Embryology

胚胎学
  • 文章类型: Journal Article
    选择性剪接(AS)作为胚胎发育过程中重要的转录后调控机制之一,研究甚少。在这项研究中,我们全面收集和分析了人类和小鼠早期胚胎的转录组数据。我们发现AS在此过程中起着重要作用,并预测了与生殖发育相关的候选RNA结合蛋白(RBP)调节因子。发现预测的RBP,例如EIF4A3,MAK16,SRSF2和UTP23与生殖障碍有关。通过Smart-seq2测序分析,我们在Eif4a3敲低胚胎中鉴定了5445个异常可变剪接事件。这些事件优先与RNA加工相关。总之,我们在可变剪接事件的景观和潜在功能方面的工作将促进对调节哺乳动物早期胚胎发育的详细机制和关键因素的进一步研究,并促进对这一关键生物学过程中疾病的药物方法的启发。
    Alternative splicing (AS) as one of the important post-transcriptional regulatory mechanisms has been poorly studied during embryogenesis. In this study, we comprehensively collected and analyzed the transcriptome data of early embryos from human and mouse. We found that AS plays an important role in this process and predicted candidate RNA binding protein (RBP) regulators that are associated with reproductive development. The predicted RBPs such as EIF4A3, MAK16, SRSF2, and UTP23 were found to be associated with reproductive disorders. By Smart-seq2 sequencing analysis, we identified 5445 aberrant alternative splicing events in Eif4a3-knockdown embryos. These events were preferentially associated with RNA processing. In conclusion, our work on the landscape and potential function of alternative splicing events will boost further investigation of detailed mechanisms and key factors regulating mammalian early embryo development and promote the inspiration of pharmaceutical approaches for disorders in this crucial biology process.
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  • 文章类型: Journal Article
    脊椎动物胚胎的左右对称破坏需要节流。然而,在节流下介导不对称基因表达调控的分子机制仍然难以捉摸。这里,我们报告说,热休克因子1(HSF1)在存在结节流的斑马鱼胚胎的Kupffer囊泡中不对称激活。HSF1表达的缺失导致斑马鱼胚胎中节点信号蛋白的显著位点倒置和基因表达不对称性的破坏。进一步的研究表明HSF1是一种机械敏感性蛋白。HSF1的机械感觉能力在不同细胞类型的各种机械刺激中被保留。此外,纤毛和Ca2+-Akt信号轴在体外和体内机械应力下对HSF1的激活至关重要。考虑到HSF1在生物体中的保守表达,这些发现揭示了在胚胎发育和其他生理和病理转化过程中通过机械线索调节基因表达的基本机制。
    The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer\'s vesicle of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation by mechanical clues during embryonic development and other physiological and pathological transformations.
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  • 文章类型: Journal Article
    含有SET结构域7(SETD7)在人造血发育过程中的作用仍然难以捉摸。这里,我们发现,在人胚胎干细胞(hESCs)诱导造血分化过程中,SETD7的缺失减弱了造血祖细胞(HPCs)的生成.进一步的分析指出,SETD7是侧板中胚层(LPM)规格所必需的,但对于内皮祖细胞(EPCs)和HPCs的生成则是不必要的。机械上,而不是依赖于它的组蛋白甲基转移酶活性,SETD7在赖氨酸残基180处与β-连环蛋白相互作用促进其降解。SETD7表达减少导致β-catenin的积累和随后的Wnt信号通路的激活,这改变了LPM图案并促进了近轴中胚层(PM)的产生。一起来看,研究结果表明,SETD7通过Wnt/β-catenin信号通路的翻译后调节与LPM和PM模式有关,从hESCs造血分化过程中提供对中胚层规范的新见解。
    The role of SET domain containing 7 (SETD7) during human hematopoietic development remains elusive. Here, we found that deletion of SETD7 attenuated the generation of hematopoietic progenitor cells (HPCs) during the induction of hematopoietic differentiation from human embryonic stem cells (hESCs). Further analysis specified that SETD7 was required for lateral plate mesoderm (LPM) specification but dispensable for the generation of endothelial progenitor cells (EPCs) and HPCs. Mechanistically, rather than depending on its histone methyltransferase activity, SETD7 interacted with β-catenin at lysine residue 180 facilitated its degradation. Diminished SETD7 expression led to the accumulation of β-catenin and the consequent activation of the Wnt signaling pathway, which altered LPM patterning and facilitated the production of paraxial mesoderm (PM). Taken together, the findings indicate that SETD7 is related to LPM and PM patterning via posttranslational regulation of the Wnt/β-catenin signaling pathway, providing novel insights into mesoderm specification during hematopoietic differentiation from hESCs.
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  • 文章类型: Case Reports
    异位甲状腺组织是一种罕见的疾病,表现为甲状腺组织在甲状腺外的出现。这里,我们报告一例乳腺异位甲状腺组织。一名48岁的中国女性被诊断患有乳腺癌,接受了改良根治术。在随后的病理检查中发现甲状腺组织。异位甲状腺组织通过甲状腺生物标志物的免疫组织化学染色证实,包括甲状腺球蛋白,甲状腺转录因子-1和甲状腺过氧化物酶。目前,甲状腺异常下降是解释异位甲状腺组织的主要理论,尤其是舌部甲状腺.然而,异位甲状腺组织存在于虹膜等器官或远离甲状腺的组织中,心脏,肺,十二指肠,肾上腺,和椎骨。这里,我们回顾了先前的乳腺异位甲状腺组织病例,并提出了一种“内胚层迁移”理论来解释基于胚胎发育角度的远处异位甲状腺组织。
    Ectopic thyroid tissue is a rare condition manifested as the appearance of thyroid tissue outside the thyroid gland. Here, we report a case of ectopic thyroid tissue in the breast. A 48-year-old Chinese woman who was diagnosed with breast cancer received modified radical mastectomy. A thyroid tissue was found on subsequent pathological examination. The ectopic thyroid tissue was confirmed by immunohistochemistry staining of thyroid biomarkers, including thyroglobulin, thyroid transcription factor-1, and thyroid peroxidase. Currently, abnormal thyroid anlage descent is the main theory to explain ectopic thyroid tissue, especially lingual thyroid. However, it is far-fetched to explain the pathogenesis of ectopic thyroid tissues existed in organs or tissues far from thyroid such as iris, cardiac, pulmonary, duodenal, adrenal, and vertebral. Here, we reviewed the previous cases of ectopic thyroid tissue in breast and proposed a \"entoderm migration\" theory to explain distant ectopic thyroid tissues based on embryonic development perspective.
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  • 文章类型: Journal Article
    泌尿生殖窦(UGS)畸形,也称为持续性泌尿生殖窦(PUGS),是一种罕见的先天性泌尿生殖系统畸形。当尿道和阴道开口在外阴中不能正常形成并且融合不正确时,就会出现这种情况。PUGS可以作为孤立的异常或复杂综合征的一部分发生,常伴有先天性肾上腺增生(CAH)。PUGS的管理并不完善,并且没有关于何时进行手术或如何长期随访的标准化指南。在这次审查中,我们讨论胚胎发育,临床评估,诊断,和PUGS的管理。我们还回顾了病例报告和研究结果,以探索手术和后续护理的最佳实践。希望提高对PUGS的认识并改善患者的预后。
    Urogenital sinus (UGS) malformation, also known as persistent urogenital sinus (PUGS), is a rare congenital malformation of the urogenital system. It arises when the urethra and vaginal opening fail to form properly in the vulva and fuse incorrectly. PUGS can occur as an isolated abnormality or as part of a complex syndrome, and is frequently associated with congenital adrenal hyperplasia (CAH). The management of PUGS is not well-established, and there are no standardized guidelines on when to perform surgery or how to follow up with patients over the long term. In this review, we discuss the embryonic development, clinical evaluation, diagnosis, and management of PUGS. We also review case reports and research findings to explore best practices for surgery and follow-up care, in hopes of increasing awareness of PUGS and improving patient outcomes.
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  • 文章类型: Journal Article
    母猪妊娠发育的分子机制表征对猪育种性状的遗传改良具有重要意义。并为人类妊娠疾病的生物医学研究提供资源。然而,母猪妊娠多个发育阶段的转录组和代谢组仍然缺乏。在这项研究中,我们获得了84个不同的RNA测序和42个代谢组数据集,这些数据集涉及从发情期到哺乳期的6个发育阶段。我们证实了初始序列和外显子结构特征,阶段特异性分子,分子的表达或积累模式,转录组和代谢组的调控机制,和重要的妊娠相关代谢物在猪和人类。总之,我们提出了母猪从发情期到泌乳期的RNA和代谢产物之间的关键差异,并提出了关键标记。这些数据结果有望为猪育种和人类妊娠疾病的生物医学研究提供必要的资源。
    Characterization of molecular mechanisms underlying pregnancy development of sows is important for the genetic improvement of pig breeding traits, and also provides resources for biomedical research on human pregnancy diseases. However, the transcriptome and metabolome across multiple developmental stages of sow pregnancy were still lacking. In this study, we obtained 84 distinct RNA sequencing and 42 metabolome datasets of pig blood across six development stages from estrus to lactation. We confirmed the initial sequence and exonic structural features, stage-specific molecules, expression or accumulation pattern of molecules, the regulatory mechanism of transcriptome and metabolome, and important pregnancy-related metabolites both in pigs and humans. In conclusion, we proposed the key differences among the stages of sows from estrus to lactation in RNAs and metabolites and put forward key markers. These data results were expected to provide essential resources for pig breeding and biomedical research on human pregnancy disease.
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  • 文章类型: Journal Article
    背景:学生参与学习材料以及与老师和同伴在讲座前后的讨论是成功实施混合课程的关键。先前关于混合学习的研究已经报道了混合结果。这项研究评估了在混合胚胎学课程中嵌入教师监督的在线讨论平台对学生处理困难和认知挑战性任务的能力的影响的有效性。
    方法:本研究调查并比较了两种混合学习形式。对照组学生(n=85)每节课前学习网上资料,其次是课堂教学和活动,鼓励学生之间进行面对面的讨论和交流。实验组的学生(n=83)遵循类似的程序,并附加了一个由教师监督的在线讨论平台来指导,监督和评估他们的学习进度。所有参与者均为2017年入学的大连医科大学临床医学一年级医学生。所有参与者都参加了期末考试,以测试他们的学习成果。
    结果:实验组学生的胚胎学成绩明显高于对照组学生(p=0.001)。此外,实验组学生在高难度问题(p=0.003)和评估高阶认知技能问题(p=0.003)上的得分高于对照组学生;效果大小中等(η2>0.05)。
    结论:在混合胚胎学课程中,与学习者主导和面对面讨论相比,教师监督的在线讨论平台具有巨大的潜力,可以使学生获得更高的成绩并解决困难和认知上具有挑战性的任务。
    BACKGROUND: Students\' engagement with learning materials and discussions with teachers and peers before and after lectures are among the keys to the successful implementation of blended programs. Mixed results have been reported by previous studies on blended learning. This study evaluated the effectiveness of embedding a teacher-supervised online discussion platform in a blended embryology course in terms of its impact on students\' capabilities to handle difficult and cognitively challenging tasks.
    METHODS: Two forms of blended learning were investigated and compared in this study. Students in the control group (n = 85) learned online materials before each class, followed by classroom instruction and activities in which face-to-face discussion and communication between students were encouraged. Students in the experimental group (n = 83) followed a similar procedure with an additional teacher-supervised online discussion platform to guide, supervise and evaluate their learning progress. All participants were first-year medical students in clinical medicine at Dalian Medical University who had enrolled in 2017. All participants took the final exam to test their learning outcomes.
    RESULTS: The embryology grades of students in the experimental group were significantly higher than those of students in the control group (p = 0.001). Additionally, the scores of students in the experimental group on questions with a high difficulty level (p = 0.003) and questions assessing high-order cognitive skills (p = 0.003) were higher than those of students in the control group; the effect size was moderate (η2 > 0.05).
    CONCLUSIONS: In blended embryology courses, compared with learner-led and face-to-face discussion, the teacher-supervised online discussion platform has great potential to enable students to achieve higher grades and solve difficult and cognitively challenging tasks.
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  • 文章类型: Journal Article
    COVID-19疾病的流行在全球范围内造成了严重影响。各国政府认为疫苗接种是控制大流行的有效措施。然而,许多人一直在犹豫是否接种COVID-19疫苗,特别是围观和哺乳期妇女。尽管研究表明,患有COVID-19的孕妇出现不良妊娠和分娩结局的风险更高,以及严重的疾病。似乎缺乏系统和全面的证据表明,围概念和哺乳期妇女对COVID-19疫苗犹豫的患病率和决定因素。因此,有必要调查围概念和哺乳期妇女的疫苗接种观点和行为。这项研究将回顾有关围概念和哺乳期妇女疫苗犹豫的文章,以评估大流行期间COVID-19疫苗犹豫的影响。
    我们将在以下数据库中系统地搜索2019年11月1日至2021年10月30日的观测研究:WebofScience,PubMed,EMBASE,MEDLINE,科克伦图书馆,EBSCO,世卫组织COVID-19数据库,CNKI与万方数据库将使用以下医学主题词和自由文本术语:“COVID-19疫苗”和“女性”和“疫苗犹豫”。资格标准如下:人口(育龄妇女);暴露(目前怀孕,哺乳期或试图怀孕);比较(一般女性没有怀孕前,妊娠或哺乳期)和结局(COVID-19疫苗犹豫率)。文章筛选和数据提取将由两名审查人员独立进行,任何差异将通过讨论解决。我们将使用I2统计数据来评估异质性,并在提供足够同质的研究时进行荟萃分析。我们将使用亚组和荟萃回归分析来探索异质性的潜在来源。
    这项研究将使用已发表的数据,所以不需要道德批准。研究结果将通过发表在同行评审的期刊上传播。
    CRD42021257511。
    The pandemic of COVID-19 disease has caused severe impact globally. Governments consider vaccination as an effective measure to control pandemic. However, many people have been hesitant to receive COVID-19 vaccine, particularly periconceptional and lactating women. Although research has indicated that pregnant women with COVID-19 are at a higher risk of adverse pregnancy and birth outcomes, as well as severe illness. There appears to be a lack of systematic and comprehensive evidence of the prevalence and determinants of COVID-19 vaccine hesitancy among periconceptional and lactating women. As a result, it has been essential to investigate periconceptional and lactating women\'s vaccination views and behaviours. This study will review articles on vaccine hesitancy among periconceptional and lactating women to assess the impact of the COVID-19 vaccine hesitancy during the pandemic.
    We will systematically search observational studies from 1 November 2019 to 30 October 2021 in the following databases: Web of Science, PubMed, EMBASE, MEDLINE, Cochrane Library, EBSCO, WHO COVID-19 Database, CNKI and WanFang Database. The following medical subject headings and free-text terms will be used: \"COVID-19 vaccines\" AND \"female\" AND \"vaccine hesitancy\". Eligibility criteria are as follows: population (women of reproductive age); exposure (currently pregnant, lactational or trying to get pregnant); comparison (general women who are not in preconception, gestation or lactation) and outcome (the rate of COVID-19 vaccine hesitancy). Article screening and data extraction will be undertaken independently by two reviewers, and any discrepancy will be resolved through discussion. We will use I2 statistics to assess heterogeneity and perform a meta-analysis when sufficiently homogeneous studies are provided. We will explore the potential sources of heterogeneity using subgroup and meta-regression analysis.
    This study will use published data, so ethical approval is not required. The findings will be disseminated by publication in peer-reviewed journal(s).
    CRD42021257511.
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  • 文章类型: Journal Article
    具有亚细胞分辨率的厘米级标本的快速多色三维(3D)成像仍然是一项具有挑战性但引人入胜的科学追求。这里,我们提出了一个快速,成本效益高,和强大的多色全器官3D成像方法,辅助紫外线(UV)表面激发和振动辅助切片,称为平移快速紫外激发切片层析成像(TRUST)。使用廉价的UV发光二极管(UV-LED)和彩色相机,TRUST可以同时实现宽场外源分子特异性荧光和内源性含量丰富的自发荧光成像,同时保持较低的系统复杂度和系统成本。福尔马林固定的标本逐层染色以及连续机械切片,以实现具有高染色均匀性和时间效率的自动化3D成像。野生型C57BL/6小鼠所有重要器官的3D模型及其内部组件的3D结构(例如,船舶网络,肾小球,和神经束)可以在用TRUST成像后重建,以证明其快速,健壮,和高含量的多色3D成像能力。此外,其在发育生物学方面的潜力也已通过对整个小鼠胚胎进行成像得到验证(胚胎在15日的胚胎中约为2天)。TRUST为高分辨率全器官多色3D成像提供了一种快速且具有成本效益的方法,同时减轻了研究人员繁重的样品制备工作量。
    Rapid multicolor three-dimensional (3D) imaging for centimeter-scale specimens with subcellular resolution remains a challenging but captivating scientific pursuit. Here, we present a fast, cost-effective, and robust multicolor whole-organ 3D imaging method assisted with ultraviolet (UV) surface excitation and vibratomy-assisted sectioning, termed translational rapid ultraviolet-excited sectioning tomography (TRUST). With an inexpensive UV light-emitting diode (UV-LED) and a color camera, TRUST achieves widefield exogenous molecular-specific fluorescence and endogenous content-rich autofluorescence imaging simultaneously while preserving low system complexity and system cost. Formalin-fixed specimens are stained layer by layer along with serial mechanical sectioning to achieve automated 3D imaging with high staining uniformity and time efficiency. 3D models of all vital organs in wild-type C57BL/6 mice with the 3D structure of their internal components (e.g., vessel network, glomeruli, and nerve tracts) can be reconstructed after imaging with TRUST to demonstrate its fast, robust, and high-content multicolor 3D imaging capability. Moreover, its potential for developmental biology has also been validated by imaging entire mouse embryos (~2 days for the embryo at the embryonic day of 15). TRUST offers a fast and cost-effective approach for high-resolution whole-organ multicolor 3D imaging while relieving researchers from the heavy sample preparation workload.
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  • 文章类型: Clinical Trial Protocol
    形态学评估用于选择体外受精的胚胎。然而,它不能完全反映植入潜力。非整倍体的植入前遗传学检测(PGT-A)可以检测胚胎非整倍体,但活检程序是侵入性的.目前,正在评估使用废培养基的非侵入性PGT(ni-PGT)方法。然而,ni-PGT的临床获益尚未得到明确证实.需要一项多中心随机试验来验证ni-PGT是否可以成为评估胚胎的新有效工具。
    总的来说,计划招募1148对35~42岁的夫妇(女性)接受体外受精-卵胞浆内单精子注射。夫妇将以1:1的治疗比例数字随机分为(1)ni-PGT和(2)常规形态学组。主要结果将是与卵母细胞取出后6个月内的第一次转移周期相关的持续妊娠率。
    本研究方案得到北京大学第三医院伦理委员会和参与医院的批准。结果将通过国际会议和科学期刊传播。
    NCT04339166。
    Morphological evaluation is used to select embryos for in vitro fertilisation. However, it does not fully reflect the implantation potential. Preimplantation genetic testing for aneuploidies (PGT-A) can detect embryonic aneuploidy, but biopsy procedure is invasive. Currently, a non-invasive PGT (ni-PGT) approach using spent medium is being evaluated. However, the clinical benefit of ni-PGT has not been clearly demonstrated. A multicentre randomised trial is needed to verify whether ni-PGT can be an new effective tool for evaluating embryos.
    Overall, 1148 couples aged 35~42 (women) receiving in vitro fertilization-intracytoplasmic sperm injection are planned to be enrolled. Couples will be digitally randomised to (1) ni-PGT and (2) conventional morphology groups at a 1:1 treatment ratio. The primary outcome will be the ongoing pregnancy rate related to the first transfer cycle within 6 months after oocyte retrieval.
    The study protocol is approved by the Ethics Committee of Peking University Third Hospital and the participating hospitals. The results will be disseminated through international conferences and scientific journals.
    NCT04339166.
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