Overactivation of microglial cells may cause severe brain tissue damage in various neurodegenerative diseases. Therefore, the overactivation of microglia should be repressed by any means. The present study investigated the potential mechanism and signaling pathway for the repressive effect of TGF-β1, a major anti-inflammatory cytokine, on overactivation and resultant death of microglial cells. A bacterial endotoxin LPS stimulated expression of inducible NO synthase (iNOS) and caused death in cultured microglial cells. TGF-β1 markedly blocked these LPS effects. However, the LPS-evoked death of microglial cells was not solely attributed to excess production of NO. Because phosphatidylinositol 3-kinase (PI3K) was previously shown to play a crucial role in iNOS expression and cell survival signals, we further studied whether PI3K signaling was associated with the suppressive effect of TGF-β1. Like TGF-β1, the PI3K inhibitor LY294002 blocked iNOS expression and death in cultured microglial cells. Both TGF-β1 and LY294002 decreased the activation of caspases 3 and 11 and the mRNA expression of various kinds of inflammatory molecules caused by LPS. TGF-β1 was further found to decrease LPS-induced activation of PI3K and Akt. TGF-β1 and LY294002 suppressed LPS-induced p38 mitogen-activated kinase and c-Jun N-terminal kinase activity. In contrast, TGF-β1 and LY294002 enhanced LPS-induced NF-κB activity. Our data indicate that TGF-β1 protect normal or damaged brain tissue by repressing overactivation of microglial cells via inhibition of PI3K and its downstream signaling molecules.

No abstract

Multiple sclerosis (MS) is a multifactorial demyelinating disease characterized by neurodegenerative events and autoimmune response against myelin component. Citrullination or deimination, a post-translational modification of protein-bound arginine into citrulline, catalyzed by Ca(2+) dependent peptidylarginine deiminase enzyme (PAD), plays an essential role in physiological processes include gene expression regulation, apoptosis and the plasticity of the central nervous system, while aberrant citrullination can generate new epitopes, thus involving in the initiation and/or progression of autoimmune disorder like MS. Myelin basic protein (MBP) is the major myelin protein and is generally considered to maintain the stability of the myelin sheath. This review describes the MBP citrullination and its consequence, as well as offering further support for the "inside-out" hypothesis that MS is primarily a neurodegenerative disease with secondary inflammatory demyelination. In addition, it discusses the role of MBP citrullination in the immune inflammation and explores the potential of inhibition of PAD enzymes as a therapeutic strategy for the disease.

Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin markedly reduced the infarct volume after 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide and inflammatory cytokines such as TNF-alpha and IL-6 in lipopolisaccharide-stimulated microglial cells. While wogonin reduced the activity of NF-kappaB, it did not change the activity of mitogen-activated protein kinases family members, p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and cytokines was significantly blocked by various kinds of NF-kappaB inhibitors such as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may indicate that wogonin has neuroprotective effect by preventing the overactivation of microglial cells, possibly by inactivating NF-kappaB signaling pathway.

The creation of micromotors that can convert stored energy to autonomous movement would be of great value in various applications, ranging from chemical sensing to precision water-quality screening and from cleaning clogged arteries to repairing microscopic cracks. Many of micromotors, based on different propulsion mechanisms (e.g., magnetic fields, ultrasound filed, chemical fuels, light, and bubble propulsion), [1][2][3][4][5][6][7][8][9] have been designed and fabricated over the past decade. Generally, they are built of rigid materials [10] to maintain a good maneuverability, but often with limited body compliance and adaptability in confined spaces. [11][12][13] In contrast to the hard Shape-transformable liquid metal (LM) micromachines have attracted the attention of the scientific community over the past 5 years, but the inconvenience of transfer routes and the use of corrosive fuels have limited their potential applications. In this work, a shape-transformable LM micromotor that is fabricated by a simple, versatile ice-assisted transfer printing method is demonstrated, in which an ice layer is employed as a "sacrificial" substrate that can enable the direct transfer of LM micromotors to arbitrary target substrates conveniently. The resulting LM microswimmers display efficient propulsion of over 60 µm s −1 (≈3 bodylength s −1 ) under elliptically polarized magnetic fields, comparable to that of the common magnetic micro/ nanomotors with rigid bodies. Moreover, these LM micromotors can undergo dramatic morphological transformation in an aqueous environment under the irradiation of an alternating magnetic field. The ability to transform the shape and efficiently propel LM microswimmers holds great promise for chemical sensing, controlled cargo transport, materials science, and even artificial intelligence in ways that are not possible with rigid-bodies microrobots.bodied, nature has created a wide range of biological motors with deformable bodies at small scales. They often have strong ability to actively adapt to their environment, thus can perform various demanding tasks in complex environments. Inspired by nature, researchers have begun to explore the design and control shape-transformable micromotors composed of compliant materials [14,15] (e.g., hydrogels, [16] granular media, [17] lowmelting point alloys, [18,19] and electroactive polymers [14] ) to ensure maneuverability, adaptability and agility in practical applications. Liquid metals (LMs) are typical examples of highly extensible and adaptable compliant materials, [20,21] such as Gallium and gallium-containing alloys (e.g., eutectic gallium-indium (EGaIn): 75% gallium and 25% indium; Galinstan: 68.5% gallium, 21.5% indium, and 10% tin). One of the most striking features of these gallium-based liquid metals is the nearly instant formation of a passivating oxide layer on their surface in the present of oxygen. This oxide layer (mainly composed of Ga 2 O 3 ) mechanically stabilizes the liquid metals into nonequilibrium shapes [22] and can be removed ...

Intrinsic spatial inhomogeneity or phase separation in cuprates, manganites, etc., related to electronic and/or magnetic properties, has attracted much attention due to its significance in fundamental physics and applications. Here we use scanning Kerr microscopy and scanning electron microscopy with polarization analysis with in situ electric fields to reveal the existence of intrinsic spatial inhomogeneity of the magnetic response to an electric field on a mesoscale with the coexistence of looplike (nonvolatile) and butterfly-like (volatile) behaviors in Co40Fe40B20/Pb(Mg1/3Nb2/3)0.7Ti0.3O3 ferromagnetic/ferroelectric (FM/FE) multiferroic heterostructures. Both the experimental results and micromagnetic simulations suggest that these two behaviors come from the 109° and the 71°/180° FE domain switching, respectively, which have a spatial distribution. This FE domain-switching-controlled magnetism is significant for understanding the nature of FM/FE coupling on the mesoscale and provides a path for designing magnetoelectric devices through domain engineering.

No abstract

We have investigated dynamic behavior of a three-dimensional magnetic domain wall (DW) having a Bloch-point structure in a cylindrical ferromagnetic nanowire via micromagnetic simulations. We have found the existence of an onset depinning behavior of the Bloch-point domain wall (BP-DW) motion under external magnetic fields, which is originated from overcoming an intrinsic pinning barrier generated from spin configuration of the Bloch-point domain wall inner structure. Ultrafast sequential switching of Bloch-point spins is expected to have a single precessional motion with negligible ringing on a few picoseconds time scale, which might be attractive for future spintronic applications.