Differentiation最新文献_第3页

Evaluation of chondrogenesis and osteogenesis in human mesenchymal stem cells, chondrocytes, and chondroprogenitors using molecular markers, cellular markers and polarized microscopy 利用分子标记、细胞标记和极化显微镜评价人间充质干细胞、软骨细胞和软骨祖细胞的软骨形成和成骨

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-25 DOI: 10.1016/j.diff.2025.100898

Archa Suresh , Ayshath Ruksana C , Ganesh Parasuraman , Mohana Priya , Grace Rebekah , Christo Jeyaraj , Elizabeth Vinod

Purpose

Fibronectin adhesion assay progenitors (FAA-CPs) and migratory assay progenitors (MCPs), subsets of mesenchymal-like stromal cells (MSCs), exhibit superior in-vitro chondrogenic potential compared to bone marrow (BM)-MSCs and chondrocytes. To assess this potential, differentiation studies followed by confirmatory staining for collagen deposition are utilized. Polarized light microscopy (PLM), based on birefringence principles, is a valuable tool for visualizing organized collagen fibers. Its use as a predictive tool for assessing chondrogenesis and osteogenesis has not been reported.

Methods

This study involved FAA-CPs, MCPs, chondrocytes, and BM-MSCs derived from osteoarthritic knee joints (n = 3). After phenotypic characterization, the cells underwent chondrogenic and osteogenic differentiation, followed by Picrosirius red staining and PLM analysis, including immunohistochemical analysis for collagen types I, II, and X.

Results

Birefringence assessment revealed greater collagen fibril alignment and significant remodeling in the BM-MSC group, which exhibited an arcade-like pattern. The MCP group displayed well-organized collagen fibrils in pericellular zones and as a peripheral band, while chondrocytes and FAA-CPs exhibited lower intensity birefringence, indicating random alignment. Areas with higher collagen type II deposition corresponded to reduced collagen type I and the absence of collagen type X, highlighting the unique fibrillar network seen with PLM was indicative of collagen type II.

Conclusion

While its application for osteogenesis was limited, probably due to the non-fibrillar nature of collagen type X, its value for chondrogenesis is notable. Although not directly reflecting chondrogenesis, PLM can serve as a valuable tool for gaining insights into collagen remodeling, particularly concerning collagen type II during chondrogenic differentiation.

目的：纤连蛋白粘附试验祖细胞（FAA-CPs）和迁移试验祖细胞（MCPs）是间充质样基质细胞（MSCs）的亚群，与骨髓(BM)-MSCs和软骨细胞相比，它们在体外表现出更强的成软骨潜能。为了评估这一潜力，分化研究随后证实染色胶原沉积被利用。偏振光显微镜（PLM），基于双折射原理，是一个有价值的工具，可视化组织胶原纤维。它作为评估软骨形成和成骨形成的预测工具尚未报道。方法本研究涉及骨关节炎膝关节的fa - cps、MCPs、软骨细胞和BM-MSCs （n = 3）。表型鉴定后，细胞进行软骨和成骨分化，随后进行Picrosirius红染色和PLM分析，包括I型、II型和x型胶原的免疫组织化学分析。结果双折射评估显示，BM-MSC组胶原纤维排列更大，重构明显，呈拱廊状。MCP组在细胞周带和外周带中显示组织良好的胶原原纤维，而软骨细胞和fa - cps表现出较低强度的双折射，表明随机排列。II型胶原沉积较多的区域对应于I型胶原减少和X型胶原缺失，突出显示PLM中独特的纤维网络，表明II型胶原。结论X型胶原的非纤原性可能限制了其在成骨方面的应用，但其在软骨形成方面的价值是显著的。虽然PLM不能直接反映软骨形成，但它可以作为一种有价值的工具，用于深入了解胶原重塑，特别是软骨形成分化过程中的II型胶原。

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引用次数: 0

Mettl3 is required for germline function during Drosophila spermatogenesis 在果蝇精子发生过程中，Mettl3是种系功能所必需的

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-13 DOI: 10.1016/j.diff.2025.100895

Alannah Morse, Hailey Kaba, Corinne Leighty, Emily MacLean, Rosemarie Mirabella, Mary Reinaker, Rohan Harris, Jazmyn Moodie, Antonio Rockwell

The m⁶A modification is responsible for regulating several aspects of RNA metabolism. The enzyme that catalyzes this modification Mettl3, is highly conserved and required for numerous biological processes such as spermatogenesis. Here we examine the role of Mettl3 in germline function during Drosophila spermatogenesis. We find that depletion of Mettl3 in the germline results in errors in late-stage spermatogenesis, the process known as spermiogenesis. In germline knockdowns, actin cones bound to spermatids fail to remain tightly packed during the individualization process. Issues with actin cone assembly appear to disrupt progression through spermiogenesis resulting in waste bag deficiency, an indicator of abnormal spermatid individualization. These errors result in little to no sperm in seminal vesicles culminating in reduced fertility in germline knockdowns. Furthermore, our findings suggest Hsp60B is misregulated in knockdowns, which potentially explains at least some observed phenotypes. Collectively, the data presented in this investigation suggests Mettl3 has a prominent role in regulating spermatid differentiation during Drosophila spermatogenesis.

m6A修饰负责调节RNA代谢的几个方面。催化这种修饰的酶Mettl3是高度保守的，是许多生物过程（如精子发生）所必需的。在这里，我们研究了Mettl3在果蝇精子发生过程中生殖系功能中的作用。我们发现生殖系中Mettl3的缺失会导致后期精子发生的错误，这一过程被称为精子发生。在种系基因敲低中，与精子结合的肌动蛋白锥在个体化过程中不能保持紧密的包裹。肌动蛋白锥体组装的问题似乎破坏了精子发生的进程，导致废物袋缺乏，这是精子异常个体化的一个指标。这些错误导致精囊中精子很少甚至没有精子，最终导致生殖细胞敲低导致生育能力降低。此外，我们的研究结果表明Hsp60B在基因敲低中被错误调控，这可能解释了至少一些观察到的表型。总的来说，本研究的数据表明，在果蝇精子发生过程中，Mettl3在调节精细胞分化中起着重要作用。

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引用次数: 0

Bdnf and Ntrk2 functions promote but are not essential for spinal cord myelination in larval zebrafish Bdnf和Ntrk2的功能促进了斑马鱼幼体脊髓髓鞘形成，但不是必需的

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-12 DOI: 10.1016/j.diff.2025.100896

Kristen Russell , Christina A. Kearns , Macie B. Walker , Christopher S. Knoeckel , Angeles B. Ribera , Caleb A. Doll , Bruce Appel

Myelin, a specialized membrane produced by oligodendroglial cells in the central nervous system, wraps axons to enhance conduction velocity and maintain axon health. Not all axons are myelinated, and not all myelinated axons are uniformly wrapped along their lengths. Several lines of evidence indicate that neuronal activity can influence myelination, however, the cellular and molecular mechanisms that mediate communication between axons and oligodendrocytes remain poorly understood. Prior research showed that the neurotrophic growth factor Bdnf and its receptor Ntrk2 promote myelination in rodents, raising the possibility that Bdnf and Ntrk2 convey myelin-promoting signals from neurons to oligodendrocytes. We explored this possibility using a combination of gene expression analyses, gene function tests, and myelin sheath formation assays in zebrafish larvae. Altogether, our data indicate that, although not essential for myelination, Bdnf-Ntrk2 signaling contributes to the timely formation of myelin in the developing zebrafish spinal cord.

髓磷脂是由中枢神经系统少突胶质细胞产生的一种特殊膜，包裹轴突以提高传导速度，维持轴突健康。并不是所有的轴突都有髓鞘，也不是所有有髓鞘的轴突沿其长度均匀包裹。一些证据表明，神经元活动可以影响髓鞘形成，然而，介导轴突和少突胶质细胞之间通讯的细胞和分子机制仍然知之甚少。先前的研究表明，神经营养生长因子Bdnf及其受体Ntrk2促进啮齿动物的髓鞘形成，这提出了Bdnf和Ntrk2将髓鞘促进信号从神经元传递到少突胶质细胞的可能性。我们通过对斑马鱼幼虫的基因表达分析、基因功能测试和髓鞘形成分析来探索这种可能性。总之，我们的数据表明，尽管Bdnf-Ntrk2信号不是髓鞘形成所必需的，但它有助于发育中的斑马鱼脊髓髓鞘的及时形成。

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引用次数: 0

Corrigendum to “The mechanism of EGF in promoting skeletal muscle post-injury regeneration” [Differentiation 143 (2025) 100862] “EGF促进骨骼肌损伤后再生的机制”的更正[分化143 (2025)100862]

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-01 DOI: 10.1016/j.diff.2025.100885

Huaixin Teng , Yongze Liu , Ruotong Hao , Lu Zhang , Xiaoyu Zhang , Shufeng Li , Shuang Li , Huili Tong

引用次数: 0

One Wnt to lead them all: a Wnt1 primer 一个Wnt可以引领所有Wnt：一个Wnt1引物

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-06-24 DOI: 10.1016/j.diff.2025.100884

Arne C. Lekven, Sarah Empie , Richard Saoud

Wnt1 was originally identified by virtue of its mutant phenotype in Drosophila and its causation of mammary tumors in mice, but, in its history, Wnt1 has been a nexus for ground-breaking discoveries in developmental biology, evolutionary biology, and disease. Wnt1 orthologs are found across the animal kingdom and play a role in a multitude of developmental and homeostatic mechanisms involving proliferation, cell fate specification, stem cell maintenance and tissue homeostasis. In vertebrates, Wnt1 is located in a syntenic chromosome neighborhood that is essential to its conserved expression in the developing nervous system. Wnt1 is essential for nervous system development, in particular for the midbrain and anterior hindbrain. Wnt1 also is essential for bone homeostasis, and mutant alleles are behind severe cases of recessive osteogenesis imperfecta in humans. This primer reviews the illustrious history of Wnt1, its gene structure and regulation, expression, loss-of-function consequences, and connection to human disease.

Wnt1最初是由于其在果蝇中的突变表型和在小鼠中引起乳腺肿瘤而被发现的，但是，在其历史上，Wnt1已经成为发育生物学、进化生物学和疾病领域突破性发现的纽带。Wnt1同源基因在动物王国中广泛存在，并在多种发育和体内平衡机制中发挥作用，包括增殖、细胞命运规范、干细胞维持和组织体内平衡。在脊椎动物中，Wnt1位于同染色体附近，这对其在发育中的神经系统中的保守表达至关重要。Wnt1对神经系统发育至关重要，特别是中脑和后脑前部。Wnt1也是骨稳态所必需的，突变等位基因是人类严重隐性成骨不全病例的原因。本引物回顾了Wnt1的辉煌历史、其基因结构和调控、表达、功能丧失后果以及与人类疾病的联系。

引用次数: 0

Characterization of Pumilio gene expression during early neural crest development 神经嵴发育早期Pumilio基因表达的研究

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-06-23 DOI: 10.1016/j.diff.2025.100883

Mariann Guzman-Espinoza , Helen M. Vander Wende , Jessica L. Pacheco , Alejandra Olano Roldán , Erica J. Hutchins

Neural crest cells are multipotent cells present in vertebrate embryos that give rise to a wide array of cell types and tissues. A growing number of studies have identified post-transcriptional regulatory events that are essential for multiple stages of neural crest development, though a thorough characterization of the post-transcriptional regulators controlling these events is currently lacking. From single cell RNA-sequencing data, we identified members of the Pumilio family of RNA-binding proteins, PUM1 and PUM2, as candidate post-transcriptional regulators of neural crest development. Using hybridization chain reaction (HCR) in avian embryos (Gallus gallus), we characterized the spatiotemporal expression of Pumilio family mRNAs during early stages of cranial neural crest development. We show that Pum1 and Pum2, though expressed throughout the three germ layers, were enriched in ectodermally-derived tissues, and following neurulation, Pum1 and Pum2 show distinct expression patterns. We observed that Pum1 displayed a more uniform expression throughout the neural tube and neural crest during neural crest specification and the epithelial-mesenchymal transition (EMT). In contrast, Pum2 was enriched in neural crest cells poised to undergo EMT. We thus hypothesize that PUM1 and PUM2, often speculated to be functionally redundant, may play distinct roles at key steps of neural crest development.

神经嵴细胞是存在于脊椎动物胚胎中的多能细胞，可产生多种细胞类型和组织。越来越多的研究已经确定了对神经嵴发育的多个阶段至关重要的转录后调节事件，尽管目前还缺乏对控制这些事件的转录后调节因子的全面表征。从单细胞rna测序数据中，我们确定了Pumilio家族的rna结合蛋白PUM1和PUM2，作为神经嵴发育的候选转录后调节因子。利用杂交链反应（HCR）技术，研究了禽类胚胎（Gallus Gallus）颅神经嵴发育早期Pumilio家族mrna的时空表达。我们发现Pum1和Pum2虽然在胚层中表达，但在外胚层组织中富集，并且在神经发育后，Pum1和Pum2表现出不同的表达模式。我们观察到，在神经嵴分化和上皮间质转化（EMT）过程中，Pum1在整个神经管和神经嵴中表达更加均匀。相反，在准备接受EMT的神经嵴细胞中，Pum2富集。因此，我们假设PUM1和PUM2，通常被推测为功能冗余，可能在神经嵴发育的关键步骤中发挥不同的作用。

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引用次数: 0

Developmental biology in Chile: an open window to Latin America and the world 智利的发育生物学：向拉丁美洲和世界打开的一扇窗

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-06-16 DOI: 10.1016/j.diff.2025.100882

Miguel L. Concha , Marcia Gaete , Sylvain Marcellini , Verónica Palma , Marcela Torrejón , Constanza Vásquez-Doorman

The field of developmental biology has a relatively short history in Chile. It began with the pioneering work of Luis Izquierdo in the 1950s, when he challenged the prevailing views on embryology and comparative anatomy. Since then, the developmental biology community has grown considerably, broadening its vision and perspectives, as well as its international presence. Within the Latin American context, Chile has played a leading role in promoting the discipline and training a new generation of developmental biologists. In 2024, the country hosted several impactful regional events including a hands-on course, an international conference, a global lecture series, and the inaugural congress of the Chilean Society for Developmental Biology (SBDCh). The pivotal role played by the European Molecular Biology Organisation (EMBO), the United Nations University Programme for Biotechnology in Latin America and the Caribbean (UNU-BIOLAC), and the International Society of Differentiation (ISD) in supporting Chile's leadership in the field is also worth highlighting. These organisations enabled the participation of young Latin American researchers by providing travel grants and support. This is particularly relevant in today's changing world, where global integration and collaboration are fundamental to the effective promotion of developmental biology, especially among younger generations.

发育生物学领域在智利的历史相对较短。它始于20世纪50年代路易斯·伊兹基耶多的开创性工作，当时他挑战了胚胎学和比较解剖学的主流观点。从那时起，发育生物学社区有了相当大的发展，拓宽了它的视野和观点，以及它的国际存在。在拉丁美洲范围内，智利在促进该学科和培训新一代发育生物学家方面发挥了主导作用。2024年，智利举办了几次有影响力的区域活动，包括一次实践课程、一次国际会议、一次全球系列讲座和智利发育生物学学会（SBDCh）成立大会。欧洲分子生物学组织（EMBO）、联合国大学拉丁美洲和加勒比生物技术项目（UNU-BIOLAC）和国际分化学会（ISD）在支持智利在该领域的领导地位方面发挥的关键作用也值得强调。这些组织通过提供旅行资助和支持，使年轻的拉丁美洲研究人员能够参与。这在当今不断变化的世界中尤为重要，因为全球一体化与合作是有效促进发育生物学，特别是在年轻一代中促进发育生物学的根本。

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引用次数: 0

Enteric neural crest development in Astyanax mexicanus surface fish and cavefish 面鱼和穴居鱼肠道神经嵴发育的研究

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-06-13 DOI: 10.1016/j.diff.2025.100881

Pavani Ponnimbaduge Perera , Kaitlyn Webster , Misty R. Riddle

The enteric nervous system (ENS) regulates gastrointestinal (GI) functions such as secretion, blood flow, and motility, yet how its structure and function evolve with dietary adaptations remains unclear. Astyanax mexicanus, a teleost fish with surface and cave morphotypes, offers a model to explore these changes; cavefish exhibit altered GI motility and transit that may help them adapt to their unique diet. We compared early ENS development in surface fish and cavefish, tracking enteric neural crest cell (ENCC) migration and differentiation using phox2bb and HuC/D markers. We found that ENCCs reach the gut by 36 hours post-fertilization (hpf) in both morphotypes but migrate and differentiate more rapidly along the gut in cavefish. To explore the genetic basis of this difference, we used available genomic datasets to compare the predicted peptide sequences of genes important for ENS development in other species and identified mutations that could impact protein function, for example in the endothelin signaling genes important for ENCC migration and differentiation. We specifically examined the expression of endothelin-3 (edn3) and endothelin receptor-b a (ednrba) during ENCC migration and found that the localization of edn3, but not ednrba, is consistent with a potential role in ENS development. Overall, our findings establish A. mexicanus as a model for studying evolution of ENS development.

肠神经系统（ENS）调节胃肠道（GI）功能，如分泌、血流和运动，但其结构和功能如何随着饮食适应而进化尚不清楚。Astyanax mexicanus，一种具有表面和洞穴形态的硬骨鱼，为探索这些变化提供了一个模型；洞穴鱼表现出改变的胃肠道运动和运输，这可能有助于它们适应独特的饮食。我们比较了表层鱼和洞穴鱼的早期ENS发育，利用phox2bb和HuC/D标记跟踪了肠神经嵴细胞（enteric neural crest cell， ENCC）的迁移和分化。我们发现，两种形态的ENCCs在受精后36小时到达肠道，但在洞穴鱼中，ENCCs沿着肠道迁移和分化的速度更快。为了探索这种差异的遗传基础，我们使用现有的基因组数据集来比较其他物种ENS发育重要基因的预测肽序列，并确定可能影响蛋白质功能的突变，例如对ENCC迁移和分化重要的内皮素信号基因。我们专门检查了内皮素-3 （edn3）和内皮素受体-b - a （ednrba）在ENCC迁移过程中的表达，发现edn3的定位，而不是ednrba，与ENS发展的潜在作用一致。总的来说，我们的研究结果建立了墨西哥拟南猿作为研究ENS发展进化的模型。

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引用次数: 0

Origin stories of neural crest roles in craniofacial development: A tale of the meninges 颅面发育中神经嵴作用的起源故事：脑膜的故事

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-06-05 DOI: 10.1016/j.diff.2025.100880

Diana Rigueur , Julia C. Boughner

As developmental biologists, we tell origin stories to explain differences in vertebrate craniofacial form and complexity. Some of these differences are linked to diseases, notably of patients born with congenital malformations, many of them syndromic. These defective processes impede proper neural crest cell migration, differentiation, and patterning of bones, cartilage, joints, muscle and other connective tissues, including of the head. For example, a rare form of holoprosencephaly called cyclopia is a particular quandary in its diverse presentation. This syndromic congenital disease includes lost brain frontal lobe septation and development of a single eye. Subsequent craniofacial midline defects include frontal suture synostosis, absent nose and medial maxilla, and a restructuring of facial bones to accommodate one eye. The meningeal tissues in contact with both the underlying brain and the overlying calvarial bone are derived at least in part from neural crest cells. This Perspectives piece re-examines communication between the neural crest cell-brain axis, explores the direct involvement of the meninges in this communication process, and proposes an expanded origin story about the etiology of craniofacial patterning and disease.

作为发育生物学家，我们讲述起源故事来解释脊椎动物颅面形态和复杂性的差异。其中一些差异与疾病有关，特别是先天性畸形患者，其中许多是综合征。这些缺陷阻碍了正常的神经嵴细胞迁移、分化和骨骼、软骨、关节、肌肉和其他结缔组织（包括头部）的形成。例如，一种罕见的被称为独眼畸形的无前脑畸形在其多样化的表现中是一个特别的困境。这种先天性综合征包括丧失大脑额叶分隔和单眼发育。随后的颅面中线缺损包括额骨缝缝闭合，鼻和上颌骨内侧缺失，以及面骨重建以适应一只眼睛。与下颅脑和上颅骨接触的脑膜组织至少部分来源于神经嵴细胞。这篇透视文章重新审视了神经嵴细胞-脑轴之间的交流，探讨了脑膜在这一交流过程中的直接参与，并提出了颅面模式和疾病病因学的扩展起源故事。

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引用次数: 0

Proteins and peptides responsible for bone remodeling 负责骨重塑的蛋白质和多肽

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-05-29 DOI: 10.1016/j.diff.2025.100872

Jorge Alejandro Barbosa-Nuñez , José Nabor Haro-González , Eristeo García-Márquez , Hugo Espinosa-Andrews , Eduardo Padilla-Camberos , Sara Elisa Herrera-Rodríguez

Bones are living tissues that are periodically renewed through the bone remodeling process. It starts when monocyte-macrophage-type cells begin to proliferate and recruit into the bone tissue due to the action of various proteins. The proteins are generated by the body in response to a lack of calcium in the blood or a damaged bone tissue. Then, other chemical signals promote the differentiation of monocyte-macrophage-type cells into osteoclasts. Finally, osteoclasts carry out a process known as bone resorption in which they degrade bone tissue. After, bone resorption a process known as osteogenesis takes place. In osteogenesis, pluripotent mesenchymal stem cells proliferate and recruit in the bone damaged by bone resorption in response to the action of different compounds. Then, pluripotent mesenchymal stem cells differentiate into osteoblasts due to the effect of specific proteins. Finally, osteoblasts generate new bone tissue, completing the bone remodeling process. This review aims to summarize and provide recent findings of the proteins and chemical signals involved in osteoclast and osteoblast proliferation, recruitment and maturation during the bone resorption and osteogenesis processes. The information found about these molecules could help to better understand all the complex mechanisms that directly or indirectly influence the bone remodeling process. In this sense, the mechanisms of different bone disorders and diseases could be elucidated in a better way, leading to the generation of efficient and specific treatments for each of them in the future.

骨骼是活的组织，通过骨骼重塑过程周期性地更新。当单核巨噬细胞型细胞开始增殖并在各种蛋白质的作用下进入骨组织时，它就开始了。这种蛋白质是人体在血液中缺钙或骨组织受损时产生的。然后，其他化学信号促进单核-巨噬细胞型细胞向破骨细胞分化。最后，破骨细胞进行被称为骨吸收的过程，在这个过程中它们降解骨组织。之后，发生骨吸收过程，称为成骨。在成骨过程中，多能间充质干细胞在不同化合物的作用下，在骨吸收损伤的骨中增殖和再生。多能间充质干细胞在特定蛋白的作用下向成骨细胞分化。最后，成骨细胞生成新的骨组织，完成骨重塑过程。本文综述了骨吸收和成骨过程中破骨细胞和成骨细胞增殖、募集和成熟过程中涉及的蛋白质和化学信号的最新发现。发现这些分子的信息有助于更好地理解所有直接或间接影响骨重塑过程的复杂机制。从这个意义上说，可以更好地阐明不同骨紊乱和疾病的机制，从而在未来为每种疾病产生有效和特异性的治疗方法。

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引用次数: 0