RESUMO
Endometriosis (EMs)-related infertility commonly has decreased endometrial receptivity and normal decidualization is the basis for establishing and maintaining endometrial receptivity. However, the potential molecular regulatory mechanisms of impaired endometrial decidualization in patients with EMs have not been fully clarified. We confirmed the existence of reduced endometrial receptivity in patients with EMs by scanning electron microscopy and quantitative real-time PCR. Here we identified an lncRNA, named BMPR1B-AS1, which is significantly downregulated in eutopic endometrium in EMs patients and plays an essential role in decidual formation. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and rescue analyses revealed that BMPR1B-AS1 positively regulates decidual formation through interaction with the RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Downregulation of IGF2BP2 led to a decreased stability of BMPR1B-AS1 and inhibition of activation of the SMAD1/5/9 pathway, an inhibitory effect which diminished decidualization in human endometrial stromal cells (hESCs) decidualization. In conclusion, our identified a novel regulatory mechanism in which the IGF2BP2-BMPR1B-AS1-SMAD1/5/9 axis plays a key role in the regulation of decidualization, providing insights into the potential link between abnormal decidualization and infertility in patients with EMs, which will be of clinical significance for the management and treatment of infertility in patients with EMs.
Assuntos
Endometriose , RNA Longo não Codificante , Proteínas de Ligação a RNA , Adulto , Feminino , Humanos , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Decídua/metabolismo , Decídua/patologia , Endometriose/metabolismo , Endometriose/genética , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Infertilidade Feminina/metabolismo , Infertilidade Feminina/genética , Infertilidade Feminina/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Células Estromais/metabolismo , Proteínas Smad , Adulto JovemRESUMO
BACKGROUND: Monoamine oxidases (MAOs) is an enzyme that catalyzes the deamination of monoamines. The current research on this enzyme is focused on its role in neuropsychiatric, neurodevelopmental, and neurodegenerative diseases. Indeed, MAOs with two isoforms, namely, A and B, are located on the outer mitochondrial membrane and are widely distributed in the central nervous system and peripheral tissues. Several reports have described periodic changes in the levels of this enzyme in the human endometrial tissue. RESULTS: The novel role of MAOs in endometrial receptivity establishment and embryonic development by maintaining monoamine homeostasis was investigated in this study. MAOs activity was observed to be enhanced during the first trimester in both humans and mice under normal conditions. However, under pathological conditions, MAOs activity was reduced and was linked to early pregnancy failure. During the secretory phase, the endometrial stromal cells differentiated into decidual cells with a stronger metabolism of monoamines by MAOs. Excessive monoamine levels cause monoamine imbalance in decidual cells, which results in the activation of the AKT signal, decreased FOXO1 expression, and decidual dysfunction. CONCLUSIONS: The findings suggest that endometrial receptivity depends on the maintenance of monoamine homeostasis via MAOs activity and that this enzyme participates in embryo implantation and development.
Assuntos
Implantação do Embrião , Endométrio , Homeostase , Monoaminoxidase , Feminino , Monoaminoxidase/metabolismo , Endométrio/metabolismo , Humanos , Implantação do Embrião/fisiologia , Camundongos , Animais , Gravidez , Desenvolvimento Embrionário/fisiologia , Monoaminas Biogênicas/metabolismoRESUMO
The surface tension and viscosity values of N-methyldiethanolamine (MDEA) aqueous solutions promoted by tetramethylammonium arginate ([N1111][Arg]) were measured and modeled. The experimental temperatures were 303.2 to 323.2 K. The mass fractions of MDEA (wMDEA) and [N1111][Arg] (w[N1111][Arg]) were 0.300 to 0.500 and 0.025 to 0.075, respectively. The measured surface tension and viscosity values were satisfactorily fitted to thermodynamic models. With the aid of experimentally viscosity data, the activation energy (Ea) and H2S diffusion coefficient (DH2S) of MDEA-[N1111][Arg] aqueous solution were deduced. The surface entropy and surface enthalpy of the solutions were calculated using the fitted model of the surface tension. The quantitative relationship between the calculated values (surface tension, surface entropy, surface enthalpy, viscosity, activation energy, and H2S diffusion coefficient) and the operation conditions (mass fraction and temperature) was demonstrated.
RESUMO
Dingkun Pill (DK) is one of the representative traditional Chinese medicines, which has been used in the treatment of gynecological diseases for hundreds of years. Accumulative observations and evidence have shown the beneficial effects of DK, including enhancing the function of hypothalamic-pituitary-ovarian axis. However, the underlying mechanisms remain elusive. In this study, the effects of DK on uterine receptivity and implantation were explored by a series of studies with different mouse models. The results showed that DK can advance the time of implantation by influencing the expression of estrogen target genes to facilitate embryo implantation. DK was efficient to activate embryo implantation at the presence of suboptimal estrogen in delayed implantation mouse model. Our further study revealed that the improvement of DK on receptivity establishment is attributed to the differential regulation of DK on implantation-associated genes. This study provides previously unappreciated molecular mechanism of DK in embryo implantation and benefits the potential clinical application of DK in human reproduction improvement.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Implantação do Embrião/efeitos dos fármacos , Medicina Tradicional Chinesa , Útero/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/fisiologia , Estrogênios/metabolismo , Feminino , Camundongos , Gravidez , Receptores de Progesterona/metabolismo , Comprimidos , Útero/fisiologiaRESUMO
The automated segmentation of Intracranial Arteries (IA) in Digital Subtraction Angiography (DSA) plays a crucial role in the quantification of vascular morphology, significantly contributing to computer-assisted stroke research and clinical practice. Current research primarily focuses on the segmentation of single-frame DSA using proprietary datasets. However, these methods face challenges due to the inherent limitation of single-frame DSA, which only partially displays vascular contrast, thereby hindering accurate vascular structure representation. In this work, we introduce DIAS, a dataset specifically developed for IA segmentation in DSA sequences. We establish a comprehensive benchmark for evaluating DIAS, covering full, weak, and semi-supervised segmentation methods. Specifically, we propose the vessel sequence segmentation network, in which the sequence feature extraction module effectively captures spatiotemporal representations of intravascular contrast, achieving intracranial artery segmentation in 2D+Time DSA sequences. For weakly-supervised IA segmentation, we propose a novel scribble learning-based image segmentation framework, which, under the guidance of scribble labels, employs cross pseudo-supervision and consistency regularization to improve the performance of the segmentation network. Furthermore, we introduce the random patch-based self-training framework, aimed at alleviating the performance constraints encountered in IA segmentation due to the limited availability of annotated DSA data. Our extensive experiments on the DIAS dataset demonstrate the effectiveness of these methods as potential baselines for future research and clinical applications. The dataset and code are publicly available at https://doi.org/10.5281/zenodo.11401368 and https://github.com/lseventeen/DIAS.
RESUMO
A catalyst (V-Cu-Ce-ZSM-5) was explored to simultaneously remove the SO2 and NOx from flue gas by use of the ZSM-5 molecular sieve as the carrier, V and Cu as the active components, and Ce as the additive in low temperature of 150 °C. The performance of V-Cu-Ce-ZSM-5 was evaluated for the oxidation of NO and SO2 before and after the addition of graphene oxide (GO). The results showed that V-Cu-Ce-ZSM-5@GO0.5 had the best performance at a reaction temperature of 150 °C, and the oxidation efficiency of SO2 and NO was 94.60% and 83.64%, respectively. The multiple structural characterizations (BET, SEM, Raman, XRD, and XPS) revealed that the loading of V and Cu with the additive Ce expanded the specific surface area and pore volume of ZSM-5, provided more adsorption sites for SO2 and NO, and had good desulfurization and denitration activity. The addition of GO further improved the dispersibility of active components and auxiliaries, increased the number of active sites in the reaction process, and significantly improved catalytic activity.
Assuntos
Temperatura Baixa , Dióxido de Enxofre , Temperatura , Oxirredução , CatáliseRESUMO
Cerebrovascular segmentation in digital subtraction angiography (DSA) images is the gold standard for clinical diagnosis. However, owing to the complexity of cerebrovascular, automatic cerebrovascular segmentation in DSA images is a challenging task. In this paper, we propose a CNN-based Two-branch Boundary Enhancement Network (TBENet) for automatic segmentation of cerebrovascular in DSA images. The TBENet is inspired by U-Net and designed as an encoder-decoder architecture. We propose an additional boundary branch to segment the boundary of cerebrovascular and a Main and Boundary branches Fusion Module (MBFM) to integrate the boundary branch outcome with the main branch outcome to achieve better segmentation performance. The TBENet was evaluated on HMCDSA (an in-house DSA cerebrovascular dataset), and reaches 0.9611, 0.7486, 0.7152, 0.9860 and 0.9556 in Accuracy, F1 score, Sensitivity, Specificity, and AUC, respectively. Meanwhile, we tested our TBENet on the public vessel segmentation benchmark DRIVE, and the results show that our TBENet can be extended to diverse vessel segmentation tasks.
Assuntos
Circulação Cerebrovascular , HumanosRESUMO
Recurrent implantation failure (RIF) is defined as the failed pregnancy after good embryo transfer over 3 cycles during in vitro fertilization (IVF).The human endometrium plays a vital role in providing the site for embryo implantation, with several factors implicated in unsatisfactory endometrial receptivity in RIF. Our present results revealed that women with pregnancy loss or infertility have a higher serum epinephrine level, indicating a potential correlation between psychological stress and pregnancy failure. RNA-sequencing of the tissues collected at the endometrial receptive phase in normal and RIF women showed that stress hormones could affect the functional status of endometrial receptivity. Subsequent analysis revealed that the epinephrine signaling acts as an important regulator of endometrial receptivity through the PI3K-AKT and FOXO1 signaling pathways. We also found that patients with RIF show attenuated expression of the alpha-2C-adrenergic receptor (ADRA2C) and that its down regulation induced by high level epinephrine could inhibit the decidualization. Early pregnant mice treated with stress showed high serum epinephrine levels, defective uterine adrenergic receptor expression, and low pregnancy rates. Altogether, our findings indicate that mental stress during early pregnancy can alter the functional status of endometrial receptivity.
Assuntos
Implantação do Embrião , Fosfatidilinositol 3-Quinases , Animais , Ansiedade , Implantação do Embrião/fisiologia , Epinefrina/farmacologia , Feminino , Humanos , Camundongos , Gravidez , Receptores AdrenérgicosRESUMO
Endometriosis is an inflammation-dependent disorder characterized by the abnormal growth of endometrium-like lesions. In recent years, there is a great deal of interest in the development of anti-inflammatory therapy. Herein, an acid-sensitive calcium carbonate nanoparticle (CaNP) incorporated BML-111 (BML@CaNP) was prepared. BML@CaNP acted as a Ca2+ nanomodulator for efferocytosis (macrophages engulf apoptotic cells). Specifically, BML@CaNP induced the apoptosis of endometriotic stromal cells and enhanced the efferocytosis of macrophages. In addition, the particle can also deliver BML to the ectopic lesion for resolving the inflammatory response. In vivo BML@CaNP effectively suppressed lesion growth in endometriosis mice model, which could be attributed to the enhancing efferocytosis of cells and the lower levels of inflammatory factors in peritoneal fluid. In addition, these nanoparticles did not show side effects. In all, we provide a new anti-inflammatory strategy by both enhancing efferocytosis and resolving inflammation for the treatment of endometriosis.
Assuntos
Endometriose , Nanopartículas Multifuncionais , Camundongos , Humanos , Animais , Feminino , Endometriose/tratamento farmacológico , Fagocitose , Macrófagos , Inflamação/tratamento farmacológicoRESUMO
To high efficiently remove H2S from low partial pressure coke oven gas (COG), a novel activator (tetramethylammonium arginine, [N1111][Arg]) was used to blend with N-methyldiethanolamine (MDEA) for the absorption of H2S. High concentrated [N1111][Arg]-MDEA aqueous solution was used as absorbent. Thermodynamic properties including absorption amount and H2S loading values were measured, then the kinetic apparent absorption rate was calculated based on the change of absorption amount with time. The removal efficiency of H2S in simulated COG was verified in tray towers. Compared with monoethanolamine (MEA)-MDEA and tetramethylammonium glycinate ([N1111][Gly])-MDEA aqueous solutions, [N1111][Arg]-MDEA aqueous solution takes advantages of higher absorption capacity, absorption rate and removal efficiency. Our results showed that the proposed absorbent has good industrial application prospect in coke oven gas desulfurization, because it achieved 100% removal of H2S in the tray tower containing only 4 sieve plates under high concentrated condition (water content < 45%), which may significantly decrease the energy consumption.