The FEBS journal最新文献_第6页

The m6A demethylase FTO promotes C/EBPβ-LIP translation to perform oncogenic functions in breast cancer cells.

The FEBS journal Pub Date : 2025-02-28 DOI: 10.1111/febs.70033

Hidde R Zuidhof, Christine Müller, Gertrud Kortman, René Wardenaar, Ekaterina Stepanova, Fabricio Loayza-Puch, Cornelis F Calkhoven

{"title":"The m6A demethylase FTO promotes C/EBPβ-LIP translation to perform oncogenic functions in breast cancer cells.","authors":"Hidde R Zuidhof, Christine Müller, Gertrud Kortman, René Wardenaar, Ekaterina Stepanova, Fabricio Loayza-Puch, Cornelis F Calkhoven","doi":"10.1111/febs.70033","DOIUrl":"https://doi.org/10.1111/febs.70033","url":null,"abstract":"N6-methyladenosine (m6A) is a prevalent posttranscriptional mRNA modification involved in the regulation of transcript turnover, translation, and other aspects of RNA fate. The modification is mediated by multicomponent methyltransferase complexes (so-called writers) and is reversed through the action of the m6A-demethylases fat mass and obesity-associated (FTO) and alkB homolog 5 (ALKBH5) (so-called erasers). FTO promotes cell proliferation, colony formation and metastasis in models of triple-negative breast cancer (TNBC). However, little is known about genome-wide or specific downstream regulation by FTO. Here, we examined changes in the genome-wide transcriptome and translatome following FTO knockdown in TNBC cells. Unexpectedly, FTO knockdown had a limited effect on the translatome, while transcriptome analysis revealed that genes related to extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are regulated through yet unidentified mechanisms. Differential translation of CEBPB mRNA into the C/EBPβ transcription factor isoform C/EBPβ-LIP is known to act in a pro-oncogenic manner in TNBC cells through regulation of EMT genes. Here we show that FTO is required for efficient C/EBPβ-LIP expression, suggesting that FTO has oncogenic functions through regulation of C/EBPβ-LIP.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532281","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}

引用次数: 0

Matriptase-mediated PAR2 activation drives monocyte-to-macrophage differentiation and polarization under hypoxic conditions.

The FEBS journal Pub Date : 2025-02-27 DOI: 10.1111/febs.70046

Arpana Singh, Avinandan Bhoumick, Prosenjit Sen

{"title":"Matriptase-mediated PAR2 activation drives monocyte-to-macrophage differentiation and polarization under hypoxic conditions.","authors":"Arpana Singh, Avinandan Bhoumick, Prosenjit Sen","doi":"10.1111/febs.70046","DOIUrl":"https://doi.org/10.1111/febs.70046","url":null,"abstract":"Within the intricate landscape of the tumour microenvironment (TME), hypoxia stands out as a pivotal factor profoundly shaping immune cell dynamics. Our study delves into this dynamic interplay, uncovering a cascade of events triggered by hypoxia. We unveil the emergence of protease-activated receptor 2 (PAR2; also known as F2R-like trypsin receptor 1 [F2RL1]) expression in monocyte cell lines (THP1) and peripheral blood mononuclear cells (PBMCs), orchestrated by the active serine protease matriptase (TMPRSS2; also known as transmembrane protease serine 2). Hypoxic conditions set the stage for a dual mechanism: lactate accumulation drives extracellular pH reduction, and facilitates matriptase activation from its latent form. A 10 mm lactate threshold activates matriptase, which in turn activates PAR2, driving monocytes towards M1 macrophage differentiation through the AKT2-NF-κβ axis. This triggers miR155 expression, which suppresses cytokine signaling 1 (SOCS1), a key regulator of M1-M2 polarisation, while NF-κβ enhances proinflammatory responses. Notably, our study reveals a temporal switch in this hypoxia-driven process. After 48 h of hypoxia, lactate levels rise to 25 mm, suppressing matriptase activation and driving a shift towards M2 polarisation. This transition, marked by reduced miR155 expression via AKT2-NFκβ axis inactivation, highlights the dynamic nature of macrophage polarisation. Our findings demonstrate matriptase as a key regulator driving macrophage polarisation towards the M1 phenotype within hypoxic microenvironments. This insight into macrophage behaviour under hypoxia suggests new strategies for immune modulation to counter tumour progression.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525680","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}

引用次数: 0

Crystal structure and biochemical analysis of the dimeric transaminase DoeD provides insights into ectoine degradation. 二聚体转氨酶 DoeD 的晶体结构和生化分析提供了对异辛酸降解的深入了解。

The FEBS journal Pub Date : 2025-02-27 DOI: 10.1111/febs.70043

Amalie C A Skogvold, Heidi T Brakestad, Heidi Erlandsen, Ingar Leiros

{"title":"Crystal structure and biochemical analysis of the dimeric transaminase DoeD provides insights into ectoine degradation.","authors":"Amalie C A Skogvold, Heidi T Brakestad, Heidi Erlandsen, Ingar Leiros","doi":"10.1111/febs.70043","DOIUrl":"https://doi.org/10.1111/febs.70043","url":null,"abstract":"The pyridoxal-5'-phosphate-dependent enzyme DoeD is a L-2,4-diaminobutyric acid (DABA) transaminase that is part of the degradation pathway of the compatible solute ectoine. Ectoines are used by halophilic organisms to maintain osmotic balance under fluctuating salt concentrations (osmoadaptation). Classified under class III ω-aminotransferases, DoeD utilizes substrates with terminal amines, facilitated by dual substrate recognition involving two binding pockets, the O-pocket and the P-pocket. In this study, we have determined the first crystal structure of DoeD at 1.5 Å and conducted a biochemical and biophysical characterization of the dimeric DABA transaminase from the halophilic bacterium and model organism Chromohalobacter salexigens DSM 3043. Our findings reveal that pyruvate is the preferred co-substrate and that DoeD has a broad pH tolerance, minimal salt requirements, and can utilize a variety of amino donors. The crystal structure and substrate specificity studies of this highly expressed and stable DoeD suggest opportunities for enhancing enzymatic activity through targeted mutagenesis, optimizing it for industrial applications in green chemistry for chiral amine synthesis.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525678","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}

引用次数: 0

Human glycolysis isomerases are inhibited by weak metabolite modulators.

The FEBS journal Pub Date : 2025-02-27 DOI: 10.1111/febs.70049

Yiming Yang Jónatansdóttir, Óttar Rolfsson, Jens G Hjörleifsson

{"title":"Human glycolysis isomerases are inhibited by weak metabolite modulators.","authors":"Yiming Yang Jónatansdóttir, Óttar Rolfsson, Jens G Hjörleifsson","doi":"10.1111/febs.70049","DOIUrl":"https://doi.org/10.1111/febs.70049","url":null,"abstract":"Modulation of enzyme activity by metabolites represents the most efficient and rapid way of controlling metabolism. Investigating enzyme-metabolite interactions can deepen our understanding of metabolic control and aid in identifying enzyme modulators with potential therapeutic applications. These interactions vary in strength, with dissociation constants (Kd) ranging from strong (nm) to weak (μm-mm). However, weak interactions are often overlooked due to the challenges in studying them. Despite this, weak modulators can reveal unknown binding modes and serve as starting points for compound optimization. In this study, we aimed to identify metabolites that weakly modulate the activity of human glucose-6-phosphate isomerase (GPI) and triosephosphate isomerase (TPI), which are potential therapeutic targets in tumor glycolysis. Through a combination of activity and binding assays, the screening revealed multiple weak inhibitors for the two targets, causing partial attenuation of their activity, with Kd and Ki in the low mm range. X-ray crystallography revealed six orthosteric ligands binding to the active sites - four inhibitors of GPI and two of TPI. Our findings underscore the role of weak interactions in enzyme regulation and may provide structural insights that could aid the design of inhibitors targeting human GPI and TPI in cancer intervention.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525679","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}

引用次数: 0

Biophysical investigation of the molecular interaction between minichromosome maintenance protein 6 and Bloom syndrome helicase.

The FEBS journal Pub Date : 2025-02-25 DOI: 10.1111/febs.70047

Min June Yang, Haeun Lee, Donguk Kang, Chin-Ju Park

{"title":"Biophysical investigation of the molecular interaction between minichromosome maintenance protein 6 and Bloom syndrome helicase.","authors":"Min June Yang, Haeun Lee, Donguk Kang, Chin-Ju Park","doi":"10.1111/febs.70047","DOIUrl":"https://doi.org/10.1111/febs.70047","url":null,"abstract":"The minichromosome maintenance protein (MCM) complex and Bloom syndrome helicase (BLM) are crucial components in DNA replication and cell division. MCM, a hexameric helicase that unwinds double-stranded DNA, serves as an important diagnostic and prognostic biomarker for cancer cells and a target for anticancer drug development. BLM, associated with G-quadruplex structures, is another key helicase in maintaining genomic stability. In this study, we investigate the interaction between MCM6 and BLM at the atomic level, as their expression levels are highly correlated in various cancer types, with elevated levels indicating poor prognosis. To elucidate the molecular basis of MCM6/BLM interaction, we employed fluorescence polarization anisotropy analysis, NMR chemical shifts perturbation analysis (CSP), and paramagnetic relaxation enhancement (PRE) experiments. MCM6 binding domain (MBD) C and D exhibit similar binding affinities to MCM6 winged-helix domain (WHD). However, significant CSPs with MBD-D and PRE experiments suggested that MBD-D is closer to MCM6 WHD than MBD-C. Despite both proteins containing numerous negatively charged residues, hydrophobic interactions govern the association between MCM6 WHD and BLM MBD-D. This biophysical characterization of the MCM6/BLM interaction provides new insights into their functional relationship and challenges existing models. Our findings reveal that MCM6 binds BLM at a different site than its other known partner chromatin licensing and DNA replication factor. Understanding these protein-protein interactions at the molecular level may contribute to the development of novel anticancer therapies targeting the MCM6/BLM interaction.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506671","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}

引用次数: 0

Stbd1 stimulates AMPK signaling and alleviates insulin resistance in an in vitro hepatocyte model. 在体外肝细胞模型中，Stbd1 可刺激 AMPK 信号转导并缓解胰岛素抵抗。

The FEBS journal Pub Date : 2025-02-25 DOI: 10.1111/febs.70040

Andria Theodoulou, Thilo Speckmann, Louiza Potamiti, Otto Baba, Tsuyoshi Morita, Anthi Drousiotou, Mihalis I Panayiotidis, Annette Schürmann, Petros P Petrou

{"title":"Stbd1 stimulates AMPK signaling and alleviates insulin resistance in an in vitro hepatocyte model.","authors":"Andria Theodoulou, Thilo Speckmann, Louiza Potamiti, Otto Baba, Tsuyoshi Morita, Anthi Drousiotou, Mihalis I Panayiotidis, Annette Schürmann, Petros P Petrou","doi":"10.1111/febs.70040","DOIUrl":"https://doi.org/10.1111/febs.70040","url":null,"abstract":"Starch-binding domain-containing protein 1 (Stbd1) is a glycogen-binding protein which localizes to the endoplasmic reticulum (ER) membrane and ER-mitochondria contact sites (ERMCs). The protein undergoes N-myristoylation, which is a major determinant of its subcellular targeting. Stbd1 has been implicated in the control of glucose homeostasis, as evidenced by the finding that mice with targeted inactivation of Stbd1 display insulin resistance associated with increased ERMCs in the liver. In the present study, we addressed the effects of increased Stbd1 expression levels on insulin signaling. We show that Stbd1 overexpression enhances cellular sensitivity to insulin and improves insulin resistance in an in vitro hepatocyte cell model. We further demonstrate that increased Stbd1 expression levels are associated with enhanced activation of the AMP-activated protein kinase (AMPK), which is a central regulator of metabolism and an attractive therapeutic target for metabolic disorders related to insulin resistance, such as type 2 diabetes (T2D). The activation of AMPK signaling and the improved cellular response to insulin induced by Stbd1 overexpression occurred independently of N-myristoylation and associated changes in the number of ERMCs, glycogen levels, mitochondrial calcium, mitochondrial morphology, and respiratory function. Collectively, our findings uncover a new level of interaction between Stbd1 and AMPK, with Stbd1 acting as an upstream activator of AMPK signaling. Given that first-line drug treatments for insulin resistance and T2D are known activators of the AMPK pathway, these findings may provide a new perspective for the development of more effective therapeutic strategies.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506676","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}

引用次数: 0

Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy.

The FEBS journal Pub Date : 2025-02-25 DOI: 10.1111/febs.70011

Manuel Flores-León, Tiago F Outeiro

{"title":"Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy.","authors":"Manuel Flores-León, Tiago F Outeiro","doi":"10.1111/febs.70011","DOIUrl":"https://doi.org/10.1111/febs.70011","url":null,"abstract":"A possible consequence of the process of protein aggregation in neurodegenerative diseases is the depletion of soluble protein species (proteinopenia), which may, at least in some cases, reduce protein function/activity. This concept, which is often overlooked, may play a role in synucleinopathies such as Parkinson's disease (PD), and dementia with Lewy bodies (DLB), where the protein α-synuclein (aSyn) is known to accumulate in insoluble inclusions. aSyn is at the crossroads between cellular proteostasis and lipidostasis networks and, therefore, we must be aware of the complexity we face when we try to understand the molecular basis of synucleinopathies. Importantly, aSyn and β-glucocerebrosidase (GCase), a sphingolipid hydrolase also strongly implicated in PD and DLB, are connected to lipid biology and to protein quality control function. Thus, changes in the normal relationship between these two proteins may shift the balance in the cell and lead to proteinopathy and/or proteinopenia, while also affecting lipidostasis of cells in the brain. Thus, pathological mechanisms that are a consequence of (a) loss-of-function, (b) gain-of-toxic function, and (c) alterations in lipidostasis need to be carefully analyzed and integrated in our study of the molecular underpinnings of neurodegenerative mechanisms. Here, we highlight implications of the depletion of the soluble form of aSyn, and of GCase, and discuss how state-of-the-art 'omics technologies' could be deployed to assist in the clinical assessment of synucleinopathies.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495136","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}

引用次数: 0

A naturally evolved metal ion transfer mechanism that improves the catalytic performance and stability of superoxide dismutase.

The FEBS journal Pub Date : 2025-02-25 DOI: 10.1111/febs.70041

Jingjing Zhang, Jingjing Liu, Xuehua Wan, Linbo Sun, Jingbo Gong, Jiabin Li, Yijia Wang, Fang Zhao, Wei Wang

{"title":"A naturally evolved metal ion transfer mechanism that improves the catalytic performance and stability of superoxide dismutase.","authors":"Jingjing Zhang, Jingjing Liu, Xuehua Wan, Linbo Sun, Jingbo Gong, Jiabin Li, Yijia Wang, Fang Zhao, Wei Wang","doi":"10.1111/febs.70041","DOIUrl":"https://doi.org/10.1111/febs.70041","url":null,"abstract":"Inadequate binding of metal ions is a major cause of low activity and loss of function in metalloenzymes such as superoxide dismutase (SOD). In this study, we report a previously undescribed metal ion transfer mechanism mediated by the metal ion binding domain (MIBD) of SOD, which significantly improves SOD activity and stability. MIBD is mainly found in the N-terminal domain of SOD from Paenibacillus, which evolves under a metal ion deficient environment. MIBD can capture and transfer Fe2+ to the conserved functional domain of SOD (SODA) via inter- and intramolecular interactions to maintain and enhance enzymatic activity at different ion concentrations. MIBD also exhibits a similar positive effect on the activity and stability of SOD from other species. Moreover, MIBD does not affect the optimum temperature and optimum pH of SOD, but it increases SOD activity to varying degrees compared with SODA at different temperatures and pHs. This unique MIBD also significantly improves the resistance of SOD to protein denaturants and detergents such as Gdn-HCl, Urea, and SDS, and improves physiological stability of SOD in simulated digestive fluids. This naturally evolved mechanism of SOD provides valuable insights into the design of well-performing metalloenzymes.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506667","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}

引用次数: 0

Human transmembrane protein 68 links triacylglycerol synthesis to membrane lipid homeostasis.

The FEBS journal Pub Date : 2025-02-25 DOI: 10.1111/febs.70044

Fansi Zeng, Christoph Heier, Qing Yu, Huimin Pang, Feifei Huang, Zheng Zhao, Pingan Chang

引用次数: 0

Interaction of TFAP2A with the Ku70/80 complex is crucial for HIF-dependent activation of hypoxia-inducible genes.

The FEBS journal Pub Date : 2025-02-24 DOI: 10.1111/febs.70025

Amalia Kanoura, Antonis Giakountis, Chrysa Filippopoulou, Angeliki Karagiota, George Stamatakis, Martina Samiotaki, George Panayotou, George Simos, Georgia Chachami

{"title":"Interaction of TFAP2A with the Ku70/80 complex is crucial for HIF-dependent activation of hypoxia-inducible genes.","authors":"Amalia Kanoura, Antonis Giakountis, Chrysa Filippopoulou, Angeliki Karagiota, George Stamatakis, Martina Samiotaki, George Panayotou, George Simos, Georgia Chachami","doi":"10.1111/febs.70025","DOIUrl":"https://doi.org/10.1111/febs.70025","url":null,"abstract":"Hypoxia can be established under pathological conditions, such as cancer, due to the imbalance between oxygen supply and consumption. Hypoxia-inducible transcription factor HIF-1 mediates the physiological response to hypoxia but also regulates multiple steps of carcinogenesis. Despite its well-defined oxygen-dependent activation, many aspects of HIF-1 transcriptional activity as well as interaction with chromatin remain elusive. We have recently shown that hypoxia triggered deSUMOylation of TFAP2A. To study the possible role of TFAP2A in the transcriptional response to hypoxia, we performed ChIP-seq analysis. Our results have now shown that TFAP2A resides together with HIF-1α on the promoters of a subset of hypoxia-regulated genes, the mRNA expression of which is downregulated by silencing of TFAP2A. Interestingly, CRISPR-mediated knockdown of TFAP2A expression under hypoxia decreased the occupancy of HIF-1α on these promoters and affected chromatin accessibility. Mechanistically, we reveal that the Ku70/Ku80 protein complex interacts with deSUMOylated TFAP2A under hypoxia and participates in HIF-dependent gene expression. Moreover, using stable expression of TFAP2A forms that either lack or constitutively carry a SUMO modification, we could show that SUMOylation affects binding of TFAP2A to chromatin. Overall, our data suggest that TFAP2A is an important co-regulator of the HIF-1-dependent transcriptional response to hypoxia and SUMOylation fine-tunes this regulation. As both TFAP2A and HIF-1 play critical roles in cancer progression, a detailed characterization of their crosstalk could lead to novel therapeutic strategies for targeting and killing cancer cells in hypoxic tumors.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495139","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}

引用次数: 0