Developmental Dynamics最新文献

{"title":"Modest alterations in Drosophila denticle morphology reveal genetic interactions between actin disassembly proteins and ck/Myosin VIIA.","authors":"Adeline Boettcher, Hannah Jones, Mary Leskovec, Helen Majer, Brooke Allen, Jennifer Sallee","doi":"10.1002/dvdy.70089","DOIUrl":"https://doi.org/10.1002/dvdy.70089","url":null,"abstract":"<p><strong>Background: </strong>Building and disassembling actin filaments is essential for the remodeling of the actin cytoskeleton. In large structures, like Drosophila bristles, the loss of function of actin disassembly proteins can lead to smaller and misshapen bundled actin. Here we investigate whether mutant alleles of the disassembly genes twinstar (tsr), flare (flr), and twinfilin (twf) show similar phenotypes in smaller embryonic actin-based denticles. We also examined potential genetic interactions between F-actin disassembly proteins and the molecular motor ck/myosin VIIA, a protein necessary for denticle formation.</p><p><strong>Results: </strong>Cuticle preparations of late-stage embryos were examined for denticle hook orientation, height, and width. There were mild morphological phenotypes such as loss of hook polarity across the genes. Single mutants for the disassembly genes showed that loss of tsr caused denticles to be longer, loss of twf resulted in shorter denticles, and mutant flr alleles showed varied effects. Double mutants of tsr and twf showed a genetic interaction in widths of denticles while ck was epistatic to twf and flr for width.</p><p><strong>Conclusion: </strong>These results demonstrate that actin disassembly proteins and ck/myosin VIIA are involved in denticle formation, and the lack of wild type gene function in tsr, twf, flr, and ck causes measurable defects in denticle morphology.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279311","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":"Expression of mutant TIE2 p.L914F during mouse development causes embryonic lethality and defects in vascular remodeling.","authors":"Lindsay J Bischoff, Sandra Schrenk, Kara Soroko, Chhiring Sherpa, Ashok Arasu, Damien Reynaud, Elisa Boscolo","doi":"10.1002/dvdy.70087","DOIUrl":"https://doi.org/10.1002/dvdy.70087","url":null,"abstract":"<p><strong>Background: </strong>Sporadic venous malformation (VM) is associated with the hyperactivating p.L914F mutation in TIE2, a receptor tyrosine kinase essential for vascular development. This mutation is not found in hereditary VM, suggesting incompatibility with life when expressed during early vascular development. Therefore, we utilized a genetic mouse model that expresses TIE2 p.L914F to determine its phenotypical effects during development.</p><p><strong>Results: </strong>B6-Tg(Rosa26-TIE2^L914F)^EBos (TIE2^L914F) mice were generated and then validated for the presence of the transgene. The constitutive endothelial-specific Tie2-Cre line was used to activate expression of the mutant gene during early embryonic development. Tie2-Cre;TIE2^L914F embryos experienced lethality at approximately embryonic day (E)9.5. Three-dimensional imaging of embryos and yolk sacs revealed impaired vascular remodeling in mutant animals, resulting in malformed vasculature with disorganized, dilated, and non-functional blood vessels. The abnormal yolk sac vascular phenotype was not associated with total loss of erythroid cells or increased cell proliferation.</p><p><strong>Conclusions: </strong>The TIE2^L914F mice used in this study represent a novel genetic model of TIE2 p.L914F-driven vascular disease. This study provides the first experimental evidence that this mutation is incompatible with early prenatal development due to its deleterious effects on the vasculature, illustrating the vital role of balanced TIE2 signaling during vessel development and remodeling.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274189","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":"Cryopreservation of sea urchin (Lytechinus pictus) embryos and development through metamorphosis.","authors":"Victor D Vacquier, Amro Hamdoun","doi":"10.1002/dvdy.70081","DOIUrl":"https://doi.org/10.1002/dvdy.70081","url":null,"abstract":"<p><strong>Background: </strong>Sea urchins have contributed to knowledge of fertilization, embryonic development, and cell physiology for 150 years. Their evolutionary position, as basal deuterostomes, and their long background in developmental biology motivate establishing a genetically enabled sea urchin species. Because of its relatively short generation time of 4-6 months and ease of culture, our lab has focused on the California sea urchin Lytechinus pictus as a multigenerational model and produced knockout and transgenic lines using this species. To ensure that diverse genetic lines can be preserved, methods must be developed to cryopreserve gametes and embryos. We have previously reported methods for cryopreservation of sperm, but robust methods to preserve embryos remain lacking.</p><p><strong>Results: </strong>Here, we describe a relatively simple method to cryopreserve late gastrulae embryos of L. pictus. Importantly, we show that, after thawing and culturing, the embryos progress through larval development, undergo metamorphosis, and yield juvenile adults, indicating the method is robust.</p><p><strong>Conclusion: </strong>The cryopreservation of embryos is an important advance that will facilitate the biobanking, sharing, and long-term preservation of diverse genetic lines. This method may also eventually prove useful for cryopreservation of embryos of other marine invertebrates.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274136","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":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.70084","DOIUrl":"https://doi.org/10.1002/dvdy.70084","url":null,"abstract":"&lt;p&gt;Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in &lt;i&gt;Developmental Dynamics&lt;/i&gt; that illustrate the complex dynamics of developmental biology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Placental Influences on Craniofacial and Brain Development&lt;/b&gt;. “A head start: The relationship of placental factors to craniofacial and brain development” by Annemarie Carver, Martine Dunnwald, and Hanna Stevens.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The placenta produces and helps deliver hormones, nutrients, and oxygen to offspring in utero. Its impact on neurodevelopment and neurodevelopmental disorders, known as neuroplacentology, is an emerging field of growing scientific and research interest. Neurodevelopment is also highly coordinated with craniofacial development, as is the co-occurrence of neurodevelopmental disorders and craniofacial disorders, which has led to the adage, “the face predicts the brain, and the brain predicts the face.” This review discusses the role of placental hormone production and nutrient delivery during the development of the fetal head with a particular emphasis on hormones such as IGF1, GH, and PRL, nutrients such as calcium, sulfate, and vitamin D, and their respective signaling pathways. Further investigation into placental-specific mechanisms influencing the development of the fetal head offers the potential to better understand and possibly even prevent many common childhood health problems.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Morphogenesis of the Neural Tube&lt;/b&gt;. “An analysis of contractile and protrusive cell behaviors at the superficial surface of the zebrafish neural plate” by Claudio Araya, Raegan Boekemeyer, Francesca Farlie, Lauren Moon, Freshta Darwish, Chris Rookyard, Leanne Allison, Gema Vizcay-Barrena, Roland Fleck, Millaray Aranda, Masa Tada, and Jonathan Clarke.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The neural tube is the embryonic precursor of the brain and spinal cord. It emerges from the neuroepithelium or neural plate, and accumulating evidence shows that convergent and extension movements and apical constriction are the two dominant cell behaviors responsible for shaping the neural plate into a neural tube. Although the zebrafish (a teleost, ray-finned fish) neural plate has a different cytoarchitecture compared to other vertebrates, it still uses several morphogenetic mechanisms conserved with other vertebrates, such as non-canonical Wnt/planar cell polarity (PCP) signaling regulation of convergence-extension, through cell intercalation and axial elongation. This study used high spatial and rapid temporal in vivo imaging to define the cell surface dynamics governing zebrafish neural plate convergence and internalization, and uncovered a role for Cadherin-based cell adhesion in the protrusive activity of","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 10","pages":"1094-1095"},"PeriodicalIF":1.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://anatomypubs.onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242868","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":"Multiple gene knockouts in newts reveal novel functions of 5' Hox genes in limb development along the anterior-posterior and proximal-distal axes.","authors":"Kohei Urakawa, Yu Ito, Haruka Matsubara, Ken-Ichi T Suzuki, Masatoshi Matsunami, Shuji Shigenobu, Toshinori Hayashi, Gembu Abe, Takashi Takeuchi","doi":"10.1002/dvdy.70080","DOIUrl":"https://doi.org/10.1002/dvdy.70080","url":null,"abstract":"<p><strong>Background: </strong>5' Hox genes play crucial roles in limb patterning along the proximal-distal and anterior-posterior axes in mice. However, their functional conservation across tetrapods remains unclear. We previously found that newt Hox13 is essential for digit formation during both development and regeneration. In contrast, the functions of other 5' Hox genes (Hox9-Hox12) in newts remain u[WLYJ-108]nknown. Therefore, we generated 5' Hox knockout newts (Pleurodeles waltl) using CRISPR-Cas9.</p><p><strong>Results: </strong>Individual knockouts of Hox9, Hox10, and Hox12 disrupted all respective paralogs; however, these newts displayed no apparent abnormalities in limb skeletons. In contrast, Hox11 knockout newts exhibited skeletal defects in the posterior zeugopod and autopod of both the forelimbs and hindlimbs. Moreover, compound knockouts of Hox9 and Hox10 caused substantial loss of stylopod and anterior zeugopod/autopod elements specifically in the hindlimbs.</p><p><strong>Conclusion: </strong>These findings indicate that Hox9 and Hox10 redundantly regulate stylopod formation in the hindlimbs. Furthermore, Hox9/Hox10 and Hox11 contribute to the development of the anterior and posterior regions of the zeugopod/autopod in the hindlimbs, respectively. These novel roles of 5' Hox genes identified in newts suggest the functional diversification of 5' Hox genes in tetrapod limb development.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184990","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":"Gene expression detection methods in the African turquoise killifish brain.","authors":"Emily Whisenant, Arne C Lekven","doi":"10.1002/dvdy.70083","DOIUrl":"https://doi.org/10.1002/dvdy.70083","url":null,"abstract":"<p><strong>Background: </strong>The short-lived African turquoise killifish (Nothobranchius furzeri) is an important emerging model organism for gene expression studies, with limited tools for transcript and protein detection, especially methods that are both cost-effective and high-resolution. Brain tissue is particularly challenging to analyze due to its opacity and structural complexity, making whole-organ imaging techniques valuable. However, various tissue-clearing protocols adapted for N. furzeri are long and require specialized equipment.</p><p><strong>Results: </strong>To address these limitations for gene expression detection techniques, we optimized cryosection-compatible ISH protocols for mRNA detection and adapted the EZ-clear method for whole-brain protein visualization in N. furzeri. Using Gfap and Dat as test markers, we optimized the colorimetric ISH protocol for detecting mRNA in both thick and thin sections, achieved high signal-to-noise ratios, and confirmed expression in expected brain regions. Additionally, we adapted the EZ-clear protocol for brain tissue clearing. We demonstrate the method's compatibility with immunostaining, showing a possible upregulation in Gfap, alongside endogenous fluorescence preservation of transgenic reporter lines.</p><p><strong>Conclusions: </strong>Our protocols add to the existing cost-effective and accessible methods for gene and protein visualization in N. furzeri. The cryosection-amenable ISH and adapted EZ-clear protocols expand the methodological toolkit for studying gene expression in this emerging model system.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148297","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":"Pathogenesis and potential therapeutic targets of trichorhinophalangeal syndrome; lessons obtained from animal studies.","authors":"Naoya Saeki, Rinna Kanai, Sayuri Tatsuta, Shinichi Kawaguchi, Masatsune Itoh, Shinsuke Ohba, Makoto Abe","doi":"10.1002/dvdy.70082","DOIUrl":"https://doi.org/10.1002/dvdy.70082","url":null,"abstract":"<p><p>Trichorhinophalangeal syndrome (TRPS) is a rare genetic disease inherited in an autosomal dominant manner. It occurs in 1 in 100,000 people globally and is caused by several types of mutations of the TRPS1 gene. Since the first human patient was reported in 1966, typical and atypical pathologies, disease courses, and treatment case presentations have been reported. TRPS is characterized by sparse slow-growing fine hair, a bulbous nose with tented nares, and brachydactyly with cone-shaped epiphyses on the hands and feet. Growth retardation and hip dysplasia are also frequently observed, suggesting that hair and skeletal phenotypes are the major pathologies of TRPS. Several animal models have been established and studied intensively to address this rare disease. However, comprehensive treatment strategies for TRPS have not been established. In this review, we summarize TRPS pathologies and the characteristics of TRPS1 as an atypical GATA-type transcription factor. We review rodent strains that have contributed to our understanding of the in vivo roles of Trps1 and discuss their validity as animal models of TRPS. We also summarize diseases that demonstrate pathologies similar to TRPS and findings in their animal models.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136697","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":"Thyroid hormone receptor blockade by amiodarone disrupts angiogenesis via VEGFα, WNT7A, BMP, and PI3K/AKT pathways in chick embryo vascular development.","authors":"Juhi Vaishnav, Suresh Balakrishnan","doi":"10.1002/dvdy.70076","DOIUrl":"https://doi.org/10.1002/dvdy.70076","url":null,"abstract":"<p><strong>Background: </strong>Thyroid hormones (TH) play critical roles in embryonic vascular development, yet their precise molecular contributions remain inadequately defined. This study investigates how pharmacological blockade of thyroid hormone receptors (TR) by amiodarone disrupts angiogenesis and associated molecular signaling pathways in chick embryos.</p><p><strong>Results: </strong>Amiodarone-treated embryos exhibited notable morphological defects, including hematomas, anophthalmia, ventral wall defects, and limb anomalies, primarily affecting lateral plate mesoderm-derived tissues. Chorioallantoic membrane analysis revealed significant reductions in vessel density, branching, and total vessel length, along with increased lacunarity, indicating impaired angiogenesis. Molecular profiling showed consistent down-regulation of key angiogenic regulators such as VEGFα, WNT7A, BMP2/6, and phosphatidylinositol 3-kinase/ Ak strain transforming (PI3K/AKT) at both transcript and protein levels. In silico docking confirmed strong TRα and TRβ binding, while deiodinase activity assays and western blotting demonstrated impaired thyroxine-to-triiodothyronine (T3) conversion and reduced T3 levels, confirming systemic hypothyroidism and disrupted thyroid hormone signaling.</p><p><strong>Conclusion: </strong>Our findings underscore the essential role of thyroid hormone signaling in embryonic angiogenesis. Disruption of TR activation by amiodarone significantly impairs vascular formation through coordinated suppression of Vascular endothelial growth factor alpha (VEGFα), WNT7A, bone morphogenetic proteins, and PI3K/AKT pathways. These insights enhance our understanding of TH-related developmental disorders and may guide therapeutic strategies for managing vascular dysfunctions associated with impaired thyroid signaling.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052346","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":"Easily adaptable Fiji macro for mean linear intercept measurement of peripheral respiratory airspace.","authors":"Brielle Patlin, Yongjun Yin, Ling Li, David M Ornitz","doi":"10.1002/dvdy.70078","DOIUrl":"10.1002/dvdy.70078","url":null,"abstract":"<p><strong>Background: </strong>Mean linear intercept (MLI) is a method of evaluating lung structure and pathology that is widely used in clinical and research settings. Unfortunately, no widely available software for automation of this process is available, and many clinicians and scientists still perform these measurements manually.</p><p><strong>Results: </strong>To increase the speed and accuracy of obtaining MLI measurements, we have developed a macro for Fiji is just ImageJ (Fiji) to semi-automate the acquisition of these measurements. Twenty to 25 images from each of 43 mouse lungs, a total of 1042 images, were analyzed manually and by macro (automated) to validate the accuracy of the MLI macro. No significant difference was recorded between the manual and automated methods in mouse lung tissue of either different age (P14, P21, 8 weeks) or different condition (healthy vs. emphysema). Optimization of MLI macro parameters showed that additional measurements beyond three lines per image did not further improve accuracy. We also provide an Excel macro that summarizes the airspace data for each image and averages all the image data in a given batch of images.</p><p><strong>Conclusion: </strong>This Fiji macro can be used to automate MLI measurement in histological sections of lung tissue faster and with lower variance.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039419","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":"Role of p53 family members during development of striated muscle, with focus on p63.","authors":"Janine M Ziermann-Canabarro, Julia C Boughner, Kristen N McPike","doi":"10.1002/dvdy.70077","DOIUrl":"https://doi.org/10.1002/dvdy.70077","url":null,"abstract":"<p><strong>Background: </strong>During vertebrate development, p53 family members (p53, p63, and p73) play both discrete and redundant roles. While p63 gene mutations lead to various skeletal and organ birth defects, p63's role in muscle development is less considered. Muscles derive from embryonic mesoderm. However, head and heart muscle differentiation also depends on intrinsic cues and signals from adjacent epithelia. In p63 mutant mice, ectoderm- and endoderm-derived epithelia are defective, implying defective myogenesis. We review the evidence that p63 is important for the differentiation of striated muscles, including cardiopharyngeal field-derived head and heart musculature.</p><p><strong>Results: </strong>Several p63 isoforms act during mesoderm induction, myoblast proliferation, cell cycle exit, and cell differentiation. Of particular interest, TAp63γ is expressed in embryonic myoblasts and endoderm. In striated muscles, TAp63γ functions in myogenic proliferation and differentiation and participates in sarcomere development and myofibril assembly.</p><p><strong>Conclusions: </strong>p63 is active during all muscle development stages, from mesoderm induction to myocyte differentiation. Different p53 family members, including several p63 isoforms, have overlapping functions. This redundancy could explain the limited myopathies described in p63 mouse mutants. As these defects may be subtler and more age/stage-dependent than appreciated, they warrant further study.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039329","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}