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Background and purposeA growing number of studies have demonstrated that oxytocin (OT) plays an analgesic role in modulation of nociception and pain. Most work to date has focused on the central mechanisms of OT analgesia, but little is known about whether peripheral mechanisms are also involved. Acid-sensing ion channels (ASICs) are distributed in peripheral sensory neurons and participate in nociception. Here, we investigated the effects of OT on the activity of ASICs in dorsal root ganglion (DRG) neurons.Experimental approachElectrophysiological experiments were performed on neurons from rat DRG. Nociceptive behaviour was induced by acetic acid in rats and mice lacking vasopressin, V1A receptors.Key resultsOT inhibited the functional activity of native ASICs. Firstly, OT dose-dependently decreased the amplitude of ASIC currents in DRG neurons. Secondly, OT inhibition of ASIC currents was mimicked by arginine vasopressin (AVP) and completely blocked by the V1A receptor antagonist SR49059, but not by the OT receptor antagonist L-368899. Thirdly, OT altered acidosis-evoked membrane excitability of DRG neurons and significantly decreased the amplitude of the depolarization and number of action potentials induced by acid stimuli. Finally, peripherally administered OT or AVP inhibited nociceptive responses to intraplantar injection of acetic acid in rats. Both OT and AVP also induced an analgesic effect on acidosis-evoked pain in wild-type mice, but not in V1A receptor knockout mice.Conclusions and implicationsThese results reveal a novel peripheral mechanism for the analgesic effect of OT involving the modulation of native ASICs in primary sensory neurons mediated by V1A receptors.

Background: Dengue fever (DF) and West Nile fever (WNF) have become endemic worldwide in the last two decades. Studies suggest that individuals with diabetes mellitus (DM) are at a higher risk of developing severe complications from these diseases. Identifying the factors associated with a severe clinical presentation is crucial, as prompt treatment is essential to prevent complications and fatalities. This article aims to summarize and assess the published evidence regarding the link between DM and the risk of severe clinical manifestations in cases of DF and WNF. Methodology/Principal findings: A systematic search was conducted using the PubMed and Web of Science databases. 27 studies (19 on DF, 8 on WNF) involving 342,873 laboratory-confirmed patients were included in the analysis. The analysis showed that a diagnosis of DM was associated with an increased risk for severe clinical presentations of both DF (OR 3.39; 95% CI: 2.46, 4.68) and WNF (OR 2.89; 95% CI: 1.89, 4.41). DM also significantly increased the risk of death from both diseases (DF: OR 1.95; 95% CI: 1.09, 3.52; WNF: OR 1.74; 95% CI: 1.40, 2.17). Conclusions/Significance: This study provides strong evidence supporting the association between DM and an increased risk of severe clinical manifestations in cases of DF and WNF. Diabetic individuals in DF or WNF endemic areas should be closely monitored when presenting with febrile symptoms due to their higher susceptibility to severe disease. Early detection and appropriate management strategies are crucial in reducing the morbidity and mortality rates associated with DF and WNF in diabetic patients. Tailored care and targeted public health interventions are needed to address this at-risk population. Further research is required to understand the underlying mechanisms and develop effective preventive and therapeutic approaches. Author summary: In our study, we investigated the association between diabetes mellitus (DM) and the risk of severe clinical manifestations in cases of dengue fever (DF) and West Nile fever (WNF). By analyzing 27 studies involving over 342,000 laboratory-confirmed patients, we found compelling evidence supporting a link between DM and an increased risk of severe complications in both DF and WNF. Moreover, DM was found to significantly raise the risk of mortality from these diseases. Our findings emphasize the importance of early detection and appropriate management strategies for diabetic individuals residing in endemic areas. Healthcare providers should be vigilant in monitoring diabetic patients with febrile symptoms, as they are more susceptible to developing severe disease. Tailored care and targeted interventions are crucial to minimize the morbidity and mortality rates associated with DF and WNF in diabetic individuals. These findings have significant implications for public health, highlighting the need for awareness campaigns and preventive measures aimed at diabetic individuals. Further research is needed to understand the underlying mechanisms and develop effective strategies for prevention and treatment. By addressing these issues, we can reduce the impact of DF and WNF on individuals with DM. [ABSTRACT FROM AUTHOR]

It was reported that the Wnt/β‐catenin pathway is involved in the regulation of aerobic glycolysis and that brain glycolytic dysfunction results in the development of Alzheimer's disease (AD). Icariin (ICA), an active component extracted from Epimedii Folium, has been reported to produce neuroprotective effects in multiple models of AD, but its underlying mechanism remains to be fully described. We aimed to investigate the protective effects of ICA on animal and cell models of AD and confirm whether the Wnt/β‐catenin pathway has functions in the neuroprotective function of ICA. The 3 × Tg‐AD mice were treated with ICA. HT22 cells, the Aβ25‐35 peptide and Dickkopf‐1 (DKK1) agent (a specific inhibitor of the Wnt/β‐catenin pathway) were used to further explore the underlying mechanism of ICA that produces anti‐AD effects. Behavioral examination, western blotting assay, staining analysis, biochemical test, and lactate dehydrogenase (LDH) assays were applied. We first demonstrated that ICA significantly improved cognitive function and autonomous behavior, reduced neuronal damage, and reversed the protein levels and activities of glycolytic key enzymes, and expression of protein molecules of the canonical Wnt signaling pathway, in 3 × Tg‐AD mice back to wild‐type levels. Next, we further found that ICA increased cell viability and effectively improved the dysfunctional glycolysis in HT22 cells injured by Aβ25‐35. However, when canonical Wnt signaling was inhibited by DKK1, the above effects of ICA on glycolysis were abolished. In summary, ICA exerts neuroprotective effects in 3 × Tg‐AD animals and AD cellular models by enhancing the function of glycolysis through activation of the Wnt/β‐catenin pathway. [ABSTRACT FROM AUTHOR]

The dysfunction of phospholipid metabolism enzymes and the change in membrane phospholipid composition are associated with insulin resistance, indicating that phospholipids play an important role in the regulation of insulin sensitivity. The reflection of phospholipid changes in blood might provide clues for both mechanism understanding and intervention. Using a targeted phospholipidomic approach, 199 phospholipid molecular species were identified and quantified in the plasma of 1053 middle-aged participants from a national investigation. The associations of the phospholipid matrix, clusters, and molecular species with insulin resistance were investigated. A significant association was confirmed between the phospholipid matrix and the homeostatic-model assessment of insulin resistance (HOMA-IR) by a distance-based linear model. Furthermore, three clustered phospholipid modules and 32 phospholipid molecular species were associated with HOMA-IR with the strict control of demographic and lifestyle parameters, family history of diabetes, BMI, WC, and blood lipid parameters. The overall decline in lysophosphatidylcholines (LPCs), the decrease in saturated lysophosphatidylethanolamines (LPEs), the decrease in polyunsaturated/plasmenyl phosphatidylcholines (PCs), and the increase in polyunsaturated phatidylethanolamines (PEs) were the prominent characters of plasma phospholipid perturbation associated with insulin resistance. This suggested that PC- and PE-related metabolic pathways were widely involved in the process of insulin resistance, especially the disorder of LPC acylation to diacyl-PC. [ABSTRACT FROM AUTHOR]

Two colossal global challenges remain energy scarcity and environmental pollution, having evolved into problems that human society cannot ignore. Therefore, developing a material with efficient electromagnetic (EM) interference shielding and electrocatalytic properties has become imperative in promoting sustainable development and establishing environmental protection systems. Herein, a heterodimensional structure is prepared by assembling 3D spirally grown VS2 with 2D FeCo‐LDH, which precisely manipulates macroscopic EM and electrochemical characteristics through defect and interface engineering. The results show that the heterodimensional structure presents an efficient shielding effectiveness of 30.2 dB at 18 GHz. Heterodimensional structure exhibits a low overpotential of 279 mV, achieving a current density of 10 mA cm−2 and a desirable stability. In addition, based on the unique electrochemical properties and EM response characteristics of the material, a special protective helmet is innovated. The helmet incorporating an autonomous oxygen supply, advanced pressure surveillance, and dynamic stealth supports a more exhaustive safeguard for missions amidst noxious gases, and situations necessitating clandestine operations. This research provides a new idea for the development of multifunctional EM active materials, showing great application prospects in the fields of aerospace engineering, energy, and EM security protection. [ABSTRACT FROM AUTHOR]