BackgroundA possible relationship between periodontitis and Alzheimer’s disease (AD) has been reported. However, there is limited information on the association between the Porphyromonas gingivalis (P. gingivalis) periodontal infection and the pathological features of AD. The hypothesis that P. gingivalis periodontal infection may cause cognitive impairment via age-dependent neuroinflammation was tested.ResultsThirty 4-week-old (young) female C57BL/6 J mice were randomly divided into two groups, the control group and the experimental group. Thirty 12-month-old (middle-aged) were grouped as above. The mouth of the mice in the experimental group was infected with P. gingivalis. Morris water maze(MWM) was performed to assess the learning and memory ability of mice after 6 weeks. Moreover, the expression levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the mice brain tissues were determined by Quantitative real-time polymerase chain reaction (qRT-PCR), Enzyme Linked Immunosorbent Assay(ELISA) and immunohistochemistry. Our results showed that the learning and memory abilities of the middle-aged P. gingivalis infected mice were impaired. Moreover, the expression levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the brain tissues of the middle-aged P. gingivalis infected mice were increased.ConclusionsThese results suggest that P. gingivalis periodontal infection may cause cognitive impairment via the release of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the brain tissues of middle-aged mice.Electronic supplementary materialThe online version of this article (10.1186/s12979-017-0110-7) contains supplementary material, which is available to authorized users.

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Liver tumorigenesis Lung metastasis p53 mut/+ Highlights Tsc1 deficiency facilitates p53 (haplo)insufficiency-mediated activation of the PTEN/Akt/mTOR axis to drive HCC tumorigenesis and metastasis. Inhibiting mTOR activation is a potential therapeutic strategy for p53 insufficiency and Tsc1 insufficiency-driven hepatocarcinogenesis. The oncogenic activity of the Akt/mTOR axis relies on Abcc4, which labels an aggressive subtype of human HCC.

Development of nonflammable separators with excellent properties is in urgent need by next-generation advanced and safe energy storage devices. However, it has been extremely challenging to simultaneously achieve fire resistance, high mechanical strength, good thermomechanical stability, and low ion-transport resistance for polymeric separators. Herein, to address all these needs, we report an in situ formed silica@silica-imbedded polyimide (in situ SiO2@(PI/SiO2)) nanofabric as a new high-performance inorganic–organic hybrid separator. Different from conventional ceramics-modified separators, this in situ SiO2@(PI/SiO2) hybrid separator is realized for the first time via an inverse in situ hydrolysis process. Benefiting from the in situ formed silica nanoshell, the in situ SiO2@(PI/SiO2) hybrid separator shows the highest tensile strength of 42 MPa among all reported nanofiber-based separators, excellent wettability to the electrolyte, good thermomechanical stability at 300 °C, and fire resistance. The LiFePO4 half-cell assembled with this hybrid separator showed a high capacity of 139 mAh·g–1@5C, which is much higher than that of the battery with the pristine PI separator (126.2 mAh·g–1@5C) and Celgard-2400 separator (95.1 mAh·g–1@5C). More importantly, the battery showed excellent cycling stability with no capacity decay over 100 cycles at the high temperature of 120 °C. This study provides a novel method for the fabrication of high-performance and nonflammable polymeric–inorganic hybrid battery separators.

Dysregulation of tumor-relevant proteins may contribute to human hepatocellular carcinoma (HCC) tumorigenesis. FBXO45 is an E3 ubiquitin ligase that is frequently elevated expression in human HCC. However, it remains unknown whether FBXO45 is associated with hepatocarcinogenesis and how to treat HCC patients with high FBXO45 expression. Here, IHC and qPCR analysis revealed that FBXO45 protein and mRNA were highly expressed in 54.3% (57 of 105) and 52.2% (132 of 253) of the HCC tissue samples, respectively. Highly expressed FBXO45 promoted liver tumorigenesis in transgenic mice. Mechanistically, FBXO45 promoted IGF2BP1 ubiquitination at the Lys190 and Lys450 sites and subsequent activation, leading to the upregulation of PLK1 expression and the induction of cell proliferation and liver tumorigenesis in vitro and in vivo. PLK1 inhibition or IGF2BP1 knockdown significantly blocked FBXO45-driven liver tumorigenesis in FBXO45 transgenic mice, primary cells, and HCCs. Furthermore, IHC analysis on HCC tissue samples revealed a positive association between the hyperexpression of FBXO45 and PLK1/IGF2BP1, and both had positive relationship with poor survival in HCC patients. Thus, FBXO45 plays an important role in promoting liver tumorigenesis through IGF2BP1 ubiquitination and activation, and subsequent PLK1 upregulation, suggesting a new strategy for treating HCC by targeting FBXO45/IGF2BP1/PLK1 axis.

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