{"title":"RING1 dictates GSDMD-mediated inflammatory response and host susceptibility to pathogen infection","authors":"Yuanyuan Li, Wenqing Gao, Yuxin Qiu, Jiasong Pan, Qingqing Guo, Xuehe Liu, Lu Geng, Yajie Shen, Yifan Deng, Zhidong Hu, Suhua Li, Shanshan Liu, Adi Idris, Jinqing Huang, Hua Yang, Baoxue Ge, Xiaoyong Fan, Xiangjun Chen, Jixi Li","doi":"10.1038/s41418-025-01527-2","DOIUrl":"https://doi.org/10.1038/s41418-025-01527-2","url":null,"abstract":"<p>RING1 is an E3 ligase component of the polycomb repressive complex 1 (PRC1) with known roles in chromatin regulation and cellular processes such as apoptosis and autophagy. However, its involvement in inflammation and pyroptosis remains elusive. Here, we demonstrate that human RING1, not RING2, promotes K48-linked ubiquitination of Gasdermin D (GSDMD) and acts as a negative regulator of pyroptosis and bacterial infection. Indeed, we showed that loss of <i>Ring1</i> increased <i>S. typhimurium</i> infectious load and mortality in vivo. Though RING1 deletion initially reduced <i>M. tuberculosis</i> (Mtb) infectious load in vivo, increased lung inflammation and impaired immune defense responses were later observed. Moreover, <i>Ring1</i> knockout exacerbated acute sepsis induced by lipopolysaccharide (LPS) in vivo. Mechanistically, RING1 directly interacts with GSDMD and ubiquitinates the K51 and K168 sites of GSDMD for K48-linked proteasomal degradation, thereby inhibiting pyroptosis. Inhibition of RING1 E3 ligase activity by direct mutation or with the use of small molecule inhibitors increased GSDMD level and cell death during pyroptosis. Our findings reveal that RING1 dictates GSDMD-mediated inflammatory response and host susceptibility to pathogen infection, highlighting RING1 as a potential therapeutic target for combating infectious diseases.</p><figure></figure>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"117 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ARID1A loss enhances sensitivity to c-MET inhibition by dual targeting of GPX4 and iron homeostasis, inducing ferroptosis","authors":"Xu Zhang, Zihuan Wang, Yilin He, Kejin Wang, Cheng Xiang, Yongfeng Liu, Yijiang Song, Aimin Li, Zhen Wang, Yingnan Yu, Wenxuan Peng, Side Liu, Joong Sup Shim, Changjie Wu","doi":"10.1038/s41418-025-01510-x","DOIUrl":"https://doi.org/10.1038/s41418-025-01510-x","url":null,"abstract":"<p>ARID1A, a subunit of the SWI/SNF chromatin-remodeling complex, functions as a tumor suppressor in various cancer types. Owing to its high frequency of inactivating mutations, ARID1A has emerged as a promising target for the development of anticancer drugs. In this study, we report that ARID1A-deficient colorectal cancer (CRC) cells induce synthetic lethality when treated with inhibitors of c-MET receptor tyrosine kinase. c-MET specific inhibitor PHA-665752 as well as two other FDA-approved drugs, crizotinib and cabozantinib, selectively inhibited the growth of ARID1A-deficient CRC cells in vitro and in xenograft tumor models. Mechanistically, we identified a tripartite functional association among ARID1A, c-MET, and NRF2, where ARID1A and c-MET pathways converge on the NRF2 transcription factor, which regulates the transcription of GPX4, a key regulator of ferroptosis. ARID1A inactivation reduces c-MET expression, decreasing NRF2 nuclear localization and its binding to the GPX4 promoter, resulting in reduced GPX4 transcription. This creates a cellular dependency on the residual c-MET for minimal GPX4 expression to survive the ferroptotic cell death. Additionally, we demonstrate that ARID1A loss leads to increased intracellular labile iron accumulation by downregulating the iron-exporting protein SLC40A1, thereby increasing cellular susceptibility to ferroptosis. Inhibition of c-MET in ARID1A-deficient CRC cells diminishes GPX4 expression, resulting in elevated lipid peroxidation and glutathione depletion, ultimately inducing ferroptosis. This study reveals a novel synthetic lethal relationship between ARID1A and c-MET signaling in promoting ferroptosis and proposes c-MET inhibitors as a potential therapeutic strategy for ARID1A-deficient CRC.</p><figure></figure>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"10 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sven Jonckheere, Joachim Taminau, Jamie Adams, Jef Haerinck, Jordy De Coninck, Jeroen Verstappe, Kato De Clercq, Evelien Peeters, Alexander Gheldof, Eva De Smedt, Vera Goossens, Dominique Audenaert, Aurélie Candi, Matthias Versele, Dominic De Groote, Hanne Verschuere, Marc Stemmler, Thomas Brabletz, Peter Vandenabeele, Andreu Casali, Kyra Campbell, Steven Goossens, Geert Berx
{"title":"Development and validation of a high-throughput screening pipeline of compound libraries to target EMT","authors":"Sven Jonckheere, Joachim Taminau, Jamie Adams, Jef Haerinck, Jordy De Coninck, Jeroen Verstappe, Kato De Clercq, Evelien Peeters, Alexander Gheldof, Eva De Smedt, Vera Goossens, Dominique Audenaert, Aurélie Candi, Matthias Versele, Dominic De Groote, Hanne Verschuere, Marc Stemmler, Thomas Brabletz, Peter Vandenabeele, Andreu Casali, Kyra Campbell, Steven Goossens, Geert Berx","doi":"10.1038/s41418-025-01515-6","DOIUrl":"https://doi.org/10.1038/s41418-025-01515-6","url":null,"abstract":"<p>Epithelial to Mesenchymal transitions (EMT) drive cell plasticity and are associated with cell features such as invasiveness, migration and stemness. They are orchestrated by select families of EMT-associated transcription factors, which exhibit pleiotropic roles in the malignant progression of various cancer types, such as breast and colorectal cancer (CRC). This has spurred interest in EMT as a promising target for the development of novel therapeutic strategies. In this study, we developed a phenotypic dual EMT Sensor screening assay, amendable to efficient high-throughput identification of small molecules interfering with EMT. In a proof-of-concept screening we identified anti-EMT repurposing drugs. From these, we validated RepSox, a selective inhibitor of the TGF-β type I receptor ALK5, and demonstrated that it is potently blocking EMT in both breast and colorectal cancer cell lines in vitro. In addition, utilizing a <i>Drosophila melanogaster</i> metastatic CRC model we confirmed the ability of the identified anti-EMT hits to suppress metastatic behavior in vivo.</p>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"24 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyan Lu, Dongshi Chen, Min Wang, Xiangping Song, Kaylee Ermine, Suisui Hao, Anupma Jha, Yixian Huang, Ying Kang, Haibo Qiu, Heinz-Josef Lenz, Song Li, Zhendong Jin, Jian Yu, Lin Zhang
{"title":"Depletion of oxysterol-binding proteins by OSW-1 triggers RIP1/RIP3-independent necroptosis and sensitization to cancer immunotherapy","authors":"Xinyan Lu, Dongshi Chen, Min Wang, Xiangping Song, Kaylee Ermine, Suisui Hao, Anupma Jha, Yixian Huang, Ying Kang, Haibo Qiu, Heinz-Josef Lenz, Song Li, Zhendong Jin, Jian Yu, Lin Zhang","doi":"10.1038/s41418-025-01521-8","DOIUrl":"https://doi.org/10.1038/s41418-025-01521-8","url":null,"abstract":"<p>Oxysterol-binding proteins (OSBPs), lipid transfer proteins functioning at intracellular membrane contact sites, are recently found to be dysregulated in cancer and promote cancer cell survival. However, their role as potential targets in cancer therapy remains largely unexplored. In this study, we found OSW-1, a natural compound and OSBP inhibitor, potently and selectively kills colon cancer cells by activating a previously unknown necroptosis pathway that is independent of receptor-interacting protein 1 (RIP1) and RIP3. OSW-1 stabilizes p53 and degrades OSBPs to promote endoplasmic reticulum (ER) stress and glycogen synthase kinase 3β (GSK3β)/Tip60-mediated p53 acetylation at Lysine 120, which selectively induces its target PUMA. PUMA-mediated mitochondrial calcium influx activates calcium/calmodulin-dependent protein kinase IIδ (CamKIIδ) to promote mixed lineage kinase domain-like (MLKL) phosphorylation and necroptotic cell death. Furthermore, OSW-1-induced necroptosis is highly immunogenic and sensitizes syngeneic colorectal tumors to anti-PD-1 immunotherapy. Together, our results identified a novel RIP1/RIP3-independent necroptosis pathway underlying the extremely potent anticancer activity of OSW-1, which can be harnessed to develop new anticancer therapies by selectively stimulating antitumor immunity.</p>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"9 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liangbo Sun, Meng He, Dong Liu, Meihua Shan, Lingxi Chen, Mingzhen Yang, Xufang Dai, Jie Yao, Tao Li, Yan Zhang, Yang Zhang, Li Xiang, An Chen, Yingxue Hao, Fengtian He, Haojun Xiong, Jiqin Lian
{"title":"Deacetylation of ANXA2 by SIRT2 desensitizes hepatocellular carcinoma cells to donafenib via promoting protective autophagy","authors":"Liangbo Sun, Meng He, Dong Liu, Meihua Shan, Lingxi Chen, Mingzhen Yang, Xufang Dai, Jie Yao, Tao Li, Yan Zhang, Yang Zhang, Li Xiang, An Chen, Yingxue Hao, Fengtian He, Haojun Xiong, Jiqin Lian","doi":"10.1038/s41418-025-01499-3","DOIUrl":"https://doi.org/10.1038/s41418-025-01499-3","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is one of the most lethal forms of cancer globally. HCC cells frequently undergo macroautophagy, also known as autophagy, which can lead to tumor progression and chemotherapy resistance. Annexin A2 (ANXA2) has been identified as a potential therapeutic target in HCC and is involved in the regulation of autophagic process. Here, we for the first time showed that ANXA2 deacetylation plays a crucial role in donafenib-induced autophagy. Mechanistically, donafenib increased SIRT2 activity via triggering both SIRT2 dephosphorylation and deacetylation by respectively downregulating cyclin E/CDK and p300. Moreover, elevation of SIRT2 activity by donafenib caused ANXA2 deacetylation at K81/K206 sites, leading to a reduction of the binding between ANXA2 and mTOR, which resulted in a decrease of mTOR phosphorylation and activity, and ultimately promoted protective autophagy and donafenib insensitivity in HCC cells. Additionally, ANXA2 deacetylation at K81/K206 sites was positively correlated with poor prognosis in HCC patients. Meanwhile, we found that selective inhibition of SIRT2 increased the sensitivity of donafenib in HCC cells by strengthening ANXA2 acetylation. In summary, this study reveals that donafenib induces protective autophagy and decreases its sensitivity in HCC cells through enhancing SIRT2-mediated ANXA2 deacetylation, which suggest that targeting ANXA2 acetylation/deacetylation may be a promising strategy for improving the sensitivity of donafenib in HCC treatment.</p>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"8 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Scott Layzell, Alessandro Barbarulo, Geert van Loo, Rudi Beyaert, Benedict Seddon
{"title":"Correction: NF-κB regulated expression of A20 controls IKK dependent repression of RIPK1 induced cell death in activated T cells.","authors":"Scott Layzell, Alessandro Barbarulo, Geert van Loo, Rudi Beyaert, Benedict Seddon","doi":"10.1038/s41418-024-01424-0","DOIUrl":"10.1038/s41418-024-01424-0","url":null,"abstract":"","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":" ","pages":"989"},"PeriodicalIF":13.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Qiu, Juliana A. Hüther, Bianca Wank, Antonia Rath, René Tykwe, Maceler Aldrovandi, Bernhard Henkelmann, Julia Mergner, Toshitaka Nakamura, Sabine Laschat, Marcus Conrad, Daniela Stöhr, Markus Rehm
{"title":"Interplay of ferroptotic and apoptotic cell death and its modulation by BH3-mimetics","authors":"Yun Qiu, Juliana A. Hüther, Bianca Wank, Antonia Rath, René Tykwe, Maceler Aldrovandi, Bernhard Henkelmann, Julia Mergner, Toshitaka Nakamura, Sabine Laschat, Marcus Conrad, Daniela Stöhr, Markus Rehm","doi":"10.1038/s41418-025-01514-7","DOIUrl":"https://doi.org/10.1038/s41418-025-01514-7","url":null,"abstract":"<p>Ferroptosis and apoptosis are widely considered to be independent cell death modalities. Ferroptotic cell death is a consequence of insufficient radical detoxification and progressive lipid peroxidation, which is counteracted by glutathione peroxidase-4 (GPX4). Apoptotic cell death can be triggered by a wide variety of stresses, including oxygen radicals, and can be suppressed by anti-apoptotic members of the BCL-2 protein family. Mitochondria are the main interaction site of BCL-2 family members and likewise a major source of oxygen radical stress. We therefore studied if ferroptosis and apoptosis might intersect and possibly interfere with one another. Indeed, cells dying from impaired GPX4 activity displayed hallmarks of both ferroptotic and apoptotic cell death, with the latter including (transient) membrane blebbing, submaximal cytochrome-c release and caspase activation. Targeting BCL-2, MCL-1 or BCL-XL with BH3-mimetics under conditions of moderate ferroptotic stress in many cases synergistically enhanced overall cell death and frequently skewed primarily ferroptotic into apoptotic outcomes. Surprisingly though, in other cases BH3-mimetics, most notably the BCL-XL inhibitor WEHI-539, counter-intuitively suppressed cell death and promoted cell survival following GPX4 inhibition. Further studies revealed that most BH3-mimetics possess previously undescribed antioxidant activities that counteract ferroptotic cell death at commonly employed concentration ranges. Our results therefore show that ferroptosis and apoptosis can intersect. We also show that combining ferroptotic stress with BH3-mimetics, context-dependently can either enhance and convert cell death outcomes between ferroptosis and apoptosis or can also suppress cell death by intrinsic antioxidant activities.</p>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"18 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Congyang Li, Jiashuo Li, Siyu Du, Yunfei Ma, Yueshuai Guo, Xiangzheng Zhang, Bing Wang, Shuai Zhu, Huiqing An, Ming Chen, Junjie Guo, Longsen Han, Juan Ge, Xu Qian, Tim Schedl, Xuejiang Guo, Qiang Wang
{"title":"FTDC1/2, oocyte-specific cofactors of DNMT1 required for epigenetic regulation and embryonic development","authors":"Congyang Li, Jiashuo Li, Siyu Du, Yunfei Ma, Yueshuai Guo, Xiangzheng Zhang, Bing Wang, Shuai Zhu, Huiqing An, Ming Chen, Junjie Guo, Longsen Han, Juan Ge, Xu Qian, Tim Schedl, Xuejiang Guo, Qiang Wang","doi":"10.1038/s41418-025-01518-3","DOIUrl":"https://doi.org/10.1038/s41418-025-01518-3","url":null,"abstract":"<p>The unique epigenetic patterns during gametogenesis and embryonic development indicate the existence of specialized methylation machinery. In the present study, we describe the discovery of two oocyte-specific cofactors of DNA methyltransferase 1 (DNMT1), encoded by uncharacterized genes, ferritin domain containing 1 and 2 (<i>Ftdc1</i> and <i>Ftdc2</i>). Genetic ablation of <i>Ftdc1</i> or <i>Ftdc2</i> causes midgestation defects and female infertility. FTDC1 or FTDC2 depletion induces the progressive loss of DNA methylation including imprinted regions in early embryos. This loss correlates with a marked reduction in DNMT1 protein due to increased degradation, likely via the ubiquitin-proteasome pathway. Mechanistically, we find that FTDC1, FTDC2 and DNMT1 form a complex by direct interactions, thereby stabilizing each other. Surprisingly, knockout of <i>Ftdc1</i> or <i>Ftdc2</i> displayed stronger DNA demethylation phenotypes and earlier embryonic lethality than the <i>Dnmt1</i>-null mutant, implying their unique functions. These data suggest that FTDC1/2 are crucial players specifically involved in maintaining genomic methylation during embryogenesis, offering new insights into the epigenetic control of mammalian development.</p>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"7 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Isil Yapici, Eric Seidel, Alina Dahlhaus, Josephine Weber, Christina Schmidt, Adriano de Britto Chaves Filho, Ming Yang, Maria Nenchova, Emre Güngör, Jenny Stroh, Ioanna Kotouza, Julia Beck, Ali T. Abdallah, Jan-Wilm Lackmann, Christina M. Bebber, Ariadne Androulidaki, Peter Kreuzaler, Almut Schulze, Christian Frezza, Silvia von Karstedt
{"title":"An atlas of ferroptosis-induced secretomes","authors":"F. Isil Yapici, Eric Seidel, Alina Dahlhaus, Josephine Weber, Christina Schmidt, Adriano de Britto Chaves Filho, Ming Yang, Maria Nenchova, Emre Güngör, Jenny Stroh, Ioanna Kotouza, Julia Beck, Ali T. Abdallah, Jan-Wilm Lackmann, Christina M. Bebber, Ariadne Androulidaki, Peter Kreuzaler, Almut Schulze, Christian Frezza, Silvia von Karstedt","doi":"10.1038/s41418-025-01517-4","DOIUrl":"https://doi.org/10.1038/s41418-025-01517-4","url":null,"abstract":"<p>Cells undergoing regulated necrosis systemically communicate with the immune system via the release of protein and non-protein secretomes. Ferroptosis is a recently described iron-dependent type of regulated necrosis driven by massive lipid peroxidation. While membrane rupture occurs during ferroptosis, a comprehensive appraisal of ferroptotic secretomes and their potential biological activity has been lacking. Here, we apply a multi-omics approach to provide an atlas of ferroptosis-induced secretomes and reveal a novel function in macrophage priming. Proteins with assigned DAMP and innate immune system function, such as MIF, heat shock proteins (HSPs), and chaperones, were released from ferroptotic cells. Non-protein secretomes with assigned inflammatory function contained oxylipins as well as TCA- and methionine-cycle metabolites. Interestingly, incubation of bone marrow-derived macrophages (BMDMs) with ferroptotic supernatants induced transcriptional reprogramming consistent with priming. Indeed, exposure to ferroptotic supernatants enhanced LPS-induced cytokine production. These results define a catalog of ferroptosis-induced secretomes and identify a biological activity in macrophage priming with important implications for the fine-tuning of inflammatory processes.</p>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"30 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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