Downregulated INHBB in endometrial tissue of recurrent implantation failure patients impeded decidualization through the ADCY1/cAMP signalling pathway.

PURPOSE: This study aims to identify the mechanism of Inhibin Subunit Beta B (INHBB), a member of the transforming growth factor-ß (TGF-ß) family involved in the regulation of human endometrial stromal cells (HESCs) decidualization in recurrent implantation failure (RIF). METHODS: RNA-seq was conducted to identify the differentially expressed genes in the endometria from control and RIF patients. RT-qPCR, WB, and immunohistochemistry were performed to analyse the expression levels of INHBB in endometrium and decidualised HESCs. RT-qPCR and immunofluorescence were used to detect changes in the decidual marker genes and cytoskeleton after knockdown INHBB. Then, RNA-seq was used to dig out the mechanism of INHBB regulating decidualization. The cAMP analogue (forskolin) and si-INHBB were used to investigate the involvement of INHBB in the cAMP signalling pathway. The correlation of INHBB and ADCY expression was analysed by Pearson's correlation analysis. RESULTS: Our results showed significantly reduced expression of INHBB in endometrial stromal cells of women with RIF. In addition, INHBB was increased in the endometrium of the secretory phase and significantly induced in in-vitro decidualization of HESCs. Notably, with RNA-seq and siRNA-mediated knockdown approaches, we demonstrated that the INHBB-ADCY1-mediated cAMP signalling pathway regulates the reduction of decidualization. We found a positive association between the expression of INHBB and ADCY1 in endometria with RIF (R2 = 0.3785, P = 0.0005). CONCLUSIONS: The decline of INHBB in HESCs suppressed ADCY1-induced cAMP production and cAMP-mediated signalling, which attenuated decidualization in RIF patients, indicating that INHBB is an essential component in the decidualization process.

Prolonging the time of progesterone supplementation to improve the pregnancy outcomes of single day 6 blastocyst transfer in frozen-thawed cycles: study protocol for a randomized controlled trial.

BACKGROUND: Infertility is one of the most important and underappreciated reproductive health problems in developing countries. Currently, in vitro fertilization and embryo transfer is the most effective treatment strategy for infertility. In a frozen-thawed cycle, single-blastocyst transfer can not only ensure relatively higher pregnancy and live birth rates but also effectively reduce the risk of maternal and neonatal complications. In frozen-thawed cycles, progesterone is initiated to promote the final phase of endometrial preparation prior to embryo transfer. However, the optimal duration of exposure to progesterone has remained inconclusive. Therefore, we designed a randomized controlled trial (RCT) to compare the effects of different prolonged progesterone transformation times (P+6 and P+7) on the pregnancy outcomes of D6 single blastocyst transfer in a frozen-thawed cycle. METHODS: This is a single-center, prospective, randomized controlled clinical trial involving 900 patients with single blastocyst transfer in the frozen-thawed cycle, aged from 20 to 38 years, with less than three transfers, and with HRT-cycle single D6 blastocyst transfer in the current cycle. Participants will be randomly assigned (1:1) into two parallel groups: the transfer of day 6 blastocysts on the 7th day of progesterone supplementation and the transfer of day 6 blastocysts on the 6th day of progesterone supplementation. The primary outcome measure is the clinical pregnancy rate. Secondary outcome measures include the miscarriage rate and live birth rate. DISCUSSION: This is the first randomized controlled trial to compare the transfer of day 6 blastocysts on the 6th and 7th day of progesterone supplementation. The results of this study will provide evidence for whether to prolong the duration of exposure to progesterone prior to embryo transfer. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT04938011. Registered on 19 June 2021.

Multi-Gas Detection System Based on Non-Dispersive Infrared (NDIR) Spectral Technology.

Automobile exhaust gases, such as carbon dioxide (CO2), carbon monoxide (CO), and propane (C3H8), cause the greenhouse effect, photochemical smog, and haze, threatening the urban atmosphere and human health. In this study, a non-dispersive infrared (NDIR) multi-gas detection system consisting of a single broadband light source, gas cell, and four-channel pyroelectric detector was developed. The system can be used to economically detect gas concentration in the range of 0-5000 ppm for C3H8, 0-14% for CO, and 0-20% for CO2. According to the experimental data, the concentration inversion model was established using the least squares between the voltage ratio and the concentration. Additionally, the interference coefficient between different gases was tested. Therefore, the interference models between the three gases were established by the least square method. The concentration inversion model was experimentally verified, and it was observed that the full-scale error of the sensor changed less than 3.5%, the detection repeatability error was lower than 4.5%, and the detection stability was less than 2.7%. Therefore, the detection system is economical and energy efficient and it is a promising method for the analysis of automobile exhaust gases.

Association between gestational trophoblastic disease (GTD) history and clinical outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.

BACKGROUND: Gestational trophoblastic disease (GTD) usually affects young women of childbearing age. After treatment for GTD, 86% of women wish to achieve pregnancy. On account of the impacts of GTD and treatments as well as patient anxiety, large numbers of couples turn to assisted reproductive technology (ART), especially in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). But few studies have investigated whether a history of GTD affects the outcomes of IVF/ICSI in secondary infertile patients and how it occurs. We investigate whether a history of GTD affects the IVF/ICSI outcomes and the live birth rates in women with secondary infertility. METHODS: This retrospective cohort study enrolled 176 women with secondary infertility who underwent IVF/ICSI treatment at the reproductive medical center of Nanjing Drum Tower Hospital from January 1, 2016, to December 31, 2020. Participants were divided into the GTD group (44 women with GTD history) and control group (132 women without GTD history matched from 8318 secondary infertile women). The control group and the study group were matched at a ratio of 3:1 according to patient age, infertility duration, number of cycles and body mass index (BMI). We assessed retrieved oocytes and high-grade embryos, biochemical pregnancy, miscarriage, ectopic pregnancy, gestational age at delivery, delivery mode and live birth rates. RESULT(S): We found a significantly reduced live-birth rate (34.1% vs 66.7%) associated with IVF/ICSI cycles in patients with a GTD history compared to those without a GTD history. The biochemical pregnancy and miscarriage rates of the GTD group were slightly higher than those of the control group. In addition, there was a difference in gestational age at delivery between the GTD and control groups (p < 0.001) but no differences in the mode of delivery (p = 0.267). Furthermore, the number of abandoned embryos in the GTD group was greater than that in the control group (p = 0.018), and the number of good-quality embryos was less than that in the control group (p = 0.019). The endometrial thickness was thinner (p < 0.001) in the GTD group. Immunohistochemistry (IHC) showed abnormal endometrial receptivity in the GTD group. CONCLUSION(S): The GTD history of patients undergoing IVF/ICSI cycles had an impact on the live-birth rate and gestational age at delivery, which might result from the thinner endometrium and abnormal endometrial receptivity before embryo transfer.

The Influence of Oil leaking rate and Ocean Current Velocity on the Migration and Diffusion of Underwater Oil Spill.

Severe environmental pollution and huge economic losses would be caused by submarine oil spill with the increasing development of petroleum energy in sea. In order to predict the law of migration of oil spill from submarine pipelines accurately, the volume of fluid (VOF) model and realizable k-ε turbulence model were employed to establish numerical simulation of submarine oil spill, and the experiments were used to verify the feasibility of the numerical models. Different oil leaking rate and ocean velocity were simulated in the study. The simulation results indicated that comparing with oil leaking rate (set vertical migration velocity, Uo), current velocity (set horizontal migration velocity, Uw) has a greater influence on the migration of the oil spilling; the actual vertical migration velocity (Uo1), actual horizontal migration velocity (Uw1) and R1 (the ratio of Uo1 and Uw1) are positively correlated with R (the ratio of Uo and Uw), and they both fluctuate within a small range no matter how large R is; when 20 ≤ R ≤ 150, R1 fits a linear fit curve with curve as R1 = 0.66932 + 0.00215 R, which can provide a theoretical reference to the recovery system of underwater pipeline oil spilling emergency.

Lactate enhanced the effect of parathyroid hormone on osteoblast differentiation via GPR81-PKC-Akt signaling.

Osteoblast uses aerobic glycolysis to meet the metabolic needs in differentiation process. Lactate, the end product of glycolysis, presents in the environment with elevated PTH and osteoblast differentiation. Although previous findings showed that lactate promoted osteoblast differentiation, whether lactate affects PTH-mediated osteoblast differentiation is unclear. To investigate this, pre-osteoblast cell line MC3T3-E1 was treated PTH with or without physiological dose of lactate. Lactate increases ALP positive cell formation, increases ALP activity and expression of differentiation related markers, enriches the CREB transcriptional factor target genes in PTH treated cells. Using inhibitors for MCT-1 reveales that lactate effects are MCT-1 independent. Lactate selectively increases Akt and p38 activation but not Erk1/2 and ß-Catenin activation. The inhibitors for Akt and p38 inhibit lactate effects on PTH mediated osteoblast differentiation. Using inhibitors for Gαi signaling of GPR81 further increases Alp mRNA levels in lactate and PTH co-treatment cells. However, with the inhibitors for Gßγ-PLC-PKC signaling, the effect of lactate on PTH mediated osteoblast differentiation is inhibited. Our data demonstrate that lactate activates GPR81-Gßγ-PLC-PKC-Akt signaling to regulate osteoblast differentiation that mediated by PTH treatment.