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Based on our super-slip groove design, three-dimensional numerical models for liquid film under boundary conditions of no slip and super slip at the groove bottom of spiral groove, Tesla groove, and double spiral groove liquid film seals were established. The evolution characteristics of cavitation under different rotational speeds and ambient temperatures were studied, and visualization experiments were carried out through a self-built cavitation visualization test bench. The findings reveal that the super-slip design demonstrates groove universality, preserving the integrity of the liquid film while significantly reducing cavitation rate, enhancing opening force, minimizing leakage, and lowering liquid film temperature. Notably, the experimental observations align closely with the numerical results. • Visualization experiments have verified the accuracy of numerical simulation method for super-slip groove liquid film seals. • The proposed super-slip groove design offers groove universality. • The super-slip groove design significantly mitigates cavitation and enhances the performance of liquid film seals. [ABSTRACT FROM AUTHOR]

• CUS induced down-regulation of RAGE and GLT-1 in hippocampus DG. • RAGE knockdown in hippocampus DG elicited depressive-like behaviors. • RAGE knockdown caused down-regulation of GLT-1, p-CREB and p-p65. • RAGE signaling in hippocampus involved in dysfunction of GLT-1 induced by CUS. A pivotal role of glutamatergic neurotransmission in the pathophysiology of major depressive disorder (MDD) has been supported in preclinical and clinical studies. Glutamate transporters are responsible for rapid uptake of glutamate to maintain glutamate homeostasis. Down-regulation of glutamate transporters has been reported in MDD patients and animal models. However, the mechanism for stress-induced modulation of glutamate transporter expression is poorly understood. Receptor for advanced glycosylation end products (RAGE), a member of immunoglobulin family, is found expressed widely in brain and play important roles in neuronal development, neurite growth, neurogenesis and neuroinflammation. Our study showed chronic unpredictable stress (CUS) induced depressive-like behaviors and reduced RAGE expression in hippocampus DG, CA1 and CA3 areas. The protein levels of GLT-1, p-CREB and p-p65 decreased in hippocampus DG as well. Knockdown of RAGE expression in hippocampus DG with RAGE shRNA lentivirus particles induced depressive-like behaviors. Meanwhile, the protein and mRNA levels of GLT-1 were significantly decreased as well as phosphorylation of CREB and p65. Neither CUS nor RAGE knockdown altered GLAST protein and mRNA levels. These findings suggested that RAGE/CREB-NF-κB signaling pathway in hippocampus DG involved in modulation of GLT-1 expression, which possibly contributed to the depressive-like behavior induced by CUS. [ABSTRACT FROM AUTHOR]

The incidence of diabetic cognitive dysfunction is increasing year by year, and it has gradually become a research hot spot. Studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists can improve cognitive dysfunction in diabetic patients. This study focuses on whether small molecule GLP-1R agonists from traditional Chinese medicine (TCM) can improve the diabetic cognitive dysfunction. The small molecules from TCM were screened by cell membrane chromatography (CMC) with GLP-1R-HEK293 cell membrane column. MTT assay, flow cytometry, immunofluorescence cytochemistry and other methods were used to determine the effects of mollugin on the apoptosis rate and reactive oxygen species (ROS) level of high glucose (HG)/hydrogen peroxide (H 2 O 2) induced PC12 cells. Real-Time PCR was used to detect mRNA expression in mouse cerebral cortex. Water maze test was further used to confirm the effect of mollugin on cognitive dysfunction in T2DM mice. Mollugin bound to GLP-1R, promoted Ca2+ influx, increased insulin secretion and cAMP content in β-TC-6 cells. Mollugin enhanced the cell viability, ameliorated apoptosis, reduced intracellular ROS levels in HG/H 2 O 2 -injured PC12 cells. Mollugin reduced the T2DM mice's escape latency, improved neuronal cell damage, decreased the expression of Pik3ca, Akt1 and Mapk1 mRNA in the cerebral cortex tissue. The results suggest that mollugin could improve cognitive dysfunction in T2DM mice through activating GLP-1R/cAMP/PKA signal pathway. [ABSTRACT FROM AUTHOR]