Developmental biology最新文献

{"title":"A zebrafish model of nicotinamide adenine dinucleotide (NAD⁺) deficiency-derived congenital disorders.","authors":"Visakuo Tsurho, Carla Gilliland, Jessica Ensing, Elizabeth A VanSickle, Nathan J Lanning, Paul R Mark, Stephanie Grainger","doi":"10.1016/j.ydbio.2025.09.022","DOIUrl":"10.1016/j.ydbio.2025.09.022","url":null,"abstract":"<p><p>Developmental NAD⁺ deficiency is associated with diverse congenital malformations. Congenital NAD deficiency disorder (CNDD) is a multisystem developmental condition characterized by cardiac, renal, vertebral, and limb anomalies, among others. It is caused by biallelic pathogenic variants in genes involved in the nicotinamide adenine dinucleotide (NAD⁺) synthesis pathway. CNDD anomalies overlap with clinical features described in vertebral-anal-cardiac-tracheoesophageal fistula-renal-limb (VACTERL) association, suggesting a possible shared etiological link through NAD⁺ deficiency. However, the aberrant developmental mechanisms of NAD⁺-deficient congenital anomalies remain poorly understood. To dynamically explore NAD⁺-deficiency-induced congenital malformations, we developed a zebrafish model of NAD⁺ disruption. Zebrafish embryos treated with 2-amino-1,3,4-thiadiazole (ATDA), a known NAD⁺ metabolism disruptor, exhibited cardiac, tail, spinal cord, and craniofacial defects, which were partially rescued by nicotinamide (NAM) in a dose-dependent manner. Our work establishes zebrafish as a useful model for investigating how NAD⁺ deficiency contributes to multisystem congenital anomalies.</p>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211808","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":"Ovary organization and oogenesis in two species of cave-living clitellate annelids from the genus Delaya (Clitellata, Pelodrilidae)","authors":"Piotr Świątek,&nbsp;Łukasz Gajda,&nbsp;Anna Z. Urbisz","doi":"10.1016/j.ydbio.2025.09.021","DOIUrl":"10.1016/j.ydbio.2025.09.021","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Clitellate annelids (Clitellata) are hermaphrodites with gonads localized in specific segments in the anterior body part. Localization of gonads and the structure of the reproductive systems are considered conservative traits of clitellate evolution and are used as crucial features in their taxonomy and in phylogenetic considerations. The study aimed to present the ovary morphology, histology, and ultrastructure in two &lt;em&gt;Delaya&lt;/em&gt; species. The genus &lt;em&gt;Delaya&lt;/em&gt; groups poorly known cave-living clitellate annelids, and their ovary organization and oogenesis are entirely unknown. Moreover, their taxonomic status is under debate. According to recent molecular analyses, &lt;em&gt;Delaya&lt;/em&gt; and two other genera form the family Pelodrilidae, closely related to earthworms. To enhance our understanding of these cave-living animals' reproductive biology and provide new characters that may aid in phylogenetic considerations, the light and electron microscopic techniques were used to study the organization of the ovaries and the course of oogenesis in two species: one from a cave in Greece (&lt;em&gt;Delaya&lt;/em&gt; sp. GR) and the other from a cave in France (&lt;em&gt;Delaya&lt;/em&gt; sp. FR). In both species studied, two pairs of ovaries are located in two consecutive segments – XII and XIII. Each ovary consists of 3–5 functional units. The ovarian units are polarized: their apical parts (attached to the septum) contain oogonia and early meiotic cells, while the broader distal ends contain growing oocytes and nurse cells. Initially, Germline cyst formation in cells (oogonia and early meiotic cells) develop synchronously, forming syncytial cysts in which each cell is connected via a single ring canal to the central cytoplasm (cytophore). Then, during meiotic prophase (in diplotene), synchrony is lost, and it is likely that one cell per cyst begins accumulating nutrients and differentiating into an oocyte. As oocytes detach from the cyst and continue oogenesis as individual cells, the remaining cells stay interconnected, do not grow, and are regarded as nurse cells. Yolk absorption is not completed in the ovary; vitellogenic oocytes are transferred to the ovisacs, where they continue to accumulate nutrients. Ovisacs are paired, long, sac-like structures, extending through several body segments (XII-XV). &lt;em&gt;Delaya&lt;/em&gt; produces mesolecithic eggs with prominent yolk spheres, lipid droplets, and glycogen granules. Only some minor differences were observed between the two studied species. The most notable difference concerns the cytophore shape and volume in cysts connecting nurse cells. In &lt;em&gt;Delaya&lt;/em&gt; sp. FR, the cytophore is reticular and inconspicuous, whereas in &lt;em&gt;Delaya&lt;/em&gt; sp. GR, the cytophore is more prominent and may contain nurse cell nuclei.&lt;/div&gt;&lt;div&gt;The obtained results confirm that the formation of the germline cysts equipped with the cytophore is a conservative phase of oogenesis in clitellates. Morphological observations suggest that in &lt;em&gt;Del","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 13-34"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205886","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":"The challenge of teaching K-12 genetic principles: A new approach emphasizing polygenic traits, gene-environment interactions, and genetic non-essentialism to improve genetics literacy and reduce racial stereotyping","authors":"Jamie R. Shuda ,&nbsp;Valerie G. Butler ,&nbsp;Robert Vary ,&nbsp;Darby W. Sweeney ,&nbsp;Fernando L. Wagner ,&nbsp;Steven A. Farber","doi":"10.1016/j.ydbio.2025.09.020","DOIUrl":"10.1016/j.ydbio.2025.09.020","url":null,"abstract":"<div><div>BioEYES is a K-12 life science outreach program that uses zebrafish to teach Mendelian genetics through hands-on activities. The program has operated for 20+ years, promoting academic equity and fostering scientific literacy for all students. While middle school participants show knowledge gains and improved attitudes about science, ∼50% struggle to master foundational genetic concepts. To address this, the authors compared virtual vs. in-person programming, finding minimal differences in learning outcomes but higher gains on simpler survey questions. Rigorous assessments, however, reveal that many students retain only a basic understanding of genetics. Teaching single-gene inheritance, moreover, may reinforce racial stereotypes through \"biological essentialism.\" To counter this, BioEYES staff will be piloting approaches that focus on human polygenic traits, such as skin color, that is taught alongside a hands-on experiment with a zebrafish pigment mutant. Future efforts emphasize developing curriculum around polygenic traits, gene-environment interactions, and challenging stereotypes about race, which research suggests could improve genetics comprehension while reducing racial stereotyping. We invite community feedback in these efforts to enhance K-12 genetics education strategies.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 35-45"},"PeriodicalIF":2.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184787","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":"Secreted frizzled-related protein 1a regulates hematopoietic development in a dose-dependent manner","authors":"Amber D. Ide,&nbsp;Kelsey A. Carpenter,&nbsp;Mohamed T. Elaswad,&nbsp;Katherine Opria,&nbsp;Kendersley Marcellin,&nbsp;Carla Gilliland,&nbsp;Stephanie Grainger","doi":"10.1016/j.ydbio.2025.09.019","DOIUrl":"10.1016/j.ydbio.2025.09.019","url":null,"abstract":"<div><div>Hematopoietic stem and progenitor cells (HSPCs) are only generated during embryonic development, and their identity specification, emergence from the floor of the dorsal aorta, and proliferation are all tightly regulated by molecular mechanisms such as signaling cues. Among these, Wnt signaling is crucial for HSPC specification, differentiation, and self-renewal, requiring precise regulation for proper development and homeostasis. Wnt signaling begins when a Wnt ligand binds to cell surface receptors, such as those encoded by the <em>frizzled</em> gene family, activating intracellular pathways that regulate gene expression. Secreted frizzled-related proteins (Sfrps) are known to modulate Wnt signaling, acting as both agonists and antagonists. However, the <em>in vivo</em> roles of Sfrps in HSPC development are not fully understood. Here, we show that Sfrp1a influences zebrafish HSPC development and hematopoietic differentiation in a dose-dependent manner. Sfrp1a loss-of-function animals display an upregulation of canonical Wnt signaling, increased HSPC proliferation, and reduced differentiation into lymphoid and myeloid lineages. Conversely, low-dose overexpression of <em>sfrp1a</em> leads to decreased HSPC numbers and enhanced lymphoid differentiation. High-dose <em>sfrp1a</em> overexpression mimics the loss-of-function phenotype, with elevated canonical Wnt signaling, increased HSPCs, and decreased lymphoid and myeloid differentiation. These results emphasize the importance of dose-dependent Sfrp regulation, paralleling observations in hematopoietic cancers where SFRP1 variants can either promote or inhibit tumor development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 1-12"},"PeriodicalIF":2.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184991","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":"VEGF and its receptors expression in relation to reduced vasculature phenotype in heme oxygenase 1 knockout mouse embryos","authors":"Meenakshi Rana ,&nbsp;Gouri Nandi ,&nbsp;Sidhant Jain ,&nbsp;Divya Bajaj","doi":"10.1016/j.ydbio.2025.09.018","DOIUrl":"10.1016/j.ydbio.2025.09.018","url":null,"abstract":"<div><div>Vascular development is a pivotal aspect of embryogenesis, and its disruption can lead to developmental abnormalities or lethality. Although numerous studies have demonstrated a significant association between heme oxygenase 1 (Hmox1) and vascular biology, this link has not been reported so far during mouse embryonic development. Hmox1 is the rate-limiting enzyme that catalyzes the breakdown of heme to equimolar amounts of biliverdin, carbon monoxide, and ferrous iron. Here, we report that embryos lacking Hmox1 exhibit significant reductions in superficial blood vessel formation during mid-gestation, accompanied by organ-specific disruptions in vascular patterning. A comparative analysis of VEGF, VEGFR2, and CD31 revealed tissue-specific disruptions in angiogenic signaling and endothelial integrity in the brain, heart, and lungs of Hmox1-deficient embryos. The localization and abundance of these molecules were altered in affected organs, with isoform- and receptor subtype–specific expression changes raising the possibility of an impact on the structural integrity of developing vascular networks. These findings suggest that the absence of Hmox1 disrupts essential regulatory mechanisms required for angiogenesis, potentially contributing to the partial prenatal lethality observed in knockout embryos. Our results point to a previously unrecognized role for Hmox1 in regulating organ-specific vascular development during late gestation, with its deficiency leading to tissue-specific disruptions in angiogenesis and impaired blood vessel formation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 264-276"},"PeriodicalIF":2.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181844","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":"The patterning and proliferation roles of Shh are partitioned on distinct exosomes","authors":"Ankita Walvekar ,&nbsp;Shivangi Pandey ,&nbsp;Siddhesh S. Kamat ,&nbsp;Raj K. Ladher ,&nbsp;Neha Vyas","doi":"10.1016/j.ydbio.2025.09.017","DOIUrl":"10.1016/j.ydbio.2025.09.017","url":null,"abstract":"<div><div>Sonic hedgehog (Shh) is a pivotal morphogen in spinal cord development, orchestrating both ventral neural patterning and progenitor proliferation. How these distinct outcomes are specified has remained elusive. Here, we uncover that Shh is secreted via two biochemically and functionally distinct exosomal pools. A dense vesicle fraction, Shh-P150, drives Smoothened–Gli1 signalling to establish ventral progenitor identities, while a lighter pool, Shh-P450, activates a Smoothened–Gαi–dependent pathway that enhances progenitor proliferation without inducing ventral fate. We identify Rab7, a late endosomal regulator, as essential for Shh-P150 biogenesis and for notochord-mediated ventral neural patterning. Loss of Rab7 biases secretion toward the proliferative Shh-P450 pool and disrupts morphogenetic signalling. These findings establish exosomal packaging as a molecular switch that toggles Shh between its mitogenic and morphogenetic roles. By linking exosome biogenesis to developmental outcomes, our work reveals a novel mechanism that safeguards the balance between pattern formation and progenitor expansion during neural tube development, with implications for both developmental disorders and disease contexts where Shh signalling is misregulated.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 239-254"},"PeriodicalIF":2.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155730","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":"Corrigendum to “A low-cost, high-throughput pipeline for 3D imaging of embryonic mouse hearts using lightsheet microscopy” [Develop. Biol. 527 (2025) 26–38]","authors":"Xiangyang Liu ,&nbsp;Jianfeng Wang ,&nbsp;Youshi Chen ,&nbsp;Hongjun Shi","doi":"10.1016/j.ydbio.2025.09.015","DOIUrl":"10.1016/j.ydbio.2025.09.015","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Page 216"},"PeriodicalIF":2.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118840","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":"WNT4 deficiency impacts heart, diaphragm, and palate development: Insights from human genetics, machine learning, and mouse models","authors":"Andrés Hernández-García ,&nbsp;Bum Jun Kim ,&nbsp;David Chitayat ,&nbsp;Patrick Shannon ,&nbsp;Stephanie Hedges ,&nbsp;Maria Al Bandari ,&nbsp;Maria J. Guillen Sacoto ,&nbsp;Emily Anne Bates ,&nbsp;Yunus H. Ozekin ,&nbsp;Victor Faundes ,&nbsp;Pamela N. Luna ,&nbsp;Chad A. Shaw ,&nbsp;Tara L. Rasmussen ,&nbsp;Chih-Wei Hsu ,&nbsp;Daryl A. Scott","doi":"10.1016/j.ydbio.2025.09.016","DOIUrl":"10.1016/j.ydbio.2025.09.016","url":null,"abstract":"<div><div>WNT4 is a secreted protein that plays a critical role in the regulation of cell fate and embryogenesis. Biallelic variants in <em>WNT4</em> have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses. Additional features seen in a subset of affected fetuses included ventricular septal defect (VSD), congenital diaphragmatic hernia (CDH), and orofacial clefting (OFC). To determine if these additional features were likely to be caused by WNT4 deficiency, we used machine learning to compare <em>WNT4</em> to genes known to cause VSD, CDH, and OFC. When compared to all RefSeq genes, WNT4's rank annotation scores for these congenital anomalies were 94%, 99%, and 98.5%, respectively, indicating a high level of similarity. We subsequently identified a second consanguineous family with SERKAL syndrome in which an affected fetus had CDH and an affected child had OFC. We then demonstrated that a subset of <em>Wnt4</em> null embryos have perimembranous VSDs, anterior and posterior sac CDH, and soft palate clefts. These findings suggest that WNT4 deficiency can cause VSD, CDH, and palatal anomalies in mice and humans with SERKAL syndrome. These studies also suggest that our machine learning approach can be used as a candidate gene prioritization tool, and that targeted mouse phenotyping can serve as a means of confirming the roles of candidate genes in mammalian development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 66-80"},"PeriodicalIF":2.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136991","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":"Primitive means first, not worst: Critical roles for primitive endoderm in embryos and embryo models","authors":"Marcelio A. Shammami ,&nbsp;Alyssa Virola-Iarussi ,&nbsp;Ian McCrary ,&nbsp;Amy Ralston","doi":"10.1016/j.ydbio.2025.09.008","DOIUrl":"10.1016/j.ydbio.2025.09.008","url":null,"abstract":"<div><div>In mammals, extraembryonic tissues, such as the placenta and yolk sac, are the first cell types to be specified during development because they enable the embryo to take residence and thrive in the uterine environment. Among extraembryonic tissue types, primitive endoderm (PrE), which will eventually contribute to the yolk sac, is especially fascinating. The PrE itself is named for functioning like the embryo's original gut-like tissue. For many years, our understanding of the PrE was limited by the intrinsically challenging nature of accessing and observing this tissue. However, pioneering studies in mouse have gradually revealed that the PrE is more than just nutritive in function. In fact, the PrE lineage gives rise to signaling centers that oversee developmental processes within the fetus – through processes that are very likely conserved between rodents and primates. Thus, understanding the stages between PrE and yolk sac promises clinically relevant models, including stem cell embryo models, which could lead to enhanced success for <em>in vitro</em> fertilization (IVF). Here, we examine the functions of PrE in the context of embryos, stem cells, and embryo models.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 255-263"},"PeriodicalIF":2.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124393","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":"A Transcriptomic Atlas of Adult Tissues of the Sea Urchin Lytechinus variegatus Identifies Early Transitions in Gonadogenesis.","authors":"Cosmo Pieplow, Madison Silvia, Allex Gourley, Andrew Rhyne, Nathalie Oulhen, Gary Wessel","doi":"10.1016/j.ydbio.2025.09.013","DOIUrl":"https://doi.org/10.1016/j.ydbio.2025.09.013","url":null,"abstract":"<p><p>Sea urchins have been a well-used model of fertilization and of the molecular biology of embryonic development. Our understanding of the molecular identity of adult tissues, on the other hand, has lagged significantly, a deficiency all too apparent following recent successes in mutational analyses in transgenerational studies. Here we present molecular analyses of gonadogenesis, with particular reference to developmental features emerging when a juvenile first begins to make eggs and sperm. We observed great variation in developmental time to reach fertility in Lytechinus variegatus, with the earliest gamete-producing adult at 4.5 months post-fertilization. Instead of age, or just size, we find the mass to test size ratio of 120 mg/mm test diameter is far more predictive of sexual maturity. Body size is also correlated with external developmental metrics of secondary spine formation, and opening of the gonadopores. In young juveniles, we identify an internal sac-like structure that by both morphological and transcriptomic analysis appears to be an indeterminant gonad that transitions into an ovary or testis. We follow this development into adulthood and compare the transcriptomes of these developing sacs and gonads to transcriptomes of all 16 major tissues of the adult. This result reveals a broad definition of the tissue types in a sea urchin, and displays genes that are differentially enriched, and/or specifically expressed by each tissue. Ovaries of developing juveniles and of adults show the greatest number of differentially expressed genes compared to all other tissues. These datasets serve as a guide for gene selection in traditional CRISPR/Cas9 mutagenesis, for design of integrated transposase reporters, and for parsing out unique functions in tissues that in combination give this animal its unique attributes.</p>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102526","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}