{"title":"Inherent fast inactivation particle of Nav channels as a new binding site for a neurotoxin.","authors":"Xi Zhou,Haiyi Chen,Shuijiao Peng,Yuxin Si,Gaoang Wang,Li Yang,Qing Zhou,Minjuan Lu,Qiaoling Xie,Xi He,Meijing Wu,Xin Xiao,Xiaoqing Luo,Xujun Feng,Wenxing Wang,Sen Luo,Yaqi Li,Jiaxin Qin,Minzhi Chen,Qianqian Zhang,Weijun Hu,Songping Liang,Tingjun Hou,Zhonghua Liu","doi":"10.1038/s44318-025-00438-9","DOIUrl":"https://doi.org/10.1038/s44318-025-00438-9","url":null,"abstract":"Neurotoxins derived from animal venoms are indispensable tools for probing the structure and function of voltage-gated sodium (Nav) channels. Utilizing a novel centipede peptide toxin called rpTx1, we show that the \"inherent inactivation particle\" of Nav channels represents a binding site for a neurotoxin. The toxin comprises two functional domains: one for cell penetration and one for modulating Nav channel activity. After crossing the cell membrane, rpTx1 preferentially binds to and stabilizes the IFMT motif (the conserved core region of the fast inactivation particle in mammalian Nav channels) in the unbound state, preventing this motif from associating with its receptor site and thereby inhibiting the fast inactivation of Nav channels. This competition between rpTx1 and the receptor site for interacting with the IFMT motif may account for the higher activity of rpTx1 on Nav1.8 than on other Nav subtypes, given the weaker relative affinity between the receptor site and the IFMT motif of Nav1.8. Overall, this study should promote the investigation of the intracellular modulation of Nav channels by neurotoxins.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866572","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}
The EMBO JournalPub Date : 2025-04-22DOI: 10.1038/s44318-025-00440-1
Phi-Long Tran,Okhwa Kim,Cheol Hwangbo,Hyo-Jin Kim,Young-Myeong Kim,Jeong-Hyung Lee
{"title":"SDCBP/Syntenin-1 stabilizes BACH1 by disassembling the SCFFBXO22-BACH1 complex in triple-negative breast cancer.","authors":"Phi-Long Tran,Okhwa Kim,Cheol Hwangbo,Hyo-Jin Kim,Young-Myeong Kim,Jeong-Hyung Lee","doi":"10.1038/s44318-025-00440-1","DOIUrl":"https://doi.org/10.1038/s44318-025-00440-1","url":null,"abstract":"BACH1 is a redox-sensitive transcription factor facilitating tumor progression in triple-negative breast cancer (TNBC). However, the molecular mechanisms regulating BACH1 function in TNBC remain unclear. In this study, we demonstrate that SDCBP, a tandem-PDZ-domain protein, stabilizes BACH1 by disassembling the Skp1-Cullin1-FBXO22 (SCFFBXO22)-BACH1 complex via a heme/heme-oxygenase-1-independent manner in TNBC cells. Our data revealed that SDCBP and BACH1 expression show a significant positive correlation in TNBC cells and TNBC patients tumor tissues. Mechanistically, SDCBP via its PDZ1 domain disassembles the SCFFBXO22-BACH1 complex via its PDZ1 domain, thereby preventing BACH1 K48-linked polyubiquitination and proteasomal degradation. Knocking down SDCBP induces BACH1 degradation and downregulates expressions of BACH1-induced metastatic genes, thereby suppressing tumor progression in mice bearing TNBC tumors. Moreover, depleting SDCBP leads to upregulation of BACH1-repressed electron transport chain (ETC) genes, such as NDUFA4 and COX6B2, and increases mitochondrial activity, enhancing anti-tumor efficacy of metformin against TNBC both in vitro and in vivo. These data demonstrate a novel alternative mechanism for BACH1 stabilization mediated by SDCBP, implicating the SDCBP-BACH1 axis as a potential target for enhancing ETC inhibitor efficacy in TNBC combinational therapy.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866574","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}
The EMBO JournalPub Date : 2025-04-17DOI: 10.1038/s44318-025-00426-z
Nicola J Smyllie,Alex A Koch,Antony D Adamson,Andrew P Patton,Adam Johnson,James S Bagnall,Olivia Johnson,Qing-Jun Meng,Andrew S I Loudon,Michael H Hastings
{"title":"Quantitative measures of clock protein dynamics in the mouse suprachiasmatic nucleus extends the circadian time-keeping model.","authors":"Nicola J Smyllie,Alex A Koch,Antony D Adamson,Andrew P Patton,Adam Johnson,James S Bagnall,Olivia Johnson,Qing-Jun Meng,Andrew S I Loudon,Michael H Hastings","doi":"10.1038/s44318-025-00426-z","DOIUrl":"https://doi.org/10.1038/s44318-025-00426-z","url":null,"abstract":"The suprachiasmatic nucleus (SCN) synchronises circadian rhythmicity (~24 h) across the body. The SCN cell-autonomous clock is modelled qualitatively as a transcriptional-translational feedback loop (TTFL), with heteromeric complexes of transcriptional activator and repressor proteins driving cyclical gene expression. How these proteins really behave within the SCN, individually and in relation to each other, is poorly understood. Imaging SCN slices from a novel array of knock-in reporter mice, we quantify the dynamic behaviours of combined repressors PERIOD2 (PER2) and CRYPTOCHROME1 (CRY1), and activator BMAL1. We reveal a spectrum of protein-specific intracellular and spatiotemporal behaviours that run counter to the qualitative TTFL model. We also show that PER and CRY1 exert independent actions on TTFL oscillations, and that their individual stabilities play a critical role in SCN circadian dynamics. These results reveal a rich and unanticipated complexity in the dynamic behaviours and functions of endogenous circadian proteins, prompting re-appraisal of current transcriptional-translational feedback loop models of the suprachiasmatic nucleus.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849426","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}
The EMBO JournalPub Date : 2025-04-16DOI: 10.1038/s44318-025-00433-0
Nikita V Ivanisenko,Corinna König,Laura K Hillert-Richter,Maria A Feoktistova,Sabine Pietkiewicz,Max Richter,Diana Panayotova-Dimitrova,Thilo Kaehne,Inna N Lavrik
{"title":"Oligomerised RIPK1 is the main core component of the CD95 necrosome.","authors":"Nikita V Ivanisenko,Corinna König,Laura K Hillert-Richter,Maria A Feoktistova,Sabine Pietkiewicz,Max Richter,Diana Panayotova-Dimitrova,Thilo Kaehne,Inna N Lavrik","doi":"10.1038/s44318-025-00433-0","DOIUrl":"https://doi.org/10.1038/s44318-025-00433-0","url":null,"abstract":"The necrosome is the key macromolecular signaling platform initiating necroptosis, i.e., a RIPK1/RIPK3-dependent program of cell death with an important role in the control of inflammation in multicellular organisms. However, the composition and structure of the necrosome remain incompletely understood. Here we use biochemical assays, quantitative mass spectrometry, and AlphaFold modeling to decipher the composition and derive a structural model of the CD95L/BV6-induced necrosome. We identify RIPK1 as the central component of the necrosome, forming the core of this complex. In addition, AlphaFold modeling provides insights into the structural mechanisms underlying RIPK1 oligomerization, highlighting the critical role of type-II interactions between the Death Domains (DDs) of FADD and RIPK1 in the assembly of RIPK1-mediated complexes. The role of type-II DD interactions in necroptosis induction is further validated through structure-guided site-directed mutagenesis. Our findings could be useful for the pharmacological targeting of the necroptosis network to treat diseases associated with dysregulated cell death and inflammation.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846320","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}
{"title":"Glutamylation of centrosomes ensures their function by recruiting microtubule nucleation factors.","authors":"Shi-Rong Hong,Yi-Chien Chuang,Wen-Ting Yang,Chiou-Shian Song,Hung-Wei Yeh,Bing-Huan Wu,I-Hsuan Lin,Po-Chun Chou,Shiau-Chi Chen,Lohitaksh Sharma,Jui-Chen Lu,Rou-Ying Li,Ya-Chu Chang,Kuan-Ju Liao,Hui-Chun Cheng,Won-Jing Wang,Lily Hui-Ching Wang,Yu-Chun Lin","doi":"10.1038/s44318-025-00435-y","DOIUrl":"https://doi.org/10.1038/s44318-025-00435-y","url":null,"abstract":"Centrosomes are tubulin-based organelles that undergo glutamylation, a post-translational modification that conjugates glutamic acid residues to tubulins. Although centrosomal glutamylation has been known for several decades, how this modification regulates centrosome structure and function remains unclear. To address this long-standing issue, we developed a method to spatiotemporally reduce centrosomal glutamylation by recruiting an engineered deglutamylase to centrosomes. We found that centrosome structure remains largely unaffected by centrosomal hypoglutamylation. Intriguingly, glutamylation physically recruits, via electrostatic forces, the NEDD1/CEP192/γ-tubulin complex to centrosomes, ensuring microtubule nucleation and proper trafficking of centriolar satellites. The consequent defect in centriolar satellite trafficking leads to reduced levels of the ciliogenesis factor Talpid3, suppressing ciliogenesis. Centrosome glutamylation also promotes proper mitotic spindle formation and mitosis. In summary, our study provides a new approach to spatiotemporally manipulate glutamylation at centrosomes, and offers novel insights into how centrosomes are organized and regulated by glutamylation.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836489","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}
The EMBO JournalPub Date : 2025-04-11DOI: 10.1038/s44318-025-00422-3
Rosa Pascual,Jinming Cheng,Amelia H De Smet,Bianca D Capaldo,Minhsuang Tsai,Somayeh Kordafshari,François Vaillant,Xiaoyu Song,Göknur Giner,Michael J G Milevskiy,Felicity C Jackling,Bhupinder Pal,Toby Dite,Jumana Yousef,Laura F Dagley,Gordon K Smyth,Naiyang Fu,Geoffrey J Lindeman,Yunshun Chen,Jane E Visvader
{"title":"Fibroblast hierarchy dynamics during mammary gland morphogenesis and tumorigenesis.","authors":"Rosa Pascual,Jinming Cheng,Amelia H De Smet,Bianca D Capaldo,Minhsuang Tsai,Somayeh Kordafshari,François Vaillant,Xiaoyu Song,Göknur Giner,Michael J G Milevskiy,Felicity C Jackling,Bhupinder Pal,Toby Dite,Jumana Yousef,Laura F Dagley,Gordon K Smyth,Naiyang Fu,Geoffrey J Lindeman,Yunshun Chen,Jane E Visvader","doi":"10.1038/s44318-025-00422-3","DOIUrl":"https://doi.org/10.1038/s44318-025-00422-3","url":null,"abstract":"Fibroblasts form a major component of the stroma in normal mammary tissue and breast tumors. Here, we have applied longitudinal single-cell transcriptome profiling of >45,000 fibroblasts in the mouse mammary gland across five different developmental stages and during oncogenesis. In the normal gland, diverse stromal populations were resolved, including lobular-like fibroblasts, committed preadipocytes and adipogenesis-regulatory, as well as cycling fibroblasts in puberty and pregnancy. These specialized cell types appear to emerge from CD34high mesenchymal progenitor cells, accompanied by elevated Hedgehog signaling. During late tumorigenesis, heterogeneous cancer-associated fibroblasts (CAFs) were identified in mouse models of breast cancer, including a population of CD34- myofibroblastic CAFs (myCAFs) that were transcriptionally and phenotypically similar to senescent CAFs. Moreover, Wnt9a was demonstrated to be a regulator of senescence in CD34- myCAFs. These findings reflect a diverse and hierarchically organized stromal compartment in the normal mammary gland that provides a framework to better understand fibroblasts in normal and cancerous states.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"110 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824782","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}
{"title":"Reconstruction of the ancient cyanobacterial proto-circadian clock system KaiABC.","authors":"Silin Li,Zengxuan Zhou,Yufeng Wan,Xudong Jia,Peiliang Wang,Yu Wang,Taisen Zuo,He Cheng,Xiaoting Fang,Shuqi Dong,Jun He,Yilin Yang,Yichen Xu,Shaoxuan Fu,Xujing Wang,Ximing Qin,Qiguang Xie,Xiaodong Xu,Yuwei Zhao,Dan Liang,Peng Zhang,Qinfen Zhang,Jinhu Guo","doi":"10.1038/s44318-025-00425-0","DOIUrl":"https://doi.org/10.1038/s44318-025-00425-0","url":null,"abstract":"Earlier in its history, the Earth used to spin faster than it does today. How ancient organisms adapted to the short day/night cycles during that time remains unclear. In this study we reconstruct and analyse the ancient circadian clock system KaiABC (anKaiABC) of cyanobacteria that existed ~0.95 billion years ago, when the daily light/dark cycle was ~18 h-long. Compared to their contemporary counterparts, anKaiABC proteins had different structures and interactions. The kinase, phosphatase, and adenosine triphosphatase (ATPase) activities of anKaiC were lower, while the anKaiA and anKaiB proteins were less effective at regulating the KaiC/anKaiC phosphorylation status. We provide evidence indicating that the anKaiABC system does not endogenously oscillate, but it can be entrained by an 18 h-long light/dark cycle. A Synechococcus strain expressing ankaiABC genes exhibits better adaptation to 9-h light/9-h dark cycles (LD9:9) that mimic the ancient 18-h day/night cycles, whereas the kaiABC-expressing strain preferentially adapts to the LD12:12 contemporary conditions. These findings suggest that, despite its lack of self-sustaining circadian oscillation, the proto-circadian system may have mediated adaptation of ancient cyanobacteria to the 18 h-long light/dark cycles present 0.95 billion years ago.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822451","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}
{"title":"Temporal refinement of Dach1 expression contributes to the development of somatosensory neurons.","authors":"Tünde Szemes,Alba Sabaté San José,Abdulkader Azouz,Maren Sitte,Gabriela Salinas,Younes Achouri,Sadia Kricha,Laurence Ris,Kristy Red-Horse,Eric J Bellefroid,Simon Desiderio","doi":"10.1038/s44318-025-00427-y","DOIUrl":"https://doi.org/10.1038/s44318-025-00427-y","url":null,"abstract":"During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state. Several transcription factors in these cells follow a broad-to-restricted expression trajectory as development proceeds, giving rise to neuron subtypes with different identities. The relevance of this temporal refinement of transcription factor expression remains unclear as the functions of transcription factors with broad-to-restricted expression patterns have been mostly studied in those neuron subtypes in which they remain active. Here we show that Dach1 encodes a bona fide transcription factor with a broad-to-restricted expression pattern retained and required in tactile somatosensory neurons. In developing nociceptors, Prdm12 contributes to Dach1 silencing. Using genetic approaches to prevent its temporal restriction during mouse somatosensory development, we reveal that Dach1 expression refinement is a prerequisite for the acquisition of an appropriate transcriptional profile in those somatosensory neuron subtypes in which it becomes ultimately silenced. These findings highlight the essential role played by Dach1 during somatosensory neuron development and demonstrate that the temporal pattern of broad-to-restricted expression followed by several transcription factors is physiologically important for the development of somatosensory neurons.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"217 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819025","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}
{"title":"Ductal or Ngn3+ cells do not contribute to adult pancreatic islet beta-cell neogenesis in homeostasis.","authors":"Xiuzhen Huang,Huan Zhao,Hui Chen,Zixin Liu,Kuo Liu,Zan Lv,Xiuxiu Liu,Ximeng Han,Maoying Han,Jie Lu,Qiao Zhou,Bin Zhou","doi":"10.1038/s44318-025-00434-z","DOIUrl":"https://doi.org/10.1038/s44318-025-00434-z","url":null,"abstract":"The adult pancreatic ducts have long been proposed to contain rare progenitors, some of which expressing Ngn3, that generate new beta cells in endocrine-islet homeostasis. Due to their postulated rarity and the lack of definitive markers, the existence or absence of ductal endocrine progenitors remains unsettled despite many studies. Genetic lineage tracing of ductal cells or Ngn3+ cells with currently available CreER drivers has been complicated by off-target labeling of pre-existing beta cells. Here, using dual-recombinase-mediated intersectional genetic strategy and newly-derived Ngn3-2A-CreER and Hnf1b-2A-CreER knock-in drivers, we succeeded in specifically labeling Ngn3-positive cells and Hnf1b-positive ductal cells without marking pre-existing beta cells. These data revealed no evidence of de novo generation of insulin-producing beta cells from ductal cells or endogenous Ngn3-positive cells in the adult pancreas during homeostasis.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819397","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}
{"title":"SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation.","authors":"Wei Li,Jing Han,Bin Huang,Tengteng Xu,Yihong Wan,Dan Luo,Weiyao Kong,Ying Yu,Lei Zhang,Yong Nian,Bo Chu,Chengqian Yin","doi":"10.1038/s44318-025-00369-5","DOIUrl":"https://doi.org/10.1038/s44318-025-00369-5","url":null,"abstract":"Ferroptosis, an iron-dependent form of programmed cell death characterized by excessive lipid hydroperoxides accumulation, emerges as a promising target in cancer therapy. Among the solute carrier (SLC) superfamily, the cystine/glutamate transporter system antiporter components SLC3A2 and SLC7A11 are known to regulate ferroptosis by facilitating cystine import for ferroptosis inhibition. However, the contribution of additional SLC superfamily members to ferroptosis remains poorly understood. Here, we use a targeted CRISPR-Cas9 screen of the SLC superfamily to identify SLC25A1 as a critical ferroptosis regulator in human cancer cells. SLC25A1 drives citrate export from the mitochondria to the cytosol, where it fuels acetyl-CoA synthesis by ATP citrate lyase (ACLY). This acetyl-CoA supply sustains FSP1 acetylation and prevents its degradation by the proteasome via K29-linked ubiquitin chains. K168 is the primary site of FSP1 acetylation and deacetylation by KAT2B and HDAC3, respectively. Pharmacological inhibition of SLC25A1 and ACLY significantly enhances cancer cell susceptibility to ferroptosis both in vitro and in vivo. Targeting the SLC25A1-ACLY axis is therefore a potential therapeutic strategy for ferroptosis-targeted cancer intervention.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062080","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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