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Distributions of parvalbumin, calbindin-D28k, and calretinin in the cerebrum of Chinese tree shrews ( Tupaia belangeri chinensis): A high-resolution neuroanatomical resource. 中国树鼩(Tupaia belangeri chinensis)大脑中细小蛋白、钙结合蛋白- d28k和钙黄蛋白的分布:高分辨率神经解剖学资源。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.095
Rong Zhang, Jia-Li Long, Yi-Fan Ye, Hao-Yun Ye, Xiao-Nan Zhao, Xing Cai, Li Lu

The Chinese tree shrew (Tupaia belangeri chinensis) has gained prominence as a model organism due to its phylogenetic proximity to primates, offering distinct advantages over traditional rodent models in biomedical research. However, the neuroanatomy of this species remains insufficiently defined, limiting its utility in neurophysiological and neuropathological studies. In this study, immunofluorescence microscopy was employed to comprehensively map the distribution of three calcium-binding proteins, parvalbumin, calbindin D-28k, and calretinin, across the tree shrew cerebrum. Serial brain sections in sagittal, coronal, and horizontal planes from 12 individuals generated a dataset of 3 638 cellular-resolution images. This dataset, accessible via Science Data Bank (https://doi.org/10.57760/sciencedb.23471), provides detailed region- and laminar-selective distributions of calcium-binding proteins valuable for the cyto- and chemoarchitectural characterization of the tree shrew cerebrum. This resource will not only advance our understanding of brain organization and facilitate basic and translational neuroscience research in tree shrews but also enhance comparative and evolutionary analyses across species.

中国树鼩作为一种模式生物,由于其系统发育接近灵长类动物,在生物医学研究中比传统的啮齿动物模型具有明显的优势。然而,该物种的神经解剖学仍然不够明确,限制了其在神经生理学和神经病理学研究中的应用。本研究采用免疫荧光显微镜综合绘制了三种钙结合蛋白parvalbumin、calbindin D-28k和calretinin在树鼩大脑中的分布。12个个体的矢状面、冠状面和水平面的连续脑切片生成了3张 638张细胞分辨率图像的数据集。该数据集可通过科学数据库(https://doi.org/10.57760/sciencedb.23471)访问,提供了详细的钙结合蛋白的区域和层流选择分布,对树鼩大脑的细胞和化学结构特征有价值。这一资源不仅将促进我们对大脑组织的理解,促进树鼩的基础和转化神经科学研究,而且还将加强跨物种的比较和进化分析。
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引用次数: 0
YAP1 promotes adipogenesis by regulating the negative feedback mechanism of the Hippo signaling pathway via LATS2. YAP1通过调节Hippo信号通路LATS2的负反馈机制促进脂肪形成。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2024.404
Mei Zhou, Yue-Qi Zhao, Wei Yan, Xue-Feng Fu, Li-Hui Zhang, Hong-Yan Zhang, Ge-Gen-Tu-Ya Bao, Dong-Jun Liu

Adipose-derived mesenchymal stem cells (ADSCs) represent a readily accessible and important source of mesenchymal stem cells (MSCs) capable of multilineage differentiation. The Hippo signaling pathway effector YAP has emerged as a pivotal regulator of stem cell fate, yet the specific molecular mechanism by which it modulates lipogenic differentiation of ADSCs has not been clearly defined. In this study, goat ADSCs (gADSCs) isolated from Albas goats in Inner Mongolia were used to investigate the role of YAP1 in adipogenic differentiation. Overexpression of YAP1 significantly promoted the differentiation of ADSCs into adipocytes, an effect accompanied by up-regulation of LATS2 and activation of the negative feedback loop of the Hippo signaling pathway. Elevated LATS2 expression induced YAP phosphorylation, leading to reduced nuclear levels of YAP and TAZ and their subsequent accumulation in the cytoplasm. YAP1 overexpression up-regulated LATS2 expression, which, in turn, enhanced the adipogenic differentiation of ADSCs. This pro-adipogenic effect of YAP1 was dependent on LATS2 kinase activity. These findings indicate that overexpression of YAP1 promotes ADSC adipogenesis by inducing LATS2 expression and activating the Hippo pathway negative feedback loop. Elucidating the molecular role of YAP in ADSC lipogenic differentiation holds great significance for regulating stem cell fate, treating metabolic disorders, and promoting hair follicle growth.

脂肪源性间充质干细胞(ADSCs)是具有多系分化能力的间充质干细胞(MSCs)的重要来源。Hippo信号通路效应因子YAP已成为干细胞命运的关键调节因子,但其调节ADSCs脂质分化的具体分子机制尚未明确定义。本研究利用从内蒙古阿尔巴斯山羊分离的山羊ADSCs (gADSCs)研究YAP1在成脂分化中的作用。YAP1过表达可显著促进ADSCs向脂肪细胞的分化,同时伴有LATS2的上调和Hippo信号通路负反馈回路的激活。升高的LATS2表达诱导YAP磷酸化,导致细胞核中YAP和TAZ水平的降低以及随后在细胞质中的积累。YAP1过表达上调LATS2表达,进而促进ADSCs的成脂分化。YAP1的促脂肪作用依赖于LATS2激酶的活性。这些发现表明,YAP1过表达通过诱导LATS2表达和激活Hippo通路负反馈回路促进ADSC脂肪形成。阐明YAP在ADSC脂质分化中的分子作用,对调节干细胞命运、治疗代谢紊乱、促进毛囊生长具有重要意义。
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引用次数: 0
Discovery of an ancient Himalayan birch mouse lineage illuminates the evolution of the family Sicistidae (Rodentia: Dipodoidea), with descriptions of a new genus and two new species. 一个古老的喜马拉雅桦树小鼠谱系的发现阐明了桦树家族的进化(啮齿目:双足科),描述了一个新属和两个新种。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.013
Zhong-Xu Zhu, Quan Li, Wen-Yu Song, Xue-You Li, Andrey Lissovsky, Mu-Yang Wang, Xiao-Xin Pei, Kang Luo, Jing Luo, Ming-Jin Pu, Chang-Zhe Pu, Hong-Jiao Wang, Zhu Liu, Zhong-Zheng Chen, Xue-Long Jiang

Birch mice (family Sicistidae) are small dipodoid rodents distributed in regions surrounding the Qinghai-Xizang Plateau and extending across the Palearctic. In China, members of the genus Sicista are rarely recorded, and their systematics remain poorly resolved. As part of the Second Xizang Plateau Expedition by the Kunming Institute of Zoology, Chinese Academy of Sciences, systematic surveys conducted in southern Xizang and the western Tianshan Mountains yielded two previously unrecognized species. Two specimens from southern Xizang were found to occupy a deeply divergent phylogenetic position within Sicistidae. Morphological assessments and molecular phylogenetic analyses of both extant and fossil Sicistidae, along with total-evidence dating and ancestral distribution reconstruction, identified these specimens as representatives of an ancient extant lineage that diverged from Sicista approximately 20.38 million years ago. This lineage is designated as a new genus, defined by the new species Breviforamen shannanensis gen. et sp. nov. Furthermore, 11 specimens from the Tianshan Mountains are described as a second new species, Sicista brevicauda sp. nov., based on diagnostic morphological and genetic features. Ancestral distribution reconstructions, combined with fossil records, indicate an early Miocene origin for Sicistidae across a broad region spanning the "Gobi" Desert to parts of North America. Climatic deterioration and increasing desertification during the mid-Miocene likely drove southward dispersal of Breviforamen gen. nov. into southern Xizang prior to the complete formation of the Yarlung Zangbo River. Overall, these findings broaden current understanding of Sicistidae diversity, elucidate the origin and dispersal patterns of the family, and highlight the presence of an ancient relict lineage in China.

桦鼠是一种分布在青藏高原周边地区、横跨古北大陆的小型双足目啮齿类动物。在中国,Sicista属的成员很少被记录,它们的系统分类仍然很不清楚。作为中国科学院昆明动物研究所第二次西藏高原考察的一部分,在西藏南部和天山西部进行的系统调查发现了两种以前未被认识的物种。西藏南部的两个标本被发现在西西里岛科中占有一个非常不同的系统发育位置。现存和化石Sicistidae的形态评估和分子系统发育分析,以及总证据定年和祖先分布重建,确定这些标本是大约2038万年前从Sicistidae分化出来的古代现存谱系的代表。将该谱系作为新种(Breviforamen shannanensis gen. et sp. nov.)定义为新属。此外,根据诊断形态学和遗传特征,将天山地区的11个标本描述为新种(Sicista brevicauda sp. nov.)。祖先分布重建与化石记录相结合,表明Sicistidae起源于中新世早期,横跨“戈壁”沙漠到北美部分地区的广阔地区。在雅鲁藏布江完全形成之前,中新世中期气候恶化和沙漠化加剧可能促使短孔虫向南扩散到西藏南部。总的来说,这些发现拓宽了目前对猪尾科多样性的认识,阐明了猪尾科的起源和分布模式,并强调了中国古代遗存谱系的存在。
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引用次数: 0
Genomic insights into the convergent evolution of desert adaptation in camels and antelopes. 骆驼和羚羊沙漠适应趋同进化的基因组见解。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2024.440
Jiong Zhou, Xiao-Fang Zhou, Hui-Shan Yue, Wu Chen, Bin Li, Bo-Tong Zhou, Zi-He Li, Ze-Cheng Du, Yi-Fan Mao, Wen Wang, Dong-Dong Wu, Ge Han, Bao Wang, Lei Chen

Extreme heat and chronic water scarcity present formidable challenges to large desert-dwelling mammals. In addition to camels, antelopes within the Hippotraginae and Alcelaphinae subfamilies also exhibit remarkable physiological and genetic specializations for desert survival. Among them, the critically endangered addax ( Addax nasomaculatus) represents the most desert-adapted antelope species. However, the evolutionary and molecular mechanisms underlying desert adaptations remain largely unexplored. Herein, a high-quality genome assembly of the addax was generated to investigate the molecular evolution of desert adaptation in camels and desert antelopes. Comparative genomic analyses identified 136 genes harboring convergent amino acid substitutions implicated in crucial biological processes, including water reabsorption, fat metabolism, and stress response. Notably, a convergent R146S amino acid mutation in the prostaglandin EP2 receptor gene PTGER2 significantly reduced receptor activity, potentially facilitating large-mammal adaptation to arid environments. Lineage-specific innovations were also identified in desert antelopes, including previously uncharacterized conserved non-coding elements. Functional assays revealed that several of these elements exerted significant regulatory effects in vitro, suggesting potential roles in adaptive gene expression. Additionally, signals of introgression and variation in genetic load were observed, indicating their possible influence on desert adaptation. These findings provide insights into the sequential evolutionary processes that drive physiological resilience in arid environments and highlight the importance of convergent evolution in shaping adaptive traits in large terrestrial mammals.

极端高温和长期缺水给大型沙漠哺乳动物带来了巨大的挑战。除骆驼外,羚羊亚科和羚羊亚科也表现出显著的沙漠生存生理和遗传特化。其中,极度濒危的阿达克斯(addax nasomaculatus)是最能适应沙漠环境的羚羊。然而,沙漠适应的进化和分子机制在很大程度上仍未被探索。本文构建了骆驼和沙漠羚羊的高质量基因组,以研究骆驼和沙漠羚羊的沙漠适应分子进化。比较基因组分析确定了136个基因,这些基因含有与水重吸收、脂肪代谢和应激反应等关键生物过程有关的聚合氨基酸取代。值得注意的是,前列腺素EP2受体基因PTGER2的R146S氨基酸突变显著降低了受体活性,可能有助于大型哺乳动物适应干旱环境。在沙漠羚羊中也发现了特定谱系的创新,包括以前未表征的保守非编码元素。功能分析显示,其中一些元件在体外发挥了显著的调节作用,提示在适应性基因表达中可能起作用。此外,还观察到遗传负荷的渗入和变异信号,表明它们可能对沙漠适应产生影响。这些发现提供了对干旱环境中驱动生理恢复力的顺序进化过程的见解,并强调了趋同进化在塑造大型陆生哺乳动物适应特征方面的重要性。
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引用次数: 0
Phenotypic, transcriptomic, and genomic analyses reveal the spatiotemporal patterns and associated genes of coarse hair density in goats. 表型、转录组学和基因组分析揭示了山羊粗毛密度的时空模式和相关基因。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.034
Ji-Pan Zhang, Min Xiao, Jia-Bei Fang, De-Li Huang, Yong-Ju Zhao

The genetic regulation of hair density in animals remains poorly understood. The Dazu black goat, characterized by its black coarse hair and white skin, provides a unique model for dissecting coarse hair density (CHD). Using high-resolution micro-camera imaging, this study analyzed 905 skin images, 33 skin transcriptomes, 272 whole-genome sequences, and 182 downloaded transcriptomes. Morphological assessment from juvenile to adult stages revealed the thickening of hair shafts accompanied by a progressive decline in density, largely attributable to rapid surface expansion of the trunk skin. Transcriptomic comparison between high- and low-CHD individuals identified 572 differentially expressed genes (DEGs). A genome-wide association study detected 25 significant single nucleotide polymorphisms ( P<9.07e-8) and mapped 48 annotated genes, with the most prominent association signal located near GJA1 on chr9.15931585-18621011. Literature review and Venn analysis highlighted six genes ( GJA1, GPRC5D, CD1D, CD207, TFAM, and CXCL12) with documented roles in skin and hair biology, and three genes ( GJA1, GPRC5D, and ATP6V1B1) overlapped with DEGs. Multiple-tissue transcriptomic profiling, western blotting, immunohistochemical staining, and skin single-cell RNA sequencing confirmed that GJA1 and GPRC5D were highly and specifically expressed in skin, particularly within hair follicles. Expression was localized predominantly to follicular stem cells and dermal papilla cells, suggesting a significant role in folliculogenesis and structural maintenance. Cross-validation using four public datasets further demonstrated positive correlations between GJA1 and GPRC5D expression and hair follicle density. The innovative micro-camera application allowed the elucidation of spatiotemporal patterns and genes associated with CHD, thereby addressing a significant knowledge gap in animal hair density.

动物毛发密度的遗传调控仍然知之甚少。大足黑山羊以其黑色粗毛和白色皮肤为特征,为解剖粗毛密度(CHD)提供了独特的模型。利用高分辨率微相机成像,本研究分析了905张皮肤图像、33个皮肤转录组、272个全基因组序列和182个下载的转录组。从幼年期到成虫期的形态学评估显示毛干的增厚伴随着密度的逐渐下降,这主要是由于躯干皮肤表面的快速扩张。高、低冠心病个体的转录组学比较鉴定出572个差异表达基因(DEGs)。一项全基因组关联研究检测到chr9_15831585-18621011上25个显著的单核苷酸多态性(PGJA1)。文献回顾和Venn分析强调了六个基因(GJA1, GPRC5D, CD1D, CD207, TFAM和CXCL12)在皮肤和头发生物学中有记录的作用,三个基因(GJA1, GPRC5D和ATP6V1B1)与deg重叠。多组织转录组学分析、western blotting、免疫组织化学染色和皮肤单细胞RNA测序证实,GJA1和GPRC5D在皮肤,特别是毛囊内高度特异性表达。表达主要局限于滤泡干细胞和真皮乳头细胞,表明在滤泡发生和结构维持中起重要作用。使用4个公开数据集进行交叉验证,进一步证实GJA1和GPRC5D表达与毛囊密度呈正相关。这一创新的微型相机应用程序允许阐明与冠心病相关的时空模式和基因,从而解决了动物毛发密度方面的重大知识空白。
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引用次数: 0
Static magnetic field exposure modulates gut microbiota and host metabolism to alleviate high-fat diet-induced metabolic dysfunction-associated fatty liver disease. 静磁场暴露调节肠道微生物群和宿主代谢,以减轻高脂肪饮食诱导的代谢功能障碍相关的脂肪肝疾病。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2024.462
Guo-Fu Chen, Juan-Juan Liu, Jing-Ming Fu, Chuan-Lin Feng, Guo-Feng Cheng, Ze-Min Fang, Xin Zhang, Xiao-Fei Tian

Static magnetic field (SMF) exposure exerts notable regulatory effects on metabolic disorders, yet its influence on metabolic dysfunction-associated fatty liver disease (MAFLD) and gut microbiota during disease progression remains unclear. In this study, MAFLD was induced in mice via a high-fat diet (HFD), followed by exposure to a 0.2 T SMF for 12 h per day over a 10 week period. SMF treatment significantly attenuated body weight gain, alleviated hepatic lipid accumulation, and improved liver function. Sequencing analysis of intestinal contents revealed a significant increase in microbial diversity and enrichment of beneficial bacterial taxa under SMF exposure. Integrated multi-omics analysis and Spearman correlation further demonstrated that SMF significantly reduced the expression of genes involved in fatty acid synthesis and modulated pathways related to polyunsaturated fatty acid and glutamate metabolism, in close association with shifts in beneficial gut microbiota. Furthermore, transcriptomic profiling of liver tissue indicated that SMF inhibited fatty acid synthesis and elongation by regulating the expression of peroxisome proliferator-activated receptor γ ( PPARγ), thereby contributing to reduced hepatic burden. These findings highlight SMF as a promising non-invasive strategy for MAFLD intervention and provide insights into the microbiota-mediated metabolic axis underlying its therapeutic effects.

静磁场(SMF)暴露对代谢紊乱具有显著的调节作用,但其对代谢功能障碍相关脂肪性肝病(MAFLD)和疾病进展期间肠道微生物群的影响尚不清楚。在这项研究中,通过高脂肪饮食(HFD)在小鼠中诱导mald,然后在10周内每天暴露于0.2 T SMF 12小时。SMF治疗可显著减轻体重增加,减轻肝脏脂质积累,改善肝功能。肠道内容物测序分析显示,SMF暴露下微生物多样性显著增加,有益菌群丰富。综合多组学分析和Spearman相关性进一步表明,SMF显著降低了脂肪酸合成相关基因的表达,以及与多不饱和脂肪酸和谷氨酸代谢相关的调控途径,与有益肠道菌群的变化密切相关。此外,肝脏组织的转录组学分析表明,SMF通过调节过氧化物酶体增殖物激活受体γ (PPARγ)的表达来抑制脂肪酸的合成和延长,从而有助于减轻肝脏负担。这些发现强调了SMF作为一种有前途的非侵入性干预MAFLD策略,并为其治疗效果背后的微生物介导的代谢轴提供了见解。
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引用次数: 0
Insight into molecular and neural mechanisms of general anesthesia from the invertebrate model Drosophila melanogaster. 从无脊椎动物模型黑腹果蝇观察全身麻醉的分子和神经机制。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.021
Jia-Yue Gao, Tao Luo, Chang Liu

General anesthesia (GA) is a pharmacologically induced, reversible state characterized by unconsciousness, amnesia, analgesia, and immobility in response to noxious stimuli. Accumulating evidence from animal models has elucidated diverse mechanisms of the action underlying GA, including disruption of large-scale brain network connectivity, regulation of multiple neural pathways, and modulation of specific receptors and ion channels. Despite advances in dissecting the neurobiological basis of anesthetic action, the precise cellular and circuit-level processes remain incompletely understood, limiting the development of safer and more effective strategies. Recent studies in Drosophila melanogaster, a genetically tractable model organism offering robust genetic analysis, advanced imaging capabilities, and compact neural architecture, have yielded critical insights into the conserved neurobiological mechanisms of GA, offering translational value for mammalian systems. This review outlines: 1) experimental paradigms used to evaluate anesthetic sensitivity and behavioral responses in Drosophila; 2) molecular targets and their mechanistic roles in mediating GA; and 3) neural circuit architectures and activity patterns shared by GA and sleep. Cross-species comparisons are integrated to highlight conserved mechanisms that may guide the development of more refined anesthetic strategies.

全身麻醉(GA)是一种药物诱导的可逆状态,其特征是对有害刺激的反应,表现为无意识、健忘症、镇痛和不动。从动物模型中积累的证据已经阐明了GA的多种作用机制,包括大规模脑网络连接的破坏,多种神经通路的调节,以及特定受体和离子通道的调节。尽管在解剖麻醉作用的神经生物学基础方面取得了进展,但精确的细胞和回路水平过程仍然不完全清楚,这限制了更安全和更有效策略的发展。黑腹果蝇是一种遗传上易于处理的模式生物,具有强大的遗传分析能力、先进的成像能力和紧凑的神经结构,最近的研究已经对遗传遗传的保守神经生物学机制产生了重要的见解,为哺乳动物系统提供了翻译价值。本文概述了:1)用于评估果蝇麻醉敏感性和行为反应的实验范式;2)遗传介导的分子靶点及其机制;3)遗传与睡眠共享的神经回路结构和活动模式。跨物种比较整合,以突出保守的机制,可能指导更精细的麻醉策略的发展。
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引用次数: 0
Evolutionary history of Old World cellar spiders in the context of Neo-Tethyan sea-land transformations. 在新特提斯海陆转换的背景下,旧大陆地窖蜘蛛的进化史。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.325
Zhi-Yuan Yao, Shu-Qiang Li

The ancient Neo-Tethyan region underwent profound tectonic transformations, including the orogenesis of the Xizang Plateau and the westward retreat and ultimate closure of the Neo-Tethyan Ocean. These events significantly influenced the diversification and biogeography of aquatic animals. However, the impact of these large-scale sea-land shifts on the long-range evolutionary history of terrestrial fauna remains unclear. This study investigated how geological changes in the Neo-Tethyan region shaped the evolutionary trajectories and dispersal patterns of Pholcus sensu lato cellar spiders across the Old World. Molecular dating, ancestral area reconstructions, and diversity analyses were conducted using sequences from seven genes across 234 samples representing 209 species. Results indicated that these spiders originated in the eastern Neo-Tethyan region during the Early Eocene, with their subsequent diversification driven by a series of concomitant geological events. The Eurasian (ER) Group dispersed into Europe following the westward retreat of the Neo-Tethyan Ocean in the Early Miocene, while the African (AF) Group migrated into Africa via the Arabian Plate land bridge following the closure of the Neo-Tethyan Ocean in the Oligocene. The East Asian (EA) Group, which expanded along the southeastern margin of the Himalayas, experienced explosive diversification in response to sustained orogenesis at the Eocene-Oligocene boundary. These findings illustrate how large-scale geological processes and sea-land changes shaped the evolutionary history of terrestrial fauna in the Neo-Tethyan region.

古新特提斯地区经历了深刻的构造改造,包括西藏高原的造山作用和新特提斯洋的西退和最终闭合。这些事件显著影响了水生动物的多样性和生物地理。然而,这些大规模的海陆转换对陆生动物的长期进化史的影响仍不清楚。本研究调查了新特提斯地区的地质变化如何塑造了旧大陆Pholcus sensu lato地窖蜘蛛的进化轨迹和扩散模式。利用来自209个物种的234个样本的7个基因序列进行了分子定年、祖先区域重建和多样性分析。结果表明,这些蜘蛛在始新世早期起源于新特提斯东部地区,随后在一系列伴随的地质事件的推动下进行了多样化。早中新世,欧亚(ER)群随着新特提斯洋的西退而分散到欧洲,而渐新世,非洲(AF)群随着新特提斯洋的关闭而通过阿拉伯板块陆桥迁移到非洲。东亚群在始新世—渐新世边界的持续造山活动中经历了爆发性的多样化。这些发现说明了大规模的地质过程和海陆变化如何塑造了新特提斯地区陆生动物的进化史。
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引用次数: 0
Author Correction: DNA methylation-mediated expression of zinc finger protein 615 affects embryonic development in Bombyx mori. 作者更正:DNA甲基化介导的锌指蛋白615的表达影响家蚕胚胎发育。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.215
Guan-Feng Xu, Cheng-Cheng Gong, Yu-Lin Tian, Tong-Yu Fu, Yi-Guang Lin, Hao Lyu, Yu-Ling Peng, Chun-Mei Tong, Qi-Li Feng, Qi-Sheng Song, Si-Chun Zheng
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引用次数: 0
Subcutaneous delivery of icariin via a gelatin methacryloyl (GelMA) hydrogel sustained-release system improves ovarian function in reproductively aged mice. 经明胶甲基丙烯酰(GelMA)水凝胶缓释系统皮下递送淫羊藿苷可改善育龄小鼠卵巢功能。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2024.447
Jia-Lian Mao, Xiang-Yi Wu, Ling-Xi Li, Ning Li, Ya-Xuan Wang, Zhi-Wei Jiang, Chuan-Ming Liu, Hui-Dan Zhang, Ji-Dong Zhou, Yang Zhang, Li Chen, Gui-Jun Yan, Hai-Xiang Sun, Yi-Fan Li, Li-Jun Ding

Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age. Icariin (ICA), a flavonoid compound derived from Epimedium species, has demonstrated potential as an agent for ovarian restoration. In this study, a subcutaneous implantation system using gelatin methacryloyl (GelMA) hydrogel embedded with ICA was developed to restore ovarian function in aged female mice. Mice were assigned to receive subcutaneous implantation of GelMA alone (GelMA group), GelMA containing ICA (GelMA/ICA group), or a sham operation. Ovarian morphology, serum hormone levels, follicle counts across developmental stages, and reproductive outcomes were evaluated. In vitro fertilization (IVF) and embryo culture assays were performed to assess oocyte developmental potential, while a 10 day natural mating trial was conducted to determine fertility restoration. RNA sequencing (RNA-seq) and RT-qPCR were performed to elucidate the underlying molecular mechanisms. Results showed that GelMA/ICA treatment significantly increased ovarian index (0.19±0.01 vs. 0.13±0.01, P<0.0001) and follicle numbers at all developmental stages, including primordial (383.33±151.65 vs. 107.14±32.26, P<0.0001), primary (203.33±83.22 vs. 91.43±27.04, P=0.003), and secondary follicles (154.17±52.00 vs. 59.28±20.50, P=0.029) compared to the sham controls. Hormonal analyses revealed a significant reduction in serum follicle-stimulating hormone (FSH, 11.97±3.53 vs. 53.10±17.89 ng/mL, P=0.0008), accompanied by elevated anti-Müllerian hormone (AMH, 22.97±2.26 vs. 5.54±1.56 ng/mL, P<0.0001) and estradiol (E 2, 315.30±37.62 vs. 168.5±14.78 pg/mL, P<0.0001). Oocyte yield and developmental potential improved significantly, as reflected by the increased number of superovulated MII oocytes (17.83±5.15 vs. 4.83±4.79, P=0.0002), and higher proportions of two-cell (85.90%±6.16% vs. 50.00%±10.00%, P=0.0009), four-cell (81.67%±9.76% vs. 50.00%±10.00%, P=0.0061), and blastocyst stage embryos (64.25%±10.55% vs. 23.33%±15.28%, P=0.0067). Live birth numbers were significantly increased following GelMA/ICA treatment (6.90±3.21 vs. 1.72±2.05, P=0.0001). Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization ( Vil1, Tubb3), lipid storage ( Soat2, Plin4), oocyte maturation ( Oosp2), and cytokine secretion ( Cxcl12). Collectively, these findings suggest that GelMA/ICA hydrogels effectively reverse key hallmarks of ovarian aging and restore reproductive function in aged mice, offering a promising platform for fertility preservation and a novel therapeutic for future investigations into ovarian aging.

卵巢衰老的特点是卵母细胞的质量和数量随着年龄的增长而逐渐下降。淫羊藿苷(Icariin, ICA)是一种从淫羊藿中提取的类黄酮化合物,已被证明有潜力作为卵巢修复剂。本研究采用明胶甲基丙烯酰(GelMA)水凝胶包埋ICA,建立了一种用于恢复老年雌性小鼠卵巢功能的皮下植入系统。小鼠分别接受单独GelMA皮下植入(GelMA组)、含有ICA的GelMA (GelMA/ICA组)或假手术。评估卵巢形态、血清激素水平、发育阶段卵泡计数和生殖结果。通过体外受精(IVF)和胚胎培养试验来评估卵母细胞的发育潜力,同时进行10天的自然交配试验来确定生育恢复情况。通过RNA测序(RNA-seq)和RT-qPCR来阐明潜在的分子机制。结果显示,与假对照组相比,GelMA/ICA治疗组卵巢指数(0.19±0.01比0.13±0.01,PPP=0.003)和次级卵泡(154.17±52.00比59.28±20.50,P=0.029)显著升高。激素分析显示,血清促卵泡激素(FSH, 11.97±3.53 vs. 53.10±17.89 ng/mL, P=0.0008)显著降低,抗勒氏激素(AMH, 22.97±2.26 vs. 5.54±1.56 ng/mL, P2, 315.30±37.62 vs. 168.5±14.78 pg/mL, PP=0.0002)升高,二细胞胚胎(85.90%±6.16% vs. 50.00%±10.00%,P=0.0009)、四细胞胚胎(81.67%±9.76% vs. 50.00%±10.00%,P=0.0061)和囊胚期胚胎(64.25%±10.55% vs. 23.33%±15.28%,P=0.0067)比例较高。GelMA/ICA治疗组活产数显著增加(6.90±3.21比1.72±2.05,P=0.0001)。转录组学分析显示,与细胞骨架组织(Vil1, Tubb3)、脂质储存(Soat2, Plin4)、卵母细胞成熟(Oosp2)和细胞因子分泌(Cxcl12)相关的基因上调。总之,这些发现表明GelMA/ICA水凝胶有效地逆转了卵巢衰老的关键标志,恢复了老年小鼠的生殖功能,为生育能力的保存提供了一个有希望的平台,并为未来卵巢衰老的研究提供了一种新的治疗方法。
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