Developmental biology最新文献

{"title":"Enhanced expression of the myogenic factor Myocyte enhancer factor-2 in imaginal disc myoblasts activates a partial, but incomplete, muscle development program","authors":"Elizabeth M. Trujillo,&nbsp;Samuel R. Lee,&nbsp;Antonio Aguayo,&nbsp;Tylee C. Torosian,&nbsp;Richard M. Cripps","doi":"10.1016/j.ydbio.2024.08.004","DOIUrl":"10.1016/j.ydbio.2024.08.004","url":null,"abstract":"<div><p>The Myocyte enhancer factor-2 (MEF2) transcription factor plays a vital role in orchestrating muscle differentiation. While MEF2 cannot effectively induce myogenesis in naïve cells, it can potently accelerate myogenesis in mesodermal cells. This includes in <em>Drosophila melanogaster</em> imaginal disc myoblasts, where triggering premature muscle gene expression in these adult muscle progenitors has become a paradigm for understanding the regulation of the myogenic program. Here, we investigated the global consequences of MEF2 overexpression in the imaginal wing disc myoblasts, by combining RNA-sequencing with RT-qPCR and immunofluorescence. We observed the formation of sarcomere-like structures that contained both muscle and cytoplasmic myosin, and significant upregulation of muscle gene expression, especially genes essential for myofibril formation and function. These transcripts were functional since numerous myofibrillar proteins were detected in discs using immunofluorescence. Interestingly, muscle genes whose expression is restricted to the adult stages were not activated in these adult myoblasts. These studies confirm a broad activation of the myogenic program in response to MEF2 expression and suggest that additional regulatory factors are required for promoting the adult muscle-specific program. Our findings contribute to understanding the regulatory mechanisms governing muscle development and highlight the multifaceted role of MEF2 in orchestrating this intricate process.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"516 ","pages":"Pages 82-95"},"PeriodicalIF":2.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0012160624002094/pdfft?md5=345971f7a0bc88b5e0d79838bd425306&pid=1-s2.0-S0012160624002094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple method for gene expression in endo- and ectodermal cells in mouse embryos before neural tube closure","authors":"Yurie Maeda ,&nbsp;Jingwen Ding ,&nbsp;Mai Saeki ,&nbsp;Naohiro Kuwayama ,&nbsp;Yusuke Kishi","doi":"10.1016/j.ydbio.2024.08.001","DOIUrl":"10.1016/j.ydbio.2024.08.001","url":null,"abstract":"<div><p>The lack of a widely accessible method for expressing genes of interest in wild-type embryos is a fundamental obstacle to understanding genetic regulation during embryonic development. In particular, only a few methods are available for introducing gene expression vectors into cells prior to neural tube closure, which is a period of drastic development for many tissues. In this study, we present a simple technique for injecting vectors into the amniotic cavity and allowing them to reach the ectodermal cells and the epithelia of endodermal organs of mouse embryos at E8.0 via in utero injection, using only a widely used optical fiber with an illuminator. Using this technique, retroviruses can be introduced to facilitate the labeling of cells in various tissues, including the brain, spinal cord, epidermis, and digestive and respiratory organs. We also demonstrated in utero electroporation of plasmid DNA into E7.0 and E8.0 embryos. Taking advantage of this method, we reveal the association between Ldb1 and the activity of the Neurog2 transcription factor in the mouse neocortex. This technique can aid in analyzing the roles of genes of interest during endo- and ectodermal development prior to neural tube closure.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"516 ","pages":"Pages 114-121"},"PeriodicalIF":2.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0012160624002069/pdfft?md5=38b3222bb15994e6e8e130d55fc49e37&pid=1-s2.0-S0012160624002069-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An RNA interference approach for functional studies in the sea urchin and its use in analysis of nodal signaling gradients","authors":"Keen Wilson ,&nbsp;Carl Manner ,&nbsp;Esther Miranda ,&nbsp;Alejandro Berrio ,&nbsp;Gregory A. Wray ,&nbsp;David R. McClay","doi":"10.1016/j.ydbio.2024.08.002","DOIUrl":"10.1016/j.ydbio.2024.08.002","url":null,"abstract":"<div><p>Dicer substrate interfering RNAs (DsiRNAs) destroy targeted transcripts using the RNA-Induced Silencing Complex (RISC) through a process called RNA interference (RNAi). This process is ubiquitous among eukaryotes. Here we report the utility of DsiRNA in embryos of the sea urchin <em>Lytechinus variegatus (Lv).</em> Specific knockdowns phenocopy known morpholino and inhibitor knockdowns, and DsiRNA offers a useful alternative to morpholinos. Methods are described for the design of specific DsiRNAs that lead to destruction of targeted mRNA. DsiRNAs directed against <em>pks1</em>, an enzyme necessary for pigment production, show how successful DsiRNA perturbations are monitored by RNA <em>in situ</em> analysis and by qPCR to determine relative destruction of targeted mRNA. DsiRNA-based knockdowns phenocopy morpholino- and drug-based inhibition of <em>nodal</em> and <em>lefty</em>. Other knockdowns demonstrate that the RISC operates early in development as well as on genes that are first transcribed hours after gastrulation is completed. Thus, DsiRNAs effectively mediate destruction of targeted mRNA in the sea urchin embryo. The approach offers significant advantages over other widely used methods in the urchin in terms of cost, and ease of procurement, and offers sizeable experimental advantages in terms of ease of handling, injection, and knockdown validation.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"516 ","pages":"Pages 59-70"},"PeriodicalIF":2.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An essential role for Cmtr2 in mammalian embryonic development","authors":"Alena V. Yermalovich ,&nbsp;Zarin Mohsenin ,&nbsp;Mitzy Cowdin ,&nbsp;Bruno Giotti ,&nbsp;Akansha Gupta ,&nbsp;Alice Feng ,&nbsp;Lior Golomb ,&nbsp;Douglas B. Wheeler ,&nbsp;Kelly Xu ,&nbsp;Alexander Tsankov ,&nbsp;Ondine Cleaver ,&nbsp;Matthew Meyerson","doi":"10.1016/j.ydbio.2024.07.019","DOIUrl":"10.1016/j.ydbio.2024.07.019","url":null,"abstract":"<div><p>CMTR2 is an mRNA cap methyltransferase with poorly understood physiological functions. It catalyzes 2′-O-ribose methylation of the second transcribed nucleotide of mRNAs, potentially serving to mark RNAs as “self” to evade the cellular innate immune response. Here we analyze the consequences of Cmtr2 deficiency in mice. We discover that constitutive deletion of <em>Cmtr2</em> results in mouse embryos that die during mid-gestation, exhibiting defects in embryo size, placental malformation and yolk sac vascularization. Endothelial cell deletion of <em>Cmtr2</em> in mice results in vascular and hematopoietic defects, and perinatal lethality. Detailed characterization of the constitutive <em>Cmtr2</em> KO phenotype shows an activation of the p53 pathway and decreased proliferation, but no evidence of interferon pathway activation. In summary, our study reveals the essential roles of <em>Cmtr2</em> in mammalian cells beyond its immunoregulatory function.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"516 ","pages":"Pages 47-58"},"PeriodicalIF":2.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0012160624001994/pdfft?md5=11141a95d42586c54c497ef2b9711b26&pid=1-s2.0-S0012160624001994-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural changes shaping the Drosophila ellipsoid body ER-neurons during development and aging","authors":"Sandra Koch ,&nbsp;Pratyush Kandimalla ,&nbsp;Eddie Padilla ,&nbsp;Sabrina Kaur ,&nbsp;Rabina Kaur ,&nbsp;My Nguyen ,&nbsp;Annie Nelson ,&nbsp;Satkartar Khalsa ,&nbsp;Amelia Younossi-Hartenstein ,&nbsp;Volker Hartenstein","doi":"10.1016/j.ydbio.2024.07.018","DOIUrl":"10.1016/j.ydbio.2024.07.018","url":null,"abstract":"<div><p>The ellipsoid body (EB) of the insect brain performs pivotal functions in controlling navigation. Input and output of the EB is provided by multiple classes of R-neurons (now referred to as ER-neurons) and columnar neurons which interact with each other in a stereotypical and spatially highly ordered manner. The developmental mechanisms that control the connectivity and topography of EB neurons are largely unknown. One indispensable prerequisite to unravel these mechanisms is to document in detail the sequence of events that shape EB neurons during their development. In this study, we analyzed the development of the <em>Drosophila</em> EB. In addition to globally following the ER-neuron and columnar neuron (sub)classes in the spatial context of their changing environment we performed a single cell analysis using the multi-color flip out (MCFO) system to analyze the developmental trajectory of ER-neurons at different pupal stages, young adults (4d) and aged adults (∼60d). We show that the EB develops as a merger of two distinct elements, a posterior and anterior EB primordium (prEBp and prEBa, respectively. ER-neurons belonging to different subclasses form growth cones and filopodia that associate with the prEBp and prEBa in a pattern that, from early pupal stages onward, foreshadows their mature structure. Filopodia of all ER-subclasses are initially much longer than the dendritic and terminal axonal branches they give rise to, and are pruned back during late pupal stages. Interestingly, extraneous branches, particularly significant in the dendritic domain, are a hallmark of ER-neuron structure in aged brains. Aging is also associated with a decline in synaptic connectivity from columnar neurons, as well as upregulation of presynaptic protein (Brp) in ER-neurons. Our findings advance the EB (and ER-neurons) as a favorable system to visualize and quantify the development and age-related decline of a complex neuronal circuitry.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"516 ","pages":"Pages 96-113"},"PeriodicalIF":2.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mosaic Atoh1 deletion in the chick auditory epithelium reveals a homeostatic mechanism to restore hair cell number","authors":"Nishant Singh ,&nbsp;Raman Kaushik ,&nbsp;Anubhav Prakash ,&nbsp;Surjit Singh Saini ,&nbsp;Sonal Garg ,&nbsp;Adrija Adhikary ,&nbsp;Raj K. Ladher","doi":"10.1016/j.ydbio.2024.07.017","DOIUrl":"10.1016/j.ydbio.2024.07.017","url":null,"abstract":"<div><p>The mechanosensory hair cell of the vertebrate inner ear responds to the mechanical deflections that result from hearing or change in the acceleration due to gravity, to allow us to perceive and interpret sounds, maintain balance and spatial orientation. In mammals, ototoxic compounds, disease, and acoustic trauma can result in damage and extrusion of hair cells, without replacement, resulting in hearing loss. In contrast, non-mammalian vertebrates can regenerate sensory hair cells. Upon damage, hair cells are extruded and an associated cell type, the supporting cell is transformed into a hair cell. The mechanisms that can trigger regeneration are not known. Using mosaic deletion of the hair cell master gene, Atoh1, in the embryonic avian inner ear, we find that despite hair cells depletion at E9, by E12, hair cell number is restored in sensory epithelium. Our study suggests a homeostatic mechanism can restores hair cell number in the basilar papilla, that is activated when juxtracrine signalling is disrupted. Restoration of hair cell numbers during development may mirror regenerative processes, and our work provides insights into the mechanisms that trigger regeneration.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"516 ","pages":"Pages 35-46"},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Squamates as a model to understand key dental features of vertebrates","authors":"Daria Razmadze,&nbsp;Lotta Salomies,&nbsp;Nicolas Di-Poï","doi":"10.1016/j.ydbio.2024.07.011","DOIUrl":"10.1016/j.ydbio.2024.07.011","url":null,"abstract":"<div><p>Thanks to their exceptional diversity, teeth are among the most distinctive features of vertebrates. Parameters such as tooth size, shape, number, identity, and implantation can have substantial implications for the ecology and certain social behaviors of toothed species. Despite decades of research primarily focused on mammalian dentition, particularly using the laboratory mouse model, squamate reptiles (“lizards” and snakes) offer a wide array of tooth types and dentition variations. This diversity, which includes differences in size, shape, function, and replacement capacity, provides invaluable opportunities for investigating these fundamental properties. The central bearded dragon (<em>Pogona vitticeps</em>), a popular pet species with well-established husbandry practices, is of particular interest. It features a broad spectrum of morphs and spontaneous mutants and exhibits a wide range of heterodont phenotypes, including variation in the size, shape, number, implantation, and renewal of teeth at both posterior and anterior positions. These characteristics position the species as a crucial model organism for developmental studies in tooth research and for gaining deeper insights into evolutionary patterns of vertebrate dentitions. In this article, we provide an overview of the current understanding of squamate dentition, its diversity, development, and replacement. Furthermore, we discuss the significant advantages offered by squamate species as model organisms for investigating the evolutionary and developmental aspects of vertebrate dentition.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"516 ","pages":"Pages 1-19"},"PeriodicalIF":2.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S001216062400191X/pdfft?md5=eb854793f141fc998d49b71f2fa28996&pid=1-s2.0-S001216062400191X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sall4 regulates downstream patterning genes during limb regeneration","authors":"J.R. Erickson ,&nbsp;S.E. Walker ,&nbsp;C.M. Arenas Gomez ,&nbsp;K. Echeverri","doi":"10.1016/j.ydbio.2024.07.015","DOIUrl":"10.1016/j.ydbio.2024.07.015","url":null,"abstract":"<div><p>Many salamanders can completely regenerate a fully functional limb. Limb regeneration is a carefully coordinated process involving several defined stages. One key event during the regeneration process is the patterning of the blastema to inform cells of what they must differentiate into. Although it is known that many genes involved in the initial development of the limb are re-used during regeneration, the exact molecular circuitry involved in this process is not fully understood. Several large-scale transcriptional profiling studies of axolotl limb regeneration have identified many transcription factors that are up-regulated after limb amputation. <em>Sall4</em> is a transcription factor that has been identified to play essential roles in maintaining cells in an undifferentiated state during development and also plays a unique role in limb development. Inactivation of <em>Sall4</em> during limb bud development results in defects in anterior-posterior patterning of the limb. <em>Sall4</em> has been found to be up-regulated during limb regeneration in both <em>Xenopus</em> and salamanders, but to date it function has been untested. We confirmed that <em>Sall4</em> is up-regulated during limb regeneration in the axolotl using qRT-PCR and identified that it is present in the skin cells and also in cells within the blastema. Using CRISPR technology we microinjected gRNAs specific for <em>Sall4</em> complexed with cas9 protein into the blastema to specifically knockout <em>Sall4</em> in blastema cells only. This resulted in limb regenerate defects, including missing digits, fusion of digit elements, and defects in the radius and ulna<strong>.</strong> This suggests that during regeneration <em>Sall4</em> may play a similar role in regulating the specification of anterior-proximal skeletal elements.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"515 ","pages":"Pages 151-159"},"PeriodicalIF":2.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0012160624001957/pdfft?md5=76aaf6372fcfd36912e273ea74dead98&pid=1-s2.0-S0012160624001957-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic circuitry controlling Drosophila female germline overgrowth","authors":"Qian Zhang,&nbsp;Le Li,&nbsp;Qi Zhang,&nbsp;Yang Zhang,&nbsp;Lizhong Yan,&nbsp;Yanfang Wang,&nbsp;Yuejia Wang,&nbsp;Shaowei Zhao","doi":"10.1016/j.ydbio.2024.07.016","DOIUrl":"10.1016/j.ydbio.2024.07.016","url":null,"abstract":"<div><p>Germ cells mutant for <em>bam</em> or <em>bgcn</em> are locked in a germline stem cell (GSC)-like state, leading to tumor-like overgrowth in <em>Drosophila</em> ovaries. Our previous studies have demonstrated that germline overgrowth in <em>bam</em> mutants can be suppressed by defects in the miRNA pathway but enhanced by a null mutation in <em>hippo</em>. However, the genetic epistasis between the miRNA and Hippo pathways still remains unknown. Here, we determined that the miRNA pathway acts downstream of the Hippo pathway in regulating this process. Germ cells mutant for <em>bam</em> or <em>bgcn</em> and defective in both pathways divide very slowly, phenocopying those defective only in the miRNA pathway. In addition, we found that Yki, a key oncoprotein in the Hippo pathway, promotes the growth of both wild-type germ cells and <em>bam</em> mutant GSC-like cells. Like wild-type GSCs, <em>bam</em> mutant GSC-like cells predominantly stay in the G2 phase. Remarkably, many of those defective in the miRNA pathway are arrested before entering this phase. Furthermore, our studies identified <em>bantam</em> as a critical miRNA promoting germline overgrowth in <em>bam</em> or <em>bgcn</em> mutants. Taken together, these findings establish a genetic circuitry controlling <em>Drosophila</em> female germline overgrowth.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"515 ","pages":"Pages 160-168"},"PeriodicalIF":2.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic duo: Cell–extracellular matrix interactions in hair follicle development and regeneration","authors":"Hironobu Fujiwara","doi":"10.1016/j.ydbio.2024.07.012","DOIUrl":"10.1016/j.ydbio.2024.07.012","url":null,"abstract":"<div><p>Ectodermal organs, such as hair follicles, originate from simple epithelial and mesenchymal sheets through a complex developmental process driven by interactions between these cell types. This process involves dermal condensation, placode formation, bud morphogenesis, and organogenesis, and all of these processes require intricate interactions among various tissues. Recent research has emphasized the crucial role of reciprocal and dynamic interactions between cells and the extracellular matrix (ECM), referred to as the “dynamic duo”, in the development of ectodermal organs. These interactions provide spatially and temporally changing biophysical and biochemical cues within tissues. Using the hair follicle as an example, this review highlights two types of cell–ECM adhesion units—focal adhesion-type and hemidesmosome-type adhesion units—that facilitate communication between epithelial and mesenchymal cells. This review further explores how these adhesion units, along with other cell–ECM interactions, evolve during hair follicle development and regeneration, underscoring their importance in guiding both developmental and regenerative processes.</p></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"516 ","pages":"Pages 20-34"},"PeriodicalIF":2.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0012160624001921/pdfft?md5=7bf44563a24cae4510ff9c3ebd710c86&pid=1-s2.0-S0012160624001921-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}