Andrographolide influences IDD cell autophagy and oxidative stress under mechanical pressure via miR-9/FoxO3/PINK1/Parkin molecular axis.

Intervertebral disc degeneration (IDD) is characterized by the decreased function and number of nucleus pulposus cells (NPCs) caused by excessive intervertebral disc (IVD) pressure. This research aims to provide novel insights into IDD prevention and treatment by clarifying the effect of andrographolide (ANDR) on IDD cell autophagy and oxidative stress under mechanical stress. Human primary NPCs were extracted from the nucleus pulposus tissue of non-IDD trauma patients. An IDD cell model was established by posing mechanical traction on NPCs. Through the construction of an IDD rat model, the influence of ANDR on IDD pathological changes was explored in vivo. The proliferation and autophagy of NPCs were decreased while the apoptosis rate and oxidative stress reaction were increased by mechanical traction. ANDR intervention obviously alleviated this situation. MiR-9 showed upregulated expression in IDD cell model, while FoxO3 and PINK1/Parkin were downregulated. Decreased proliferation and autophagy as well as enhanced apoptosis and oxidative stress response of NPCs were observed following miR-9 mimics and H89 intervention, while the opposite trend was observed after FoxO3 overexpression. FoxO3 is a direct target downstream miR-9. The in vivo experiments revealed that after ANDR intervention, the number of apoptotic cells in rat IVD tissue decreased and the autophagy increased. In conclusion, ANDR improves NPC proliferation, and autophagy, inhibits apoptosis and oxidative stress, and alleviates the pathological changes of IDD via the miR-9/FoxO3/PINK1/Parkin axis, which may be a new and effective treatment for IDD in the future.

Preparation and Properties of Hollow Glass Microspheres/Dicyclopentadiene Phenol Epoxy Resin Composite Materials.

With the development of the integrated circuit and chip industry, electronic products and their components are becoming increasingly miniaturized, high-frequency, and low-loss. These demand higher requirements for the dielectric properties and other aspects of epoxy resins to develop a novel epoxy resin system that meets the needs of current development. This paper employs ethyl phenylacetate cured dicyclopentadiene phenol (DCPD) epoxy resin as the matrix and incorporates KH550 coupling-agent-treated SiO2 hollow glass microspheres to produce composite materials with low dielectric, high heat resistance, and high modulus. These materials are applied as insulation films for high density interconnect (HDI) and substrate-like printed circuit board (SLP) boards. The Fourier transform infrared spectroscopy (FTIR) technique was used to characterize the reaction between the coupling agent and HGM, as well as the curing reaction between the epoxy resin and ethyl phenylacetate. The curing process of the DCPD epoxy resin system was determined using differential scanning calorimetry (DSC). The various properties of the composite material with different HGM contents were tested, and the mechanism of the impact of HGM on the properties of the composite material was discussed. The results indicate that the prepared epoxy resin composite material exhibits good comprehensive performance when the HGM content is 10 wt.%. The dielectric constant at 10 MHz is 2.39, with a dielectric loss of 0.018. The thermal conductivity is 0.1872 Wm-1 k-1, the coefficient of thermal expansion is 64.31 ppm/K, the glass transition temperature is 172 °C, and the elastic modulus is 1221.13 MPa.

Divergent Connectivity Changes in Gray Matter Structural Covariance Networks in Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease.

Alzheimer's disease (AD) has a long preclinical stage that can last for decades prior to progressing toward amnestic mild cognitive impairment (aMCI) and/or dementia. Subjective cognitive decline (SCD) is characterized by self-experienced memory decline without any evidence of objective cognitive decline and is regarded as the later stage of preclinical AD. It has been reported that the changes in structural covariance patterns are affected by AD pathology in the patients with AD and aMCI within the specific large-scale brain networks. However, the changes in structural covariance patterns including normal control (NC), SCD, aMCI, and AD are still poorly understood. In this study, we recruited 42 NCs, 35 individuals with SCD, 43 patients with aMCI, and 41 patients with AD. Gray matter (GM) volumes were extracted from 10 readily identifiable regions of interest involved in high-order cognitive function and AD-related dysfunctional structures. The volume values were used to predict the regional densities in the whole brain by using voxel-based statistical and multiple linear regression models. Decreased structural covariance and weakened connectivity strength were observed in individuals with SCD compared with NCs. Structural covariance networks (SCNs) seeding from the default mode network (DMN), salience network, subfields of the hippocampus, and cholinergic basal forebrain showed increased structural covariance at the early stage of AD (referring to aMCI) and decreased structural covariance at the dementia stage (referring to AD). Moreover, the SCN seeding from the executive control network (ECN) showed a linearly increased extent of the structural covariance during the early and dementia stages. The results suggest that changes in structural covariance patterns as the order of NC-SCD-aMCI-AD are divergent and dynamic, and support the structural disconnection hypothesis in individuals with SCD.