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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
Author Correction: Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection. 作者更正:CD163点突变的转基因猪对HP-PRRSV感染具有抗性。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.304
Ying Liu, Lin Yang, Hong-Yong Xiang, Ming Niu, Jia-Cheng Deng, Xue-Yuan Li, Wen-Jie Hao, Hong-Sheng Ou-Yang, Tong-Yu Liu, Xiao-Chun Tang, Da-Xin Pang, Hong-Ming Yuan
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引用次数: 0
Genomic architecture of ant social evolution. 蚂蚁社会进化的基因组结构。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.290
Weiwei Liu, Guo Ding, Zijun Xiong, Guojie Zhang
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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。
{"title":"Subcutaneous delivery of icariin via a gelatin methacryloyl (GelMA) hydrogel sustained-release system improves ovarian function in reproductively aged mice.","authors":"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","doi":"10.24272/j.issn.2095-8137.2024.447","DOIUrl":"10.24272/j.issn.2095-8137.2024.447","url":null,"abstract":"<p><p>Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age. Icariin (ICA), a flavonoid compound derived from <i>Epimedium</i> 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. <i>In vitro</i> 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, <i>P</i><0.0001) and follicle numbers at all developmental stages, including primordial (383.33±151.65 vs. 107.14±32.26, <i>P</i><0.0001), primary (203.33±83.22 vs. 91.43±27.04, <i>P</i>=0.003), and secondary follicles (154.17±52.00 vs. 59.28±20.50, <i>P</i>=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, <i>P</i>=0.0008), accompanied by elevated anti-Müllerian hormone (AMH, 22.97±2.26 vs. 5.54±1.56 ng/mL, <i>P</i><0.0001) and estradiol (E <sub>2</sub>, 315.30±37.62 vs. 168.5±14.78 pg/mL, <i>P</i><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, <i>P</i>=0.0002), and higher proportions of two-cell (85.90%±6.16% vs. 50.00%±10.00%, <i>P</i>=0.0009), four-cell (81.67%±9.76% vs. 50.00%±10.00%, <i>P</i>=0.0061), and blastocyst stage embryos (64.25%±10.55% vs. 23.33%±15.28%, <i>P</i>=0.0067). Live birth numbers were significantly increased following GelMA/ICA treatment (6.90±3.21 vs. 1.72±2.05, <i>P</i>=0.0001). Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization ( <i>Vil1</i>, <i>Tubb3</i>), lipid storage ( <i>Soat2</i>, <i>Plin4</i>), oocyte maturation ( <i>Oosp2</i>), and cytokine secretion ( <i>Cxcl12</i>). 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.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":"46 4","pages":"863-876"},"PeriodicalIF":4.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From injury to recovery: Spatiotemporal dynamics of the visual pathway during spontaneous structural and functional regeneration after optic nerve transection in zebrafish. 从损伤到恢复:斑马鱼视神经横断后自发结构和功能再生过程中视觉通路的时空动态。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.020
Bao-Guo Shen, Yuan Wen, Sheng-Jian Lu, Hong-Yuan Wei, Shu-Rui Huang, Guang-Ming Zhou, Wen-Tao Yan, Wen-Can Wu, Yi-Kui Zhang

In adult mammals, optic nerve injury leads to irreversible vision loss due to its extremely limited regenerative capacity. In contrast, adult zebrafish possess a robust capacity for spontaneous visual system regeneration, although the spatiotemporal coordination of recovery across the retina, optic nerve, and brain remains poorly understood. In the present study, the regenerative dynamics following optic nerve transection were systematically characterized in adult zebrafish over a 5 week period using hematoxylin-eosin staining, immunohistochemistry, transmission electron microscopy, single-cell RNA sequencing, and optokinetic response (OKR) behavioral assessments. At 1 week post-injury (1 wpi), retinal ganglion cell depletion was evident but showed significant recovery by 2 wpi. Concurrently, the injured optic nerve displayed a marked increase in diameter and cell number at 2 wpi, including widespread expression of proliferating cell nuclear antigen, consistent with heightened proliferative activity. Single-cell transcriptomic profiling at 2 wpi revealed five principal cell populations: fibroblasts, mural cells, immune cells, mature oligodendrocytes, and myelin-forming oligodendrocytes. By 4-5 wpi, remyelination within the optic nerve and re-establishment of synaptic architecture in the optic tectum were strongly correlated with functional restoration of OKR behavior. These findings provide a comprehensive spatiotemporal framework of visual pathway regeneration in zebrafish, establishing a valuable model for elucidating conserved mechanisms of neural repair with translational potential for human vision restoration.

在成年哺乳动物中,视神经损伤由于其极其有限的再生能力而导致不可逆的视力丧失。相比之下,成年斑马鱼拥有强大的自发视觉系统再生能力,尽管对视网膜、视神经和大脑之间的恢复时空协调仍知之甚少。在本研究中,通过苏木精-伊红染色、免疫组织化学、透射电镜、单细胞RNA测序和光动力学反应(OKR)行为评估,系统地表征了成年斑马鱼视神经横断后的再生动力学。损伤后1周(1 wpi),视网膜神经节细胞明显减少,但在2 wpi时恢复明显。同时,受损视神经在2 wpi时直径和细胞数量明显增加,包括增殖细胞核抗原的广泛表达,与增殖活性增强一致。2 wpi时的单细胞转录组分析显示了5个主要细胞群:成纤维细胞、壁细胞、免疫细胞、成熟少突胶质细胞和髓鞘形成少突胶质细胞。在4-5 wpi时,视神经内的髓鞘再生和视神经顶盖突触结构的重建与OKR行为的功能恢复密切相关。这些发现为斑马鱼视觉通路再生提供了一个全面的时空框架,为阐明神经修复的保守机制建立了一个有价值的模型,并具有人类视觉恢复的翻译潜力。
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引用次数: 0
Single-cell RNA-seq provides insight into the underdeveloped immune system of germ-free mice. 单细胞RNA-seq提供了对无菌小鼠不发达免疫系统的深入了解。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2024.467
Yi-Fei Sheng, Wei Cheng, Yin Zhang, Qi-Jun Liao, Juan Shen, Rui-Zhen Zhao, Tai-Liang Chai, Chao Wu, Wei-Ning Hu, Xiang Huang, Bo Wei, Shan-Shan Pan, Yang-Rui Zhang, Rou-Xi Chen, Jun-Pu Mei, Hong Wei, Li-Juan Han, Xiao-Dong Fang

Germ-free mice exhibit profound immunological immaturity. Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation, the mechanisms linking microbiota absence to systemic immune deficits remain incompletely defined. Here, droplet-based single-cell RNA sequencing of bone marrow and peripheral blood from both germ-free and specific pathogen-free mice was performed, identifying 25 transcriptionally distinct cell types. Neutrophil apoptosis was elevated in germ-free mice, potentially due to the absence of niacin dehydrogenase, a metabolite primarily produced by Pseudomonas. In addition, germ-free mice exhibited increased excretion of 5'-methylthioadenosine, enhanced ERK activation driven by reactive oxygen species, and disruption of bone marrow stromal antigen 2 signaling. Monocytes and CD8 + T cells from germ-free mice showed diminished responses to interferon-β and interferon-γ, consistent with heightened viral susceptibility. These findings establish a microbiota-dependent regulatory pathway linking immunodeficiency to microbial absence in germ-free mice, confirmed through complementary validation techniques.

无菌小鼠表现出严重的免疫不成熟。尽管最近的研究强调了特定细菌衍生代谢物在免疫细胞发育和分化中的作用,但将微生物群缺失与系统性免疫缺陷联系起来的机制仍然不完全明确。在这里,研究人员对无菌小鼠和特异性无病原体小鼠的骨髓和外周血进行了基于液滴的单细胞RNA测序,鉴定出25种转录不同的细胞类型。中性粒细胞凋亡在无菌小鼠中升高,可能是由于缺乏烟酸脱氢酶,一种主要由假单胞菌产生的代谢物。此外,无菌小鼠表现出5'-甲基硫代腺苷的排泄增加,活性氧驱动的ERK活化增强,骨髓基质抗原2信号通路中断。无菌小鼠的单核细胞和CD8 + T细胞对干扰素-β和干扰素-γ的反应减弱,与病毒易感性增强一致。这些发现在无菌小鼠中建立了一种微生物依赖的调节途径,将免疫缺陷与微生物缺失联系起来,并通过互补验证技术得到证实。
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引用次数: 0
RNF122 targets STING for ubiquitination at residues K95, K117, and K155 to regulate antiviral responses in a teleost fish. RNF122靶向STING在K95、K117和K155残基上的泛素化,以调节硬骨鱼的抗病毒反应。
IF 4.7 1区 生物学 Q1 ZOOLOGY Pub Date : 2025-07-18 DOI: 10.24272/j.issn.2095-8137.2025.033
Xiao-Wei Qin, Chuan-Rui Li, Min-Cong Liang, Tian-Hao Li, Yan-Lin You, Shao-Ping Weng, Chang-Jun Guo, Jian-Guo He

Ring finger protein 122 (RNF122), an E3 ubiquitin ligase, orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination. However, its functional relevance in teleosts has yet to be clearly defined, particularly regarding the identification of substrate-specific regulatory sites. This study characterized RNF122 from mandarin fish ( Siniperca chuatsi), termed scRNF122, and investigated its regulatory impact on stimulator of interferon genes (STING)-mediated antiviral signaling. Results showed that scRNF122 expression was up-regulated in response to mandarin fish ranavirus (MRV) infection, and its overexpression suppressed scSTING-mediated interferon (IFN) production and enhanced MRV replication. Co-immunoprecipitation confirmed a direct interaction between scRNF122 and scSTING. Functional assays demonstrated that scRNF122 facilitated scSTING degradation through the ubiquitin-proteasome pathway, a process impeded by MG132 treatment. Ubiquitination analyses of various scSTING mutants revealed that scRNF122 catalyzed scSTING ubiquitination at K95, K117, and K155 residues. Moreover, scRNF122 significantly impaired scSTING-dependent antiviral responses by engaging negative regulatory elements within the signaling cascade. Overall, scRNF122 was identified as a negative modulator of STING-mediated IFN signaling in mandarin fish, diminishing STING-dependent antiviral activity and promoting its degradation via the ubiquitin-proteasome pathway at lysine residues K95, K117, and K155. These findings provide mechanistic insight into the post-translational control of STING in teleosts and establish a foundation for future investigations into antiviral immune regulation.

环指蛋白122 (RNF122)是一种E3泛素连接酶,通过靶向维甲酸诱导基因1和黑色素瘤分化相关基因5来调控哺乳动物的泛素化,从而协调抗病毒免疫反应。然而,它在硬骨鱼中的功能相关性尚未明确定义,特别是关于底物特异性调节位点的鉴定。本研究鉴定了鳜鱼(sininiperca chuatsi)的RNF122,并将其命名为scRNF122,研究了其对干扰素基因刺激因子(STING)介导的抗病毒信号传导的调控作用。结果表明,scnf122在鳜鱼ranv (MRV)感染后表达上调,其过表达抑制scsting介导的干扰素(IFN)产生,增强MRV复制。共免疫沉淀证实了scRNF122和scSTING之间的直接相互作用。功能分析表明,scRNF122通过泛素-蛋白酶体途径促进scSTING降解,这一过程被MG132抑制。对不同scSTING突变体的泛素化分析显示,scnf122在K95、K117和K155位点催化scSTING泛素化。此外,scnf122通过参与信号级联中的负调控元件,显著损害了scsting依赖性抗病毒应答。总体而言,scRNF122被鉴定为鳜鱼sting介导的IFN信号的负调节因子,降低sting依赖的抗病毒活性,并通过赖氨酸残基K95、K117和K155上的泛素-蛋白酶体途径促进其降解。这些发现为硬骨鱼中STING的翻译后控制提供了机制见解,并为未来研究抗病毒免疫调节奠定了基础。
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Zoological Research
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