F&S science最新文献_第3页

Deciphering estrogen receptor alpha–driven transcription in human endometrial stromal cells via transcriptome, cistrome, and integration with chromatin landscape 通过转录组、池质和染色质景观整合，解读人类子宫内膜基质细胞中esr1驱动的转录。

F&S science

Pub Date : 2026-01-01 Epub Date: 2025-08-11 DOI: 10.1016/j.xfss.2025.08.002

Skylar G. Montague Redecke B.Sc. , Austin Bell-Hensley Ph.D. , Shuyun Li Ph.D. , MyeongJin Yi Ph.D. , Akshadha Jain , Abdull J. Massri Ph.D. , Francesco J. DeMayo Ph.D.

Objective

To investigate estrogen receptor gene 1 (ESR1) and estrogen-driven transcription in human endometrial stromal cells.

Design

RNA sequencing (RNA-seq) and Cleavage Under Targets and Release Using Nuclease (Cut&Run) were performed on telomerase-immortalized human endometrial stromal cells with Clustered Regularly Interspaced Short Palindromic Repeats–mediated ESR1 activation. Hi-C-based chromatin architecture analysis (H3K27ac HiChIP) was conducted in primary endometrial stromal cells.

Subjects

Biopsies from two healthy, reproductive-aged volunteers with regular menstrual cycles and no history of gynecological malignancies.

Exposure

The ESR1-activated and control endometrial stromal cells were treated with estradiol (E2) or vehicle. Primary endometrial stromal cells were treated with vehicle or a decidualization cocktail.

Main Outcome Measures

Differential gene expression analysis (RNA-seq) identified ligand-independent and -dependent ESR1 activity. Cut&Run profiled ESR1 genomic binding in ESR1-activated cells. H3K27ac HiChIP mapped hormone-induced changes in chromatin looping in primary cells.

Results

Among seven tested guide RNAs (gRNA), the ESR1-3 gRNA induced robust ESR1 activation and restored E2 responsiveness. Bulk RNA-seq revealed both ligand-dependent and -independent ESR1 transcriptional programs regulating inflammation, proliferation, and cancer-related pathways. Notably, 72% of differentially expressed genes overlapped with genes active in human endometrial tissue during the proliferative estrogen-dominant phase, supporting their physiological relevance. The Cut&Run-seq identified genome-wide ESR1 binding sites, with most binding sites located at distal regulatory elements. Integration of Cut&Run data with H3K27ac HiChIP chromatin loops linked distal ESR1 binding sites to gene promoters, including genes involved in decidualization (e.g., FOXO1) and endometrial cancer (e.g., ERRFI1, NRIP1, and EPAS1). Functional assays showed that ESR1 promotes cell viability and, in the presence of E2, enhances migration.

Conclusion

The CRISPR-mediated ESR1 activation restores estrogen responsiveness in endometrial stromal cells. Combined transcriptomic, cistromic, and chromatin architecture analyses reveal ESR1’s role in regulating decidualization and inflammation-related gene networks, with relevance to endometrial pathologies including endometrial cancer. This model serves as a powerful tool to study estrogen signaling in endometrial stromal cell biology and related pathologies.

目的：探讨ESR1基因在人子宫内膜基质细胞中的表达及雌激素驱动的转录。设计：通过crispr介导的ESR1激活，对端粒酶永生化的人子宫内膜基质细胞进行RNA-seq和Cut&Run。在原发性子宫内膜间质细胞中进行了基于hi - c的染色质结构分析（H3K27ac HiChIP）。研究对象：两名健康的育龄志愿者，月经周期规律，无妇科恶性肿瘤史。暴露：esr1激活和对照的子宫内膜基质细胞用雌二醇（E2）或对照物处理。原发子宫内膜间质细胞用载体或去个体化混合物处理。主要结果测量：差异基因表达分析（RNA-seq）鉴定了与配体无关和依赖的ESR1活性。Cut&Run分析了ESR1激活细胞中的ESR1基因组结合。H3K27ac HiChIP绘制了原代细胞中激素诱导的染色质环变化。结果：在7个测试的引导rna （gRNA）中，ESR1-3 gRNA诱导了ESR1的强大激活并恢复了E2的响应性。Bulk RNA-seq揭示了配体依赖性和非依赖性ESR1转录程序调节炎症、增殖和癌症相关途径。值得注意的是，在增殖性雌激素优势期，72%的差异表达基因与人子宫内膜组织中活跃的基因重叠，支持它们的生理相关性。Cut&Run-seq鉴定了全基因组ESR1结合位点，大多数结合位点位于远端调控元件。将Cut&Run数据与H3K27ac HiChIP染色质环结合，将远端ESR1结合位点与基因启动子连接，包括与去个体化相关的基因（如FOXO1）和子宫内膜癌（如ERRFI1、NRIP1、EPAS1）。功能分析显示ESR1促进细胞活力，并在E2存在下增强迁移。结论：crispr介导的ESR1激活可恢复子宫内膜基质细胞的雌激素反应性。转录组学、胞浆学和染色质结构的综合分析揭示了ESR1在调节脱个体化和炎症相关基因网络中的作用，并与子宫内膜癌等子宫内膜病理相关。该模型为研究雌激素信号在子宫内膜间质细胞生物学和相关病理中的作用提供了有力的工具。

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引用次数: 0

Euploid but failing to implant? Insights from trophectoderm transcriptomics of euploid blastocysts using an in vitro model 整倍体但未能植入？利用体外模型观察整倍体囊胚的滋养外胚层转录组学。

F&S science

Pub Date : 2026-01-01 Epub Date: 2025-10-13 DOI: 10.1016/j.xfss.2025.09.003

David Ortega-Jaén M.Sc. , Antonio Capalbo Ph.D. , Ángel Martín Ph.D. , Julia Gil M.Sc. , María Luisa Pardiñas M.Sc. , Carlos Mora-Martinez Ph.D. , Mireia Boluda-Navarro Ph.D. , Amparo Mercader Ph.D. , María José de los Santos Ph.D.

Objective

To investigate transcriptomic differences in mural trophectoderm (TE) cells of euploid human blastocysts on the basis of their ability to remain attached in extended in vitro culture and to identify gene expression profiles associated with competence for implantation.

Design

Prospective in vitro experimental cohort study involving ribonucleic acid sequencing of mural TE biopsies from euploid blastocysts and extended culture up to day 11.

Subjects

Fifteen euploid blastocysts donated by 16 couples undergoing intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidy. Transcriptomic comparison focused on 10 euploid blastocysts, classified as attached (n = 5) or unattached (n = 5) after extended in vitro culture, and the rest were excluded for various reasons.

Exposure

Development outcome of euploid blastocysts during extended in vitro culture (adhesion vs. non-adhesion to the culture surface on day 11), used as the basis for differential gene expression analysis.

Main Outcome Measures

Identification of differentially expressed genes and deregulated molecular pathways between attached and unattached euploid embryos, including functional enrichment analysis to explore their potential roles in embryo viability and implantation.

Results

Transcriptomic analysis revealed 85 differentially expressed genes between unattached and attached euploid blastocysts, including genes involved in cellular adhesion (e.g., SPON2 and VTN), immune modulation (HLA-G and IL12A), metabolism (NNMT and CYP3A7), and mitochondrial function. Unattached embryos displayed down-regulation of ribosome biogenesis, mitochondrial proteins, and chromosomal segregation pathways and up-regulation of genes related to immune response and cytoskeletal organization.

Conclusion

The study demonstrates that mural TE gene expression differs significantly between euploid blastocysts that attach and those that do not, highlighting molecular pathways potentially linked to implantation success. Despite human implantation typically occurring through the polar TE, mural TE transcriptomic profiles may provide predictive value for embryo selection and deepen our understanding of early implantation biology. Further validation through proteomic studies and larger cohorts is needed to confirm these candidate biomarkers.

目的：研究整倍体人胚泡壁养外胚层（TE）细胞在体外培养中保持附着能力的转录组学差异，并鉴定与着床能力相关的基因表达谱。设计：前瞻性体外实验队列研究，涉及整倍体囊胚壁TE活检的RNA测序和延长培养至第11天。患者：16对夫妇捐赠的15个整倍体囊胚接受卵胞浆内单精子注射（ICSI）和着床前非整倍体基因检测（PGT-A）。转录组学比较集中在10个整倍体囊胚上，在体外延长培养后分为附着囊胚（n=5）和未附着囊胚（n=5），其余囊胚因各种原因被排除。主要观察指标：鉴定附着和未附着整倍体胚胎之间的差异表达基因（DEGs）和解除调控的分子通路，包括功能富集分析，以探讨其在胚胎存活和着床中的潜在作用。结果：转录组学分析显示，未附着和附着的整倍体囊胚之间存在85个deg，包括参与细胞粘附（如SPON2、VTN）、免疫调节（HLA-G、IL12A）、代谢（NNMT、CYP3A7）和线粒体功能的基因。未附着的胚胎显示核糖体生物发生、线粒体蛋白和染色体分离途径下调，与免疫反应和细胞骨架组织相关的基因上调。结论：该研究表明，壁TE基因表达在附着和未附着的整倍体囊胚之间存在显著差异，突出了与着床成功相关的潜在分子途径。尽管人类胚胎植入通常是通过极性TE进行的，但壁TE转录组谱可能为胚胎选择提供预测价值，并加深我们对早期植入生物学的理解。需要通过蛋白质组学研究和更大的队列进一步验证来确认这些候选生物标志物。

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引用次数: 0

Transvaginal shear wave elastography for measuring uterine myometrial and leiomyoma stiffness: a protocol pilot study 经阴道横波弹性成像测量子宫肌瘤和平滑肌瘤硬度：一项方案试点研究。

F&S science

Pub Date : 2026-01-01 Epub Date: 2025-09-09 DOI: 10.1016/j.xfss.2025.09.002

Hannah T. Ryles M.D. , Sumeyra Agambayev M.S. , Mervat Omran Ph.D. , Chuanhong Liao M.S. , Samar Alkhrait M.D. , Ayman Al-Hendy M.D. , Ryan Longman M.D. , Jacques Abramowicz M.D. , Obianuju Sandra Madueke-Laveaux M.D.

Objective

Recent studies suggest that the stiffness of uterine leiomyomas may be related to their growth and behavior. Shear wave elastography (SWE), a quantitative method of measuring tissue stiffness, has been increasingly studied for use in gynecologic conditions. However, no protocols have been proposed for its use in this clinical setting. This study aimed to establish a standardized protocol for transvaginal SWE to measure uterine myometrial and leiomyoma stiffness and assess the reproducibility and reliability of SWE measurements. We also assessed myometrial vs. leiomyoma stiffness, compared myometrial stiffness in participants with and without leiomyomas, and assessed menstrual phase effects on stiffness values.

Design

Transvaginal SWE ultrasound measurements of myometrial and leiomyoma stiffness were obtained. All transvaginal SWE examinations were performed by an individual sonographer. Independent raters calculated stiffness measurements. Myometrial and leiomyoma stiffness were compared across menstrual phases.

Subjects

Twenty-seven premenopausal women, 16 with leiomyomas and 11 without, were enrolled. Seventeen participants completed examinations during multiple menstrual phases.

Exposure

Tissue type (myometrium/leiomyoma), leiomyoma status (presence/absence of leiomyomas), and menstrual phase (follicular/luteal).

Main Outcome Measures

Interrater and test-retest reliability of SWE measurements. Myometrial and leiomyoma shear wave values.

Results

We successfully designed a streamlined protocol for obtaining SWE measurements in participants with and without leiomyomas. Fifty-one myometrial and 38 leiomyoma stiffness values measured by 2 independent raters achieved excellent interrater reliability: the intraclass correlation coefficients between the 2 raters were 0.990 and 0.994, respectively. Fifty myometrial and 42 leiomyoma stiffness measurements calculated by a single rater at 2 time points at least 90 days apart achieved excellent test-retest reliability: intraclass correlation coefficients of 0.992 and 0.995. The median stiffness values for leiomyomas were significantly higher than those for the surrounding myometrium (48.1 [interquartile range, 39.7–59.5] vs. 31.6 [interquartile range, 22.9–46.9] kPa). There was no significant change in myometrial or leiomyoma median stiffness values between the menstrual phases.

Conclusion

Transvaginal ultrasound SWE showed excellent reproducibility and reliability in measuring myometrial and leiomyoma stiffness. Leiomyoma stiffness was significantly higher than that for the surrounding myometrium. Together, these findings support SWE’s potential clinical utility in leiomyoma management.

目的：最近的研究表明子宫平滑肌瘤的硬度可能与其生长和行为有关。横波弹性成像是一种测量组织刚度的定量方法，在妇科疾病中的应用研究越来越多。然而，在这种临床环境中，没有提出任何方案。本研究旨在1)建立经阴道剪切波弹性成像测量子宫肌瘤和平滑肌瘤硬度的标准化方案；2)评估剪切波弹性成像测量结果的可重复性和可靠性。我们还评估了子宫肌瘤与平滑肌瘤的硬度，比较了有和没有平滑肌瘤的参与者的子宫肌瘤硬度，并评估了月经期对硬度值的影响。设计：经阴道SWE超声测量子宫肌瘤和平滑肌瘤的硬度。所有经阴道SWE检查均由单个超声医师进行。独立评级计算刚度测量。子宫肌瘤和平滑肌瘤僵硬度在月经期间进行比较。受试者：27名绝经前妇女，16名有平滑肌瘤，11名无平滑肌瘤。17名参与者在多个月经期完成了测试。暴露(s): 1。组织类型（子宫肌瘤/平滑肌瘤）平滑肌瘤状态（有无平滑肌瘤）月经期（卵泡/黄体）主要结局指标：横波弹性成像测量的间测和重测可靠性。子宫肌瘤和平滑肌瘤横波值。结果：我们成功地设计了一种简化的方案，用于在有和没有平滑肌瘤的参与者中获得剪切波弹性成像测量。结果表明：经阴道超声剪切波弹性成像测量子宫肌瘤和平滑肌瘤硬度值具有良好的重现性和可靠性，其中51个子宫肌瘤硬度值和38个子宫肌瘤硬度值具有良好的组间信度，组内相关系数为0.990。平滑肌瘤的僵硬度明显高于周围的肌层。总之，这些发现支持剪切波弹性成像在平滑肌瘤治疗中的潜在临床应用。

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引用次数: 0

Enhanced sperm cryopreservation using zinc- and copper-doped hydroxyapatite with glutathione and raffinose: effects on motility, viability, deoxyribonucleic acid integrity, and oxidative stress markers 添加谷胱甘肽和棉子糖的锌和铜掺杂羟基磷灰石增强精子低温保存：对精子活力、活力、脱氧核糖核酸完整性和氧化应激标志物的影响

F&S science

Pub Date : 2026-01-01 Epub Date: 2025-10-25 DOI: 10.1016/j.xfss.2025.10.005

Asma Mahmoudi D.V.M. , Mazdak Razi Ph.D. , Marzieh Jalilpour Ph.D. , Ali Shalizar Jalali Ph.D.

Objective

To study the protective effects of zinc- and copper-doped hydroxyapatite (H) combined with glutathione (GSH) and raffinose (R) on mouse sperm motility, viability, deoxyribonucleic acid (DNA) integrity, and oxidative stress markers before and after cryopreservation.

Design

Experimental laboratory-controlled study evaluating the efficacy of combined cryoprotective formulations during sperm cryopreservation.

Subjects

Sperm samples collected from 10 healthy adult albino mice were used for in vitro cryopreservation experiments.

Intervention

Samples were divided into six groups: a control group using a commercial cryopreservation medium and five experimental groups supplemented with H, GSH, and R, either alone or in combination (H+GSH+R). All samples were cryopreserved at −196°C for 72 hours and subsequently thawed for analysis.

Main Outcome Measures

Postthaw sperm motility, viability, and DNA fragmentation were evaluated, along with biochemical markers of oxidative stress, including total antioxidant capacity, total oxidant status, lipid peroxidation, protein oxidation, and enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase.

Results

The H+GSH+R group demonstrated significantly higher motility and lower DNA fragmentation and mortality compared with the control. Total antioxidant capacity increased prefreezing, although total oxidant status was markedly reduced postthaw. Lipid and protein oxidation decreased significantly, and antioxidant enzyme activities were enhanced in the H+GSH+R group.

Conclusion

Zinc- and copper-doped H combined with GSH and R effectively improves sperm cryosurvival by enhancing antioxidant defenses and reducing oxidative damage. This formulation provides a promising cryoprotective strategy for optimizing assisted reproductive technologies.

目的研究锌和铜掺杂羟基磷灰石(H)联合谷胱甘肽（GSH）和棉子糖(R)对小鼠精子活力、活力、脱氧核糖核酸（DNA）完整性和氧化应激标志物冷冻前后的保护作用。目的：通过实验室对照研究，评价联合冷冻保护制剂在精子冷冻保存中的效果。目的：对10只健康成年白化病小鼠进行体外冷冻保存实验。干预将样品分为6组：对照组使用商业冷冻保存培养基，5个实验组添加H、GSH和R，单独或联合（H+GSH+R）。所有样品在- 196°C低温保存72小时，随后解冻分析。主要观察指标：评估解冻后精子活力、活力和DNA片段，以及氧化应激的生化指标，包括总抗氧化能力、总氧化状态、脂质过氧化、蛋白质氧化、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的酶活性。结果与对照组相比，H+GSH+R组小鼠运动能力明显提高，DNA断裂率和死亡率明显降低。冷冻前总抗氧化能力增加，但解冻后总抗氧化能力明显降低。H+GSH+R组脂质和蛋白质氧化显著降低，抗氧化酶活性增强。结论锌、铜掺杂H与GSH、R联合可有效提高精子的抗氧化防御能力，减少氧化损伤，提高精子低温存活能力。该配方为优化辅助生殖技术提供了一种有前途的冷冻保护策略。

{"title":"Enhanced sperm cryopreservation using zinc- and copper-doped hydroxyapatite with glutathione and raffinose: effects on motility, viability, deoxyribonucleic acid integrity, and oxidative stress markers","authors":"Asma Mahmoudi D.V.M. , Mazdak Razi Ph.D. , Marzieh Jalilpour Ph.D. , Ali Shalizar Jalali Ph.D.","doi":"10.1016/j.xfss.2025.10.005","DOIUrl":"10.1016/j.xfss.2025.10.005","url":null,"abstract":"<div><h3>Objective</h3><div>To study the protective effects of zinc- and copper-doped hydroxyapatite (H) combined with glutathione (GSH) and raffinose (R) on mouse sperm motility, viability, deoxyribonucleic acid (DNA) integrity, and oxidative stress markers before and after cryopreservation.</div></div><div><h3>Design</h3><div>Experimental laboratory-controlled study evaluating the efficacy of combined cryoprotective formulations during sperm cryopreservation.</div></div><div><h3>Subjects</h3><div>Sperm samples collected from 10 healthy adult albino mice were used for in vitro cryopreservation experiments.</div></div><div><h3>Intervention</h3><div>Samples were divided into six groups: a control group using a commercial cryopreservation medium and five experimental groups supplemented with H, GSH, and R, either alone or in combination (H+GSH+R). All samples were cryopreserved at −196°C for 72 hours and subsequently thawed for analysis.</div></div><div><h3>Main Outcome Measures</h3><div>Postthaw sperm motility, viability, and DNA fragmentation were evaluated, along with biochemical markers of oxidative stress, including total antioxidant capacity, total oxidant status, lipid peroxidation, protein oxidation, and enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase.</div></div><div><h3>Results</h3><div>The H+GSH+R group demonstrated significantly higher motility and lower DNA fragmentation and mortality compared with the control. Total antioxidant capacity increased prefreezing, although total oxidant status was markedly reduced postthaw. Lipid and protein oxidation decreased significantly, and antioxidant enzyme activities were enhanced in the H+GSH+R group.</div></div><div><h3>Conclusion</h3><div>Zinc- and copper-doped H combined with GSH and R effectively improves sperm cryosurvival by enhancing antioxidant defenses and reducing oxidative damage. This formulation provides a promising cryoprotective strategy for optimizing assisted reproductive technologies.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 13-26"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nano-elemental imaging reveals zinc and calcium redistribution in human sperm during capacitation and hyperactivation. 纳米元素成像揭示了人类精子在获能和超激活过程中锌和钙的再分配。

F&S science

Pub Date : 2025-12-17 DOI: 10.1016/j.xfss.2025.12.007

Cristina Tufoni, Alessandra Gianoncelli, Simone Sala, Luisa Zupin, Maik Kahnt, Stefania Luppi, Elena Giolo, Giuseppe Ricci, Lorella Pascolo

Objective: To characterize the redistribution patterns of zinc and calcium ions during human sperm capacitation and to investigate their roles in sperm maturation and fertilization.

Design: In vitro experimental study using synchrotron-based x-ray fluorescence microscopy and complementary immunohistochemistry to assess elemental changes during different capacitation stages at nanometric spatial resolution.

Subjects: Semen samples collected from healthy donors, evaluated according to World Health Organization guidelines.

Exposure: None.

Main outcome measures: Nanometric distribution and quantification of zinc and calcium in different sperm region (head, midpiece, tail, and centriole) during different stages of capacitation.

Results: The x-ray fluorescence mapping allowed to evaluate the nanometric redistribution of zinc and calcium in human sperm during capacitation. Distinct "zinc signatures" were observed during different capacitation stages, with zinc initially abundant throughout the cell, later concentrating in the midpiece after capacitation, and further decreasing during acrosomal exocytosis. A persistent presence of zinc-rich areas at the centriole was also observed, which likely helps maintain the integrity of the head and midpiece. Concurrently, increased calcium levels in the flagellum during capacitation suggest potentially linked dynamics between zinc efflux and calcium influx. These findings provide new insight into elemental dynamics underlying sperm maturation and fertilization potential.

Conclusion: A deeper understanding of male fertility may be achieved by elucidating the multifaceted role of zinc in sperm function, particularly its interaction with calcium signaling pathways. By considering both the biochemical and ionic mechanisms alongside the physical aspects of sperm activity, a more precise assessment of sperm functionality becomes possible.

目的：研究锌、钙离子在精子获能过程中的再分配规律，探讨锌、钙离子在精子成熟和受精过程中的作用。设计：体外实验研究采用基于同步加速器的x射线荧光（XRF）显微镜和互补免疫组织化学在纳米空间分辨率下评估不同获能阶段的元素变化。设置：在MAX IV实验室（隆德，瑞典）的NanoMAX光束线上进行同步加速器成像；在意大利的里雅斯特的母婴健康研究所获得和处理的精子样本。研究对象：从健康献血者采集的精液样本，根据世卫组织指南进行评估。主要观察指标：不同获能阶段精子不同区域（头部、中段、尾部、中心粒）锌和钙的纳米分布和定量。结果：XRF图谱可以评估人类精子获能过程中锌和钙的纳米级再分布。在不同的获能阶段观察到不同的“锌特征”，锌最初在整个细胞中丰富，随后在获能后集中在中间，在顶体胞吐期间进一步减少。中心粒处还观察到持续存在的富锌区域，这可能有助于保持头部和中部的完整性。同时，在能化过程中鞭毛中钙含量的增加表明锌外排和钙内流之间可能存在联系。这些发现为精子成熟和受精潜力背后的元素动力学提供了新的见解。结论：通过阐明锌在精子功能中的多方面作用，特别是其与钙信号通路的相互作用，可以更深入地了解男性生育能力。通过考虑生物化学和离子机制以及精子活动的物理方面，对精子功能进行更精确的评估成为可能。

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引用次数: 0

Shrimp peptides mitigate fatty liver-linked testicular dysfunction in rats via oxidative stress, autophagy and energy pathways. 虾肽通过氧化应激、自噬和能量途径减轻大鼠脂肪肝相关性睾丸功能障碍。

F&S science

Pub Date : 2025-12-17 DOI: 10.1016/j.xfss.2025.12.006

Arvin Pirayesh, Ebrahim Najdegerami, Mazdak Razi, Mehdi Nikoo

Objective: To study the protective effects of bioactive peptides derived from whiteleg shrimp (Litopenaeus vannamei) by-products on testicular function in a rat model of nonalcoholic fatty liver disease (NAFLD).

Design: Experimental study.

Setting: Urmia University, Urmia, Iran.

Animals: Twenty-four adults male Wistar rats (8 weeks old, average weight 230.2 ± 23 g).

Exposure: Rats were divided into four groups (n=6): control (standard chow), high-fat diet (HFD), HFD + 20 mg peptide/kg body weight (BW), and HFD + 300 mg peptide/kg BW. Peptides were enzymatically hydrolyzed at 40-60°C, yielding 60-70% low molecular weight peptides (<500 Da), and administered via oral gavage for 10 weeks.

Main outcome measures: Spermatogenic indices (tubule diameter, Sertoli/Leydig cell counts, tubular differentiation index [TDI], spermiogenesis index [SPI]), oxidative stress markers (malondialdehyde [MDA], reduced glutathione [GSH], oxidized glutathione [GSSG], total antioxidant capacity [TAC]), autophagy-related gene expression (Beclin-1, Atg7, LC3-I, p62), and glucose/lactate transporter expression (GLUT1/3, MCT1/4) assessed via quantitative PCR and immunohistochemistry.

Results: HFD significantly reduced tubule diameter, Sertoli/Leydig cell numbers, TDI, and SPI while increasing MDA (11.7 ± 2.9 vs. 8.3 ± 1.0 nmol/mL, P < 0.05) and disrupting GSH/GSSG ratio (78.6 ± 8.7 vs. 48.2 ± 9.3, P < 0.05). Autophagy genes were upregulated, and GLUT/MCT expression decreased at mRNA and protein levels. Peptide supplementation, particularly at 300 mg/kg BW, dose-dependently reversed these effects by preserving tubular structure, normalizing oxidative markers (MDA: 8.8 ± 0.55 nmol/mL; GSH/GSSG: 51.5 ± 3.0), reducing autophagy gene expression, and enhancing GLUT/MCT expression in germ and Sertoli cells (P < 0.05), with superior efficacy at the higher dose.

Conclusions: Shrimp-derived bioactive peptides mitigate NAFLD-induced testicular dysfunction by modulating oxidative stress, autophagy pathways, and energy metabolism. They are promising natural therapeutics for preserving male fertility under metabolic stress and warrant clinical investigation.

目的：研究凡纳滨对虾副产物活性肽对非酒精性脂肪性肝病（NAFLD）大鼠睾丸功能的保护作用。设计：实验研究。地点：伊朗乌尔米娅大学。实验动物：24只成年雄性Wistar大鼠（8周龄，平均体重230.2±23 g）。暴露：将大鼠分为4组（n=6）：对照组（标准饲料）、高脂饲料（HFD）、HFD + 20 mg肽/kg体重（BW）和HFD + 300 mg肽/kg体重（BW）。肽在40-60°C下酶解，得到60-70%的低分子量肽(主要结果测量：通过定量PCR和免疫组织化学评估生精指标（小管直径、Sertoli/Leydig细胞计数、小管分化指数[TDI]、生精指数[SPI]）、氧化应激标志物（丙二醛[MDA]、还原谷胱甘肽[GSH]、氧化谷胱甘肽[GSSG]、总抗氧化能力[TAC]）、自噬相关基因表达（Beclin-1、Atg7、LC3-I、p62）和葡萄糖/乳酸转运蛋白表达（GLUT1/3、MCT1/4）。结果：HFD显著降低小管直径、Sertoli/Leydig细胞数量、TDI和SPI，增加MDA(11.7±2.9比8.3±1.0 nmol/mL, P < 0.05)，破坏GSH/GSSG比值（78.6±8.7比48.2±9.3,P < 0.05）。自噬基因上调，GLUT/MCT mRNA和蛋白水平表达降低。补充多肽，特别是在300 mg/kg体重时，通过保持小管结构、使氧化标记物正常化（MDA: 8.8±0.55 nmol/mL; GSH/GSSG: 51.5±3.0）、降低自噬基因表达、增强生殖细胞和支持细胞GLUT/MCT表达（P < 0.05），剂量依赖性地逆转了这些作用（P < 0.05），且剂量越大效果越好。结论：虾源性生物活性肽通过调节氧化应激、自噬途径和能量代谢来减轻nafld诱导的睾丸功能障碍。它们是在代谢压力下保持男性生育能力的有希望的自然疗法，值得临床研究。

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引用次数: 0

Laparoscopic ovarian drilling vs. step-up gonadotropin therapy in infertile anovulatory polycystic ovary syndrome women resistant to sequential letrozole and gonadotropin-based ovulation induction cycles: a randomized controlled trial 腹腔镜卵巢钻孔（LOD）与促性腺激素强化治疗对序贯来曲唑和促性腺激素促排卵周期有抗性的不育性无排卵性多囊卵巢综合征（PCOS）：一项随机对照试验。

F&S science

Pub Date : 2025-11-01 Epub Date: 2025-08-05 DOI: 10.1016/j.xfss.2025.07.006

H.V. Bhavana M.D. , Reeta Mahey M.D., D.N.B. , Aarthi K. Jayraj M.D., D.N.B. , Ashish Datt Upadhyay Ph.D. , Archana Kumari M.D. , Garima Kachhawa M.D. , Ayushi Negi M.D. , Khushbu Bashir M.D. , Srikar Yedlapalli M.S.

<div><h3>Objective</h3><div>To study the effect of laparoscopic ovarian drilling (LOD) vs. step-up gonadotropin therapy on follicular response in infertile anovulatory polycystic ovary syndrome (PCOS) women resistant to sequential letrozole + human menopausal gonadotropin (HMG)–based ovulation induction (OVI) cycles.</div></div><div><h3>Design</h3><div>Open-labeled, pilot, randomized controlled trial.</div></div><div><h3>Subjects</h3><div>Infertile anovulatory PCOS women (diagnosed according to modified Rotterdam criteria), resistant to sequential letrozole 5 mg + HMG-based OVI cycle (no dominant follicle >10 mm after 14 days of stimulation). Other inclusion criteria were: age 19–38 years; body mass index ≤35 kg/m<sup>2</sup>; patent fallopian tubes documented on either hysterosalpingography/saline infusion sonography or laparoscopy; antimüllerian hormone (AMH) levels >6 ng/mL. Exclusion criteria were AMH ≤6 ng/mL; moderate to severe male factor infertility and endometriosis.</div></div><div><h3>Intervention</h3><div>Participants in group 1 (N = 35) underwent LOD, after which OVI cycles were started with letrozole 5 mg from the following menses. Gonadotropin were added in a sequential manner if required as per the follicular response. Women in group 2 (N = 35) were administered injection of HMG (75 IU) from day 2 of menses and dose increments were done from day 9 onward as per response.</div></div><div><h3>Main Outcome Measures</h3><div>Primary outcome was follicular response (dominant follicle >16 mm). Secondary objectives were gonadotropin requirement per cycle, duration of stimulation, time to conception (months), clinical pregnancy rate and ongoing pregnancy rate (>12 weeks). The study also compared the effect of LOD on hormonal parameters (AMH, serum testosterone) and metabolic parameters (fasting insulin, fasting blood glucose, lipid profile, homeostasis model assessment of insulin resistance) after 1–2 months of procedure.</div></div><div><h3>Results</h3><div>Majority of the study participants (82.85%) belonged to PCOS phenotype A. The baseline clinical, hormonal, and metabolic characteristics and phenotype distribution were comparable in both groups. The follicular response was significantly higher in the LOD group (93.25%; 83/89) compared with step-up gonadotropin group (28.20%; 11/39). With four spontaneous conceptions, the median time to conception in LOD group was 3.9 (0–8.4) months. The clinical pregnancy rate per patient was significantly higher in LOD group [54.28% (19/35)] as compared with step-up gonadotropin group [8.57% (3/35)]. The ongoing pregnancy rate in the LOD group was 45.71% (16/35) vs. 0% (0/35) in the gonadotropin group. There was a significant fall in the AMH levels from 15.2 ± 2.7 ng/mL to 10.2 ± 4.4 ng/mL after LOD. Although statistically insignificant, the levels of luteinizing hormone/follicle-stimulating hormone ratio, testosterone, fasting insulin, fasting glucose and homeostasis model assessment of

目的：研究腹腔镜卵巢钻孔（LOD）与促性腺激素强化治疗对序贯来曲唑+ HMG（人类绝经期促性腺激素）促排卵（OVI）周期耐药的不孕症无排卵性多囊卵巢综合征（PCOS）患者卵泡反应的影响。不孕症无排卵性多囊卵巢综合征妇女（根据修改的鹿特丹标准诊断）对序列来曲唑5mg + HMG为基础的OVI周期有耐药性（刺激14天后无显性卵泡bbb10mm）。其他入选标准为：年龄19-38岁；BMI≤35kg/m2；经子宫输卵管造影/生理盐水输注超声检查或腹腔镜检查证实输卵管未通畅；AMH水平60 - 6ng/ml。排除标准为AMH≤6 ng/ml；中度至重度男性因素不孕和子宫内膜异位症。干预：第1组（N=35）接受LOD治疗，并在随后的月经周期中使用来曲唑5mg开始OVI周期。如果需要，按卵泡反应顺序添加促性腺激素。第2组（N=35）妇女从月经第2天开始注射HMG (75 IU)，从第9天开始根据反应增加剂量。主要结局指标：主要结局是卵泡反应（显性卵泡直径16mm）。次要目标是每个周期的促性腺激素需要量、刺激持续时间、受孕时间（月）、临床妊娠率和持续妊娠率（bb0 - 12周）。该研究还比较了LOD在1-2个月后对激素参数（AMH、血清睾酮）和代谢参数（空腹胰岛素、空腹血糖、血脂、HOMA-IR）的影响。结果：绝大多数研究参与者（82.85%）属于PCOS a型，两组的基线临床、激素和代谢特征以及表型分布具有可比性。LOD组卵泡反应明显高于对照组(93.25%；83/89)与促性腺激素增强组相比(28.20%；结论：与基于促性腺激素的促排卵诱导相比，腹腔镜卵巢钻孔（LOD）显著改善了卵泡反应，导致更高的临床和持续妊娠率，同时显著降低了促性腺激素的需求。对于对序贯来曲唑+ hmg促排卵有抵抗的PCOS女性，特别是具有高AMH和高每卵巢卵泡数（FNPO）的表型A型患者，可考虑采用该方法。

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引用次数: 0

Compressive force induces differential gene and protein expression in uterine fibroids 压缩力诱导子宫肌瘤差异基因和蛋白表达。

F&S science

Pub Date : 2025-11-01 Epub Date: 2025-07-22 DOI: 10.1016/j.xfss.2025.07.004

Carolyn A. Nietupski Ph.D. , Megan R. Sax M.D. , Rose Dean B.S., M.B.A. , Andreja Moset Zupan B.S. , Emily G. Hurley M.D. , Stacey C. Schutte Ph.D.

Objective

To study how compressive forces influence fibroid and myometrial cells. Our work aimed to identify proteins and signaling pathways that are altered in fibroids in response to compressive forces.

Design

Laboratory-based.

Subjects

Patient-matched fibroid and myometrial cells were isolated from five women undergoing hysterectomy or myomectomy for the treatment of uterine fibroids. Only samples from women who had not had hormonal modulation within 3 months of surgery were used for this study. An embedded spheroid model was developed to model the fibroid tissue and provide a cushion that would help with the distribution of compressive force.

Exposure

Weights, 0 or 6.4 mm Hg, were added on top of an agarose cushion. Spheroids were cultured for 7 days.

Main Outcome Measures

Histological evaluation, RNA-sequencing (n = 5), and proteomics characterization (n = 3). Paired multi-test t-tests were performed for statistical analysis. Differentially expressed genes (DEGs) were considered clinically relevant if the same genes were also significantly differentially expressed in at least one of the four existing fibroid and myometrium RNA-sequencing datasets.

Results

A total of 61 clinically relevant DEGs were identified between cell types that were only differentially expressed when the spheroids were under compression. This included EPHB1 which encodes ephrin signaling receptor EphB1; it was upregulated log2 fold-change of 2.81 in fibroid cells (q = 5.35 × 10^-3). Compression led to the enrichment of genes involved in extracellular matrix (ECM) organization; however, the genes varied between the cell types. At the protein level, myometrial spheroids had alterations in proteins associated with uterine fibroids (q = 1.00 × 10^–33). There were alterations in collagen abundance in fibroid spheroids, but not collagen 1, although the collagenase MMP-1 was significantly lower in fibroid spheroids. Enrichment analysis identified ECM-receptor interactions as enriched in compression-induced changes between the cell types.

Conclusions

Compressive forces must be considered to study some of the important differences between fibroids and myometrium, including ephrin signaling. Enrichment analysis of the proteins with different abundances suggests that compression may also be involved in fibroid tumor initiation.

目的：研究压缩力对肌瘤和子宫肌瘤细胞的影响。我们的工作旨在确定在肌瘤中对压缩力的反应而改变的蛋白质和信号通路。设计：以实验室为基础的受试者：从5名接受子宫切除术或子宫肌瘤切除术治疗子宫肌瘤的妇女中分离出患者匹配的肌瘤细胞和子宫肌瘤细胞。这项研究只使用了手术三个月内未进行激素调节的女性样本。一个嵌入的球体模型被开发用来模拟肌瘤组织，并提供一个缓冲，这将有助于压缩力的分布。暴露：在琼脂糖垫上添加0或6.4 mmHg的重量。球体培养7天。主要结果测量：组织学评估、rna测序（n=5）和蛋白质组学表征（n=3）。采用配对多重检验t检验进行统计学分析。如果相同的基因在四个现有的肌瘤和肌层rna测序数据集中的至少一个中也存在显著差异表达，则认为差异表达基因（DEGs）具有临床相关性。结果：共鉴定出61个临床相关的deg，这些deg仅在球体受压时差异表达。其中包括编码ephrin信号受体EPHB1的EPHB1；在肌瘤细胞中上调了2.81倍的log2倍（q=5.35×10-3）。压缩导致参与细胞外基质（ECM）组织的基因富集；然而，基因在不同的细胞类型之间有所不同。在蛋白水平上，子宫肌瘤球体中与子宫肌瘤相关的蛋白发生改变（q=1.00x10-33）。虽然胶原酶MMP-1在纤维瘤球状体中明显降低，但在纤维瘤球状体中胶原丰度发生改变，但胶原1没有改变。富集分析发现，ecm受体相互作用在细胞类型之间的压缩诱导变化中富集。结论：在研究肌瘤和子宫肌层之间的一些重要差异时，必须考虑压缩力，包括ephrin信号传导。不同丰度蛋白的富集分析表明，压迫也可能参与肌瘤的发生。

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引用次数: 0

Artificial intelligence–driven oocyte assessment for predicting blastulation and high-quality blastocyst formation in severe male factor infertility 人工智能驱动的卵母细胞评估用于预测严重男性因素不育的囊胚形成和高质量囊胚形成。

F&S science

Pub Date : 2025-11-01 Epub Date: 2025-07-15 DOI: 10.1016/j.xfss.2025.07.003

Edson Borges Jr. Ph.D. , Daniela Braga Ph.D. , Maite del Collado Ph.D. , Assumpto Iaconelli Jr. M.D. , Jullin Fjeldstad M.Sc. , Natalie Mercuri M.Sc. , Parisa Mojiri M.Sc. , Amanda Setti M.Sc.

Objective

To study whether artificial intelligence (AI)–driven oocyte evaluation is associated with blastocyst development and quality in couples with severe male factor infertility (SMF) undergoing intracytoplasmic sperm injection (ICSI) cycles.

Design

Cohort study.

Subjects

Fourteen thousand six hundred two oocyte images from 2,156 ICSI cycles performed between January 2020 and May 2024 in a private, university-affiliated in vitro fertilization center. Cycles were categorized into the following two groups: SMF (n = 200 cycles, 1,478 embryos) and non-SMF (n = 1,956 cycles, 13,124 embryos). Severe male factor infertility was defined as <5 million sperm in the ejaculate.

Exposure

Oocyte images were captured before ICSI and scored using the AI tool MAGENTA. The predictive value of Magenta Scores (MS) on embryonic development was assessed. The association between MS and oocyte fertilization and blastocyst formation was analyzed.

Main Outcome Measures

Oocyte fertilization, blastulation rate, and blastocyst quality.

Results

Magenta scores were significantly lower in oocytes that failed to fertilize compared with those that successfully fertilized (5.00 ± 0.04 vs. 6.44 ± 0.03). Blastulation rate was lower in the SMF group (46.61% vs. 50.80%), and blastocysts exhibited higher MS than nonblastocysts (5.12 ± 0.3 vs. 6.69 ± 0.3). The top-quality blastocyst rate was lower in SMF (56.6% vs. 65.2%), and high-quality blastocysts had higher MS than lower-quality ones (7.2 ± 0.6 vs. 6.8 ± 0.5). Among SMF cycles, MS were lower in oocytes that failed to fertilize (4.91 ± 0.12 vs. 6.34 ± 0.10). Magenta scores also differed between embryos that reached the blastocyst stage and those that did not (6.70 ± 0.11 vs. 4.96 ± 0.10). Top-quality blastocysts had significantly higher MS than others (7.00 ± 0.21 vs. 6.39 ± 0.19). Paternal age negatively correlated with fertilization, blastulation, and blastocyst quality; however, differences remained significant after adjusting for paternal age.

Conclusion

Artificial intelligence–based oocyte evaluation is associated with fertilization, blastulation, and blastocyst quality in SMF couples undergoing ICSI cycles. Magenta score values were consistently higher for blastocysts than nonblastocysts, demonstrating the AI tool’s utility in identifying oocytes with greater developmental potential, regardless of male infertility factors. However, the absence of sperm-specific factors in the MAGENTA algorithm may limit its ability to fully account for male infertility.

目的：研究人工智能驱动的卵母细胞评估是否与接受卵浆内单精子注射（ICSI）周期的严重男性因素不育（SMF）夫妇的囊胚发育和质量有关。设计：队列研究对象：2020年1月至2024年5月在私立大学附属体外受精中心进行的2156个ICSI周期的14602个卵母细胞图像。周期分为两组：SMF （n=200个周期，1478个胚胎）和非SMF （n= 1956个周期，13124个胚胎）。SMF定义为曝光：在ICSI前捕获卵母细胞图像，并使用人工智能工具MAGENTA™进行评分。评价品红评分（Magenta Scores， MS）对胚胎发育的预测价值。分析了MS与卵母细胞受精和囊胚形成的关系。主要观察指标：卵母细胞受精、囊胚率、囊胚质量。结果：受精失败的卵母细胞的MS明显低于成功受精的卵母细胞（5.00±0.04比6.44±0.03）。结论：基于人工智能的卵母细胞评估与进行ICSI周期的SMF夫妇的受精、囊胚发育和囊胚质量有关。囊胚的MS值始终高于非囊胚，表明人工智能工具在识别具有更大发育潜力的卵母细胞方面的实用性，无论男性不育因素如何。然而，MAGENTA™算法中缺乏精子特异性因素可能会限制其完全解释男性不育的能力。

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引用次数: 0

Use of AMD3100 for bone marrow–derived mesenchymal stem cell mobilization in the treatment of murine Asherman's syndrome 利用AMD3100动员骨髓间充质干细胞治疗小鼠阿什曼综合征。

F&S science

Pub Date : 2025-11-01 Epub Date: 2025-08-14 DOI: 10.1016/j.xfss.2025.08.003

Valerie A. Flores M.D., Pablo A. Delis M.D., Ramanaiah Mamillapalli Ph.D., Hugh S. Taylor M.D.

Objective

Asherman syndrome (AS) is characterized by intrauterine adhesions/fibrosis, resulting from damage to the endometrial basalis layer. The consequences of AS include infertility, recurrent pregnancy loss, preterm rupture of membranes, and placental abruption. Hysteroscopic adhesiolysis does not consistently restore endometrial function; there is a need for more effective treatments. Bone marrow–derived mesenchymal stem cells (BMD-MSCs) circulate systemically and contribute to tissue repair/regeneration, suggesting that they may serve as a source of progenitor cells for endometrial regeneration. Increasing the supply of BMD-MSCs to the endometrium may treat AS by allowing for regeneration/replenishment of endometrial progenitor cells. Mobilization of autologous BMD-MSCs using AMD3100, a CXC-motif-receptor-4 antagonist, is approved for bone marrow transplantation. We aimed to determine whether the optimal timing of AMD3100 administration—on the basis of CXCL12 production—would better recruit BMD-MSCs in a murine model of severe AS and restore functioning endometrium/fertility.

Design

Severe AS murine model.

Subjects

C57BL/6 mice in the diestrus phase undergoing surgical AS induction.

Exposure

Single injection with AMD3100 (treatment) or vehicle (saline). AMD3100 administration timing was based on the determination of maximum CXCL12 release after AS induction. Mice were then mated.

Main Outcome Measures

Time to pregnancy, litter size, and miscarriage rate.

Results

Maximum uterine CXCL12 production occurred 48 hours after AS induction; thus, AMD3100 vs. saline was administered 48 hours after induction. Of the AMD3100-treated mice, all achieved pregnancy and delivered. The treatment group became pregnant and delivered significantly sooner, indicating a faster time to conception (20 vs. 26 days). The treatment group had significantly larger litter sizes (6.5 vs. 4.2 pups) and significantly more live pups at delivery than the control group (6.0 vs. 2.7).

Conclusion

AMD3100 had a significant effect on uterine repair and regeneration in AS. The likelihood of pregnancy was significantly higher and more rapid in AS mice treated with AMD3100. Treated mice also had larger litter sizes and fewer miscarriages than controls. Furthermore, we determined for the first time the levels of CXCL12 in uteri after uterine injury, which allowed for the determination of the optimal timing of AMD3100 administration, to ensure mobilized BMD-MSCs homed to the uterus.

目的：Asherman综合征（AS）以子宫内膜基底层损伤引起的宫内粘连/纤维化为特征。AS的后果包括不孕症、反复流产、胎膜早破和胎盘早剥。宫腔镜下粘连松解术不能始终恢复子宫内膜功能；需要更有效的治疗方法。骨髓间充质干细胞（BM-MSCs）具有系统性循环，有助于组织修复/再生，这表明它们可能是子宫内膜再生的祖细胞来源。增加向子宫内膜提供BM-MSCs可能通过允许子宫内膜祖细胞的再生/补充来治疗AS。使用AMD3100（一种CXC-motif-receptor-4拮抗剂）动员自体骨髓间充质干细胞被批准用于骨髓移植。我们的目的是确定基于CXCL12生成的AMD 3100给药的最佳时间是否能更好地在严重AS小鼠模型中招募BM-MSCs，并恢复功能子宫内膜/生育能力。设计：重度AS小鼠模型研究对象：处于绝育期接受手术诱导的C57BL/6小鼠。暴露：单次注射AMD3100（治疗）或载体（生理盐水）。AMD3100给药时间基于AS诱导后CXCL12最大释放量的测定。然后对老鼠进行交配。测量的主要结果：妊娠时间、产仔数和流产率。结果：AS诱导后48小时子宫CXCL12产生量最大，因此在诱导后48小时给予AMD3100与生理盐水对照。在接受AMD3100治疗的小鼠中，所有小鼠都成功怀孕并分娩。治疗组怀孕和分娩明显更快，表明受孕时间更快（20天对26天）。治疗组产仔数明显大于对照组（6.5 vs 4.2），分娩时活仔数明显多于对照组（6.0 vs 2.7）。结论：AMD3100对AS患者的子宫修复和再生有明显的促进作用。用AMD3100治疗的AS小鼠，怀孕的可能性明显更高、更快。与对照组相比，接受治疗的小鼠产仔量更大，流产率更低。此外，我们首次测定了子宫损伤后子宫内CXCL12的水平，从而确定了AMD3100给药的最佳时机，以确保动员的BMD-MSCs回到子宫。

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