Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Background/Aims: Peri-operative cerebral ischemia reperfusion injury is one of the most serious peri-operative complications that can be aggravated in patients with diabetes. A previous study showed that microglia NOX2 (a NADPH oxidase enzyme) may play an important role in this process. Here, we investigated whether increased microglial derived gp91phox, also known as NOX2, reduced oxygen glucose deprivation (OGD) after induction of hyperglycemia (HG). Methods: A rat neuronal-microglial in vitro co-culture model was used to determine the effects of gp91phox knockdown on OGD after HG using six treatment groups: A rat microglia and neuron co-culture model was established and divided into the following six groups: high glucose + scrambled siRNA transfection (HG, n = 5); HG + gp91phoxsiRNA transfection (HG-gp91siRNA, n = 5); oxygen glucose deprivation + scrambled siRNA transfection (OGD, n = 5); OGD + gp91phoxsiRNA transfection (OGD-gp91siRNA, n = 5); HG + OGD + scrambled siRNA transfection (HG-OGD, n = 5); and HG + OGD + gp91phoxsiRNA transfection (HG-OGD-gp91siRNA, n = 5). The neuronal survival rate was measured by the MTT assay, while western blotting was used to determine gp91phox expression. Microglial derived ROS and neuronal apoptosis rates were analyzed by flow cytometry. Finally, the secretion of cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α was determined using an ELISA kit. Results: Neuronal survival rates were significantly decreased by HG and OGD, while knockdown of gp91phox reversed these rates. ROS production and cytokine secretion were also significantly increased by HG and OGD but were significantly inhibited by knockdown of gp91phoxsiRNA. Conclusion: Knockdown of gp91phoxsiRNA significantly reduced oxidative stress and the inflammatory response, and alleviated neuronal damage after HG and OGD treatment in a rat neuronal-microglial co-culture model

Performance Analysis of a Robust Controller with Neural Network Algorithm for Compliance Tendon–Sheath Actuation Lower Limb Exoskeleton

Robotic rehabilitation of the lower limb exoskeleton following neurological injury has proven to be an effective rehabilitation technique. Developing assistive control strategies that achieve rehabilitative movements can increase the potential for the recovery of the motor coordination of the participants. In this paper, the innovative contributions are to investigate a robust sliding mode controller (SMC) with radials basis function neural network algorithm (RBFNN) compensator for a novel compliance tendon–sheath actuation lower limb exoskeleton (CLLE) to provide intrinsic thigh and shank rehabilitation training. The controller employing the RBFNN compensator is proposed to reduce the impact of friction from the compliance tendon–sheath actuation system (CTSA). In the design of the compensator, a single parameter is investigated to replace the weight information of the neural network. Our proposed controller is shown to yield fast, stable, and accurate control performance regardless of uncertainties interaction. Two additional algorithms, including a robust adaptive sliding mode controller (RASMC) and a sliding mode proportional-integral controller (SMPIC), are introduced in this paper for comparison. The simulations were presented with MATLAB/SIMULINK to validate the superiority of the performance of the proposed controller

Design and Simulation Experiment of Rigid-Flexible Soft Humanoid Finger

This paper is based on the “Fast Pneumatic Mesh Driver” (FPN) used to couple a silicone rubber soft body with a rigid skeleton. A rigid-flexible coupling soft-body human-like finger design scheme is proposed to solve the problem of low load on the soft-body gripping hand. The second-order Yeoh model is used to establish the statics model of the soft humanoid finger, and the ABAQUS simulation analysis software is used for correction and comparison to verify the feasibility of the soft humanoid finger bending. The thickness of the driver cavity and the confining strain layer were determined by finite element simulation. The mold casting process is used to complete the preparation of human-like fingers and design a pneumatic control system for experiments combined with 3D printing technology. The experimental results show that the proposed rigid-flexible coupling soft body imitating the human finger structure can realize the corresponding actions, such as the multi-joint bending and side swinging, of human fingers. Compared with the traditional pure soft-body finger, the fingertip output force is significantly improved. The optimal design and simulation analysis of the human gripper and the feasibility of the application have practical guiding significance

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq

Abstract Background The stria vascularis (SV), located in the lateral wall of the cochlea, maintains cochlear fluid homeostasis and mechanoelectrical transduction (MET) activity required for sound wave conduction. The pathogenesis of a number of human inheritable deafness syndromes, age related hearing loss, drug-induced ototoxicity and noise-induced hearing loss results from the morphological changes and functional impairments in the development of the SV. In this study, we investigate the implications of intercellular communication within the SV in the pathogenesis of sensorineural hearing loss (SNHL). We aim to identify commonly regulated signaling pathways using publicly available single-cell transcriptomic sequencing (scRNA-seq) datasets. Methods We analyzed scRNA-seq data, which was derived from studying the cochlear SV in mice with SNHL compared to normal adult mice. After quality control and filtering, we obtained the major cellular components of the mouse cochlear SV and integrated the data. Using Seurat's FindAllMarkers and FindMarkers packages, we searched for novel conservative genes and differential genes. We employed KEGG and GSEA to identify molecular pathways that are commonly altered among different types of SNHL. We utilized pySCENIC to discover new specific regulatory factors in SV subpopulation cells. With the help of CellChat, we identified changes in subpopulation cells showing similar trends across different SNHL types and their alterations in intercellular communication pathways. Results Through the analysis of the integrated data, we discovered new conserved genes to SV specific cells and identified common downregulated pathways in three types of SNHL. The enriched genes for these pathways showing similar trends are primarily associated with the Electron Transport Chain, related to mitochondrial energy metabolism. Using the CellChat package, we further found that there are shared pathways in the incoming signaling of specific intermediate cells in SNHL, and these pathways have common upstream regulatory transcription factor of Nfe2l2. Combining the results from pySCENIC and CellChat, we predicted the transcription factor Nfe2l2 as an upstream regulatory factor for multiple shared cellular pathways in IC. Additionally, it serves as an upstream factor for several genes within the Electron Transport Chain. Conclusion Our bioinformatics analysis has revealed that downregulation of the mitochondrial electron transport chain have been observed in various conditions of SNHL. E2f1, Esrrb, Runx1, Yy1, and Gata2 could serve as novel important common TFs regulating the electron transport chain. Adm has emerged as a potential new marker gene for intermediate cells, while Itgb5 and Tesc show promise as potential new marker genes for marginal cells in the SV. These findings offer a new perspective on SV lesions in SNHL and provide additional theoretical evidence for the same drug treatment and prevention of different pathologies of SNHL

Beneficial Effects of Catalpol Supplementation during In Vitro Maturation of Porcine Cumulus-Oocyte Complexes

Oxidative stress degrades oocytes during in vitro maturation (IVM). Catalpol, a well-known iridoid glycoside, exhibits antioxidant, anti-inflammatory, and antihyperglycemic effects. In this study, catalpol supplementation was tested on porcine oocyte IVM and its mechanisms. Corticalgranule (GC) distribution, mitochondrial function, antioxidant capacity, DNA damage degree, and real-time quantitative polymerase chain reaction were used to confirm the effects of 10 μmol/L catalpol in the maturation medium during IVM. Catalpol treatment significantly increased the first-pole rate and cytoplasmic maturation in mature oocytes. It also increased oocyte glutathione (GSH), mitochondrial membrane potential and blastocyst cell number. However, DNA damage as well as reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Mitochondrial membrane potential and blastocyst cell number were also increased. Thus, the supplementation of 10 μmol/L catalpol in the IVM medium improves porcine oocyte maturation and embryonic development

Additional file 1 of Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq

Supplementary Material 1