Background Thin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms. Methods Ethanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays. Results Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness (P < 0.001, P < 0.05), decrease fibrous area (P < 0.0001), and promote the proliferation and angiogenesis of endometrial cells (as indicated by Ki67 and VEGF, P < 0.05, P < 0.05, respectively) in mice injured endometrium. HP-MSCs-HA could also significantly improve the embryo implantation rate (P < 0.01) compared with the ethanol group. Further mechanistic study showed the paracrine effects of HP-MSCs. They could not only promote the proliferation and migration of human endometrial stromal cells via the JNK/Erk1/2-Stat3-VEGF pathway but also facilitate the proliferation of glandular cells via Jak2-Stat5 and c-Fos-VEGF pathway. In turn, the increased VEGF in the endometrium promoted the angiogenesis of endothelial cells. Conclusion Our study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs, and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings. Graphical abstract
Intelligent sensors have attracted substantial attention for various applications, including wearable electronics, artificial intelligence, healthcare monitoring, and human−machine interactions. However, there still remains a critical challenge in developing a multifunctional sensing system for complex signal detection and analysis in practical applications. Here, we develop a machine learning-combined flexible sensor for real-time tactile sensing and voice recognition through laser-induced graphitization. The intelligent sensor with a triboelectric layer can convert local pressure to an electrical signal through a contact electrification effect without external bias, which has a characteristic response behavior when exposed to various mechanical stimuli. With the special patterning design, a smart human−machine interaction controlling system composed of a digital arrayed touch panel is constructed to control electronic devices. Based on machine learning, the real-time monitoring and recognition of the changes of voice are achieved with high accuracy. The machine learning-empowered flexible sensor provides a promising platform for the development of flexible tactile sensing, real-time health detection, human−machine interaction, and intelligent wearable devices.
Introduction: Most premenopausal women in China have normal lipid profiles while the sexual function among them was scarcely demonstrated. Aim: To find out the characteristics of the sexual function in premenopausal Chinese women without hyperlipidemia using the Female Sexual Function Index (FSFI) and the Golombok Rust Inventory of Sexual Satisfaction (GRISS). Methods: This cross-sectional study was performed to find out the characteristics of sexual function in premenopausal Chinese women without hyperlipidemia. Between January 2019 and March 2019, we recruited 216 women, 25e49 years of age. Data from questionnaires and health checkups were collected and analyzed. Main Outcome Measure: We report the prevalence of and factors related to female sexual dysfunction (FSD) in premenopausal Chinese women without hyperlipidemia in accordance with the FSFI and the GRISS. Results: The prevalence of FSD in our study was 46.2%. The mean age was 38.07 ± 6.94 years. More highly educated women suffered from FSD than those in the control group (61.1% vs 35.2%, P < .05). Binge eating was significantly different between the groups (P ¼ .023). Multiple logistic regression analyses demonstrated that total cholesterol level was positively associated with low desire (OR, 2.13; 95% CI, 1.10e4.13; P ¼ .025) and so was the low-density lipoprotein level (OR, 2.18; 95% CI, 1.03e4.62; P ¼ .0.041). The high-density lipoprotein level was inversely associated with infrequency (OR, 0.18; 95% CI, 0.06e0.59; P ¼ .004). More women with FSD had orgasm disorder than those in the control group, for 83.3% vs 35.2% in the FSFI (P < .001), 88.9% vs 54.3% in the GRISS (P < .001), respectively. Dissatisfaction remained the most common issue for the control group in both the FSFI and the GRISS (90.50% and 58.10%, respectively). Conclusions: FSD is frequent in premenopausal Chinese women without hyperlipidemia. Dissatisfaction as the common problem influenced over half of them and orgasm disorder is a severe sexual issue for women with FSD.
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