A Sensitivity-Enhanced Vertical-Resonant MEMS Electric Field Sensor Based on TGV Technology.

In order to enhance the sensitivity of wafer-level vacuum-packaged electric field sensors, this paper proposed a vertical-resonant MEMS electric field sensor based on TGV (Through Glass Via) technology. The microsensor is composed of the electric field sensing cover, the drive cover, and the SOI-based microstructures between them. TGV technology is innovatively used to fabricate the electric field sensing cover and the vertically-driven cover. The external electric field is concentrated and transmitted to the area below the silicon plate in the center of the electric field sensing cover through a metal plate and a metal pillar, reducing the coupling capacitance between the silicon plate and the packaging structure, thereby achieving the enhanced transmission of the electric field. The sensitivity-enhanced mechanism of the sensor is analyzed, and the key parameters of the sensor are optimized through finite element simulation. The fabrication process is designed and realized. A prototype is tested to characterize its performance. The experimental results indicate that the sensitivity of the sensor is 0.82 mV/(kV/m) within the electrostatic electric field ranging from 0-50 kV/m. The linearity of the sensor is 0.65%.

Cerebral endothelial cell-derived extracellular vesicles regulate microglial polarization and promote autophagy via delivery of miR-672-5p.

The interaction between cerebral endothelial cells (CEC) and brain parenchymal cells is critical to maintain neurovascular homeostasis, whereas extracellular vesicles (EVs) are essential to mediate the cell-cell communication. Previous researches demonstrated that CEC-derived EVs (CEC-EVs) confer neuroprotective actions. However, the molecular mechanisms remain unknown. In this study, we isolated EVs from CEC and assessed their immune-regulatory actions in microglial cells and mice following lipopolysaccharide (LPS) exposure. We found that CEC-EVs treatment significantly ameliorated LPS-induced inflammatory activation, shifting microglial polarization from pro-inflammatory phenotype to anti-inflammatory phenotype. Meanwhile, microglial cells can effectively internalize CEC-EVs and this process was further enhanced by immune activation. Next, the miRNA microarray analysis revealed that CEC-EVs increased expression of miR-672-5p, which was demonstrated to be the cargo of CEC-EVs. TGFß-activated kinase 1 (TAK1)-binding proteins 2 (TAB2) was identified to be the target of miR-672-5p. Through inhibiting TAB2, miR-672-5p derived from CEC-EVs suppressed TAK1-TAB signaling and thereby mitigating the downstream NF-κB activation. Furthermore, we found that by delivering miR-672-5p, CEC-EVs promoted autophagy and hence stimulating autophagic degradation of NLRP3 inflammasome. Our work firstly revealed the neuroimmune-modulating actions of CEC-EVs and further demonstrated that miR-672-5p secreted from CEC-EVs inhibits microglial pro-inflammatory polarization and facilitates autophagic process via targeting TAB2.

A Highly Sensitive and High-Resolution Resonant MEMS Electrostatic Field Microsensor Based on Electrostatic Stiffness Perturbation.

This paper proposes a highly sensitive and high-resolution resonant MEMS electrostatic field sensor based on electrostatic stiffness perturbation, which uses resonant frequency as an output signal to eliminate the feedthrough interference from the driving voltage. The sensor is composed of a resonator, driving electrode, detection electrode, transition electrode, and electrostatic field sensing plate. The working principle is that when there is an electrostatic field, an induction charge will appear at the surface of the electrostatic field sensing plate and induce electrostatic stiffness on the resonator, which will cause a resonant frequency shift. The resonant frequency is used as the output signal of the microsensor. The characteristics of the electrostatic field sensor are analyzed with a theoretical model and verified by finite element simulation. A device prototype is fabricated based on the Silicon on Insulator (SOI) process and tested under vacuum conditions. The results indicate that the sensitivity of the sensor is 0.1384Hz/(kV/m) and the resolution is better than 10 V/m.

New insights into the interplay between autophagy and oxidative and endoplasmic reticulum stress in neuronal cell death and survival.

Autophagy is a dynamic process that maintains the normal homeostasis of cells by digesting and degrading aging proteins and damaged organelles. The effect of autophagy on neural tissue is still a matter of debate. Some authors suggest that autophagy has a protective effect on nerve cells, whereas others suggest that autophagy also induces the death of nerve cells and aggravates nerve injury. In mammals, oxidative stress, autophagy and endoplasmic reticulum stress (ERS) constitute important defense mechanisms to help cells adapt to and survive the stress conditions caused by physiological and pathological stimuli. Under many pathophysiological conditions, oxidative stress, autophagy and ERS are integrated and amplified in cells to promote the progress of diseases. Over the past few decades, oxidative stress, autophagy and ERS and their interactions have been a hot topic in biomedical research. In this review, we summarize recent advances in understanding the interactions between oxidative stress, autophagy and ERS in neuronal cell death and survival.

Comprehensive Analysis of Metabolic Changes in Male Mice Exposed to Sodium Valproate Based on GC-MS Analysis.

Purpose: Sodium valproate (VPA) is the most widely used broad-spectrum antiepileptic first-line drug in clinical practice and is effective against various types of epilepsy. However, VPA can induce severe cardiotoxicity, nephrotoxicity, hepatotoxicity, and neurotoxicity, which limits its use. Metabolomic studies of VPA-induced toxicity have focused primarily on changes in serum and urine metabolites but have not evaluated changes in major organs or tissues. Methods: Central target tissues (intestine, lung, liver, hippocampus, cerebral cortex, inner ear, spleen, kidney, heart, and serum) were analyzed using gas chromatography mass spectrometry to comprehensively evaluate VPA toxicity in mouse models. Results: Multivariate analyses, including orthogonal projections of the latent structure and Student's t test, indicated that depending on the matrix used in the study (the intestine, lung, liver, hippocampus, cerebral cortex, inner ear, spleen, kidney, heart or serum) the number of metabolites differed, the lung being the poorest and the kidney the richest in number. Conclusion: These metabolites were closely related and were found to participate in 12 key pathways related to amino acid, fatty acid, and energy metabolism, revealing that the toxic mechanism of VPA may involve oxidative stress, inflammation, amino acid metabolism, lipid metabolism, and energy disorder.

Therapeutic effect of extracellular vesicles from different cell sources in traumatic brain injury.

Extracellular vesicles (EVs) are biologically active membrane vesicles secreted by many cells in the body. A variety of nucleic acids, proteins, and other biologically active substances in EVs can be used to exchange and transmit information between cells, thereby affecting the progression of various diseases. Numerous studies have demonstrated that EVs not only regulate changes in brain physiology but also regulate synaptic plasticity and neuronal regeneration in traumatic brain injury (TBI), which opens a new approach for the treatment of TBI. In view of the fact that most human cells can secrete EVs, and relevant experiments have proved that different doses of EVs have different therapeutic effects on TBI. To this end, this paper reviews the therapeutic effects of EVs from different cell sources and their doses on TBI.