An Epididymis-Specific Secretory Protein HongrES1 Critically Regulates Sperm Capacitation and Male Fertility

Mammalian sperm capacitation is an essential prerequisite to fertilizion. Although progress had been made in understanding the physiology and biochemistry of capacitation, little is known about the potential roles of epididymal proteins during this process. Here we report that HongrES1, a new member of the SERPIN (serine proteinase inhibitor) family exclusively expressed in the rat cauda epididymis and up-regulated by androgen, is secreted into the lumen and covers the sperm head. Co-culture of caudal sperms with HongrES1 antibody in vitro resulted in a significant increase in the percentage of capacitated spermatozoa. Furthermore, the percentage of capacitated spermatozoa clearly increased in rats when HongrES1 was down-regulated by RNAi in vivo. Remarkably, knockdown of HongrES1 in vivo led to reduced fertility accompanied with deformed appearance of fetuses and pups. These results identify HongrES1 as a novel and critical molecule in the regulation of sperm capacitation and male fertility

Synthesis and Structural Characterization of the Sodium Salt of a New Sulfonate-containing Water Soluble N-Donor Ligand⎯ Self-assembly in the Solid State by À−À Stacking Interactions

The synthesis, spectroscopic characterization, and X-ray crystal structure ofthe sodium salt of a new sulfonated water-soluble ligand, sodium 2-(2-pyridin-2-yl-ethylamino)-benzenesulfonate (L) are described. Compound L crystallizes in thecentrosymmetric space group Pbcn, orthorhombic, a=31.930(13) Ã¥, b=7.153(3) Ã¥,c=14.193(6) Ã¥, α=90.00, β=90.00, γ=90.00, V=3220(2) Ã¥3, Z=9. À−À stacking contactsinvolving interactions between the À-donor benzene and the À-acceptor pyridine systemsreinforce and direct the self-assembly of the structural motifs in the solid state

Threshold Effect in the Relationship between Environmental Regulations and Haze Pollution: Empirical Evidence from PSTR Estimation

The impact of environmental regulations (ER) on haze pollution control has been continuously debated in the field of sustainable development. This paper explores the direct and indirect threshold effects of ER on haze pollution, and five underlying mechanisms—technological innovation (TI), industrial structure (IS), foreign direct investment (FDI), urbanization (UR), and electricity consumption (EC)—are adopted to investigate the indirect threshold effects. Panel data, over the period 2008–2018, of 284 Chinese cities were used and the threshold effects were predicted endogenously based on the panel smooth transition regression (PSTR) model. The results showed the following: (1) For the direct threshold effect, there exists a U-shaped relationship between ER and haze pollution. ER significantly reduced haze pollution when ER < 38.86 due to “cost effects”. However, ER increased haze pollution after the threshold owing to the “green paradox”, which was not significant. (2) For the indirect threshold effect, when TI = 0.37, IS = 39.61, FDI = 7.25, and UR = 42.86, the relationships between ER and haze pollution changed. The changes and corresponding reasons for the indirect threshold effects are discussed in detail. (3) After a comprehensive analysis, the threshold effects have obvious regional distribution characteristics and internal connections. Finally, based on the results, it is essential for governments to enact appropriate environmental regulatory policies and enhance inter-regional synergies in environmental governance

A Logistic Regression Based Auto Insurance Rate-Making Model Designed for the Insurance Rate Reform

Using a generalized linear model to determine the claim frequency of auto insurance is a key ingredient in non-life insurance research. Among auto insurance rate-making models, there are very few considering auto types. Therefore, in this paper we are proposing a model that takes auto types into account by making an innovative use of the auto burden index. Based on this model and data from a Chinese insurance company, we built a clustering model that classifies auto insurance rates into three risk levels. The claim frequency and the claim costs are fitted to select a better loss distribution. Then the Logistic Regression model is employed to fit the claim frequency, with the auto burden index considered. Three key findings can be concluded from our study. First, more than 80% of the autos with an auto burden index of 20 or higher belong to the highest risk level. Secondly, the claim frequency is better fitted using the Poisson distribution, however the claim cost is better fitted using the Gamma distribution. Lastly, based on the AIC criterion, the claim frequency is more adequately represented by models that consider the auto burden index than those do not. It is believed that insurance policy recommendations that are based on Generalized linear models (GLM) can benefit from our findings

Salpingectomy may decrease antral follicle count but not live birth rate for IVF-ET patients aged 35–39 years: a retrospective study

Abstract Purpose Problems with fallopian tubes are one of the main reasons for women to undergo in vitro fertilization-embryo transfer (IVF-ET). A large proportion of women with ectopic pregnancy, fallopian tube obstruction and hydrosalpinx have had one or both fallopian tubes removed by salpingectomy. With increasing age, ovarian reserve deteriorates, the numbers of retrieved oocytes, available embryos and high-quality embryos are reduced, and the live birth rate for women treated with IVF treatment is affected. Thus, it is important to understand how salpingectomy affects live birth rates for IVF patients of different ages. This study analyzed how patients’ age and salpingectomy influenced ovarian reserve, ovarian response and pregnancy outcomes for infertile women undergoing IVF-ET. Methods A total of 1922 patients that underwent IVF-ET treatment from January 1, 2012, to December 31, 2018, were included in this retrospective study. The patients were divided into two groups according to whether or not they had a previous history of salpingectomy. The salpingectomy (group A, 534 patients) and control groups (group B, 1388 patients) were then further divided into two subgroups according to patient age (age 0.05). Age is a risk factor for the clinical pregnancy and live birth. Conclusion Salpingectomy may decrease antral follicle count but not live birth rate for IVF-ET patients aged 35–39 years. The increased female age was negative related with clinical pregnancy and live birth

1-Pyrroline-5-carboxylate released by prostate Cancer cell inhibit T cell proliferation and function by targeting SHP1/cytochrome c oxidoreductase/ROS Axis

Abstract Background Tumor cell mediated immune-suppression remains a question of interest in tumor biology. In this study, we focused on the metabolites that are released by prostate cancer cells (PCC), which could potentially attenuate T cell immunity. Methods Prostate cancer cells (PCC) media (PCM) was used to treat T cells, and its impact on T cell signaling was evaluated. The molecular mechanism was further verified in vivo using mouse models. The clinical significance was determined using IHC in human clinical specimens. Liquid chromatography mass spectroscopy (LC/MS-MS) was used to identify the metabolites that are released by PCC, which trigger T cells inactivation. Results PCM inhibits T cells proliferation and impairs their ability to produce inflammatory cytokines. PCM decreases ATP production and increases ROS production in T cells by inhibiting complex III of the electron transport chain. We further show that SHP1 as the key molecule that is upregulated in T cells in response to PCM, inhibition of which reverses the phenotype induced by PCM. Using metabolomics analysis, we identified 1-pyrroline-5-carboxylate (P5C) as a vital molecule that is released by PCC. P5C is responsible for suppressing T cells signaling by increasing ROS and SHP1, and decreasing cytokines and ATP production. We confirmed these findings in vivo, which revealed changed proline dehydrogenase (PRODH) expression in tumor tissues, which in turn influences tumor growth and T cell infiltration. Conclusions Our study uncovered a key immunosuppressive axis, which is triggered by PRODH upregulation in PCa tissues, P5C secretion in media and subsequent SHP1-mediated impairment of T cell signaling and infiltration in PCa

Additional file 1 of 1-Pyrroline-5-carboxylate inhibit T cell glycolysis in prostate cancer microenvironment by SHP1/PKM2/LDHB axis

Additional file 1: Table S1. SHP1 shRNA sequence. Figure S1. P5C inhibits T cells cytokine production and SHP1 bind proteins proteomics analysis, related to Fig. 1. Figure S2. PKM2 bind proteins proteomics analysis and P5C inhibits T cell glycolysis, related to Fig. 2. Figure S3. P5C alter the metabolites in T cells, related to Fig. 3. Figure S4. SHP1 knockdown dampens P5C effect on T cells, related to Fig. 4. Figure S5. SHP1 knockdown alter the metabolites in T cells. Figure S6. P5C antibody counter the effect of P5C, related to Fig. 5