The FEBS journal最新文献_第10页

Contact and communication: ZO-2 and the Hippo pathway.

The FEBS journal Pub Date : 2025-02-05 DOI: 10.1111/febs.17417

Miranda Thomas

引用次数: 0

CryoEM and crystal structure analyses reveal the indirect role played by Trp89 in glutamate dehydrogenase enzymatic reactions.

The FEBS journal Pub Date : 2025-02-01 DOI: 10.1111/febs.17415

Taiki Wakabayashi, Yuka Matsui, Masayoshi Nakasako

{"title":"CryoEM and crystal structure analyses reveal the indirect role played by Trp89 in glutamate dehydrogenase enzymatic reactions.","authors":"Taiki Wakabayashi, Yuka Matsui, Masayoshi Nakasako","doi":"10.1111/febs.17415","DOIUrl":"https://doi.org/10.1111/febs.17415","url":null,"abstract":"Glutamate dehydrogenase from Thermococcus profundus is a homo-hexameric enzyme that catalyzes the reversible deamination of glutamate to 2-oxoglutarate in the presence of a cofactor. In each subunit, a large active-site cleft is formed between the two functional domains, one of which displays motion to open and close the cleft. Trp89 in the cleft displays two sidechain conformers in the open cleft and a single conformer in the closed cleft. To reveal the role of the Trp89 sidechain in the domain motion, we mutated Trp89 to phenylalanine. Despite the Trp89 sidechain being located away from the reaction center, the catalytic constant decreased to 1/38-fold of that of the wild-type without a fatal reduction of the affinities to the cofactor and ligand molecules. To understand the molecular mechanism underlying this reduction, we determined the crystal structure in the unliganded state and the metastable conformations appearing in the steady stage of the reaction using cryo-electron microscopy (cryoEM). The four identified metastable conformations were similar to the three conformations observed in the wild-type, but their populations were different from those of the wild-type. In addition, a conformation with a completely closed active-site cleft necessary for the reaction to proceed was quite rare. The crystal structure and the four metastable conformations suggested that the reduction in the catalytic constant could be attributed to changes in the interactions between Gln13 and the 89th side chains, preventing the closing domain motion.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076749","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

Nature AND nurture: enabling formate-dependent growth in Methanosarcina acetivorans.

The FEBS journal Pub Date : 2025-01-31 DOI: 10.1111/febs.17409

Jichen Bao, Tejas Somvanshi, Yufang Tian, Maxime G Laird, Pierre Simon Garcia, Christian Schöne, Michael Rother, Guillaume Borrel, Silvan Scheller

{"title":"Nature AND nurture: enabling formate-dependent growth in Methanosarcina acetivorans.","authors":"Jichen Bao, Tejas Somvanshi, Yufang Tian, Maxime G Laird, Pierre Simon Garcia, Christian Schöne, Michael Rother, Guillaume Borrel, Silvan Scheller","doi":"10.1111/febs.17409","DOIUrl":"https://doi.org/10.1111/febs.17409","url":null,"abstract":"Methanosarcinales are versatile methanogens, capable of regulating most types of methanogenic pathways. Despite the versatile metabolic flexibility of Methanosarcinales, no member of this order has been shown to use formate for methanogenesis. In the present study, we identified a cytosolic formate dehydrogenase (FdhAB) present in several Methanosarcinales, likely acquired by independent horizontal gene transfers after an early evolutionary loss, encouraging re-evaluation of our understanding of formate utilization in Methanosarcinales. To explore whether formate-dependent (methyl-reducing or CO2-reducing) methanogenesis can occur in Methanosarcinales, we engineered two different strains of Methanosarcina acetivorans by functionally expressing FdhAB from Methanosarcina barkeri in M. acetivorans. In the first strain, fdhAB was integrated into the N5-methyl- tetrahydrosarcinapterin:coenzyme M methyltransferase (mtr) operon, making it capable of growing by reducing methanol with electrons from formate. In the second strain, fdhAB was integrated into the F420-reducing hydrogenase (frh) operon, instead of the mtr operon, enabling its growth with formate as the only source of carbon and energy after adaptive laboratory evolution. In this strain, one CO2 is reduced to one methane with electrons from oxidizing four formate to four CO2, a metabolism reported only in methanogens without cytochromes. Although methanogens without cytochromes typically utilize flavin-based electron bifurcation to generate the ferredoxins needed for CO2 activation, we hypothesize that, in our engineered strains, reduced ferredoxins are obtained via the Rhodobacter nitrogen fixation complex complex running in reverse. Our work demonstrates formate-dependent methyl-reducing and CO2-reducing methanogenesis in M. acetivorans that is enabled by the flexible nature of the microbe working in tandem with the nurturing provided.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070588","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

Sex-related changes in lactate dehydrogenase A expression differently impact the immune response in melanoma.

The FEBS journal Pub Date : 2025-01-31 DOI: 10.1111/febs.17423

Marta Iozzo, Giuseppina Comito, Luigi Ippolito, Giada Sandrini, Elisa Pardella, Erica Pranzini, Mariaelena Capone, Gabriele Madonna, Paolo Antonio Ascierto, Paola Chiarugi, Elisa Giannoni

{"title":"Sex-related changes in lactate dehydrogenase A expression differently impact the immune response in melanoma.","authors":"Marta Iozzo, Giuseppina Comito, Luigi Ippolito, Giada Sandrini, Elisa Pardella, Erica Pranzini, Mariaelena Capone, Gabriele Madonna, Paolo Antonio Ascierto, Paola Chiarugi, Elisa Giannoni","doi":"10.1111/febs.17423","DOIUrl":"https://doi.org/10.1111/febs.17423","url":null,"abstract":"Melanoma is more aggressive in male patients than female ones and this is associated with sexual dimorphism in immune responses. Taking into consideration the impact tumour metabolic alterations in affecting the immune landscape, we aimed to investigate the effect of the sex-dependent metabolic profile of melanoma in re-shaping immune composition. Melanoma is characterised by Warburg metabolism, and secreted lactate has emerged as a key driver in the establishment of an immunosuppressive environment. Here, we identified lactate dehydrogenase A (LDH-A) as a crucial player in modulating sex-related differences in melanoma immune responses, both in vitro and in patient-derived specimens. LDH-A is associated with higher lactate secretion in male melanoma cells, which leads to a significant enrichment in pro-tumoural regulatory T cells (Treg) with a concurrent decrease in the number and activity of anti-tumour CD8+ T cells. Remarkably, pharmacological and genetic impairment of LDH-A in male melanoma cells normalises Treg and CD8+ infiltration. In keeping with this, in vivo pharmacological targeting of LDH-A in melanoma-bearing male mice impairs tumour growth and lung colonisation, with a concomitant modulation of Treg and CD8+ T cells infiltration. Taken together, our findings highlight the sex-related differences promoted by LDH-A in immune reshaping in melanoma, and suggest that therapeutic targeting of LDH-A could be leveraged as an effective strategy to abolish the sex-gap in melanoma progression.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070591","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 cellular model of TDP-43 induces phosphorylated TDP-43 aggregation with distinct changes in solubility and autophagy dysregulation.

The FEBS journal Pub Date : 2025-01-31 DOI: 10.1111/febs.17413

Matthew B Dopler, Muhammad I Abeer, Sanaz Arezoumandan, Keyshawn Cox, Tyler L Petersen, Esther H Daniel, Carlton L Cannon, Angelica Bautista, Kennedy D Blancher, Alysia M Bland, Kylie J Bond, Dominque A Davis, Jessica M Francois, Eliana J McCray, Justin M Morgan, Jessica L Pulliam, Zymir A Robinson, Mykia J Taylor, James A Dowell, Nigel J Cairns, Michael A Gitcho

{"title":"A cellular model of TDP-43 induces phosphorylated TDP-43 aggregation with distinct changes in solubility and autophagy dysregulation.","authors":"Matthew B Dopler, Muhammad I Abeer, Sanaz Arezoumandan, Keyshawn Cox, Tyler L Petersen, Esther H Daniel, Carlton L Cannon, Angelica Bautista, Kennedy D Blancher, Alysia M Bland, Kylie J Bond, Dominque A Davis, Jessica M Francois, Eliana J McCray, Justin M Morgan, Jessica L Pulliam, Zymir A Robinson, Mykia J Taylor, James A Dowell, Nigel J Cairns, Michael A Gitcho","doi":"10.1111/febs.17413","DOIUrl":"10.1111/febs.17413","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that affects neurons in the brain and spinal cord, causing loss of muscle control, and eventually leads to death. Phosphorylated transactive response DNA binding protein-43 (TDP-43) is the major pathological protein in both sporadic and familial ALS, forming cytoplasmic aggregates in over 95% of cases. Of the 10-15% of ALS cases that are familial, mutations in TDP-43 represent about 5% of those with a family history. We have developed an in vitro overexpression model by introducing three familial ALS mutations (A315T, M337V, and S379P) in the TDP-43 (TARDBP) gene which we define as 3X-TDP-43. This overexpression model TDP-43 shows deficits in autophagy flux and colocalization of TDP-43 with stress granules. We also observe a progressive shift of TDP-43 to the cytoplasm in this model. This overexpression model shows a reduction in solubility of phosphorylated TDP-43 from RIPA to urea soluble. Four glycolytic enzymes, phosphoglycerate kinase one (PGK1), aldolase A (ALDOA), enolase 1 (ENO1), and pyruvate dehydrogenase kinase 1 (PDK1) show significant time-dependent decreases in 3X-TDP-43 expressing cells. Shotgun proteomic analysis shows global changes in the importin subunit alpha-1 (KPNA2), heat shock 70 kDa protein 1A (HSPA1A), and protein disulfide-isomerase A3 (PDIA3) expression levels and coimmunoprecipitation reveals that these proteins complex with TDP-43. Overall, these results suggest that the 3X-TDP-43 model may provide new insights into pathophysiology and an avenue for drug screening in vitro for those suffering from ALS and related TDP-43 proteinopathies.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070583","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

Words of advice for young scientists in developing countries.

The FEBS journal Pub Date : 2025-01-31 DOI: 10.1111/febs.17425

Max Chavarría

{"title":"Words of advice for young scientists in developing countries.","authors":"Max Chavarría","doi":"10.1111/febs.17425","DOIUrl":"https://doi.org/10.1111/febs.17425","url":null,"abstract":"As scientists, change is the only constant in our journey. We often find ourselves in transition from one laboratory to another, and during our training we are fortunate to experience the excitement of pursuing postgraduate studies abroad in well-funded, high-level research centers. However, after completing doctoral or postdoctoral training, we are frequently drawn to return to our home countries, where funding and support for science are significantly more limited. In this brief commentary, first, I would like to highlight the challenges faced by scientists from developing countries who have had the opportunity to train internationally and then choose to return home, driven both by personal motivations (e.g., family) and by the desire to contribute to the scientific advancement of their regions. Second, I would like to share some advice that has been especially useful to me in establishing my laboratory, defining research topics, and maintaining academic productivity. I hope these insights can be useful to colleagues in similar situations across different regions. Although starting a research group in regions with less investment in Research and Development is challenging, it is achievable with perseverance and the implementation of concrete actions.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069576","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

Structural insights into substrate transport and drug inhibition of the human vesicular monoamine transporter 2 (VMAT2).

The FEBS journal Pub Date : 2025-01-30 DOI: 10.1111/febs.70003

Di Wu, Yan Zhao, Daohua Jiang

{"title":"Structural insights into substrate transport and drug inhibition of the human vesicular monoamine transporter 2 (VMAT2).","authors":"Di Wu, Yan Zhao, Daohua Jiang","doi":"10.1111/febs.70003","DOIUrl":"https://doi.org/10.1111/febs.70003","url":null,"abstract":"Vesicular monoamine transporter 2 (VMAT2) is a proton-monoamine antiporter that is widely expressed in central and peripheral neurons and plays a crucial role in loading monoamine neurotransmitters into secretory vesicles. Dysfunction of VMAT2 causes many neuropsychiatric disorders, such as depression and Parkinson's disease. Consequently, VMAT2 is a valid and important therapeutic target. Reserpine alleviates symptoms of hypertension via potent inhibition of VMAT2. Tetrabenazine selectively inhibits VMAT2 and has been used for the management of chorea, including Huntington's disease. Decades of extensive studies have defined the substrate specificity and transport kinetics of VMAT2. However, the structure and precise mechanisms of monoamine recognition and drug inhibition in VMAT2 remain unknown. Recently, we determined an ensemble of high-resolution cryo-EM structures of human VMAT2 in three distinct states bound to multiple substrates and inhibitors. These results lay a structural foundation for a comprehensive understanding of substrate recognition and transport, drug inhibition, and proton coupling in VMAT2 and shed light on future therapeutic development.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070593","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

Versatile roles of disordered transcription factor effector domains in transcriptional regulation.

The FEBS journal Pub Date : 2025-01-30 DOI: 10.1111/febs.17424

Rhea R Datta, Dilan Akdogan, Elif B Tezcan, Pinar Onal

{"title":"Versatile roles of disordered transcription factor effector domains in transcriptional regulation.","authors":"Rhea R Datta, Dilan Akdogan, Elif B Tezcan, Pinar Onal","doi":"10.1111/febs.17424","DOIUrl":"https://doi.org/10.1111/febs.17424","url":null,"abstract":"Transcription, a crucial step in the regulation of gene expression, is tightly controlled and involves several essential processes, such as chromatin organization, recognition of the specific genomic sequences, DNA binding, and ultimately recruiting the transcriptional machinery to facilitate transcript synthesis. At the center of this regulation are transcription factors (TFs), which comprise at least one DNA-binding domain (DBD) and an effector domain (ED). Although the structure and function of DBDs have been well studied, our knowledge of the structure and function of effector domains is limited. EDs are of particular importance in generating distinct transcriptional responses between protein members of the same TF family that have similar DBDs and specificities. The study of transcriptional activity conferred by effector domains has traditionally been conducted through examining protein-protein interactions. However, recent research has uncovered alternative mechanisms by which EDs regulate gene expression, such as the formation of condensates that increase the local concentration of transcription factors, cofactors, and coregulated genes, as well as DNA binding. Here, we provide a comprehensive overview of the known roles of transcription factor EDs, with a specific focus on disordered regions. Additionally, we emphasize the significance of intrinsically disordered regions (IDRs) during transcriptional regulation. We examine the mechanisms underlying the establishment and maintenance of transcriptional specificity through the structural properties of predominantly disordered EDs. We then provide a comprehensive overview of the current understanding of these domains, including their physical and chemical characteristics, as well as their functional roles.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070596","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

Diel modulation of perireceptor activity influences olfactory sensitivity in diurnal and nocturnal mosquitoes.

The FEBS journal Pub Date : 2025-01-30 DOI: 10.1111/febs.17418

Tanwee Das De, Julien Pelletier, Satyajeet Gupta, Madhavinadha Prasad Kona, Om P Singh, Rajnikant Dixit, Rickard Ignell, Krishanpal Karmodiya

{"title":"Diel modulation of perireceptor activity influences olfactory sensitivity in diurnal and nocturnal mosquitoes.","authors":"Tanwee Das De, Julien Pelletier, Satyajeet Gupta, Madhavinadha Prasad Kona, Om P Singh, Rajnikant Dixit, Rickard Ignell, Krishanpal Karmodiya","doi":"10.1111/febs.17418","DOIUrl":"https://doi.org/10.1111/febs.17418","url":null,"abstract":"Olfaction and diel-circadian rhythm regulate different behaviors, including host-seeking, feeding, and locomotion, in mosquitoes that are important for their capacity to transmit disease. Diel-rhythmic changes of the odorant-binding proteins (OBPs) in olfactory organs are primarily accountable for olfactory rhythmicity. To better understand the molecular rhythm regulating nocturnal and diurnal behaviors in mosquitoes, we performed a comparative RNA-sequencing study of the peripheral olfactory and brain tissues of female Anopheles culicifacies and Aedes aegypti. Data analysis revealed a significant upregulation of genes encoding: OBPs and xenobiotic-metabolizing enzymes including Cytochrome P450 (CYP450) during photophase in Aedes aegypti and the dusk-transition phase in Anopheles culicifacies, hypothesizing their possible function in the regulation of perireceptor events and olfactory sensitivity. RNA interference studies and application of CYP450 inhibitors, coupled with electroantennographic recordings with Anopheles gambiae and Aedes aegypti, established that CYP450 plays a role in odorant detection and antennal sensitivity. Furthermore, brain tissue transcriptome and RNAi-mediated knockdown revealed that daily temporal modulation of neuronal serine proteases may have a crucial function in olfactory signal transmission, thereby affecting olfactory sensitivity. These findings provide a rationale to further explore the species-specific rhythmic expression pattern of the neuro-olfactory encoded molecular factors, which could pave the way to develop and implement successful mosquito control methods.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070586","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

Characterization of multiple binding sites on microtubule associated protein 2c recognized by dimeric and monomeric 14-3-3ζ.

The FEBS journal Pub Date : 2025-01-29 DOI: 10.1111/febs.17405

Séverine Jansen, Subhash Narasimhan, Paula Cabre Fernandez, Lucia Iľkovičová, Aneta Kozeleková, Kateřina Králová, Jozef Hritz, Lukáš Žídek

{"title":"Characterization of multiple binding sites on microtubule associated protein 2c recognized by dimeric and monomeric 14-3-3ζ.","authors":"Séverine Jansen, Subhash Narasimhan, Paula Cabre Fernandez, Lucia Iľkovičová, Aneta Kozeleková, Kateřina Králová, Jozef Hritz, Lukáš Žídek","doi":"10.1111/febs.17405","DOIUrl":"https://doi.org/10.1111/febs.17405","url":null,"abstract":"Microtubule associated protein 2 (MAP2) interacts with the regulatory protein 14-3-3ζ in a cAMP-dependent protein kinase (PKA) phosphorylation dependent manner. Using selective phosphorylation, calorimetry, nuclear magnetic resonance, chemical crosslinking, and X-ray crystallography, we characterized interactions of 14-3-3ζ with various binding regions of MAP2c. Although PKA phosphorylation increases the affinity of MAP2c for 14-3-3ζ in the proline rich region and C-terminal domain, unphosphorylated MAP2c also binds the dimeric 14-3-3ζ via its microtubule binding domain and variable central domain. Monomerization of 14-3-3ζ leads to the loss of affinity for the unphosphorylated residues. In neuroblastoma cell extract, MAP2c is heavily phosphorylated by PKA and the proline kinase ERK2. Although 14-3-3ζ dimer or monomer do not interact with the residues phosphorylated by ERK2, ERK2 phosphorylation of MAP2c in the C-terminal domain reduces the binding of MAP2c to both oligomeric variants of 14-3-3ζ.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061851","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