Developmental biology最新文献

{"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 ,&nbsp;Madison Silvia ,&nbsp;Allex N. Gourlay ,&nbsp;Andrew L. Rhyne ,&nbsp;Nathalie Oulhen ,&nbsp;Gary M. Wessel","doi":"10.1016/j.ydbio.2025.09.013","DOIUrl":"10.1016/j.ydbio.2025.09.013","url":null,"abstract":"<div><div>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 <em>Lytechinus variegatus,</em> 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 specific functions in tissues that in combination give this animal its unique attributes.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 130-141"},"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}

{"title":"Genetic knockout suggests Isl1 enhancer redundancy in mouse hindlimb development","authors":"Seth Olson ,&nbsp;Hiroko Kawakami ,&nbsp;Alexandra Maria Nichitean ,&nbsp;Corinne Boerner ,&nbsp;Amel Awad ,&nbsp;Dylan Corcoran ,&nbsp;Cailin McMahon ,&nbsp;Ryuichi Nishinakamura ,&nbsp;Maureen Cetera ,&nbsp;Yasuhiko Kawakami","doi":"10.1016/j.ydbio.2025.09.014","DOIUrl":"10.1016/j.ydbio.2025.09.014","url":null,"abstract":"<div><div><em>Isl1</em> encodes a LIM homeodomain transcription factor, which is expressed in hindlimb progenitor cells in the lateral plate mesoderm and is required for initiating hindlimb development. Previous studies by lacZ transgenesis in mouse embryos identified a cis-element located 3’ to the <em>Isl1</em> gene, which could drive lacZ reporter expression in hindlimb progenitor cells and the branchial arch ectoderm. We refer to this cis-element as the <em>Isl1</em> hindlimb progenitor enhancer (HLPE). Our previous study also showed that SALL4, a transcription factor, is enriched at the <em>Isl1</em> HLPE, suggesting that SALL4 may regulate <em>Isl1</em> expression through <em>Isl1</em> HLPE. We sought to determine whether <em>Isl1</em> HLPE regulates <em>Isl1</em> expression and created mutant mice that lack the <em>Isl1</em> HLPE sequence by CRISPR/Cas9. The <em>Isl1</em> HLPE^−/− mouse lines, established after breeding with wild-type mice, did not exhibit gross morphological defects, except that their long bones are shorter than those of wild type. The shorter long bone phenotype was observed in the mid-gestation stage and was associated with misregulation of the expression of several chondrogenic genes, suggesting that the deletion of HLPE affects chondrogenesis. Although <em>Sall4</em> regulation of <em>Isl1</em> through <em>Isl1</em> HLPE was suspected, skeletal analysis did not exhibit any synergy between <em>Isl1</em> HLPE^−/− and conditional <em>Sall4</em> mutation. In situ hybridization showed seemingly normal expression of <em>Isl1</em> and its downstream gene <em>Tbx4</em> in <em>Isl1</em> HLPE^−/−, <em>TCre; Sall4</em>^fl/fl mutants, and <em>Isl1</em> HLPE^−/−; <em>TCre; Sall4</em>^fl/fl mutants. Finally, by quantitative gene expression analysis, <em>Isl1</em> expression is reduced but not abolished in <em>Isl1</em> HLPE^−/− and <em>Isl1</em>^+/−; <em>Isl1</em> HLPE ^± embryos, compared to wild-type embryos. Similarly, quantitative imaging analysis after immunostaining showed reduced ISL1 signals in the branchial arch ectoderm in <em>Isl1</em> HLPE^−/− embryos. These results support our notion that the <em>Isl1</em> HLPE sequence functions as an enhancer for <em>Isl1</em> expression in hindlimb progenitor cells and branchial arch ectoderm cells and suggest that multiple redundant enhancers co-regulate <em>Isl1</em> expression.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 217-227"},"PeriodicalIF":2.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091246","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":"Reorganization of H3K9me2-modified chromatin regions during mouse embryonic development","authors":"Diana Fulmer ,&nbsp;Emily J. Shields ,&nbsp;Andrey Poleshko ,&nbsp;Jonathan A. Epstein ,&nbsp;Cheryl L. Smith","doi":"10.1016/j.ydbio.2025.09.005","DOIUrl":"10.1016/j.ydbio.2025.09.005","url":null,"abstract":"<div><div>The three-dimensional organization of chromatin in the nucleus is critical in regulating gene expression. There are two classes of large genomic regions demarcated by the repressive chromatin modification histone H3 lysine 9 dimethyl (H3K9me2) and enriched at the nuclear periphery: lamina-associated domains (LADs); and H3K9me2-only domains (KODs) which have minimal lamina contact and are highly enriched for transcriptional enhancers. LADs have been studied in multiple cell types. In contrast, KODs have been characterized only in pluripotent cells and it remains to be determined whether they are fixed or rearrange according to cell type. Analysis of KODs from various embryonic mouse tissues revealed that KODs adopt cell type-specific configurations that correlate with changes in lineage-specific enhancer activity. Within KODs, local cell type-specific depletion of H3K9me2 was enriched for H3K27ac peaks at active lineage-specific enhancers. KODs were also enriched across ultra-long regulatory regions suggesting a role for KODs in long-range gene regulation. These results suggest that KODs are cell-type specific and maintain cell type-specific enhancers in a repressed state to allow for tissue- and stage-specific gene activation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 188-203"},"PeriodicalIF":2.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091276","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":"Scarecrow, a homolog of mammalian Nkx2.1, regulates the temporal progression and glial differentiation of medulla neuroblasts for the optic lobe development in Drosophila melanogaster","authors":"Cheol-Ho Yun ,&nbsp;Kyungjun Seok ,&nbsp;Gyunghee G. Lee ,&nbsp;Jae H. Park ,&nbsp;Siuk Yoo","doi":"10.1016/j.ydbio.2025.09.012","DOIUrl":"10.1016/j.ydbio.2025.09.012","url":null,"abstract":"<div><div>The <em>Drosophila</em> medulla is the largest structure in the adult visual nervous system. It contains a vast population of interneurons comprising over 80 different cell types generated by medulla neuroblasts (NBs). Aging NBs express a series of temporal transcription factors (tTFs) that contribute to neuronal diversity. Recent studies have shown that an NK-2 homeobox gene <em>scarecrow</em> (<em>scro</em>) works as a tTF covering from middle to late temporal windows; however, how its expression is established over multiple windows and what roles it plays in individual windows remain largely elusive. We found the lack of <em>scro</em> expression in the middle of the Dichaete (D) domain, implying its expression is not in a continuum as previously eluded. Overexpression and knockdown assays of <em>scro</em> or other tTFs using various <em>tTF-Gal4</em> drivers further revealed distinctive roles played by Scro at each window, including the last one. The oldest NBs positive for Tll and Scro found at the most proximal region of the developing medulla field attained expression of Gcm (the master factor of glial differentiation) and Nerfin-1 (a suppressor of dedifferentiation via Notch suppression), which in turn led to NB-to-glia differentiation. Downregulation of either <em>gcm</em> or <em>nerfin-1</em> resulted in the formation of ectopic NBs at the expense of glial cells. Moreover, <em>scro-</em>knockdown led to a loss of Gcm, Nerfin-1, and Prospero expression, misregulation of Notch expression, formation of ectopic NBs, and a substantial reduction in glial cell population, suggesting that Scro acts upstream of Gcm and Nerfin-1. The chromatin-immunoprecipitation (ChIP) assays support that Scro regulates the expression of <em>gcm</em>, <em>nerfin-1</em>, and <em>pros</em>, as well as several tTFs, the expression of which overlaps with Scro. In summary, this study not only verified previously suggested roles of Scro but also uncovered novel features of this gene in various temporal windows, including the promotion of NB-to-glial transition and discontinuous expression within the D domain.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 277-294"},"PeriodicalIF":2.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085417","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":"Intraocular vasculature formation precedes extraocular vasculature penetration of mouse eyes","authors":"Satoshi Imanishi ,&nbsp;Yohei Tomita ,&nbsp;Kazuno Negishi ,&nbsp;Kazuo Tsubota ,&nbsp;Toshihide Kurihara","doi":"10.1016/j.ydbio.2025.09.010","DOIUrl":"10.1016/j.ydbio.2025.09.010","url":null,"abstract":"<div><div>The posterior ocular circulatory system comprises choroidal vasculature and central retinal and posterior ciliary arteries (PCAs) that are fundamental for ocular tissue maintenance. Much is known about the development of the retinal vascular system, but that of the posterior ocular circulation system remain obscure. Therefore, we aimed to clarify the development of the intraocular vasculature involved in the posterior ocular circulation system. Choriocapillaris and hyaloid capillaries are formed <em>in situ</em> and <em>de novo</em> through the endothelial differentiation of hemangioblasts. The intraocular segments of the hyaloid artery penetrate the retina before extraocular segments appear. The intraocular segments of PCAs arise from the hyaloid artery before the extraocular segments reach the eye. The posterior ocular circulation system apparently synchronizes with events throughout the entire process of ocular development. The intraocular vasculature notably formed before the extraocular segments reached the eyes. Our findings provide a novel perspective on ocular development and might facilitate understanding of eye diseases in humans.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 152-162"},"PeriodicalIF":2.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085397","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}