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Reduced lymphoid enhancer-binding factor 1 (LEF1) expression in patients with adenomyosis during the mid-secretory phase leads to impaired endometrial receptivity, affecting embryo implantation. This study investigated the molecular mechanisms underlying reduced endometrial receptivity in 25 adenomyosis patients and 25 controls. Functional experiments were conducted using human endometrial stromal cells (HESCs) and TERT-immortalized HESCs(T-HESCs), with final validation performed using a mouse model. Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) analyses revealed that patients with adenomyosis showed a marked decrease in LEF1 expression in the stromal cells of the endometrium during the mid-secretory phase. In vitro experiments demonstrated that LEF1 knockdown in stromal cells led to impaired decidualization. Transcriptome sequencing, dual-luciferase reporter assays, and chromatin immunoprecipitation (ChIP) experiments showed that LEF1 could bind to the promoter region of interleukin (IL)-11 and promote its transcription, and IL-11 expression was also found to be downregulated in adenomyosis patients. Overexpression of IL-11 rescued the impaired decidualization caused by decreased LEF1 expression. In the in vitro co-culture model, LEF1/IL-11 knockdown led to a reduction in embryo implantation area, which was partially restored upon IL-11 overexpression. In the adenomyosis mouse model, we observed a decrease in LEF1 expression and a reduction in implantation sites compared to control mice, accompanied by impaired decidualization and receptivity. Notably, supplementation with IL-11 restored the number of implantation sites. The decrease in fertility due to reduced endometrial receptivity in adenomyosis patients is a significant clinical issue in assisted reproductive technology. This research provides insights into one potential molecular mechanism underlying this decreased receptivity, with a specific focus on the reduced expression of LEF1 in the endometrial stromal cells during the mid-secretory phase in adenomyosis patients. Our findings offer new perspectives for clinical strategies to improve endometrial receptivity in patients with adenomyosis, potentially enhancing their chances of successful pregnancy.

To effectively identify the key material parameters of different zones of concrete face rockfill dams and improve the efficiency of parameter optimization, a global sensitivity analysis method of parameters based on sparse polynomial chaotic expansion (sPCE) is proposed in this paper. The latin hypercube sampling method is used to select multiple groups of material parameters, and then finite element method is used to calculate the displacement of dam characteristic nodes in dam body. On this basis, the displacement is expanded by sPCE, and the polynomial basis function is reconstructed by orthogonal matching pursuit to improve the construction and analysis efficiency of the proxy model. According to the chaos coefficients, Sobol’ indices are calculated to evaluate the influence of the material parameters and their interaction on different displacements of the dam. The results show that the sPCE model can accurately simulate dam displacement and its statistical characteristics with a relatively small sample size. The sensitivity of the same parameter has spatial variability, and under the influence of parameter levels and spatial distribution of different materials, the parameter sensitivity ranking of different zones has certain differences. The proposed method provides a new reference to sensitivity analysis and uncertainty analysis for practical engineering.

Background The precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) remains unclear. This study was aimed at exploring the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF. Methods Mid-secretory phase endometrial tissue samples were obtained from the following two groups of women who had undergone IVF: (a) 24 patients with RIF and (b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed using immunohistochemistry, qPCR, and western blotting. Effects of overexpression and knockdown of CD44v3 on proliferation and decidualization of immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and western blot analysis. A heterologous coculture system of embryo implantation was constructed to mimic the process of trophoblast invasion during implantation. Results The expression of CD44v3 was significantly higher in the mid-secretory phase of endometrial stromal cells than in the proliferation phase, but was notably lower in RIF patients. Knockdown of CD44v3 significantly downregulated cell proliferation both in T-HESCs and HESCs. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following the knockdown of CD44v3, whereas the expression of both PRL and IGFBP1 increased after its overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed significant deficiency in supporting trophoblast outgrowth in a coculture system of embryo implantation; however, overexpression of CD44v3 in HESCs promoted trophoblast outgrowth. Conclusion The reduced expression of CD44v3 suppresses the proliferation and decidualization of HESCs, which might play a pivotal role in poor endometrial receptivity in women with RIF.

Background The gonadotropin-releasing hormone (GnRH) antagonist protocol for in vitro fertilization (IVF) often leads to lower pregnancy rates compared to the GnRH agonist protocol. Decreased endometrial receptivity is one reason for the lower success rate, but the mechanisms underlying this phenomenon remain poorly understood. The S100 calcium protein P (S100P) is a biomarker for endometrial receptivity. Both GnRH antagonist and S100P are involved in mediating cell apoptosis. However, the involvement of S100P in reduced endometrial receptivity during the GnRH antagonist protocol remains unclear. Methods Endometrial tissue was collected at the time of implantation window from patients undergoing the GnRH agonist (GnRH-a) or GnRH antagonist (GnRH-ant) protocols, as well as from patients on their natural cycles. Endometrial cell apoptosis and expression levels of S100P, HOXA10, Bax, and Bcl-2 were assessed. Ishikawa cells were cultured to evaluate the effects that GnRH antagonist exposure or S100P up- or down- regulation had on apoptosis. Results Endometrial tissue from patients in the GnRH-ant group showed elevated apoptosis and decreased expression of the anti-apoptotic marker Bcl-2. In addition, endometrial expression of S100P was significantly reduced in the GnRH-ant group, and expression of HOXA10 was lower. Immunofluorescence colocalization analysis revealed that S100P was mainly distributed in the epithelium. In vitro experiments showed that knockdown of S100P in Ishikawa cells induced apoptosis, decreased expression of Bcl-2, while overexpression of S100P caused the opposite effects and decreased expression of Bax. Furthermore, endometrial epithelial cells exposed to GnRH antagonist expressed lower levels of S100P and Bcl-2, increased expression of Bax, and had higher rates of apoptosis. The increased apoptosis induced by GnRH antagonist treatment could be rescued by overexpression of S100P. Conclusions We found that GnRH antagonist treatment induced endometrial epithelial cell apoptosis by down-regulating S100P, which was detrimental to endometrial receptivity. These results further define a mechanistic role for S100P in contributing to endometrial apoptosis during GnRH antagonist treatment, and suggest that S100P is a potential clinical target to improve the success of IVF using the GnRH antagonist protocol.

Background Impaired endometrial receptivity was the main cause of recurrent implantation failure (RIF); however, its underlying mechanisms had not been elucidated. This study aimed to determine the expression level of high-mobility group box protein 1 (HMGB1) in the endometrium with RIF and its effect on endometrial receptivity. Methods and results Genome-wide expression profiling, real-time reverse transcription PCR, immunohistochemical staining, western blot, and in vitro assays were performed in this study. We found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility and successfully achieve conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to that in the control group (P = 0.001), consistent with the results of the genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells dramatically displayed a marked deficiency in supporting blastocysts and human embryonic JAR cells adhesion, which mimic the process of embryo adhesion. Conclusion These findings strongly indicated that increased HMGB1 levels suppressed the epithelial cell adhesion capability, therefore contributing to impaired endometrial receptivity in patients with recurrent implantation failure, which can be used as a target for the recognition and treatment of recurrent implantation failure in clinical practice.

IntroductionSemen quality has decreased gradually in recent years, and lifestyle changes are among the primary causes for this issue. Thus far, the specific lifestyle factors affecting semen quality remain to be elucidated.Materials and methodsIn this study, data on the following factors were collected from 5,109 men examined at our reproductive medicine center: 10 lifestyle factors that potentially affect semen quality (smoking status, alcohol consumption, staying up late, sleeplessness, consumption of pungent food, intensity of sports activity, sedentary lifestyle, working in hot conditions, sauna use in the last 3 months, and exposure to radioactivity); general factors including age, abstinence period, and season of semen examination; and comprehensive semen parameters [semen volume, sperm concentration, progressive and total sperm motility, sperm morphology, and DNA fragmentation index (DFI)]. Then, machine learning with the XGBoost algorithm was applied to establish a primary prediction model by using the collected data. Furthermore, the accuracy of the model was verified via multiple logistic regression following k -fold cross-validation analyses.ResultsThe results indicated that for semen volume, sperm concentration, progressive and total sperm motility, and DFI, the area under the curve (AUC) values ranged from 0.648 to 0.697, while the AUC for sperm morphology was only 0.506. Among the 13 factors, smoking status was the major factor affecting semen volume, sperm concentration, and progressive and total sperm motility. Age was the most important factor affecting DFI. Logistic combined with cross-validation analysis revealed similar results. Furthermore, it showed that heavy smoking (>20 cigarettes/day) had an overall negative effect on semen volume and sperm concentration and progressive and total sperm motility (OR = 4.69, 6.97, 11.16, and 10.35, respectively), while age of >35 years was associated with increased DFI (OR = 5.47).ConclusionThe preliminary lifestyle-based model developed for semen quality prediction by using the XGBoost algorithm showed potential for clinical application and further optimization with larger training datasets.

Background Poor response patients with PCOS who are not susceptible to gonadotropin stimulation are more likely to have canceled cycles or poor clinical outcomes during IVF treatment. However, some limitations exist in the present therapies. In this study, we evaluated the effects of using the transvaginal ovarian drilling (TVOD) followed by controlled ovarian stimulation (COS) from the second day of these poor responders. Methods During IVF, 7 poor responders with PCOS and 28 PCOS patients (14 normal and 14 high responders) were recruited. All patients received COS with the gonadotropin-releasing hormone antagonist protocol. For the poor responders, after undergoing 10 to 14 days of ovulation induction with no response, the TVOD was applied and then ovarian stimulation was performed from the next day at the same gonadotropin dose. Serum samples during COS and follicular fluid samples from the dominant follicles on the oocyte pick-up (OPU) day in all three groups were collected. Besides, follicular fluid from small follicles (diameter < 1 cm) in the normal and high responders on the OPU day and those in the poor responders on the TVOD day were gathered. Hormonal levels were examined in all samples using immunometric assays. Results All the poor responders restored ovary response after receiving TVOD. There was no significant difference in the stimulation duration, total gonadotrophin dose used and the clinical outcomes among the three groups. The body mass index, serum and follicular levels of anti-Müllerian hormone (AMH) and testosterone in poor responders were higher than those in the other two groups, and the application of TVOD significantly decreased the levels of AMH and testosterone in both serum and follicular fluid. Conclusions TVOD followed by ovulation induction from the next day is effective and convenient for poor responders with PCOS. The decline of AMH and testosterone resulted from TVOD may be the main reason resulting in the recovery of ovary sensitivity to gonadotropins. The small sample size is the primary limitation of this study, future studies using a large population cohort and monitoring the long-term outcomes of this strategy will be required. Trial registration ChiCTR1900023612 . Registered 04 June 2019-Retrospectively registered.

This study assesses the risk of coal and gas outburst using the theory of rock engineering system, selects seven prediction indices that are significantly related to outburst, and improves on the Back Propagation (BP) neural network technique by applying the Sparrow Search Algorithm (SSA). The improved SSA-BP network is expected to yield discoveries with higher calculation accuracy. Simultaneously, quantitative and qualitative indicators are obtained, and a coal and gas outburst prediction model is constructed based on the cloud drop chart's subordination degree of outburst indicators. The created cloud model predicts the hazard of coal and gas outburst in analyzed coal seams. Eight of the previous nine measurement locations are at risk of medium coal and gas outburst, while only one is at risk of a super big coal and gas outburst.

Ebola virus disease （EVD）, formerly known as Ebola hemorrhagic fever, is a severe infectious disease caused by Ebola virus （EBOV） species [1, 2]. EBOV caused an epidemic in West Africa in 2013-2015 [1, 2]. Early diag- nosis of EVD is not only essential for implementation of effective interventions but also critical for prevention of the spread of infection, especially in regions with fragile and underfunded health system [2].

Background Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits. Methods In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared. Results CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p < 0.001), had less symptoms related with rhinitis/sinusitis and gastroesophageal reflux (p < 0.05) than CA patients. Comorbidities including rhinitis and gastroesophageal reflux were similar, while the proportion of COPD and bronchiectasis was higher in CA patients. There were no differences in FeNO levels, sputum eosinophil and neutrophil counts, FEV1 (%pred) decreased from CVA to CPA to CA patients (p < 0.001). Cough sensitivity was higher in CVA and CPA compared to CA (p < 0.001), and was positively correlated with LCQ scores. Conclusions CVA, CPA and CA can be distinguished by the presence of laryngeal symptoms, cough sensitivity and airflow obstruction. Asthma-associated chronic cough was not associated with airway inflammation or comorbidities in our cohort. Trial registration The Chinese Clinical Trial Registration Center, ChiCTR-POC-17011646, 13 June 2017