Gαq-PKD/PKCµ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy.

Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here, we demonstrated that knockout of Gαq lead to an aberrantly enhanced inflammatory state during decidualization. Furthermore, we showed that deficiency of Gαq resulted in over-activation of nuclear factor (NF)-κB signaling, due to the decreased expression of NFκBIA, which encode the IκB protein and is the negative regulator for NF-κB. Mechanistically, Gαq deficiency decreased the Protein kinase D (PKD, also called PKCµ) phosphorylation levels, leading to attenuated HDAC5 phosphorylation and thus its nuclear export. Aberrantly high level of nuclear HDAC5 retarded histone acetylation to inhibit the induced NFκBIA transcription during decidualization. Consistently, pharmacological activation of the PKD/PKCµ or inhibition of the HDAC5 restored the inflammatory state and proper decidual response. Finally, we disclosed that over-active inflammatory state in Gαq-deficient decidua deferred the blastocyst hatching and adhesion in vitro, and the decidual expression of Gαq was significantly lower in women with recurrent pregnancy loss compared with normal pregnancy. In brief, we showed here that Gαq as a key regulator of the inflammatory cytokine's expression and decidual homeostasis in response to differentiation cues, which is required for successful implantation and early pregnancy.

Osteoprotegerin interacts with syndecan-1 to promote human endometrial stromal decidualization by decreasing Akt phosphorylation.

STUDY QUESTION: Does osteoprotegerin (OPG) promote human endometrial stromal decidualization? SUMMARY ANSWER: OPG is essential for human endometrial stromal decidualization through its interaction with syndecan-1 to decrease Akt phosphorylation. WHAT IS KNOWN ALREADY: OPG (a cytokine receptor) levels are significantly increased in the circulation of pregnant women. However, the role and mechanism of OPG in human endometrial stromal cell (ESC) decidualization remain elusive. STUDY DESIGN, SIZE, DURATION: We analyzed the endometrial expression of OPG in endometrial tissue samples collected from women with regular menstrual cycles (ranging from 25 to 35 days), and decidual tissue samples collected from woman with normal early pregnancy or recurrent pregnancy loss (RPL) who visited the Department of Gynecology and Obstetrics at a tertiary care center from January to October 2018. None of the subjects had hormonal treatment for at least 3 months prior to the procedure. In total, 16 women with normal early pregnancy and 15 with RPL were selected as subjects for this study. The function of OPG in decidualization was explored in a human endometrial stromal cell (HESC) line and primary cultures of HESCs. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected endometrial tissues (by biopsy) from the subjects during their menstrual cycle and decidual tissues from subjects with a normal early pregnancy and those with RPL at the time of dilation and curettage. The control group comprised randomly selected women who underwent termination of an apparently normal early pregnancy. The endometrial OPG expression was analyzed using immunohistochemical staining and quantitative RT-PCR (qRT-PCR). Immunofluorescence staining and western blot, and qRT-PCR were used to explore the mRNA and protein expression, respectively, of OPG in an immortalized HESC line and in primary cultures of HESC during proliferation and decidualization. siRNA-mediated knockdown experiments were performed to examine the function of OPG in HESC proliferation and decidualization. Flow cytometry and the cell proliferation MTS assay were performed to further examine the role of OPG in HESC proliferation. We also analyzed decidual marker gene expression by qRT-PCR to assess the consequences of OPG loss for HESC decidualization. A co-immunoprecipitation (IP) assay was used to determine the potential interaction between the OPG and Syndecan-1. Western blot analysis of the rescue experiments performed using the phosphatidylinositol 3-kinase (PI3K) signaling-specific inhibitor LY294002 was used to investigate the downstream signaling pathways through which OPG could mediate HESC decidualization. MAIN RESULTS AND THE ROLE OF CHANCE: OPG was expressed in both the human endometrium and in vitro decidualized ESCs. Knockdown experiments revealed that OPG loss impaired the expression of IGF-binding protein-1 (IGFBP-1) (P < 0.05) and prolactin (PRL) (P < 0.05), two specific markers of decidualization, in HESC undergoing decidualization. We also uncovered that OPG knockdown induced the aberrant activation of Akt (protein kinase B) during HESC decidualization (P < 0.05). The inhibition of Akt activation could rescue the impaired expression of the decidual markers PRL (P < 0.05) and IGFBP-1 (P < 0.05) in response to OPG knockdown. Syndecan-1 was considered a potential receptor candidate, as it was expressed in both the endometrium and in vitro cultured stromal cells. Subsequent co-IP experiments demonstrated the interaction between OPG and Syndecan-1 during decidualization. In addition, Syndecan-1 knockdown not only clearly attenuated the decidualization markers PRL (P < 0.05) and IGFBP-1 (P < 0.05) but also induced the aberrant enhancement of Akt phosphorylation in decidualized cells, consistent with the phenotype of OPG knockdown cells. Finally, we revealed that the transcript and protein expression of both OPG and Syndecan-1 was significantly lower in the decidual samples of women with RPL than in those of women with normal pregnancy (P < 0.05). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, based on a number of approaches, it was demonstrated that OPG mediated the repression of Akt that occurs during human stromal cell decidualization, however, the molecular link between OPG and Akt signaling was not determined, and still requires further exploration. WIDER IMPLICATIONS OF THE FINDINGS: OPG is required for decidualization, and a decrease in OPG levels is associated with RPL. These findings provide a new candidate molecule for the diagnosis and potential treatment of RPL. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China U1605223 (to G.S.), 81701457 (to Y.J.) and 81601349 (to Y.J.). The authors have no conflicts of interest to disclose.

Plasma treated TiO2/C nanofibers as high performance anode materials for sodium-ion batteries.

TiO2 has been a promising anode material for sodium-ion batteries because it is low-cost and environment-friendly. However, its electrochemical performance at high rates is still not acceptable. Herein, we synthesized a TiO2/C nanofiber material by the electrospinning method, and introduced air plasma treatments to modify the obtained material. Characterization results indicate that after the plasma treatments, the C fibers may have reacted with the plasma, and the surface areas of the nanofibers are increased. Electrochemical tests show this plasma treatment may be beneficial to the rate performance. The TiO2/C nanofiber with plasma treatment could deliver a high redox capacity of 191 mA h g-1 after 500 cycles at a very high rate of 10C (3300 mA g-1). The superior effects of the plasma treatment on the rate performance may provide new insights for developing better materials for practical sodium-ion batteries.

[Immunogenicity comparision of Listeria monocytogenes inactivated by gamma-irradiation or traditional treatments].

OBJECTIVE: Listeria monocytogenes (LM) is a gram-positive facultative intracellular pathogen that can cause animal and human listeriosis. In order to use killed LM in vaccination, we compared, in a mouse model, the immunogenicity of LM that were lethally inactivated by gamma-irradiation, traditional heat or formalin treatment. METHODS: BALB/c mice were inoculated intraperitoneally with these killed vaccine candidates. We detected the serum antibody titers with indirect enzyme-linked immunosorbent assay (ELISA) and evaluated the protective efficacy of each vaccine candidates by the resistance to lethal dose challenge of homologous live LM and the effect of bacterial elimination in the spleen and liver of immunized mice. Adoptive transfer of Flow Cytometry sorted T splenocytes from immunized mice to naïve recipients, subsequently challenged with high dose of LM, we determined the possible role of T cell. RESULTS: The serum antibody level of mice inoculated with gamma-irradiated LM was the highest, up to 1:1280 as determined by ELISA, while the level of mice immunized with heat-killed or formalin-killed LM was 1:640 or 1:160, respectively. The protective efficacy of gamma-irradiated,heat-killed or formalin-killed vaccines candidates were 100%, 35% or 30%. As judged by the bacterial elimination in the organs, mice inoculated with gamma-irradiated LM were the most efficiently protected group. Adoptive T cell transfer assay showed that gamma-irradiated LM can trigger T cell protective immune response. CONCLUSION: All the results indicated the superiority of gamma-irradiation over traditional heat or formalin treatment in generating LM killed vaccine candidate. gamma-irradiation may be applied to numerous bacterial vaccine candidates, and could have important potential in development of killed vaccines.