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Background Members of the transient receptor potential canonical (TRPC) protein family are widely distributed in the hippocampus of mammals and exert respective and cooperative influences on the functions of neurons. The relationship between specific TRPC subtypes and neuroinflammation is receiving increasing attention. Methods Using Cx3cr1CreERIL-10−/− transgenic mice and their littermates to study the relationship between TRPC channels and memory impairment. Results We demonstrated that Cx3cr1CreERIL-10−/− mice displayed spatial memory deficits in object location recognition (OLR) and Morris water maze (MWM) tasks. The decreased levels of TRPC4 and TRPC5 in the hippocampal regions were verified via reverse transcription polymerase chain reaction, western blotting, and immunofluorescence tests. The expression of postsynaptic density protein 95 (PSD95) and synaptophysin in the hippocampus decreased with an imbalance in the local inflammatory environment in the hippocampus. The number of cells positive for ionized calcium-binding adaptor molecule 1 (Iba1), a glial fibrillary acidic protein (GFAP), increased with the high expression of interleukin 6 (IL-6) in Cx3cr1CreERIL-10−/− mice. The nod-like receptor protein 3 (NLRP3) inflammasome was also involved in this process, and the cytokines IL-1β and IL-18 activated by NLRP3 were also elevated by western blotting. The co-localization of TRPC5 and calmodulin-dependent protein kinase IIα (CaMKIIα) significantly decreased TRPC5 expression in excitatory neurons. AAV9-CaMKIIα-TRPC5 was used to upregulate TRPC5 in excitatory neurons in the hippocampus. Conclusions The results showed that the upregulation of TRPC5 improved the memory performance of Cx3cr1CreERIL-10−/− mice related to inhibiting NLRP3 inflammasome-associated neuroinflammation. Graphical Abstract

Depression has a growing impact on public health. Accumulating evidence supports an association between depression and increased immune system activity. IL-10 is a key cytokine that inhibits excessive inflammatory responses and is related to the anti-inflammatory and protective functions of the central nervous system (CNS). Cx3cr1CreERIL-10-/- mice were used in our study. We aimed to identify the role of IL-10 in microglia in depression and anxiety-like behavior. We performed a series of behavioral tests on the mice; the Cx3cr1CreERIL-10-/- male mice showed depression- and anxiety-like behavior compared with the littermates. The expression of transient receptor potential canonical 5 (TRPC5) decreased in both the medial prefrontal cortex (mPFC) and amygdala regions. The cytokines IL-1β and IL-6 increased, and IL-10 was decreased by western blotting. The knockout mice showed different trends in the effects of synaptic proteins. In the mPFC, IL-10 knockout induced a decrease in NR2B and synaptophysin; in the amygdala region, there was a significant increase in NR2B and PSD95. IL-10 knockout from microglia induced a decrease in GAD67 and parvalbumin (Pv) in the mPFC, but not in the amygdala. Our results showed enhanced depression and anxiety-like behavior in the Cx3cr1CreER IL-10-/- mice, which could be related to an imbalance in local excitatory and inhibitory transmission, as well as neuroinflammation in the mPFC and amygdala. This imbalance was associated with increased local inflammation. Although many studies have demonstrated the role of TRPC channels in emotional responses, our study showed that TRPC was not involved in this process in Cx3cr1CreERIL-10-/- mice.

BackgroundHeart failure (HF) is the most common outcome of cardiovascular disease, and an increasing number of patients with heart failure die from noncardiac causes, such as cancer. Epidemiological data suggest that ischemic cardiomyopathy–induced HF (ischemic HF) may be associated with an increased incidence of cancer. This study aimed to investigate the possible mechanisms of the association between ischemic HF and cancer, as well as potential therapeutic targets.MethodsWeighted gene co-expression network analysis was performed to analyze the correlations between phenotypes and gene modules using immune cells as phenotypes. Differential analysis was then performed to screen differentially expressed genes (DEGs) in ischemic HF and normal control samples. The macrophage-related Brown module was identified as the key module, and immune-related DEGs were obtained by taking the intersection of the Brown module, DEGs, and immune-related genes using a Venn diagram. DDX58 was identified as the key gene using a protein–protein interaction network and expression analyses and validated using immunohistochemistry. Kaplan–Meier survival analysis was performed to analyze the correlation between DDX58 expression and tumor prognosis. Spearman correlation analysis was performed to assess the correlation between DDX58 expression and immune cell infiltration.ResultsDDX58 was identified as a key immune-related gene associated with ischemic HF and was highly expressed in most cancer types. The survival analysis revealed a significant negative correlation between high DDX58 expression and prognosis in multiple tumor types. Moreover, DDX58 expression was significantly associated with immune cell infiltration and immune checkpoint gene expression in many cancer types.ConclusionDDX58 is a key immune-related gene in ischemic HF and may play a crucial role in the relationship between ischemic HF and cancer. Pan-cancer analysis suggests that DDX58 is a promising clinical prognostic marker for most cancers and may be a therapeutic target for cancer patients and ischemic HF patients at an increased risk of cancer.

Members of the transient receptor potential canonical (TRPC) protein family are widely distributed in the hippocampus of mammals and exert respective and cooperative influences on the functions of neurons. The relationship between specific TRPC subtypes and neuroinflammation is receiving increasing attention. Here, using Cx3cr1CreER IL-10−/−transgenic mice and their littermates, we demonstrated that Cx3cr1CreER IL-10−/− mice displayed spatial memory deficits in object location recognition (OLR) and Morris water maze (MWM) tasks. The decreased levels of TRPC4 and TRPC5 in the hippocampal regions were verified via reverse transcription polymerase chain reaction, western blotting, and immunofluorescence tests. The expression of postsynaptic density protein 95 (PSD95) and synaptophysin in the hippocampus decreased with an imbalance in the local inflammatory environment in the hippocampus. The number of cells positive for ionized calcium binding adaptor molecule 1 (Iba1), a glial fibrillary acidic protein (GFAP), increased with the high expression of interleukin 6 (IL-6) in Cx3cr1CreER IL-10−/− mice. The nod-like receptor protein 3 (NLRP3) inflammasome was also involved in this process, and the cytokines IL-1β and IL-18 activated by NLRP3 were also elevated by western blotting. The colocalization of TRPC5 and calmodulin-dependent protein kinase IIα (CaMKIIα) significantly decreased TRPC5 expression in excitatory neurons. AAV9-CaMKIIα-TRPC5 was used to upregulate TRPC5 in excitatory neurons in the hippocampus. The results showed that the upregulation of TRPC5 improved the memory performance of Cx3cr1CreER IL-10−/− mice by inhibiting NLRP3 inflammasome-associated inflammatory activity.

An experiment and simulation was conducted to investigate the influence of wrinkling behavior on formability and thickness distribution in tube hydroforming. The wrinkles can be classified into three categories, i.e. useful wrinkles, dead wrinkles, and bursting wrinkles. The dead wrinkles and the bursting wrinkles are defects in tube hydroforming. The formability improvement and the sound part with a larger expansion ratio can be obtained by the useful wrinkles with an advantage of no additional preform process. The thickness of the part is not uniform along the axial direction in the forming area. The top zone of wrinkle waves has the minimum thickness, whereas the maximum thickness appears in the bottom zone of wrinkle wave. The useful wrinkle should meet both the stress condition and the geometrical condition during calibrating. If the stress condition cannot be met, then bursting wrinkles occur. If the geometrical condition is not satisfaction, then dead wrinkles appear.