The FEBS journal最新文献

{"title":"Stress-inducible phosphoprotein 1 (Sti1/Stip1/Hop) sequesters misfolded proteins during stress.","authors":"Benjamin S Rutledge, Young J Kim, Donovan W McDonald, Juan C Jurado-Coronel, Marco A M Prado, Jill L Johnson, Wing-Yiu Choy, Martin L Duennwald","doi":"10.1111/febs.17389","DOIUrl":"https://doi.org/10.1111/febs.17389","url":null,"abstract":"<p><p>Co-chaperones are key elements of cellular protein quality control. They cooperate with the major heat shock proteins Hsp70 and Hsp90 in folding proteins and preventing the toxic accumulation of misfolded proteins upon exposure to stress. Hsp90 interacts with the co-chaperone stress-inducible phosphoprotein 1 (Sti1/Stip1/Hop) and activator of Hsp90 ATPase protein 1 (Aha1) among many others. Sti1 and Aha1 control the ATPase activity of Hsp90, but Sti1 also facilitates the transfer of client proteins from Hsp70 to Hsp90, thus connecting these two major branches of protein quality control. We find that misbalanced expression of Sti1 and Aha1 in yeast and mammalian cells causes severe growth defects. Also, deletion of STI1 causes an accumulation of soluble misfolded ubiquitinated proteins and a strong activation of the heat shock response. We discover that, during proteostatic stress, Sti1 forms cytoplasmic inclusions in yeast and mammalian cells that overlap with misfolded proteins. Our work indicates a key role of Sti1 in proteostasis independent of its Hsp90 ATPase regulatory functions by sequestering misfolded proteins during stress.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911342","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":"Multisubstrate-based system: a kinetic mechanism study of catechol-O-methyltransferase.","authors":"Fangyuan Wang, Xianglu Zhou, Haonan Wang, Ziqiong Zhou, Ling Yang, Yonghong Hu, Shenglan Qi, Ping Wang","doi":"10.1111/febs.17372","DOIUrl":"https://doi.org/10.1111/febs.17372","url":null,"abstract":"<p><p>Catechol-O-methyltransferase (COMT, EC 2.1.1.6) can transfer the methyl group from S-adenosyl-l-methionine (SAM) to one of the hydroxyl groups of a catechol substrate in the presence of Mg²⁺. However, there is no consensus view of the kinetic mechanism of COMT involving multiple substrates. Further progress requires the development of methods for determining enzyme kinetic behavior and the binding mode of ligands to the protein. Here, we establish a multisubstrate kinetic system covering the fluorescence and mass spectrometry techniques to quantify the products in a COMT-catalyzed reaction. The catechol substrate, 3-BTD, can be methylated by COMT to form a single product, 3-BTMD, with a sensitive fluorescence response and the conversion of SAM to S-adenosyl-l-homocysteine (SAH) was monitored by LC-MS/MS. The kinetic assays suggested that the reaction occurred via an ordered sequential mechanism, in which SAM first bound to COMT, followed by the addition of Mg²⁺ and 3-BTD. The chemical step involved a quaternary complex of COMT-SAM-Mg²⁺-3-BTD, followed by the ordered dissociation of 3-BTMD, Mg²⁺, and SAH. In cooperation with molecular dynamics simulation, the binding of COMT to Mg²⁺ induced a shape change in the catechol-binding site, which accommodated 3-BTD binding and facilitated catalysis. These findings provide new insights into the kinetic mechanism of COMT, contributing to the development of previously undescribed functional COMT ligands.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901444","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":"Inhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction-associated steatohepatitis.","authors":"Isabeau Vermeulen, Mengying Li, Hester van Mourik, Tulasi Yadati, Gert Eijkel, Benjamin Balluff, Roger Godschalk, Lieve Temmerman, Erik A L Biessen, Aditya Kulkarni, Jan Theys, Tom Houben, Berta Cillero-Pastor, Ronit Shiri-Sverdlov","doi":"10.1111/febs.17358","DOIUrl":"https://doi.org/10.1111/febs.17358","url":null,"abstract":"<p><p>The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) progressing to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatic inflammation, has significantly increased in recent years due to unhealthy dietary practices and sedentary lifestyles. Cathepsin D (CTSD), a lysosomal protease involved in lipid homeostasis, is linked to abnormal lipid metabolism and inflammation in MASH. Although primarily intracellular, CTSD can be secreted extracellularly. Our previous proteomics research has shown that inhibition of extracellular CTSD results in more anti-inflammatory effects and fewer potential side effects compared to intracellular CTSD inhibition. However, the correlation between reduced side effects and alterations in the hepatic lipid composition remains unknown. This study aims to investigate the correlation between intra- and extracellular CTSD inhibition and potential alterations in the hepatic lipid composition in MASH. Low-density lipoprotein receptor knockout (Ldlr^-/-) mice were fed a high-fat diet for 10 weeks and received subcutaneous injections every 2 days of vehicle, intracellular CTSD inhibitor (GA-12), or extracellular CTSD inhibitor (CTD-002). Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize and compare the lipid composition in liver tissues. Hepatic phosphatidylcholine remodeling was observed with both inhibitors, suggesting their therapeutic potential in treating MASH. Treatment with an intracellular CTSD inhibitor resulted in elevated levels of cardiolipin, reactive oxygen species, phosphatidylinositol, phosphatidylethanolamine, and lipids that are linked to mitochondrial dysfunction and inflammation, and induced more oxidative stress. The observed modifications in lipid composition demonstrate the clinical advantages of extracellular CTSD inhibition as a potentially beneficial therapeutic approach for MASH.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901443","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":"Increasing recombinant protein production in E. coli via FACS-based selection of N-terminal coding DNA libraries.","authors":"Štěpán Herynek, Jakub Svoboda, Maroš Huličiak, Yoav Peleg, Ľubica Škultétyová, Pavel Mikulecký, Bohdan Schneider","doi":"10.1111/febs.17376","DOIUrl":"https://doi.org/10.1111/febs.17376","url":null,"abstract":"<p><p>Here, we present a previously undescribed approach to modify N-terminal sequences of recombinant proteins to increase their production yield in Escherichia coli. Prior research has demonstrated that the nucleotides immediately following the start codon can significantly influence protein expression. However, the impact of these sequences is construct-specific and is not universally applicable to all proteins. Most of the previous research has been limited to selecting from a few rationally designed sequences. In contrast, we used a directed evolution-based methodology, screening large numbers of diversified sequences derived from DNA libraries coding for the N-termini of investigated proteins. To facilitate the identification of cells with increased expression of the target construct, we cloned a GFP gene at the C-terminus of the expressed genes and used fluorescent activated cell sorting (FACS) to separate cells based on their fluorescence. By following this systematic workflow, we successfully elevated the yield of soluble recombinant proteins of multiple constructs up to over 30-fold.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901408","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":"Amelioration of signaling deficits underlying metabolic shortfall in TREM2^R47H human iPSC-derived microglia.","authors":"Foteini Vasilopoulou, Thomas M Piers, Jingzhang Wei, John Hardy, Jennifer M Pocock","doi":"10.1111/febs.17353","DOIUrl":"https://doi.org/10.1111/febs.17353","url":null,"abstract":"<p><p>The microglial triggering receptor expressed on myeloid cells 2 (TREM2) is required for diverse microglia responses in neurodegeneration, including immunometabolic plasticity, phagocytosis, and survival. We previously identified that patient iPSC-derived microglia (iPS-Mg) harboring the Alzheimer's disease (AD) TREM2^R47H hypomorph display several functional deficits linked to metabolism. To investigate whether these deficits are associated with disruptions in metabolite signaling, we generated common variant, TREM2^R47H and TREM2^-/- variant human iPS-Mg. We assessed the ability of supplementation with citrate or succinate, key metabolites and cell cycle breaking points upon microglia activation, to overcome these functional deficits with potential impact on neurons. Succinate supplementation was more effective than citrate at overcoming mitochondrial deficits in OXPHOS and did not promote a glycolytic switch. Citrate enhanced the lipid content of TREM2^R47H iPS-Mg and was more effective at overcoming Αβ phagocytic deficits, whereas succinate increased lipid content and phagocytic capacity in TREM2^-/- iPS-Mg. Microglia cytokine secretion upon pro-inflammatory activation was moderately affected by citrate or succinate showing a condition-dependent increasing trend. Neither metabolite altered basal levels of soluble TREM2 shedding. In addition, neither citrate nor succinate enhanced glycolysis; instead, drove their effects through oxidative phosphorylation. IPS-neurons exposed to conditioned medium from TREM2 variant iPS-Mg showed changes in oxidative phosphorylation, which could be ameliorated when iPS-Mg were first treated with citrate or succinate. Our data point to discrete pathway linkage between microglial metabolism and functional outcomes with implications for AD pathogenesis and treatments.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901391","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":"A guide to RNA structure analysis and RNA-targeting methods.","authors":"Rodrigo Aguilar, Constanza Mardones, Adrian A Moreno, Marjorie Cepeda-Plaza","doi":"10.1111/febs.17368","DOIUrl":"https://doi.org/10.1111/febs.17368","url":null,"abstract":"<p><p>RNAs are increasingly recognized as promising therapeutic targets, susceptible to modulation by strategies that include targeting with small molecules, antisense oligonucleotides, deoxyribozymes (DNAzymes), or CRISPR/Cas13. However, while drug development for proteins follows well-established paths for rational design based on the accurate knowledge of their three-dimensional structure, RNA-targeting strategies are challenging since comprehensive RNA structures are yet scarce and challenging to acquire. Numerous methods have been developed to elucidate the secondary and three-dimensional structure of RNAs, including X-ray crystallography, cryo-electron microscopy, nuclear magnetic resonance, SHAPE, DMS, and bioinformatic methods, yet they have often revealed flexible transcripts and co-existing populations rather than single-defined structures. Thus, researchers aiming to target RNAs face a critical decision: whether to acquire the detailed structure of transcripts in advance or to adopt phenotypic screens or sequence-based approaches that are independent of the structure. Still, even in strategies that seem to rely only on the nucleotide sequence (like the design of antisense oligonucleotides), researchers may need information about the accessibility of the compounds to the folded RNA molecule. In this concise guide, we provide an overview for researchers interested in targeting RNAs: We start by revisiting current methodologies for defining secondary or three-dimensional RNA structure and then we explore RNA-targeting strategies that may or may not require an in-depth knowledge of RNA structure. We envision that complementary approaches may expedite the development of RNA-targeting molecules to combat disease.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883872","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":"Attenuated NIX in impaired mitophagy contributes to exacerbating cellular senescence in experimental periodontitis under hyperglycemic conditions.","authors":"Danni Song, Beibei Chen, Tianfan Cheng, Lijian Jin, Jiangfeng He, Yongming Li, Chongshan Liao","doi":"10.1111/febs.17352","DOIUrl":"https://doi.org/10.1111/febs.17352","url":null,"abstract":"<p><p>Premature accumulation of senescent cells results in tissue destruction, and it is one of the potential primary mechanisms underlying the accelerated progression of diabetes and periodontitis. However, whether this characterized phenomenon could account for periodontal pathogenesis under hyperglycemic conditions remains unclear. In this study, we assessed the senescent phenotypic changes in experimental periodontitis under hyperglycemic conditions. Next, we investigated the mitochondrial function and the potential mitophagy pathways in cellular senescence in vitro and in vivo. Our findings showed that significant senescence occurred in the gingival tissues of diabetic periodontitis mice with increased expression of senescence-related protein p21^Cip1 and the senescence-associated secretory phenotype response as well as the decreased expression of NIP3-like protein X (NIX), a mitochondrial receptor. Likewise, we showed that mitochondrial dysfunction (e.g., reduction of mitochondrial membrane potential and accumulation of reactive oxygen species) was attributed to cellular senescence in: human periodontal ligament cells (hPDLCs) through hyperglycemia-induced and Porphyromonas gingivalis lipopolysaccharide (P.g-LPS)-induced oxidative stresses. Notably, the resulting reduced NIX expression was reversed by the use of the mitochondrial reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC), thus correcting the mitochondrial dysfunction. We further verified the expression of inflammatory mediators and senescence-related factors in mice gingival tissues and identified the possible regulatory pathways. Taken together, our work demonstrates the critical role of cellular senescence and mitochondrial dysfunction in periodontal pathogenesis under hyperglycemic conditions. Hence, restoration of mitochondrial function may be a potential novel therapeutic approach to tackling periodontitis in diabetic patients.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883878","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":"SignatureFinder enables sequence mining to identify cobalamin-dependent photoreceptor proteins.","authors":"Yuqi Yu, Laura N Jeffreys, Harshwardhan Poddar, Adam Hill, Linus Johannissen, Fanzhuo Dai, Michiyo Sakuma, David Leys, Derren J Heyes, Shaowei Zhang, Nigel S Scrutton","doi":"10.1111/febs.17377","DOIUrl":"https://doi.org/10.1111/febs.17377","url":null,"abstract":"<p><p>Photoreceptors control cellular processes in response to light. Most photoreceptors sense blue or red light, but the recent discovery of the cobalamin-dependent photoreceptor, CarH, has expanded the wavelength range of photoreception to other regions of the electromagnetic spectrum to include the green light region. Further identification of cobalamin-dependent green light-sensitive photoreceptors has been hampered owing to poor annotation of the light responsiveness of cobalamin-binding domains (CBDs) in public databases. Here we report a computational workflow, SignatureFinder, that uses a combination of sequence and structural analyses to identify new light-responsive CBD-containing proteins. The light response of exemplar proteins containing the proposed signature were confirmed experimentally. A structural analysis of these new photoreceptors, including the crystal structure of a new CBD domain, highlights how the signature elements interact with the cobalamin chromophore to sense light. Database mining of 128 000 CBD-containing sequences using the identified signature revealed more diverse CBD-containing photoreceptors, thereby expanding the family of green-light photoreceptors. A SignatureFinder web server is available (https://enzymeevolver.com) for wider applications, including the identification of signature sequences of other biological ligands of interest.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883882","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":"The gut microbiota mediates memory impairment under high-altitude hypoxia via the gut-brain axis in mice.","authors":"Wenhao Li, Yuhao Wang, Yi Shi, Fenfen He, Zaihua Zhao, Jingchun Liu, Zhenbo Gao, Jianbin Zhang, Xuefeng Shen","doi":"10.1111/febs.17365","DOIUrl":"https://doi.org/10.1111/febs.17365","url":null,"abstract":"<p><p>Hypoxia is a predominant risk factor at high altitudes, and evidence suggests that high-altitude hypoxia alters the gut microbiota, which plays an essential regulatory role in memory function. However, the causal relationship between the gut microbiota and memory impairment under hypoxic conditions remains unclear. In this study, we employed a high-altitude hypoxia model combined with fecal microbiota transplantation (FMT) approach in mice to explore the effects of the gut microbiota on memory impairment in a hypoxic environment. We observed that high-altitude hypoxia exposure reduced short- and long-term memory and hippocampus-dependent fear memory abilities, along with decreased relative abundance of Ligilactobacillus and Muribaculum. Moreover, hypoxic conditions increased intestinal and blood-brain barrier permeability. FMT from hypoxia-exposed mice into naïve antibiotic-treated mice resulted in similar memory impairments, Ligilactobacillus and Muribaculum abundance changes, and increased intestinal/blood-brain barrier permeability. Correlation analysis showed a robust positive association between Ligilactobacillus and Muribaculum with hippocampus-dependent contextual fear memory. Likewise, Ligilactobacillus was positively correlated with short-term memory. Therefore, Ligilactobacillus and Muribaculum may be key microbes in reducing memory ability in hypoxia, with the intestinal and blood-brain barriers as primary pathways. Our findings provide further evidence for the potential regulatory mechanism by which gut microbiota dysbiosis may contribute to memory impairment in a high-altitude environment.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883887","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":"Transglutaminase 2 is an RNA-binding protein: experimental verification and characterisation of a novel transglutaminase feature.","authors":"Bianka Csaholczi, Anna Renáta Csuth, Ilma Rita Korponay-Szabó, László Fésüs, Róbert Király","doi":"10.1111/febs.17373","DOIUrl":"https://doi.org/10.1111/febs.17373","url":null,"abstract":"<p><p>Transglutaminase 2 (TG2) is a uniquely versatile protein with diverse catalytic activities, such as transglutaminase, protein disulfide isomerase, GTPase and protein kinase, and participates in several biological processes. According to information available in the RBP2GO database, TG2 can act as an RNA-binding protein (RBP). RBPs participate in posttranscriptional gene expression regulation, therefore influencing the function of RNA, whereas RNA molecules can also modulate the biological activity of RBPs. The present study aimed to confirm this novel characteristic of TG2 in human umbilical cord vein endothelial cells (HUVEC), which physiologically express TG2. First, UV cross-linked RNA-protein complexes were isolated from immortalised HUVECs using orthogonal organic phase separation. Compared with the RBP2GO database, mass spectrometry identified 392 potential RBPs, including TG2 and 20 previously undescribed, endothelium-related RBPs. Recombinant human TG2 was also pulled down by magnetic bead-immobilised total RNA from HUVEC. Complex formation between TG2 and a 43-mer RNA molecule with a secondary structure as well as a homo-oligomeric single-stranded poly(dG), but not poly(dA), could be observed in magnetic RNA-protein pull-down experiments. Experiments with TG2 inhibitors NC9 and GTPγS, which stabilise its open and closed conformation, respectively, revealed that the open conformation of the enzyme favoured RNA-binding. Biolayer interferometry revealed a high binding affinity between TG2 and RNA with a K_D value of 88 nm. Based on modelling and site-directed mutagenesis studies, we propose that superficial residues on the catalytic core domain (173-177 amino acids), present in a hidden position in the closed TG2 conformation, are involved in RNA binding. The present study demonstrates the previously uncharacterised RNA-binding ability of TG2, opening new avenues for understanding its multifunctionality.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883893","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}