Intermittent hypoxia exacerbates anxiety in high-fat diet-induced diabetic mice by inhibiting TREM2-regulated IFNAR1 signaling.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are mutual risk factors, with both conditions inducing cognitive impairment and anxiety. However, whether OSA exacerbates cognitive impairment and anxiety in patients with T2DM remains unclear. Moreover, TREM2 upregulation has been suggested to play a protective role in attenuating microglia activation and improving synaptic function in T2DM mice. The aim of this study was to explore the regulatory mechanisms of TREM2 and the cognitive and anxiety-like behavioral changes in mice with OSA combined with T2DM. METHODS: A T2DM with OSA model was developed by treating mice with a 60% kcal high-fat diet (HFD) combined with intermittent hypoxia (IH). Spatial learning memory capacity and anxiety in mice were investigated. Neuronal damage in the brain was determined by the quantity of synapses density, the number and morphology of brain microglia, and pro-inflammatory factors. For mechanism exploration, an in vitro model of T2DM combined with OSA was generated by co-treating microglia with high glucose (HG) and IH. Regulation of TREM2 on IFNAR1-STAT1 pathway was determined by RNA sequencing and qRT-PCR. RESULTS: Our results showed that HFD mice exhibited significant cognitive dysfunction and anxiety-like behavior, accompanied by significant synaptic loss. Furthermore, significant activation of brain microglia and enhanced microglial phagocytosis of synapses were observed. Moreover, IH was found to significantly aggravate anxiety in the HFD mice. The mechanism of HG treatment may potentially involve the promotion of TREM2 upregulation, which in turn attenuates the proinflammatory microglia by inhibiting the IFNAR1-STAT1 pathway. Conversely, a significant reduction in TREM2 in IH-co-treated HFD mice and HG-treated microglia resulted in the further activation of the IFNAR1-STAT1 pathway and consequently increased proinflammatory microglial activation. CONCLUSIONS: HFD upregulated the IFNAR1-STAT1 pathway and induced proinflammatory microglia, leading to synaptic damage and causing anxiety and cognitive deficits. The upregulated TREM2 inT2DM mice brain exerted a negative regulation of the IFNAR1-STAT1 pathway. Mice with T2DM combined with OSA exacerbated anxiety via the downregulation of TREM2, causing heightened IFNAR1-STAT1 pathway activation and consequently increasing proinflammatory microglia.

Green synthesis of Poria cocos polysaccharides-silver nanoparticles and their applications in food packaging.

To reduce pollution caused by traditional plastic packaging and preparation of silver nanoparticles (AgNPs), this work aims to develop biological macromolecular packaging films with green synthesized AgNPs. In this study, a novel P. cocos polysaccharide (PCP) with a unique monosaccharide composition was extracted from Poria cocos (Schw.) Wolf. Then, this polysaccharide containing 24.68 % rhamnose was used as a stabilizer for the green synthesis of PCP-AgNPs for the first time. PCP-AgNPs exhibited excellent antibacterial activity against P. aeruginosa, E. coli, and S. aureus, with the highest antibacterial activity against E. coli (inhibition zone diameter = 11.14 ± 0.79 mm). Subsequently, PCP-AgNPs/chitosan (CS) film was successfully prepared by incorporating PCP-AgNPs into the CS film solution. Several experiments demonstrated that the addition of this nanomaterial promoted the formation of noncovalent interactions between CS and PCP-AgNPs, resulting in a more regular and denser film. Compared to the CS film and control group, the PCP-AgNPs/CS film significantly maintained the quality indexes of strawberries. Therefore, this composite film successfully extended the shelf life of strawberries. Regarding safety, these packaging films were not cytotoxic toward RAW264.7 cells. In conclusion, the environmentally friendly PCP-AgNPs/CS film has the potential to replace some traditional food packaging materials.

Oncogenic role of Skp2 and p27Kip1 in intraductal proliferative lesions of the breast / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate whether the connection of p27(Kip1) to S-phase kinase-associated protein 2 (Skp2) plays an oncogenic role in intraductal proliferative lesions of the breast.</p><p><b>METHODS</b>Here we investigated the mechanism involved in association of Skp2’s degradation of p27(Kip1) with the breast carcinogenesis by immunohistochemical method through detection of Skp2 and p27(Kip1) protein levels in 120 paraffin-embedded tissues of intraductal proliferative lesions including usual ductal hyperplasia (UDH, n=30), atypical ductal hyperplasia (n=30), flat epithelial atypia (FEA, n=30), and ductal carcinoma in situ (DCIS, n=30). Moreover, the expression status of Skp2 and p27(Kip1) in 30 cases of the normal breast paraffin-embedded tissues were explored.</p><p><b>RESULTS</b>The DCIS group was with the highest Skp2 level and the lowest p27(Kip1) level, and the UDH group was with the lowest Skp2 level and the highest p27(Kip1) level.Both Skp2 and p27(Kip1) levels in the DCIS group were significantly different from those in the UDH group (all P<0.01).The levels of Skp2 and p27(Kip1) in the FEA group were significantly different from both the DCIS and UDH groups (all P<0.05).p27(Kip1) was negatively correlated with Skp2 in both the UDH group (r=-0.629, P=0.026) and DCIS group (r=-0.893, P=0.000).</p><p><b>CONCLUSION</b>Overexpression of Skp2 might be the mechanism underlying p27(Kip1) over degradation.</p>