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This paper explores the learning effect of introducing eye-tracking games in college game design courses and tests the impact of innovative introduction of cutting-edge interactive content on students' learning in higher education in the field of digital media. The results show that a stronger perceived interactivity is linked to stronger user perceived control and more positive flow experience. Furthermore, due to the higher perceived interactivity brought by eye-tracking games than traditional games, the improvement of flow experience after teaching also brings obvious improvement of students' learning interest and continuous learning intention. It is worth noting that this effect seems to have a more robust gain effect in the group of sophomores, while the effect shows a transient characteristic in the group of juniors. The difference may be related to students' learning ability. At the same time, three main factors for the positive influence of eye-tracking games on teaching were extracted, including 'Technology Sensitive', 'Operational' and 'adventures by Difference'. Three main factors for the negative effects were also found, including 'Unattractive Game Types', 'Self-caused Resistance' and 'Game Maturity Deficiency'. The results of the study explored how to amplify the help of eye-tracking games in the teaching process and reduce the possible drawbacks from the extracted multiple constructs. Therefore, as an innovative teaching case with strong interaction, the adoption of eye-tracking game learning is indeed helpful to the course of digital media major. • Students' Perceived Interactivity of game design class cases can influence Flow through a partially mediated effect. • Learning to make interactive game cases enables sophomores to learn better in all psychological dimensions. • For junior students, learning to make interactive game cases has significantly improve their Learning Interest. • The main positive and negative reasons for students' perception of interactive cases were explored. [ABSTRACT FROM AUTHOR]

Female sex hormones affect the immune response in the lower female genital tract. To understand their mechanisms of action, it is essential to define cell types expressing estrogen receptor (ER) and/or progesterone receptor (PR) in the human vaginal mucosa (VM). Here, we report that none of the dendritic cell (DC) subsets in the human VM expressed ERα or PR in situ. However, they were capable of expressing ERα, but not PR, after in vitro culture of the whole VM tissues. Similarly, ERα and/or PR expression by T cells in the VM tissues was also inducible rather than constitutive. In contrast, ERα and/or PR were constitutively expressed in HLA-DR− non-immune cell types (vimentin+, desmin+, or CD10+). These new findings will help us understand the mechanisms of action of female sex hormones in the modulation of immune response in the human VM and lower female genital tract. • ERα and PR expressions in human vaginal mucosa (VM) are cell type-specific. • ERα expression by Langerhans cell/CD1c+ VM dendritic cell is inducible. • VM T cell expression of ERα/PR is also inducible rather than constitutive. • Desmin+, vimentin+, and CD10+ non-immune cell types constitutively express ERα/PR. • These help us understand how female sex hormones affect immune response in the VM. [ABSTRACT FROM AUTHOR]

Abstract: FK506-binding proteins (FKBPs) are cellular receptors for the immunosuppressant FK506 and rapamycin. They belong to the ubiquitous peptidyl-prolyl cis/trans isomerases (PPIases) family, which can catalyze the cis/trans isomerization of peptidyl-prolyl bond in peptides and proteins. In previous work, we revealed that mouse FKBP23 binds immunoglobulin binding protein (BiP), the major heat shock protein (Hsp) 70 chaperone in the ER, and the binding is interrelated with [Ca2+]. Furthermore, the binding can suppress the ATPase activity of BiP through the PPIase activity of FKBP23. In this work, FKBP23 is demonstrated to mediate functions of BiP by catalyzing the Pro117 cis/trans conformational interconversion in the ATPase domain of BiP. This result may provide new understanding to the novel role of PPIase as a molecular switch. [Copyright &y& Elsevier]

Zinc and ring finger 2 (ZNRF2), an E3 ubiquitin ligase, plays a crucial role in many diseases. However, its role in cerebral ischemia/reperfusion injury (CIRI) still remains unknown. In this study, the function and molecular mechanism of ZNRF2 in CIRI in vivo and vitro was studied. ZNRF2 was found to be dramatically downregulated in CIRI. Overexpression of ZNRF2 could significantly reduce the neurological deficit, brain infarct volume and histopathological damage of cortex in middle cerebral artery occlusion/reperfusion. Concomitantly, overexpression of ZNRF2 increased the primary neuronal viability and decreased the neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Mechanistically, overexpression of ZNRF2 inhibited the over-induction of autophagy induced by OGD/R which was abolished by mTORC1 inhibitor rapamycin. It can be concluded that ZNRF2 plays a protective effect in CIRI and the underlying mechanism may be related to the inhibition of mTORC1-mediated autophagy. • ZNRF2, an E3 ubiquitin ligase, decreased markedly in ischemia stroke. • ZNRF2 plays a protective role in cerebral ischemia-reperfusion injury by regulating autophagy. • ZNRF2 protects the oxygen-glucose deprivation/reoxygenation-induced cortical neurons injury by regulating the mTORC1-mediated autophagy. • ZNRF2 may involve in the regulation of mTOR. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. Our previous study has shown that MRTF-A promote the migration of MDA-MB-231 cells and WDR1 promotes breast cancer cell migration. But the exact molecular mechanism on metastasis is still not fully understood, we now report that WDR1 enhanced the effect of MRTF-A induced-MDA-MB-231 cell migration by promoting the expression of the EMT markers and migration markers via RhoA-MRTF-A signaling pathway. Importantly, WDR1 promoted the nuclear importion of MRTF-A by affecting the expression of nuclear transport protein importin. But WDR1 did not affect the expression of MRTF-A. Interestingly, MRTF-A promoted the expression of miR-206 via its promoter CArG box but miR-206 inhibits the migration of breast cancer cells through suppressing the expression of WDR1 and MRTF-A via targeted their 3′UTR. Our data thus provide important and novel insights into MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) plays an important role in breast cancer cell metastasis. Both (megakaryoblastic leukemia)/myocardin-like 1 (MKL-1) and Signal transducer and activator of transcription 3 (STAT3) have been implicated in the control of cellular metabolism, survival and growth. Our previous study has shown that cooperativity of MKL-1 and STAT3 promoted breast cancer cell migration. Herein, we demonstrate a requirement for MKL-1 and STAT3 in miRNA-mediated cellular EMT to affect breast cancer cell migration. Here we show that cooperativity of MKL-1 and STAT3 promoted the EMT of MCF-7 cells. Importantly, MKL-1 and STAT3 promoted the expression of Vimentin via its promoter CArG box. Interestingly, miR-93-5p inhibits the EMT of breast cancer cells through suppressing the expression of MKL-1 and STAT3 via targeted their 3’UTR. These results demonstrated a novel pathway through which miR-93-5p regulates MKL-1 and STAT3 to affect EMT controlling breast cancer cell migration. [ABSTRACT FROM AUTHOR]

Large amount of clinical evidence has demonstrated that insulin resistance is closely related to oncogenesis of endometrial cancer (EC). Despite recent studies showed the up-regulatory role of insulin in G protein-coupled estrogen receptor (GPER/GPR30) expression, GPER expression was not decreased compared to control when insulin receptor was blocked even in insulin treatment. The purpose of this study was to explore the possible mechanism by which insulin up-regulates GPER that drives EC cell proliferation. For this purpose, we first investigated the GPER expression in tissues of endometrial lesions, further explored the effect of GPER on EC cell proliferation in insulin resistance context. Then we analyzed the role of Ten-Eleven Translocation 1 (TET1) in insulin-induced GEPR expression and EC cell proliferation. The results showed that GPER was highly expressed in endometrial atypical hyperplasia and EC tissues. Mechanistically, insulin up-regulated TET1 expression and the latter played an important role in up-regulating GPER expression and activating PI3K/AKT signaling pathway. TET1 mediated GPER up-regulation was another mechanism that insulin promotes EC cell proliferation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of miR-702-5p on diabetic encephalopathy (DE) and the interaction of miR-702-5p/12/15-LOX in the central nervous system (CNS). In this study, db/db mice were used as DE animal model and HT22 cells were treated with high-glucose (HG). Based on the bioinformatics prediction of possible binding sites between miR-702-5p and 12/15-LOX, we found that the expression of miR-702-5p was significantly down-regulated while 12/15-LOX up-regulated in vivo and in vitro, and the expression changes were inversely correlated. In vivo, diabetic mice with cognitive dysfunction and hippocampal neuronal damage had a concomitant increase in amyloid precursor protein (APP), amyloid beta(Aβ), tau, BAX protein expressions; by contrast, Bcl-2 protein expression was significantly decreased. Overexpression of miR-702-5p significantly reduced the histopathological damage of the hippocampus, improved the learning and memory function of db/db mice, down-regulated 12/15-LOX, APP, Aβ, tau, BAX protein expressions significantly and up-regulated the expression of Bcl-2. In vitro, miR-702-5p mimic reversed the decline in cell viability and the increase in cell apoptosis induced by HG. Simultaneously, reduced 12/15-LOX, APP, Aβ, BAX protein expressions, and increased Bcl-2 protein expression were detected in the miR-702-5p mimic group. Moreover, combined administration of miR-702-5p mimic and 12/15-LOX overexpression lentivirus significantly reversed the protective effect of up-regulation of miR-702-5p. In conclusion, miR-702-5p has a neuroprotective effect on DE, and this effect was achieved by inhibiting 12/15-LOX. However, miR-702-5p had an endogenous regulatory effect on 12/15-LOX rather than a direct targeting relationship. [Display omitted] • In this work, we firstly investigated the protective effect of miR-702-5p on Diabetic encephalopathy (DE). • Our results indicated that the expression of miR-702-5p was significantly downregulated while 12/15-LOX upregulated in the hippocampal of db/db mice. Overexpression of miR-702-5p significantly ameliorated diabetic cognitive dysfunction, reduced 12/15-LOX, APP, Aβ, tau, BAX protein expressions, and increased Bcl-2 protein expression. • MiR-702-5p effectively protected HT22 cells against injury caused by high glucose (HG). While when miR-702-5p mimic was combined with 12/15-LOX overexpression lentivirus, its protective effect was attenuated. • Our results suggested that miR-702-5p could ameliorate diabetic cognitive dysfunction via downregulating the expression of 12/15-LOX endogenously and further reducing Aβ levels without influencing the levels of blood glucose, TC, and TG. • Our present results will contribute to clarify the mechanism of cognitive dysfunction caused by diabetes and be helpful to discover therapeutic target for DE. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To explore the relationship between metabolic abnormalities and DPE (disordered proliferative endometrium), EH (endometrial hyperplasia) and type I EC (endometrial cancer). Methods: We conducted a prospective cross-sectional study that lasted from September 2011 to September 2012 at the Obstetrics and Gynecology Hospital of Fudan University. 314 cases were enrolled, including 56 cases of DPE, 194 cases of EH and 25 cases of type I EC. 39 healthy female cases were collected as a control group. General information was collected, and blood tests, including blood lipids, OGTT (75-g oral glucose tolerance test) and insulin release tests were examined. Statistical analysis was performed using SPSS 19.0 (Chicago, USA), and 0.05 was chosen as the significance test level. Results: The median (inter-quartile) age of the 314 study subjects was 44 (12) years, with the ages ranging from 21 to 75years. Elevated insulin level was correlated with DPE, EH without/with atypia and EC. The risk increased when HOMA-IR (homeostasis model assessment-insulin resistance)≥2.95 (the lower limit of the top quartile of HOMA-IR distribution in non-diabetic patients); the OR (odds ratio) for DPE was 9.973 (95% CI (coefficient interval): 2.038–48.789, P=0.005), that for EH without atypia was 8.481 (95% CI:1.860–38.672, P=0.006), that for EH with atypia was 18.716 (95% CI: 3.091–113.335, P=0.001) and that for type I EC was 45.199 (95% CI: 5.886–347.065, P<0.001). Opposite trends were observed for the QUICKI (Quantitative Insulin Sensitivity Check Index). Conclusions: Hyperinsulinemia is associated with DPE and EH without/with atypia, not only with type I EC, and it might be a key factor that initiates and promotes endometrial hyperplastic lesions. [Copyright &y& Elsevier]