensitivity and specificity. This review highlights the recent advancements in the development of fluorescent probes for the detection of ONOO^- in diverse disease models and provides an in-depth examination of their design and application.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"29 1","pages":"2430157"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710924","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":"A reactive oxygen species-related signature predicts the prognosis and immunosuppressive microenvironment in gliomas.","authors":"Xia Shan, Ruoyu Huang, Kuanyu Wang, Pei Yang","doi":"10.1080/13510002.2024.2433396","DOIUrl":"10.1080/13510002.2024.2433396","url":null,"abstract":"<p><strong>Objective: </strong>Intracellular redox homeostasis is crucial for a series of physiological processes. Reactive oxygen species (ROS) play important roles in redox processes. ROS can maintain cell reproduction and survival at moderate levels while promoting the initiation and progression of tumors at high levels.</p><p><strong>Methods: </strong>Based on a comprehensive analysis of ROS-related gene expression profiles, we established a gene signature associated with ROS to explore its influence on prognosis and immune microenvironment in gliomas.</p><p><strong>Results: </strong>The ROS-related gene expression profile dichotomized patients into two groups with different clinicopathological features and prognoses. A 19-gene ROS-related signature was used to robustly predict prognosis in both training and validation datasets. Functional analysis indicated an association between ROS levels and the immune microenvironment. The expression of immune checkpoints and M2-type markers was upregulated in the high-risk group, which suggested the immunosuppressive function of ROS.</p><p><strong>Conclusion: </strong>ROS-related signature is an independent prognostic factor in gliomas and could potentially exert immunosuppressive effects on the tumor microenvironment.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"29 1","pages":"2433396"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751039","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":"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":"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":"29 1","pages":"2371173"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637001/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating anticancer activity of emodin by enhancing antioxidant activities and affecting PKC/ADAMTS4 pathway in thioacetamide-induced hepatocellular carcinoma in rats.","authors":"Hanan M Hassan, Ahmed M Hamdan, Abdullah Alattar, Reem Alshaman, Omar Bahattab, Mohammed M H Al-Gayyar","doi":"10.1080/13510002.2024.2365590","DOIUrl":"10.1080/13510002.2024.2365590","url":null,"abstract":"<p><p>Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"29 1","pages":"2365590"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306738","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>CISD2</i> regulates oxidative stress and mitophagy to maintain the balance of the follicular microenvironment in PCOS.","authors":"Hong-Hui Wu, Qi Zhu, Na Liang, Yu Xiang, Tian-Yue Xu, Zi-Chao Huang, Jie-Yu Cai, Ling-Lin Weng, Hong-Shan Ge","doi":"10.1080/13510002.2024.2377870","DOIUrl":"10.1080/13510002.2024.2377870","url":null,"abstract":"<p><strong>Objectives: </strong>To observe the CISD2 expression among PCOS patients and to explore its profound impact on the follicular microenvironment. Moreover, we want to elucidate the intricate mechanistic contribution of <i>CISD2</i> to the onset and progression of PCOS.</p><p><strong>Methods: </strong>Oxidase NOX2, mitophagy-related proteins, and CISD2 were detected by WB. The changes in mitochondrial structure and quantity were observed by transmission electron microscopy. Mitochondrial and lysosome colocalization was used to detect the changes of mitophagy. MDA kit, GSH and GSSG Assay kit and ROS probe were used to detect oxidative stress damage.</p><p><strong>Results: </strong>We found that CISD2, mitophagy and oxidase in the GCs of PCOS patients were significantly increased. Testosterone stimulation leads to the increase of oxidase, mitophagy, and CISD2 in KGN cells. <i>CISD2</i> inhibition promoted the increase of mitophagy, and the activation of mitochondria-lysosome binding, while alleviating the oxidative stress.</p><p><strong>Conclusions: </strong>Inhibition of CISD2 can improve the occurrence of oxidative stress by increasing the level of mitophagy, thus affecting the occurrence and development of PCOS diseases.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"29 1","pages":"2377870"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC467114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620855","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":"TOM5 regulates the mitochondrial membrane potential of alveolar epithelial cells in organizing pneumonia.","authors":"Yan Qian, Xiao Li, Xinyu Li, Xijie Zhang, Qi Yuan, Zhengxia Wang, Minghun Zhang, Mao Huang, Ningfei Ji","doi":"10.1080/13510002.2024.2354625","DOIUrl":"10.1080/13510002.2024.2354625","url":null,"abstract":"<p><p>Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"29 1","pages":"2354625"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093979","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":"Melittin alleviates sepsis-induced acute kidney injury by promoting GPX4 expression to inhibit ferroptosis.","authors":"Hongyan Zan, Jizheng Liu, Meixia Yang, Honghui Zhao, Chunyan Gao, Yunyan Dai, Zhiming Wang, Hongxuan Liu, Yunfei Zhang","doi":"10.1080/13510002.2023.2290864","DOIUrl":"10.1080/13510002.2023.2290864","url":null,"abstract":"<p><strong>Objectives: </strong>Melittin, the main component of bee venom, is a natural anti-inflammatory substance, in addition to its ability to fight cancer, antiviral, and useful in diabetes treatment. This study seeks to determine whether melittin can protect renal tissue from sepsis-induced damage by preventing ferroptosis and explore the protective mechanism.</p><p><strong>Methods: </strong>In this study, we investigated the specific protective mechanism of melittin against sepsis-induced renal injury by screening renal injury indicators and ferroptosis -related molecules and markers in animal and cellular models of sepsis.</p><p><strong>Results: </strong>Our results showed that treatment with melittin attenuated the pathological changes in mice with lipopolysaccharide-induced acute kidney injury. Additionally, we found that melittin attenuated ferroptosis in kidney tissue by enhancing GPX4 expression, which ultimately led to the reduction of kidney tissue injury. Furthermore, we observed that melittin enhanced NRF2 nuclear translocation, which consequently upregulated GPX4 expression. our findings suggest that melittin may be a potential therapeutic agent for the treatment of sepsis-associated acute kidney injury by inhibiting ferroptosis through the GPX4/NRF2 pathway.</p><p><strong>Conclusions: </strong>Our study reveals the protective mechanism of melittin in septic kidney injury and provides a new therapeutic direction for Sepsis-AKI.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"29 1","pages":"2290864"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040459","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":"Cardioprotective effects of liposomal resveratrol in diabetic rats: unveiling antioxidant and anti-inflammatory benefits.","authors":"Ahmed Z Alanazi, Mohammed Alqinyah, Abdullah S Alhamed, Hanan Mohammed, Mohammad Raish, Khaldoon Aljerian, Jawza F Alsabhan, Khalid Alhazzani","doi":"10.1080/13510002.2024.2416835","DOIUrl":"10.1080/13510002.2024.2416835","url":null,"abstract":"<p><p>As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"29 1","pages":"2416835"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576820","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}