Background: The crosstalk between trophoblast cells and decidual NK cells plays an important role in the establishment and maintenance of normal pregnancy. Recent studies reported that autophagy can induce immune tolerance at the maternal fetal interface, while the mechanism remains unclear. Methods: Autophagy levels in the villi of normal and recurrent spontaneous abortion (RSA) patients were detected by transmission electron microscopy. After co-cultured with trophoblast cells pretreated with 3-MA or rapamycin, NK cells were collected and the expression of killer receptors was detected by flow cytometry (FCM). The invasiveness of trophoblasts was tested by Cell invasion assay. Results: Compared with elective pregnancy termination patients, the level of autophagy in the villi of RSA patients was significantly decreased. Inducing the autophagy level in trophoblast cells with rapamycin could significantly inhibit the cytotoxicity of NK cells in the co-culture system, and supplement of IGF-2 could rectify this effect. Meanwhile, autophagy suppression of trophoblasts reduced the level of Paternally Expressed Gene 10 (PEG10), leading to the impairment of trophoblast cell invasion. In addition, NK cells educated by autophagy-inhibited trophoblasts further decreased the proliferation and invasiveness of trophoblasts. In pregnant mice model, injection with 3-MA promoted the cytotoxicity of uterine NK cells, and increased the embryo absorption rate. Conclusion: Autophagy suppression of trophoblasts increase the cytotoxicity of NK cells and damage the trophoblasts invasion possibly by targeting IGF-2 and PEG10, respectively, which ultimately leads to miscarriage.

In this work, a comparative study of the upconversion (UC) luminescence properties of E r 3 + − Y b 3 + -co-doped A W O 4 ( A = B a , Sr, and Ca) scheelite phosphors and E r 3 + − Y b 3 + -co-doped M g W O 4 wolframite phosphors is reported. Under 980 nm excitation, all the samples emit green and red emissions. The E r 3 + − Y b 3 + -doped M g W O 4 phosphor has a higher UC emission intensity. Furthermore, the optical temperature sensing properties in E r 3 + − Y b 3 + -co-doped A W O 4 ( A = B a , Sr, Ca, and Mg) phosphor samples are investigated. The relative sensitivity ( S r ) based on thermally coupled levels (TCLs) increases gradually with an increase in matrix phonon energy. The absolute sensitivity ( S a ) values of the samples are accurately predicted by the chemical bonding parameter ( f c ). The results of the correlation between the UC luminescence properties and the microscopic crystal structure, and the relationship of the temperature sensitivity and the host parameters, provide us with a guiding insight for the selection of a host material with ideal temperature measurement capability.

Bachground: Cervical cancer is a common malignant disease in female patients accompanied by active autophagy in tumor cells. However, much remains unknown about the regulatory factors of autophagy and its effect on immune response.Methods: Autophagy in HeLa and SiHa cells treated with IFN-γ, tryptophan depletion, kynurenine, and epacadostat was detected by western blot and autophagy detection kit. After co-cultured with pre-treated HeLa and SiHa cells, U937 was detected by flow cytometry to analyze the CD80, CD86, CD163, CD206 expression and the phagocytosis. Results: IFN-γ could significantly increase the autophagy level of HeLa and SiHa cells by promoting the indoleamine-2,3-dioxygenase-1 (IDO1) expression. HeLa and SiHa cells treated with recombinant human IFN-γ could significantly increase the phagocytosis and CD80, CD86 expression of U937, and this effect was associated with the autophagy in tumor cells. IFN-γ treatment and IDO1 overexpression promote tryptophan depletion and kynurenine accumulation in cervical cancer cells, and the latter was proved to be more potent in inducing autophagy of cervical cancer cells and promoting phagocytosis of macrophage. In vivo, IDO1 overexpression could significantly restrict the tumor growth in C57 mice, and the phagocytosis of macrophage was enhanced.Conclusions: IFN-γ promotes the autophagy of cervical cancer cell possibly through IDO1 expression and kynurenine metabolism, and further promotes macrophage phagocytosis in cervical cancer.

Background: The crosstalk between trophoblast cells and decidual NK cells plays an important role in the establishment and maintenance of normal pregnancy. Recent studies have reported autophagy can induce immune tolerance at the maternal fetal interface, but the mechanism is largely unclear. Methods: Autophagy levels in the villi of normal and recurrent spontaneous abortion (RSA) patients were detected by transmission electron microscopy. In vivo and in vitro, the expression of killer molecules in NK cells was analyzed by flow cytometry (FCM). And the invasiveness of trophoblasts was tested by Cell invasion assay. Results: Compared with normal abortion patients, the level of autophagy in the villi of RSA patients was significantly decreased. In vitro experiments indicated that co-culture with autophagy suppression of trophoblasts (3-MA-pretreated trophoblasts) increased cytotoxicity of NK cell, which was mediated by the upregulation of insulin-like growth factor-2 (IGF-2). Meanwhile, autophagy suppression of trophoblasts led to a low level of Paternally Expressed Gene 10 (PEG10), leading to impaired cell invasion. In addition, NK cells educated by autophagy-inhibited trophoblasts further decreased the proliferation and invasiveness of trophoblasts. Injection with 3-MA in vivo , the cytotoxicity of uterine NK cells in pregnant mice and the embryo absorption rate were significantly increased. Conclusion: Autophagy suppression of trophoblasts should increase the cytotoxicity of NK cells and damage the trophoblasts invasion possibly by targeting IGF-2 and PEG10, respectively, which ultimately leads to miscarriage.

The authors have withdrawn this preprint due to author disagreement.