Cell Death Discovery最新文献

{"title":"FL3 mitigates cardiac ischemia-reperfusion injury by promoting mitochondrial fusion to restore calcium homeostasis.","authors":"Zikan Zhong, Yutong Hou, Changzuan Zhou, Jiahui Wang, Longzhe Gao, Xiaoyu Wu, Genqing Zhou, Shaowen Liu, Yingjie Xu, Wen Yang","doi":"10.1038/s41420-025-02575-w","DOIUrl":"10.1038/s41420-025-02575-w","url":null,"abstract":"<p><p>This study aims to investigate the therapeutic potential of Flavagline3 (FL3) in mitigating myocardial ischemia-reperfusion (IR) injury, with a specific focus on its regulatory effects on mitochondrial fusion, mitochondrial-endoplasmic reticulum (ER) interactions, and calcium homeostasis in cardiomyocytes. Using a well-established myocardial IR injury model in mice and primary cardiomyocytes treated with FL3, the study assessed its impact on mitochondrial dynamics and intracellular signaling processes. The results demonstrated that FL3 effectively reduced myocardial apoptosis, infarct size, and cardiac dysfunction caused by IR injury. Mechanistically, FL3 promoted mitochondrial fusion in a mitofusin1 (MFN1)-dependent manner, preserving mitochondrial function under stress conditions and enhancing cellular resilience. Furthermore, FL3 facilitated mitochondrial-ER crosstalk, which played a critical role in modulating intracellular calcium levels by optimizing the transfer of calcium ions between these two organelles. This balanced regulation of mitochondrial dynamics and calcium homeostasis was associated with improved survival and functionality of cardiomyocytes following IR injury. These findings suggest that FL3 exerts robust cardioprotective effects through its ability to promote mitochondrial fusion, enhance mitochondrial-ER interactions, and maintain calcium homeostasis. As a result, FL3 holds promise as a potential therapeutic agent for reducing myocardial damage and dysfunction associated with IR injury, offering valuable insights into novel approaches for cardioprotection.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"304"},"PeriodicalIF":6.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559323","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":"Demethylzeylasteral suppresses the expression of MESP1 by reducing H3K18la level to inhibit the malignant behaviors of pancreatic cancer.","authors":"Xiaolei Ma, Mengxing Cheng, Yanxin Jia, Kun Zhang, Haocheng Zhang, Di Feng, Wenxiao Xu, Guofen Qiao","doi":"10.1038/s41420-025-02603-9","DOIUrl":"10.1038/s41420-025-02603-9","url":null,"abstract":"<p><p>Glycolysis is a hallmark metabolic pathway in pancreatic cancer (PC). As the end product of glycolysis, lactic acid accumulates significantly in PC. Lactic acid serves as a primary substrate for histone lactylation, leading to an upregulation of histone lactylation levels, which likely contributes to progression of PC. This study reveals novel insights, highlighting that H3K18la levels are elevated in PC tissues and cells. Notably, the natural compound demethylzeylasteral (DML), derived from Tripterygium wilfordii Hook F (TwHF), substantially decreases lactic acid generation in PC cells, subsequently resulting in the downregulation of H3K18la levels and inhibiting the aggressive characteristics of PC cells. To further investigate the underlying mechanisms, we conducted RNA-seq analysis on DML-treated cells and ChIP-seq analyses for H3K18la. For the first time, mesoderm-related factor 1 (MESP1) was identified as a target protein modulated by both DML and H3K18la. DML was shown to repress the expression of MESP1, while sodium lactate (Nala) was found to partially restore its expression levels. Overexpression of MESP1 was linked to the promotion of epithelial-mesenchymal transition (EMT) and apoptosis in PC cells. Furthermore, RNA-seq analyses following MESP1 silencing indicated its significant association with critical physiological processes in PC cells, including the cell cycle, apoptosis, and cell adhesion. Importantly, MESP1 has also been connected to various cancer metabolism pathways, such as MAPK, PI3K-AKT, and carbon metabolism. This research is groundbreaking in demonstrating that DML impedes the malignant behavior of PC cells by downregulating H3K18la levels and diminishing the expression of the oncogene MESP1.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"305"},"PeriodicalIF":6.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559322","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":"Transcription factor TCF3 promotes bladder cancer development via TMBIM6-Ca²⁺-dependent ferroptosis.","authors":"Wei-Feng Yang, Wei-Ming Guo, Qing-Tian Luo, Jingfen Lu, Zhou-Ke Tan, Yuan-Chun Ye, Gang Fan","doi":"10.1038/s41420-025-02585-8","DOIUrl":"10.1038/s41420-025-02585-8","url":null,"abstract":"<p><p>TMBIM6, a Ca²⁺ channel-like protein, shows an increased expression in numerous types of cancer. However, no study has reported its role in bladder cancer. This study aimed to explore the roles and mechanisms of TMBIM6 in bladder cancer. TMBIM6, ferroptosis-related proteins (GPX4, SLC7A11, and FTH1), and calmodulin (CaM) expressions in bladder cancer and paracancerous tissues were obtained by immunohistochemistry. The bladder cells were overexpressed or silenced with TCF3/TMBIM6 with ferroptosis inducer (Erastin)/Ca²⁺ blocker (BAPTA-AM) to investigate the effects on Ca²⁺-dependent ferroptosis and other functions. Finally, tumorigenicity was validated in nude mice. TMBIM6 and ferroptosis-related proteins were up-regulated in bladder cancer tissues, but CaM was downregulated. TMBIM6 overexpression enhanced proliferation, invasion, migration, GSH/GPX4 levels, and ferroptosis resistance while suppressing MDA, Fe²⁺, and lipid ROS in bladder cancer cells, effects reversed by Erastin. TCF3 was up-regulated in cancer and enriched in Ca²⁺ and ferroptosis-related pathways. TCF3 directly interacted with TMBIM6 and transcriptionally activated TMBIM6 expression. Both TCF3 and TMBIM6 overexpression exhibited comparable effects in modulating ferroptosis and other cellular processes, whereas TMBIM6 knockdown effectively reversed these phenotypic alterations. In addition, silencing TCF3 upregulated Ca²⁺ and CAM levels, while BAPTA-AM reversed these changes. In vivo, ov-TCF3 promoted tumor volume, weight, and TMBIM6 expression, and inhibited Ca²⁺ concentration, while Erastin reversed these changes. Our findings demonstrate that TCF3 facilitates bladder cancer progression through the enhancement of TMBIM6-Ca²⁺-mediated ferroptosis resistance. Both TCF3 and TMBIM6 emerge as promising biomarkers and therapeutic targets for bladder cancer intervention.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"303"},"PeriodicalIF":6.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559325","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":"Polyamines at the crossroad between cell metabolism and epigenetic regulation in acute leukemias.","authors":"Francesca Pirini, Anna Ferrari, Mouna Jandoubi, Irene Azzali, Davide Angeli, Rossana Mondrone, Chiara Bracci, Francesca Ruggieri, Giovanni Martinelli, Giorgia Simonetti","doi":"10.1038/s41420-025-02573-y","DOIUrl":"10.1038/s41420-025-02573-y","url":null,"abstract":"<p><p>Polyamines, namely putrescine, spermidine and spermine, are involved in multiple molecular pathways through their ability to bind nucleic acids and modulate protein stability. Their intracellular level is regulated through biosynthesis, catabolism and uptake from the extracellular milieu and the disruption of their homeostasis contributes to a variety of human disorders including cancer, as mainly described in solid tumors. Recently, there is an increasing interest in understanding polyamine functions in acute leukemias, due to the linkage between leukemic gene drivers, polyamine metabolism alterations and epigenetic defects. In particular, polyamine involvement in the regulation of acetylation and methylation is clinically relevant since epigenetic drugs are currently the backbone of novel therapeutic combinations, especially in acute myeloid leukemia (AML). With the exception of methylthioadenosine phosphorylase (MTAP), the enzyme leading to methionine regeneration that is frequently deleted in acute lymphoblastic leukemia (ALL), genes involved in polyamine metabolism and the interconnected methionine and arginine pathways are rarely targets of genetic lesions in acute leukemias. Conversely, functional alterations, including elevated polyamine levels and deregulated activity of enzymes involved in their metabolism, have been recently reported in leukemic cells. Notably, the polyamine catabolic enzyme spermidine/spermine N1 acetyltransferase (SAT1) that is overexpressed in AML and associated with a myeloproliferative phenotype, is a tumor suppressor gene in ALL, suggesting diverse mechanisms of action across hematological malignancies according to the lineage commitment and the differentiation stage. In light of the promising results achieved in AML and ALL by selective targeting of protein arginine methyltransferase 5 (PRMT5) and methionine adenosyltransferase 2A (MAT2A), two enzymes at the crossroad between polyamine metabolism and protein methylation, in this review we examine and discuss the role of polyamines in epigenetic regulation and other biological processes supporting leukemic cell survival, proliferation and differentiation, which provides the opportunity to discover additional polyamine-related targets and design novel therapeutic combinations.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"301"},"PeriodicalIF":6.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552460","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":"Pyroptosis, a double-edged sword during pathogen infection: a review.","authors":"Yuanhang Zhang, Dengshuai Zhao, Tianyu Wang, Ping Li, Dixi Yu, Han Gao, Mengmeng Zhao, Limei Qin, Keshan Zhang","doi":"10.1038/s41420-025-02579-6","DOIUrl":"10.1038/s41420-025-02579-6","url":null,"abstract":"<p><p>Pyroptosis, a distinctive form of programmed cell death (PCD) characterized by its inflammatory nature, is triggered by the activation of pore-forming proteins known as gasdermins (GSDMs). This process is marked by progressive expansion of a pore within the cell, ultimately leading to cellular membrane disruption and the substantial release of intracellular contents. Pyroptosis plays a pivotal role in the eradication of intracellular pathogen replication niches and in the modulation of the immune system through the release of danger signals. Emerging evidence suggests that viruses have developed sophisticated strategies to evade immune surveillance and establish persistent infections by manipulating host pyroptotic pathway This review presents recent advances on the mechanisms by which two major pathogens (virus and bacteria) activate or inhibit the pyroptosis process through their effector proteins, thereby facilitating their dissemination and blocking host immunity. These insights provide new perspectives on the regulatory mechanisms of interactions between hosts and pathogens in the pyroptosis process.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"289"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539133","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":"MCM9 deficiency impairs DNA damage repair during spermatogenesis, leading to Sertoli cell-only syndrome in humans.","authors":"Xuan Sha, Xin Zhang, Hao Geng, Yuqian Li, Xun Xia, Guotong Li, Rong Hua, Kuokuo Li, Yang Gao, Qunshan Shen, Rui Guo, Yuping Xu, Xiaojin He, Yunxia Cao, Mingxi Liu, Huan Wu","doi":"10.1038/s41420-025-02581-y","DOIUrl":"10.1038/s41420-025-02581-y","url":null,"abstract":"<p><p>Non-obstructive azoospermia (NOA) represents the most severe form of male infertility; however, its genetic etiology remains largely elusive. MCM9 is crucial for DNA damage repair in mammalian somatic cells, playing a key role in regulating both homologous recombination (HR) and mismatch repair (MMR) pathways. In mice, MCM9 deficiency leads to spermatogenic failure characterized by progressive germ cell depletion and impaired HR repair. However, the underlying mechanism remains unclear in humans. Our study identified two novel homozygous loss-of-function (LoF) mutations in MCM9 in two unrelated NOA patients presenting with Sertoli cell-only syndrome (SCOS). The absence of testicular MCM9 confirmed the pathogenicity of these LoF mutations. Furthermore, diminished HR-mediated DNA repair capacity observed in HEK293T cells, either lacking MCM9 or overexpressing mutant MCM9 plasmids, highlighted the deleterious impact of these LoF mutations on HR repair. Additionally, the confirmed interaction between human testicular MCM9 and both MSH2 and MLH1, alongside findings that human MCM9 is predominantly expressed in spermatogonial stem cells and spermatogonia, provides compelling evidence for the involvement of the MCM9-mediated MMR pathway in maintaining genomic integrity and supporting the viability and proliferation of spermatogonia in humans. Given the poor outcomes of microdissection testicular sperm extraction (micro-TESE) observed in both probands, we propose that biallelic LoF mutations in MCM9 may serve as non-invasive molecular biomarkers for predicting micro-TESE failure. These findings enhance our understanding of the genetic basis of human NOA, particularly SCOS, and provide valuable insights for genetic counseling and fertility guidance tailored to these patients.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"292"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539129","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":"N6-methyladenosine modification of MEF2A weakens cetuximab sensitivity in colorectal cancer via PD-L1/SOX12 axis.","authors":"Cao Gao, Jiajia He, Jiemin Zhao, Xuefeng Ni, Yanjie Xu","doi":"10.1038/s41420-025-02577-8","DOIUrl":"10.1038/s41420-025-02577-8","url":null,"abstract":"<p><p>Colorectal cancer (CRC) treatment is still a challenge due to chemoresistance. We explored MEF2A function and underlying mechanism on cetuximab sensitivity in CRC. In this study, cancer tissues and adjacent non-cancerous samples were harvested from CRC patients. Cell viability, proliferation and apoptosis in CRC cells were tested by CCK-8, EdU, colony formation, and flow cytometry assays. The binding of MEF2A on the PD-L1 promoter was validated using luciferase reporter assay, CHIP, and EMSA, while the relationship of PD-L1 and SOX12 mRNA, as well as RBM15/IGF2BP1 and MEF2A mRNA, was verified by RIP, RNA pull-down, or FISH combined with immunofluorescence. m6A modification level of MEF2A mRNA was assayed by MeRIP. The expressions of key genes and proteins, including MEF2A, PD-L1, SOX12, RBM15, IGF2BP1, apoptosis- and cell cycle-related proteins, were determined with RT-qPCR, western blot, or immunohistochemistry. In vivo function of MEF2A was validated by establishing a xenograft nude mice model. The results showed that MEF2A was increased in CRC cells and tissues, while it was higher in cetuximab-resistant CRC tissues. Silencing MEF2A improved the sensitivity of cetuximab in CRC cells and xenograft mice. MEF2A binds to PD-L1 promoter to transcriptionally upregulate PD-L1 expression. Increased cetuximab sensitivity was observed in PD-L1 knockout (KO) CRC cells. PD-L1 overexpression reversed the enhanced cetuximab sensitivity induced by MEF2A knockdown. PD-L1 binds to SOX12 mRNA to stabilize its expression. PD-L1 knockdown augmented cetuximab sensitivity, which was overturned by SOX12 overexpression. The m6A modification mediated by RBM15/IGF2BP1 upregulated MEF2A expression in cetuximab-resistant CRC tissues. In conclusion, m6A-modified MEF2A alleviated cetuximab sensitivity in CRC via PD-L1/SOX12 mRNA axis, indicating that MEF2A might function as a promising therapeutic target against cetuximab-resistant CRC.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"294"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539132","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":"Interplay between genes and social environment: from epigenetics to precision medicine.","authors":"Sabrina Caporali, Simone Russo, Marcel Leist, Petra H Wirtz, Ivano Amelio","doi":"10.1038/s41420-025-02580-z","DOIUrl":"10.1038/s41420-025-02580-z","url":null,"abstract":"","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"293"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539127","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":"Making sense of human colorectal cancer molecular subtypes: mice are stepping in.","authors":"Caleb Green, Pamela Roccia, Alessandro Rufini","doi":"10.1038/s41420-025-02594-7","DOIUrl":"10.1038/s41420-025-02594-7","url":null,"abstract":"","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"295"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539128","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":"Tumor metabolome remolded by low dose mitochondrial uncoupler elicites robust CD8⁺ T cell response.","authors":"Xiaoxiao Jiang, Zhijin Fan, Zhenzhen Zhang, Fanchu Zeng, Tong Sun, Yuchen Li, Guojia Huang, Liming Nie","doi":"10.1038/s41420-025-02584-9","DOIUrl":"10.1038/s41420-025-02584-9","url":null,"abstract":"<p><p>Tumor cells balance ATP production and carbon skeleton synthesis by flexibly altering catabolic pathways to sustain their significant growth advantage. Uncouplers have shown potential for tumor suppression by converting chemical energy from catabolism into heat. However, their use may be limited due to indiscriminate metabolic interference in both tumor and normal cells, as well as the uncertainty surrounding their effects on the immune microenvironment. Herein, we found that low-dose uncoupler BAM15 promoted AMPK, AKT signaling, and the TCA cycle without increasing cell proliferation or inducing cell death in vitro, suggesting an increase in futile cycling. Intratumoral injection of 50 ng/mL BAM15 accelerated catabolic processes while inhibiting anabolic pathways, resulting in a metabolomic reshaping with increased levels of linoleic acid, C5DC, and others. These changes were shown to enhance tumor-killing effects by T cells. To reduce side effects on normal tissues and improve tumor retention, BAM15 was targeted for delivery by loading it into TCVs. This TCV-BAM15 treatment significantly increased CD8+ T cell counts and granzyme B levels. Our findings highlight a previously unrecognized therapeutic effect and signaling mechanism of low-dose BAM15 treatment in tumors. We propose that this novel strategy holds promise as a tumor immunity therapy with fewer adverse effects compared to free uncoupling drugs at high concentrations.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"291"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539136","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}