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Increasing evidence indicates the major role of mitochondrial function in neurodegenerative disease. However, it is unclear whether mitochondrial dynamics directly affect postoperative neurocognitive disorder (PND). This study aimed to analyze the underlying mechanisms of mitochondrial dynamics in the pathogenesis of PND. Tibial fracture surgery was performed in elderly mice to generate a PND model in vivo. Cognitive behavior was evaluated 3 days post-surgery using novel object recognition and fear conditioning. A gradual increase in the SOX2OT mRNA level and decrease in the SOX2 mRNA level were noted, with impaired cognitive function, in the mice 3 days after tibial surgery compared with mice in the sham group. To evaluate the role of SOX2OT in PND, SOX2OT knockdown was performed in vitro and in vivo using lentivirus transfection in HT22 cells and via brain stereotactic injection of lentivirus, respectively. SOX2OT knockdown reduced apoptosis, inhibited oxidative stress, suppressed mitochondrial hyperdivision, attenuated surgery-induced cognitive dysfunction, and promoted downstream SOX2 expression in elderly mice. Furthermore, Sox2 alleviated mitochondrial functional damage by inhibiting the transcription of mitochondrial division protein Drp1. Our study findings indicate that SOX2OT knockout alleviates surgery-induced mitochondrial fission and cognitive function defects by upregulating the expression of Sox2 in mice, resulting in the inhibition of drp1 transcription. Therefore, regulation of the SOX2/Drp1 pathway may be a potential mechanism for the treatment of patients with PND. [ABSTRACT FROM AUTHOR]

Abstract With the speedy technological advances during the past few decades, human exposure to the electromagnetic field (EMF) has become increasingly common. Exposure to EMF may induce neural injuries and dysfunction of various organs, likely involving neuroinflammation and activation of microglial cells. Isoflurane preconditioning (IP) is shown to provide neuroprotection in various neurological diseases by inhibiting excessive neuroinflammatory responses. Brain samples harvested from rats exposed to electromagnetic pulse (EMP) with or without IP were subjected to qPCR, Western blot assay, and immunohistochemistry to determine the expression of pro-inflammatory/anti-inflammatory microglia markers and a variety of pro- and anti-inflammatory mediators. Suppressor of cytokine signaling 1 (SOCS1) siRNA was used in cultured N9 microglia cells to examine the roles of SOCS1 in the effect of IP. In both in vivo and in vitro experiments, EMP-exposed microglia were predominantly pro-inflammatory microglia, accompanied by increased expression of pro-inflammatory cytokines and chemokines, and activation of TLR4 pathway, leading to neuronal death. IP reversed the changes induced by EMP and switched the activated microglia to an anti-inflammatory phenotype. SOCS1 siRNA abolished the beneficial effects of IP. IP ameliorates EMP-induced neural injuries by shifting microglia polarization from pro-inflammatory to anti-inflammatory phenotype via upregulation of SOCS1. Highlights • SOCS1 siRNA abolishes the beneficial effects of IP. • IP ameliorates EMP-induced neural injuries. • IP shifts microglia polarization from pro-inflammatory to anti-inflammatory phenotype via upregulation of SOCS1. [ABSTRACT FROM AUTHOR]

• A novel photonic skin flexible sensor based on partially neutralized sodium polyacrylate is reported for the first time in this paper. • This photon skin flexible sensor has achieved relative humidity sensing for the first time. • The photonic skin flexible sensor has a relative humidity sensitivity of up to 0.1411 dB/%, with a fast response time of 170 ms. • The temperature response exhibits outstanding sensitivity (0.4 dB/°C) in the human skin surface temperature range (30 ∼ 48 °C). Biomimetic skin sensing devices play an important role in next-generation healthcare, robotics, and bioelectronics. In recent years, biomimetic skin-sensing technologies have gained significant attention due to their broad-ranging utility in the fields of healthcare and automation, and future wearable devices designed for health monitoring, robotic applications, and ultra-precise industrial positioning will necessitate the incorporation of flexible optical systems. A novel photonic skin flexible sensor (PSFS) based on partially neutralized sodium polyacrylate (PAS-50) is reported for the first time in this paper. In this study, a novel wearable sensor was designed for real-time detection of temperature and humidity. A single-mode tapered fiber (SMTF) structure based on the principle of evanescent wave is proposed for fast response and real-time monitoring of humidity and temperature. The sensor incorporates an optical micro/nanofiber (MNF) as the core sensing node, while a hydrophilic and ductile Sodium Polyacrylate (PAS) is chosen as the humidity-sensitive material that overcomes the limitation of commonly reported electrical, optical, and material-based flexible devices. Due to the strain amplification effect of the MNF, the sensitivity of the material to relative humidity (RH) is significantly improved, reaching 0.1411 dB/%. In addition, the temperature response exhibits outstanding sensitivity (0.4 dB/°C) in the human skin surface temperature range (30 ∼ 48 °C). Notably, the sensor exhibits a rapid response with a remarkable response time of 170 ms. The proposed PSFS presents novel opportunities for the advancement of future biomimetic skin devices, thus playing a pivotal role in the advancement of next-generation robotics and medical monitoring technologies. [ABSTRACT FROM AUTHOR]

• miR-665-3p was decreased by OGD in microglial cells. • miR-665-3p attenuated OGD-induced microglial apoptosis and inflammation. • TRIM8 was identified as a target gene of miR-655-3p. • miR-655-3p inhibited NF-κB activation by targeting TRIM8. Microglial inflammation induced by ischemic stroke aggravates brain damage. MicroRNAs (miRNAs) have emerged as pivotal regulators in ischemic stroke-induced inflammation in microglial cells. miR-665-3p has been reported as a critical inflammation-associated miRNA. However, whether miR-665-3p participates in regulating microglial inflammation during ischemic stroke is underdetermined. This study investigated the potential role of miR-665-3p in stroke-induced inflammation in microglial cells using a cellular model of oxygen-glucose deprivation (OGD)-stimulated microglial cells in vitro. We found that miR-665-3p expression was decreased in microglial cells exposed to OGD treatment. Functional experiments demonstrated that the overexpression of miR-665-3p attenuated OGD-induced apoptosis and inflammation in microglial cells. Notably, tripartite motif 8 (TRIM8) was identified as a target gene of miR-665-3p. TRIM8 expression was induced by OGD treatment in microglial cells and the knockdown of TRIM8 protected microglial cells from OGD -induced cytotoxicity and inflammation. Moreover, TRIM8 knockdown or miR-665-3p overexpression blocked OGD-induced activation of nuclear factor (NF)-κB signaling in microglial cells. In addition, TRIM8 overexpression partially reversed the miR-665-3p overexpression-mediated inhibitory effect on OGD-induced inflammation in microglial cells. Taken together, these results indicate that miR-665-3p up-regulation protects microglial cells from OGD-induced apoptosis and inflammatory response by targeting TRIM8 to inhibit NF-κB signaling. [ABSTRACT FROM AUTHOR]

• TRIM8 expression is increased in OGD/R-exposed neurons. • TRIM8 inhibition protects from OGD/R-induced neuronal injury. • TRIM8 inhibition enhances Nrf2 signaling by regulating AMPK. • TRIM8 regulates OGD/R-induced neuronal injury by AMPK/Nrf2 signaling. Tripartite motif 8 (TRIM8) has emerged as a crucial regulator of cell survival, apoptosis, and oxidative stress in various pathological processes. However, TRIM8's involvement in regulating neuronal injury in cerebral ischemia/reperfusion injury remains largely uncharacterized. In the present study, we aimed to investigate the potential function and molecular mechanism of TRIM8 in regulating neuronal apoptosis and oxidative stress induced by oxygen–glucose deprivation/re-oxygenation (OGD/R) in an in vitro model to study cerebral ischemia/reperfusion injury. Herein, we found that TRIM8 expression was upregulated in neurons exposed to OGD/R. Knockdown of TRIM8 improved the viability and decreased the apoptosis and reactive oxygen species (ROS) generation in OGD/R-exposed neurons, whereas TRIM8 overexpression showed the opposite effect. Notably, TRIM8 inhibition increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and enhanced the nuclear expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Moreover, TRIM8 inhibition promoted the transcriptional activity of the Nrf2/antioxidant response element (ARE). However, AMPK inhibition partially reversed TRIM8 downregulation-mediated Nrf2/ARE activation and the neuroprotective effect in OGD/R-exposed neurons. Additionally, silencing of Nrf2 also markedly abrogated TRIM8 downregulation-mediated neuroprotection. Overall, these results demonstrate that downregulation of TRIM8 protects from OGD/R-induced neuronal injury by reinforcing the activation of Nrf2/ARE antioxidant signaling via AMPK, suggesting a potential role for TRIM8 in cerebral ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]