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Background: Hyperglycemia‐induced neuroinflammation significantly contributes to diabetic neuropathic pain (DNP), but the underlying mechanisms remain unclear. Objective: To investigate the role of Sirt3, a mitochondrial deacetylase, in hyperglycemia‐induced neuroinflammation and DNP and to explore potential therapeutic interventions. Method and Results: Here, we found that Sirt3 was downregulated in spinal dorsal horn (SDH) of diabetic mice by RNA‐sequencing, which was further confirmed at the mRNA and protein level. Sirt3 deficiency exacerbated hyperglycemia‐induced neuroinflammation and DNP by enhancing microglial aerobic glycolysis in vivo and in vitro. Overexpression of Sirt3 in microglia alleviated inflammation by reducing aerobic glycolysis. Mechanistically, high‐glucose stimulation activated Akt, which phosphorylates and inactivates FoxO1. The inactivation of FoxO1 diminished the transcription of Sirt3. Besides that, we also found that hyperglycemia induced Sirt3 degradation via the mitophagy‐lysosomal pathway. Blocking Akt activation by GSK69093 or metformin rescued the degradation of Sirt3 protein and transcription inhibition of Sirt3 mRNA, which substantially diminished hyperglycemia‐induced inflammation. Metformin in vivo treatment alleviated neuroinflammation and diabetic neuropathic pain by rescuing hyperglycemia‐induced Sirt3 downregulation. Conclusion: Hyperglycemia induces metabolic reprogramming and inflammatory activation in microglia through the regulation of Sirt3 transcription and degradation. This novel mechanism identifies Sirt3 as a potential drug target for treating DNP. [ABSTRACT FROM AUTHOR]

Aims: To assess the predictive value of early‐stage physiological time‐series (PTS) data and non‐interrogative electronic health record (EHR) signals, collected within 24 h of ICU admission, for traumatic brain injury (TBI) patient outcomes. Methods: Using data from TBI patients in the multi‐center eICU database, we focused on in‐hospital mortality, neurological status based on the Glasgow Coma Score (mGCS) motor subscore at discharge, and prolonged ICU stay (PLOS). Three machine learning (ML) models were developed, utilizing EHR features, PTS signals collected 24 h after ICU admission, and their combination. External validation was performed using the MIMIC III dataset, and interpretability was enhanced using the Shapley Additive Explanations (SHAP) algorithm. Results: The analysis included 1085 TBI patients. Compared to individual models and existing scoring systems, the combination of EHR and PTS features demonstrated comparable or even superior performance in predicting in‐hospital mortality (AUROC = 0.878), neurological outcomes (AUROC = 0.877), and PLOS (AUROC = 0.835). The model's performance was validated in the MIMIC III dataset, and SHAP algorithms identified six key intervention points for EHR features related to prognostic outcomes. Moreover, the EHR results (All AUROC >0.8) were translated into online tools for clinical use. Conclusion: Our study highlights the importance of early‐stage PTS signals in predicting TBI patient outcomes. The integration of interpretable algorithms and simplified prediction tools can support treatment decision‐making, contributing to the development of accurate prediction models and timely clinical intervention. [ABSTRACT FROM AUTHOR]

Chronic varicella zoster virus (VZV) infection induced neuroinflammatory condition is the critical pathology of post-herpetic neuralgia (PHN). The immune escape mechanism of VZV remains elusive. As to mice have no VZV infection receptor, herpes simplex virus type 1 (HSV-1) infection is a well established PHN mice model. Transcriptional expression analysis identified that the protein arginine methyltransferases 6 (Prmt6) was upregulated upon HSV-1 infection, which was further confirmed by immunofluorescence staining in spinal dorsal horn. Prmt6 deficiency decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load in vivo and in vitro. Overexpression of Prmt6 in microglia dampened antiviral innate immunity and increased HSV-1 load. Mechanistically, Prmt6 methylated and inactivated STING, resulting in reduced phosphorylation of TANK binding kinase-1 (TBK1) and interferon regulatory factor 3 (IRF3), diminished production of type I interferon (IFN-I) and antiviral innate immunity. Furthermore, intrathecal or intraperitoneal administration of the Prmt6 inhibitor EPZ020411 decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load. Our findings revealed that HSV-1 escapes antiviral innate immunity and results in PHN by upregulating Prmt6 expression and inhibiting the cGAS-STING pathway, providing novel insights and a potential therapeutic target for PHN. [ABSTRACT FROM AUTHOR]

Micro(nano)plastics (MNPs) in human food system have been broadly recognized by researchers and have drawn an increasing public attention to their potential health risks, particularly the risk to the intestinal system regarding the long-term exposure to MNPs through food consumption. This study aims to review the environmental properties (formation and composition) of MNPs and MNPs pollution in human food system following the order of food production, food processing and food consumption. The current analytic and identical technologies utilized by researchers are also summarized in this review. In fact, parts of commonly consumed food raw materials, processed food and the way to take in food all become the possible sources for human MNPs ingestion. In addition, the available literatures investigating MNPs-induced intestinal adverse effect are discussed from in vitro models and in vivo mammalian experiments, respectively. Particle translocation, cytotoxicity, damaged gut barrier, intestinal inflammation as well as microbial alteration are mostly reported. Moreover, the practical remediation strategies for MNPs pollution are also illustrated in the last section. This review is expected to provide a research insight for foodborne MNPs and arouse more public awareness of MNPs pollution in food and potential risk for human intestinal health. [ABSTRACT FROM AUTHOR]