ENO1 promotes trophoblast invasion regulated by E2F8 in recurrent miscarriage.

Recurrent miscarriage (RM) is related to the dysfunction of extravillous trophoblast cells (EVTs), but the comprehensive mechanisms remain largely unexplored. We analyzed single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing and microarray datasets obtained from Gene Expression Omnibus (GEO) database to explore the hub genes in the mechanisms of RM. We identified 1724 differentially expressed genes (DEGs) in EVTs from the RM, and they were all expressed along the trajectory of EVTs. These DEGs were associated with hypoxia and glucose metabolism. Single-cell Regulatory Network Inference and Clustering (SCENIC) analysis revealed that E2F transcription factor (E2F) 8 (E2F8) was a key transcription factor for these DEGs. And the expression of ENO1 can be positively regulated by E2F8 via RNA sequencing analysis. Subsequently, we performed immunofluorescence assay (IF), plasmid transfection, western blotting, chromatin immunoprecipitation (ChIP), real-time quantitative polymerase chain reaction (qRT-PCR), and transwell assays for validation experiments. We found that the expression of alpha-Enolase 1 (ENO1) was lower in the placentas of RM. Importantly, E2F8 can transcriptionally regulate the expression of ENO1 to promote the invasion of trophoblast cells by inhibiting secreted frizzled-related protein 1/4 (SFRP1/4) to activate Wnt signaling pathway. Our results suggest that ENO1 can promote trophoblast invasion via an E2F8-dependent manner, highlighting a potential novel target for the physiological mechanisms of RM.

Co2P nanowire arrays anchored on a 3D porous reduced graphene oxide matrix embedded in nickel foam for a high-efficiency hydrogen evolution reaction.

Regulating the structural and interfacial properties of transition metal phosphides (TMPs) by coupling carbon-based materials with large surface areas to enhance hydrogen evolution reaction (HER) performance presents significant progress for water splitting technology. Herein, we constructed a composite substrate of a three-dimensional porous graphene oxide matrix (3D-GO) embedded in nickel foam (NF) to grow a Co2P electrocatalyst. Well-defined gladiolus-like Co2P nanowire arrays tightly anchored on the substrate show enhanced electrochemical characteristics for the hydrogen evolution reaction (HER) based on the promoting roles of 3D porous reduced GO (3D-rGO) derived from 3D-GO, which promotes the dispersion of active components, improves the rate of electron transfer, and facilitates the transport of water molecules. As a result, the obtained Co2P@3D-rGO/NF electrode exhibits superior HER activity in 1.0 M KOH media, achieving overpotentials of 36.5 and 264.7 mV at current densities of 10 and 100 mA cm-2, respectively. The electrode also has a low Tafel slope of 55.5 mV dec-1, a large electrochemical surface area, and small charge-transfer resistance, further revealing its mechanism of high intrinsic activity. Moreover, the electrode exhibits excellent HER stability and durability without surface morphology and chemical state changes.

Mid-term outcomes of left subclavian artery revascularization with Castor stent graft in treatment of type B aortic dissection in left subclavian artery.

Background: Here we analyzed mid-term data of thoracic endovascular aneurysm repair (TEVAR) surgery with Castor single-branched stent graft placement for the management of Stanford type B aortic dissection (STBAD) involving the left subclavian artery (LSA). Methods: Between April 2014 and February 2019, 32 patients with STBAD involving a Castor single-branched stent graft were included. We analyzed their outcomes, including technical success rate (TSR), surgical duration (SD), presence of ischemia, perioperative complications, LSA patency, and survival rate (SR), using computed tomography angiography and clinical evaluation during mid-term follow-up. Results: The mean patient age was 54.63 â€‹± â€‹12.37 years (range, 36-83 years). The TSR was 96.88% (n â€‹= â€‹31/32). The mean SD was 87.44 â€‹± â€‹10.89 with a mean contrast volume of 125.31 â€‹± â€‹19.30 â€‹mL. No neurological complications or deaths occurred during the study period. The patients had a mean hospital stay of 7.84 â€‹± â€‹3.20 days. At a mean follow-up of 68.78 â€‹± â€‹11.26 months, four non-aortic deaths (12.5%) were observed. The LSA patency rate was 100% (n â€‹= â€‹28/28). There was only one case of type I endoleak immediately after surgery (3.12%) (type I from LSA). However, none of the patients experienced type II endoleaks, and there were no cases of retrograde type A aortic dissection or stent graft-driven new distal entry. Finally, all patients exhibited good LSA patency. Conclusion: TEVAR using a Castor single-branched stent graft may be a highly feasible and efficient procedure for the management of STBAD involving the LSA.

IL-27 promotes decidualization via the STAT3-ESR/PGR regulatory axis.

Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra-/- (knockout of Il27ra) female mice. Moreover, knockout of Il27ra did not affect the estrus cycle and folliculogenesis in mice but reduced implantation rate with the impairing decidualization. Mechanistically, IL-27 upregulated the expression of ESR1, ESR2 and PGR in ESCs and DSCs, as well as the phosphorylation level of STAT3. In the presence of estrogen plus progesterone, treatment with ESCs with anti-IL-27 inhibited the activation of STAT3. Also, the expression of ESR, PGR was decreased in Il27ra-/- mice. In conclusion, these findings demonstrate that IL-27 upregulated by estrogen and progestogen promotes decidualization possibly through a STAT3-dominant pathway.

Progesterone Attenuates SIRT1-Deficiency-Mediated Pre-Eclampsia.

Pre-eclampsia is a severe hypertensive disorder of pregnancy (HDP), mainly characterized by new-onset hypertension with proteinuria after 20-week gestation. Sirtuin1 (SIRT1), a class III histone deacetylase, is associated with the regulation of various pathophysiological processes, including inflammation, immune response, metabolism, and autophagy. However, the effect of SIRT1 in the pathogenesis of pre-eclampsia remains to be elucidated. In this study, we found that the expression of SIRT1 was relatively lower in the placentas and serum samples of pre-eclampsia patients. Typical pre-eclampsia-like symptoms, such as hypertension, proteinuria, fetal growth restriction, kidney injury, and a narrow placental labyrinth layer, were observed in SIRT1 knockdown (SIRT1+/-) mice. Of note, these performances could be improved after the intraperitoneal injection of SIRT1 agonist SRT2104. More importantly, we found that the efficacy of progesterone on attenuating symptoms of PE was profoundly better than that of metformin in SIRT1+/- mice. In addition, our results suggested that progesterone can promote the invasion and inhibit the apoptosis of trophoblasts. These data suggest that SIRT1 plays an important role in pre-eclampsia and that progesterone alleviates pre-eclampsia-like symptoms mediated by SIRT1 deficiency.

Research on High Sensitivity Oil Debris Detection Sensor Using High Magnetic Permeability Material and Coil Mutual Inductance.

Metallic contaminants (solid) are generated by friction pair, causing wear of equipment by enters the lubricating system. This poses a great potential threat to the normal operation of such machines. The timely analysis and detection of debris can lead to the avoidance of mechanical failures. Abnormal wear in machinery may produce debris exceeding 10 µm. The traditional inductance detection method has low sensitivity and cannot meet the actual detection requirements. To boost the sensitivity of the inductance sensor, the mutual inductance of coils and the strong magnetic conductivity of permalloy was utilized to design a high sensitivity inductance sensor for the detection of debris in lubricating oil. This design was able to detect 10-15 µm iron particles and 65-70 µm copper particles in the oil. The experimental results illustrate that low-frequency excitation is the best for detecting ferromagnetic particles, while high-frequency excitation has the best effect for detecting non-ferromagnetic particles. This paper demonstrates the significant advantages of coil mutual inductance, and strong magnetic conductivity of permalloy in improving the detection sensitivity of oil debris sensors. This will provide technical support for wear detection in mechanical equipment and fault diagnosis.

A positive COX-2/IL-1ß loop promotes decidualization by upregulating CD82.

A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Stimulation with prostaglandin E2 (PGE2) elevated the expression of CD82 in ESCs. In contrast, celecoxib, a selective COX-2 inhibitor, significantly downregulated the expression of CD82 in decidual stromal cells (DSCs). Bioinformatics analysis and further research showed that recombinant human interleukin (IL)-1ß protein (rhIL-1ß) upregulated CD82 in ESCs. Of note, blocking IL-1ß signaling with anti-human IL-1ß neutralizing antibody could reverse the stimulatory effect of PGE2 on CD82 in ESCs. Silencing CD82 resulted in the decease of the decidualization markers PRL and IGFBP1 mRNA levels in DSCs. More importantly, we observed rhIL-1ß also upregulated the expression of COX-2, and the upregulation of PRL and IGFBP1 induced by rhIL-1ß could be abolished by celecoxib in ESCs or CD82 deficiency in DSCs. This study suggests that CD82 should be a novel promotor for decidualization under a positive regulation of the COX-2/PGE2/IL-1ß positive feedback loop.

Design and Research of Inductive Oil Pollutant Detection Sensor Based on High Gradient Magnetic Field Structure.

An inductive oil pollutant detection sensor based on a high-gradient magnetic field structure is designed in this paper, which is mainly used for online detection and fault analysis of pollutants in hydraulic and lubricating oil systems. The innovation of the sensor is based on the inductance detection method. Permalloy is embedded in the sensing region of the sensor, so that the detection area generates a high gradient magnetic field to enhance the detection accuracy of the sensor. Compared with traditional inductive sensors, the sensor has a significant improvement in detection accuracy, and the addition of permalloy greatly improves the stability of the sensor's detection unit structure. The article theoretically analyzes the working principle of the sensor, optimizes the design parameters and structure of the sensor through simulation, determines the best permalloy parameters, and establishes an experimental system for verification. Experimental results show that when a piece of permalloy is added to the sensing unit, the signal-to-noise ratio (SNR) of iron particles is increased by more than 20%, and the signal-to-noise ratio of copper particles is increased by more than 70%. When two pieces of permalloy are added, the signal-to-noise ratio for iron particles is increased by more than 70%, and the SNR for copper particles is increased several times. This method raises the lower limit of detection for ferromagnetic metal particles to 20 µm, and the lower limit for detection of non-ferromagnetic metal particles to 80 µm, which is the higher detection accuracy of the planar coil sensors. This paper provides a new and faster online method for pollutant detection in oil, which is of great significance for diagnosing and monitoring the health of oil in mechanical systems.

Myeloid-derived suppressor cells in obstetrical and gynecological diseases.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid-origin cells which have immunosuppressive activities in several conditions, such as cancer and inflammation. Recent research has also associated MDSCs with numerous obstetrical and gynecological diseases. During pregnancy, MDSCs accumulate to ensure maternal-fetal immune tolerance, whereas they are decreased in patients who suffer from early miscarriage or pre-eclampsia. While the etiology of endometriosis is still unknown, abnormal accumulation of MDSCs in the peripheral blood and peritoneal fluid, alongside an increased level of reactive oxygen species (ROS), has been observed in these patients, which is central to the cellular immune regulations by MDSCs. Additionally, the regulation of MDSCs observed in tumours is also applicable to gynecologic neoplasms, including ovarian cancer and cervical cancer. More recently, emerging evidence has shown that there are high levels of MDSCs in premature ovarian failure (POF) and in vitro fertilization (IVF), but the underlying mechanisms are unknown. In this review, the generation and mechanisms of MDSCs are summarized. In particular, the modulation of these cells in immune-related obstetrical and gynecological diseases is discussed, including potential treatment options targeting MDSCs.

Decidual stromal cells maintain decidual macrophage homeostasis by secreting IL-24 in early pregnancy.

PROBLEM: The state of self-renewal and self-maintain of decidual macrophages would be important for immune homeostasis at the maternal-fetal interface. The roles of interleukin (IL)-24 derived from decidual stromal cells (DSCs) on decidual macrophages have not been explored. METHOD OF STUDY: IL-24 expression in DSCs was interfered by lentivirus, and the transcription levels of IL-24 in DSCs were verified by real time (RT)-PCR. The levels of IL-24 receptors were determined by flow cytometry assays. The effect of recombination human IL-24 (rhIL-24) on the differentiation and apoptosis of macrophages was analyzed by flow cytometry in vitro. The viability of macrophages was detected by Cell Counting Kit-8 assays. RESULTS: The growth of DSCs was not affected obviously only by IL-24 knockdown while the growth of knockdown DSCs was inhibited significantly after co-cultured with decidual macrophages. The levels of IL-24 receptors (IL-20R1 and IL-22R1) were moderately to highly expressed on decidual macrophages and human macrophage cell line U937. The differentiation of decidual macrophages treated by rhIL-24 or co-cultured with IL-24 knockdown DSCs was not affected. Both apoptosis and viability of U937 cells were promoted by rhIL-24. The ratio of Bcl-2/Bax was down-regulated and Ki-67 was up-regulated by IL-24 treatment. The expression of Bcl-2/Bax was up-regulated while Ki-67 was down-regulated in U937 cells after co-cultured by IL-24 knockdown DSCs. CONCLUSION: IL-24 secreted by DSCs promotes the renewal and homeostasis of decidual macrophages possibly via down-regulating the ratio of Bcl-2/Bax and up-regulating of the expression of Ki-67 in early pregnancy.

Clinical Characteristics, Treatment, and Prognosis of Diabetic Foot Disease in Macao and Beijing: A Retrospective Study.

INTRODUCTION: There has been no epidemiological study of diabetes mellitus (DM) in Macao. Also, multidisciplinary treatment is yet to be popularized and complications of DM cannot be managed promptly in this region. Therefore, this study was performed to compare the clinical characteristics, treatment, and prognosis of diabetic foot disease between patients in Macao and Beijing. METHODS: A total of 243 patients with diabetic foot disease were enrolled: 124 from a tertiary hospital in Beijing and 119 from a tertiary hospital in Macao. The clinical profiles were collected and analyzed. RESULTS: The surgical treatment rate in the Beijing group (96.0%) was significantly higher than that in the Macao group (21.0%) (P < 0.05). The overall mortality rate was 14.8%, and cardiac failure was the most common cause (72.2%). Monthly household income and smoking were independent factors affecting the age of onset. Age of diabetes onset was a risk factor for the occurrence of diabetic foot disease; age, duration of diabetic foot disease, and length of smoking history were independent factors affecting the severity of diabetic foot disease. Renal dysfunction and activated partial thromboplastin time were independent factors affecting the survival time of patients with diabetic foot disease. CONCLUSIONS: Smoking may be a risk factor for the occurrence and development of diabetic foot; it can significantly reduce the onset age and aggravate the severity of this disease. The onset age of diabetic foot was lower in high-income patients, and prevention should be encouraged in this population. Elderly age may be associated with a rapidly developing and severe diabetic foot. The clinical course was also associated with the severity of diabetic foot. Renal and coagulation function should be closely monitored during the treatment of diabetic foot.

Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway.

Reactive oxygen species (ROS) can drive the de­differentiation of tumor cells leading to the process of epithelial-to-mesenchymal transition (EMT) to enhance invasion and metastasis. The invasive and metastatic phenotype of malignant cells is often linked to loss of E-cadherin expression, a hallmark of EMT. Recent studies have demonstrated that hypoxic exposure causes HIF-1-dependent repression of E-cadherin. However, the mechanism by which ROS and/or HIF suppresses E-cadherin expression remains less clear. In the present study, we found that ROS accumulation in ovarian carcinoma cells upregulated HIF-1α expression and subsequent transcriptional induction of lysyl oxidase (LOX) which repressed E-cadherin. Loss of E-cadherin facilitated ovarian cancer (OC) cell migration in vitro and promoted tumor growth in vivo. E-cadherin immunoreactivity correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation and metastasis. Negative E-cadherin expression along with FIGO stage, tumor differentiation and metastasis significantly predicted for a lower 5-year survival rate. These findings suggest that ROS play an important role in the initiation of metastatic growth of OC cells and support a molecular pathway from ROS to aggressive transformation which involves upregulation of HIF-1α and its downstream target LOX to suppress E-cadherin expression leading to an increase in cell motility and invasiveness.

Emodin augments cisplatin cytotoxicity in platinum-resistant ovarian cancer cells via ROS-dependent MRP1 downregulation.

The intracellular level of reactive oxygen species (ROS) is closely associated with chemosensitivity of cancer cells. Overexpression of ATP binding cassette transporter MRP1 is correlated with resistance to platinum drugs. In this study, we tested the hypothesis that emodin, a potent ROS generator, may increase sensitivity of cisplatin-(cDDP-) resistant ovarian carcinoma cells to cDDP cytotoxicity via ROS-mediated suppression of MRP1 expression. Using the isogenic pair of the human ovarian carcinoma cell line COC1 and its cDDP resistant variant COC1/DDP, we found that ROS level in the cDDP-sensitive ovarian cancer cells was significantly higher than that in the cDDP-resistant cells. Emodin enhanced ROS production in COC1/DDP cells and consequently sensitized them to cDDP-induced apoptosis. These effects were reversed by addition of the antioxidant N-acetyl-L-cysteine (NAC). Cotreatment with emodin and cDDP inhibited the tumor growth in vivo by increasing tumor cell apoptosis. The emodin-enhanced cDDP cytotoxicity was attributable to downregulation of multidrug resistance-related protein 1 (MRP1) expression. Together, these results suggest that emodin could act as an adjunct to enhance the anticancer effect of cDDP likely through ROS-related downregulation of MRP1 expression, and may be of therapeutic potential in cDDP-refractory ovarian carcinomas.