Histone methylation plays a crucial role in tumorigenesis. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that regulates chromatin structure and gene expression. EZH2 inhibitors (EZH2is) have been shown to be effective in treating hematologic malignancies, while their effectiveness in solid tumors remains limited. One of the major challenges in the treatment of solid tumors is their hypoxic tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key hypoxia responder that interacts with EZH2 to promote tumor progression. Here we discuss the implications of the relationship between EZH2 and hypoxia for expanding the application of EZH2is in solid tumors.
{"title":"Hypoxia makes EZH2 inhibitor not easy—advances of crosstalk between HIF and EZH2","authors":"Zhanya Huang, Yuanjun Tang, Jianlin Zhang, Jiaqi Huang, Rui Cheng, Yunyun Guo, Celina G Kleer, Yuqing Wang, Lixiang Xue","doi":"10.1093/lifemeta/loae017","DOIUrl":"https://doi.org/10.1093/lifemeta/loae017","url":null,"abstract":"\u0000 Histone methylation plays a crucial role in tumorigenesis. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that regulates chromatin structure and gene expression. EZH2 inhibitors (EZH2is) have been shown to be effective in treating hematologic malignancies, while their effectiveness in solid tumors remains limited. One of the major challenges in the treatment of solid tumors is their hypoxic tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key hypoxia responder that interacts with EZH2 to promote tumor progression. Here we discuss the implications of the relationship between EZH2 and hypoxia for expanding the application of EZH2is in solid tumors.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"50 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141010100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-26eCollection Date: 2024-08-01DOI: 10.1093/lifemeta/loae016
Wen Mi, Jianwei You, Liucheng Li, Lingzhi Zhu, Xinyi Xia, Li Yang, Fei Li, Yi Xu, Junfeng Bi, Pingyu Liu, Li Chen, Fuming Li
Bromodomain and extra-terminal domain (BET) proteins, which function partly through MYC proto-oncogene (MYC), are critical epigenetic readers and emerging therapeutic targets in cancer. Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear. Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors (pan-BETis) blunts liver cancer cell proliferation and tumor growth. BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis. Specifically, BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1 (GDH1) independent of MYC, which produces α-ketoglutarate for mitochondrial oxidative phosphorylation (OXPHOS). Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibition, and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo. Together, we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.
{"title":"BET inhibition induces GDH1-dependent glutamine metabolic remodeling and vulnerability in liver cancer.","authors":"Wen Mi, Jianwei You, Liucheng Li, Lingzhi Zhu, Xinyi Xia, Li Yang, Fei Li, Yi Xu, Junfeng Bi, Pingyu Liu, Li Chen, Fuming Li","doi":"10.1093/lifemeta/loae016","DOIUrl":"10.1093/lifemeta/loae016","url":null,"abstract":"<p><p>Bromodomain and extra-terminal domain (BET) proteins, which function partly through MYC proto-oncogene (MYC), are critical epigenetic readers and emerging therapeutic targets in cancer. Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear. Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors (pan-BETis) blunts liver cancer cell proliferation and tumor growth. BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis. Specifically, BET inhibition downregulates <i>miR-30a</i> to upregulate glutamate dehydrogenase 1 (GDH1) independent of MYC, which produces α-ketoglutarate for mitochondrial oxidative phosphorylation (OXPHOS). Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibition, and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth <i>in vitro</i> and <i>in vivo</i>. Together, we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 4","pages":"loae016"},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-13DOI: 10.1093/lifemeta/loae014
Zhongsheng Wu, Yongtao Du, Tom Kirchhausen, Kangmin He
Distinct phospholipid species display specific distribution patterns across cellular membranes, important for their structural and signaling roles and for preserving the integrity and functionality of the plasma membrane and organelles. Recent advancements in lipid biosensor technology and imaging modalities now allow for direct observation of phospholipid distribution, trafficking, and dynamics in living cells. These innovations have markedly advanced our understanding of phospholipid function and regulation at both cellular and subcellular levels. Herein, we summarize the latest developments in phospholipid biosensor design and application, emphasizing the contribution of cutting-edge imaging techniques to elucidating phospholipid dynamics and distribution with unparalleled spatiotemporal precision.
{"title":"Probing and imaging phospholipid dynamics in live cells","authors":"Zhongsheng Wu, Yongtao Du, Tom Kirchhausen, Kangmin He","doi":"10.1093/lifemeta/loae014","DOIUrl":"https://doi.org/10.1093/lifemeta/loae014","url":null,"abstract":"\u0000 Distinct phospholipid species display specific distribution patterns across cellular membranes, important for their structural and signaling roles and for preserving the integrity and functionality of the plasma membrane and organelles. Recent advancements in lipid biosensor technology and imaging modalities now allow for direct observation of phospholipid distribution, trafficking, and dynamics in living cells. These innovations have markedly advanced our understanding of phospholipid function and regulation at both cellular and subcellular levels. Herein, we summarize the latest developments in phospholipid biosensor design and application, emphasizing the contribution of cutting-edge imaging techniques to elucidating phospholipid dynamics and distribution with unparalleled spatiotemporal precision.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140706947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Obesity is considered an epidemic often accompanied by insulin resistance (IR). Heat treatment (HT) has been shown to prevent high-fat diet-induced IR in skeletal muscle, but the underlying mechanisms are poorly understood. In this study, we discovered that high temperature alleviated the hallmarks of obesity by promoting glycogen synthesis and lowering blood glucose levels in skeletal muscle tissue (SMT). Additionally, HT maintained the decay phase of heat shock factor 1 (HSF1), leading to the activation of gene expression of heat shock proteins (HSPs), which contributed to the alleviation of IR in SMT of diet-induced obese (DIO) mice. Metabolomics and lipidomics analyses showed that HT promoted ceramide (Cer) breakdown, resulting in an elevation of both sphingomyelin (SM) and sphingosine, which further contributed to the amelioration of IR in SMT of DIO mice. Importantly, the increase in sphingosine was attributed to the heightened expression of the acid ceramidase N-acylsphingosine amidohydrolase 1 (ASAH1), and the inhibition of ASAH1 attenuated HT-relieved IR in SMT of DIO mice. Surprisingly, high temperature increased the composition of Cer and cholesteryl ester in lipid droplets of skeletal muscle cells. This not only helped alleviate IR but also prevented lipotoxicity in SMT of DIO mice. These findings revealed a previously unknown connection between a high-temperature environment and sphingolipid metabolism in obesity, suggesting that high temperature can improve IR by promoting Cer catabolism in SMT of obese mice.
肥胖被认为是一种流行病，往往伴随着胰岛素抵抗（IR）。热处理（HT）已被证明能防止高脂饮食诱导的骨骼肌胰岛素抵抗，但其潜在机制却鲜为人知。在这项研究中，我们发现高温能促进糖原合成并降低骨骼肌组织（SMT）中的血糖水平，从而减轻肥胖症的特征。此外，高温还能维持热休克因子1（HSF1）的衰变阶段，从而激活热休克蛋白（HSPs）的基因表达，这有助于减轻饮食诱导肥胖（DIO）小鼠骨骼肌组织中的IR。代谢组学和脂质组学分析表明，高温促进了神经酰胺（Cer）的分解，导致鞘磷脂（SM）和鞘氨醇的增加，这进一步促进了DIO小鼠SMT中IR的改善。重要的是，鞘氨醇的增加归因于酸性神经氨酸酶 N-酰鞘氨醇酰胺水解酶 1（ASAH1）表达的增加，抑制 ASAH1 可减轻高温缓解的 DIO 小鼠 SMT 的 IR。令人惊讶的是，高温增加了骨骼肌细胞脂滴中Cer和胆固醇酯的成分。这不仅有助于缓解IR，还能防止DIO小鼠SMT的脂毒性。这些发现揭示了高温环境与肥胖症鞘脂代谢之间之前未知的联系，表明高温可以通过促进肥胖小鼠SMT中Cer的分解代谢来改善IR。
{"title":"High temperature ameliorates high-fat diet-induced obesity by promoting ceramide breakdown in skeletal muscle tissue","authors":"Qiankun Wang, Lupeng Chen, Junzhi Zhang, Yue Liu, Yi Jin, Jian Wu, Zhuqing Ren","doi":"10.1093/lifemeta/loae012","DOIUrl":"https://doi.org/10.1093/lifemeta/loae012","url":null,"abstract":"\u0000 Obesity is considered an epidemic often accompanied by insulin resistance (IR). Heat treatment (HT) has been shown to prevent high-fat diet-induced IR in skeletal muscle, but the underlying mechanisms are poorly understood. In this study, we discovered that high temperature alleviated the hallmarks of obesity by promoting glycogen synthesis and lowering blood glucose levels in skeletal muscle tissue (SMT). Additionally, HT maintained the decay phase of heat shock factor 1 (HSF1), leading to the activation of gene expression of heat shock proteins (HSPs), which contributed to the alleviation of IR in SMT of diet-induced obese (DIO) mice. Metabolomics and lipidomics analyses showed that HT promoted ceramide (Cer) breakdown, resulting in an elevation of both sphingomyelin (SM) and sphingosine, which further contributed to the amelioration of IR in SMT of DIO mice. Importantly, the increase in sphingosine was attributed to the heightened expression of the acid ceramidase N-acylsphingosine amidohydrolase 1 (ASAH1), and the inhibition of ASAH1 attenuated HT-relieved IR in SMT of DIO mice. Surprisingly, high temperature increased the composition of Cer and cholesteryl ester in lipid droplets of skeletal muscle cells. This not only helped alleviate IR but also prevented lipotoxicity in SMT of DIO mice. These findings revealed a previously unknown connection between a high-temperature environment and sphingolipid metabolism in obesity, suggesting that high temperature can improve IR by promoting Cer catabolism in SMT of obese mice.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"100 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140748777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-02eCollection Date: 2024-06-01DOI: 10.1093/lifemeta/loae013
Pingyu Liu, Hongbin Ji, Fuming Li
{"title":"MRE11 lactylation: a linker between Warburg effect and DNA repair.","authors":"Pingyu Liu, Hongbin Ji, Fuming Li","doi":"10.1093/lifemeta/loae013","DOIUrl":"10.1093/lifemeta/loae013","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 3","pages":"loae013"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.1093/lifemeta/loae007
John R. Speakman
{"title":"Results of the Second Life Metabolism Travel Awards 2024","authors":"John R. Speakman","doi":"10.1093/lifemeta/loae007","DOIUrl":"https://doi.org/10.1093/lifemeta/loae007","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"27 s78","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140224482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-14DOI: 10.1093/lifemeta/loae010
Zhen Cao, Lei Lei, Ziyun Zhou, Shimeng Xu, Linlin Wang, Weikang Gong, Qi Zhang, Bin Pan, Gaoxin Zhang, Quan Yuan, Liujuan Cui, Min Zheng, Tao Xu, You Wang, Shuyan Zhang, Pingsheng Liu
It is crucial to understand the glucose control within our bodies. Bariatric/metabolic surgeries, including laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes (T2D). For the first time, a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics. Apolipoprotein A-IV (apoA-IV) was revealed to be increased dramatically in diabetic obese patients following LSG, and a similar effect was observed in patients after RYGB surgery. Moreover, recombinant protein apoA-IV treatment was proven to enhance insulin secretion in isolated human islets. These results showed that apoA-IV may play a crucial role in glycemic control in humans, potentially through enhancing insulin secretion in human islets. ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents, through stimulating glucose-dependent insulin secretion in pancreatic β cells, partially via Gαs-coupled GPCR/cAMP (G protein-coupled receptor-cyclic adenosine monophosphate) signaling. Furthermore, T55−121, truncated peptide 55−121 of apoA-IV, was discovered to mediate the function of apoA-IV. These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control, highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.
{"title":"Apolipoprotein A-IV and its derived peptide, T55−121, improve glycemic control and increase energy expenditure","authors":"Zhen Cao, Lei Lei, Ziyun Zhou, Shimeng Xu, Linlin Wang, Weikang Gong, Qi Zhang, Bin Pan, Gaoxin Zhang, Quan Yuan, Liujuan Cui, Min Zheng, Tao Xu, You Wang, Shuyan Zhang, Pingsheng Liu","doi":"10.1093/lifemeta/loae010","DOIUrl":"https://doi.org/10.1093/lifemeta/loae010","url":null,"abstract":"\u0000 It is crucial to understand the glucose control within our bodies. Bariatric/metabolic surgeries, including laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes (T2D). For the first time, a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics. Apolipoprotein A-IV (apoA-IV) was revealed to be increased dramatically in diabetic obese patients following LSG, and a similar effect was observed in patients after RYGB surgery. Moreover, recombinant protein apoA-IV treatment was proven to enhance insulin secretion in isolated human islets. These results showed that apoA-IV may play a crucial role in glycemic control in humans, potentially through enhancing insulin secretion in human islets. ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents, through stimulating glucose-dependent insulin secretion in pancreatic β cells, partially via Gαs-coupled GPCR/cAMP (G protein-coupled receptor-cyclic adenosine monophosphate) signaling. Furthermore, T55−121, truncated peptide 55−121 of apoA-IV, was discovered to mediate the function of apoA-IV. These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control, highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"16 1part1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140242935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atherosclerosis is the major contributor to cardiovascular mortality worldwide. Alternate day fasting (ADF) has gained growing attention due to its metabolic benefits. However, the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models. The present study was designed to investigate the effect of ADF on atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice. Eleven-week-old male Apoe−/− mice fed with Western diet (WD) were randomly grouped into ad libitum (AL) group and ADF group, and ADF aggravated both the early and advanced atherosclerotic lesion formation, which might be due to the disturbed cholesterol profiles caused by ADF intervention. ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response (ISR) in the liver. The hepatic expression of activating transcription factor 3 (ATF3) was suppressed in mice treated with ADF and hepatocyte-specific overexpression of ATF3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe−/− mice. Moreover, the expression of ATF3 could be regulated by Krüppel-like factor 6 (KLF6) and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway. In conclusion, ADF aggravates atherosclerosis progression in Apoe−/− mice fed on WD. ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6, subsequently inhibiting ATF3 expression. The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe−/− mice. The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.
{"title":"Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe\u0000 −/− mice","authors":"Yajuan Deng, Xiaoyu Yang, Xueru Ye, Youwen Yuan, Yanan Zhang, Fei Teng, Danming You, Xuan Zhou, Wenhui Liu, Kangli Li, Shenjian Luo, Zhi Yang, Ruxin Chen, Guojun Shi, Jin Li, Huijie Zhang","doi":"10.1093/lifemeta/loae009","DOIUrl":"https://doi.org/10.1093/lifemeta/loae009","url":null,"abstract":"\u0000 Atherosclerosis is the major contributor to cardiovascular mortality worldwide. Alternate day fasting (ADF) has gained growing attention due to its metabolic benefits. However, the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models. The present study was designed to investigate the effect of ADF on atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice. Eleven-week-old male Apoe−/− mice fed with Western diet (WD) were randomly grouped into ad libitum (AL) group and ADF group, and ADF aggravated both the early and advanced atherosclerotic lesion formation, which might be due to the disturbed cholesterol profiles caused by ADF intervention. ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response (ISR) in the liver. The hepatic expression of activating transcription factor 3 (ATF3) was suppressed in mice treated with ADF and hepatocyte-specific overexpression of ATF3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe−/− mice. Moreover, the expression of ATF3 could be regulated by Krüppel-like factor 6 (KLF6) and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway. In conclusion, ADF aggravates atherosclerosis progression in Apoe−/− mice fed on WD. ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6, subsequently inhibiting ATF3 expression. The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe−/− mice. The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"24 105","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140260034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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