Myelin Activates FAK/Akt/NF-κB Pathways and Provokes CR3-Dependent Inflammatory Response in Murine System

Inflammatory response following central nervous system (CNS) injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI), i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3)-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-κB signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-κB activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin) and myelin basic protein (MBP, one of the major proteins of myelin) are not able to activate NF-κB signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI

Effects of adding aluminium in zinc bath on Co-Zn interfacial reaction

764-769Effects of adding 0.3 wt.% Al in Zn bath on the microstructure and reaction kinetics of intermetallic compounds have been studied using Co/Zn and Co/Zn-Al solid/liquid diffusion couples by means of scanning electron microscopy (SEM) and wave dispersive spectrometry (WDS). The intermetallic compounds in the Co-Zn interface have been identified and the diffusion process of Al in zinc bath has been analyzed. The diffusion constants of intermetallic compounds have been evaluated. The chemical potential of Al and standard Gibbs free energy of intermetallic compounds have been calculated using the Co content as a variable based on the calculation of phase diagram (CALPHAD) method. The results show that the chemical potential of Al decreases with increasing Co. At the solid/liquid interface, the Co content is high, the chemical potential of Al atoms is lower than that in other areas, uphill diffusion of Al atoms occurs, and an Al-rich metastable phase forms. The Gibbs free energy of the CoAl phase is lower than that of Co-Zn compounds; therefore, the Co atoms diffuse through the γ2 layer into the Al-rich area and nucleate to form a shape-stable CoAl layer at the solid/liquid interface and significantly inhibit the Co-Zn interfacial reaction

Effects of adding aluminium in zinc bath on Co-Zn interfacial reaction

Effects of adding 0.3 wt.% Al in Zn bath on the microstructure and reaction kinetics of intermetallic compounds have been studied using Co/Zn and Co/Zn-Al solid/liquid diffusion couples by means of scanning electron microscopy (SEM) and wave dispersive spectrometry (WDS). The intermetallic compounds in the Co-Zn interface have been identified and the diffusion process of Al in zinc bath has been analyzed. The diffusion constants of intermetallic compounds have been evaluated. The chemical potential of Al and standard Gibbs free energy of intermetallic compounds have been calculated using the Co content as a variable based on the calculation of phase diagram (CALPHAD) method. The results show that the chemical potential of Al decreases with increasing Co. At the solid/liquid interface, the Co content is high, the chemical potential of Al atoms is lower than that in other areas, uphill diffusion of Al atoms occurs, and an Al-rich metastable phase forms. The Gibbs free energy of the CoAl phase is lower than that of Co-Zn compounds; therefore, the Co atoms diffuse through the γ2 layer into the Al-rich area and nucleate to form a shape-stable CoAl layer at the solid/liquid interface and significantly inhibit the Co-Zn interfacial reaction

Enhancing the Spin–Orbit Coupling in Fe3O4 Epitaxial Thin Films by Interface Engineering

10.1021/acsami.6b0947884027353-2735

Fenofibrate suppresses corneal neovascularization by regulating lipid metabolism through PPARα signaling pathway

Purpose: The purpose of this study was to explore the potential underlying mechanism of anti-vascular effects of peroxisome proliferator–activated receptor α (PPARα) agonist fenofibrate against corneal neovascularization (CNV) through the changes of lipid metabolism during CNV.Methods: A suture-induced CNV model was established and the clinical indications were evaluated from day 1 to day 7. Treatments of vehicle and fenofibrate were performed for 5 days after suture and the CNV areas were compared among the groups. The eyeballs were collected for histological analysis, malondialdehyde (MDA) measurement, terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick end labeling (TUNEL) staining, western blot, quantitative real-time PCR (qRT-PCR) assays and immunohistochemical (IHC) staining to elucidate pathological changes and the underlying mechanism.Results: Lipi-Green staining and MDA measurement showed that lipid deposition and peroxidation were increased in the CNV cornea while the expression of long-chain acyl-coenzyme A synthetase 1 (ACSL1), carnitine palmitoyltransterase 1A(CPT1A) and medium-chain acyl-coenzyme A dehydrogenase (ACADM), which are key enzymes of fatty acid β-oxidation (FAO) and targeted genes of peroxisome proliferator-activated receptor alpha (PPARα) pathway, were decreased in CNV cornea. Fenofibrate suppressed lipid accumulation and peroxidation damage in the CNV cornea. Fenofibrate upregulated the expression levels of PPARα, ACSL1, CPT1A, and ACADM compared with vehicle group. IHC staining indicated that fenofibrate also decreased the expression of VEGFa, VEGFc, TNFα, IL1β and CD68.Conclusion: Disorder of lipid metabolism may be involved in the formation of suture-induced CNV and fenofibrate played anti-neovascularization and anti-inflammatory roles on cornea by regulating the key enzymes of lipid metabolism and ameliorating lipid peroxidation damage of cornea through PPARα signaling pathway

Corneal Alternations Induced by Topical Application of Benzalkonium Chloride in Rabbit

Benzalkonium chloride (BAC) is the most common preservative in ophthalmic preparations. Here, we investigated the corneal alternations in rabbits following exposure to BAC. Twenty-four adult male New Zealand albino rabbits were randomly divided into three groups. BAC at 0.01%, 0.05%, or 0.1% was applied twice daily to one eye each of rabbits for 4 days. The contralateral untreated eyes were used as control. Aqueous tear production and fluorescein staining scores of BAC-treated eyes were compared with those of controls. The structure of the central cornea was examined by in vivo confocal microscopy. Expression of mucin-5 subtype AC (MUC5AC) in conjunctiva was detected by immunostainig on cryosections. Corneal barrier function was assessed in terms of permeability to carboxy fluorescein (CF). The distribution and expression of ZO-1, a known marker of tight junction, and reorganization of the perijunctional actomyosin ring (PAMR) were examined by immunofluorescence analysis. Although there were no significant differences between control and BAC-treated eyes in Schirmer scores, corneal fluorescein scores and the number of conjunctival MUC5AC staining cells, in vivo confocal microscopy revealed significant epithelial and stromal defects in all BAC-treated corneas. Moreover, BAC at 0.1% resulted in significant increases in central corneal thickness and endothelial CF permeability, compared with those in control eyes, and endothelial cell damage with dislocation of ZO-1 and disruption of PAMR. Topical application of BAC can quickly impair the whole cornea without occurrence of dry eye. A high concentration of BAC breaks down the barrier integrity of corneal endothelium, concomitant with the disruption of PAMR and remodeling of apical junctional complex in vivo

Serotonin system is partially involved in immunomodulation of Nile tilapia (Oreochromis niloticus) immune cells

Serotonin (5-hydroxytryptamine) is a well-known neurotransmitter affecting emotion, behavior, and cognition. Additionally, numerous immunomodulatory functions of serotonin have been discovered in mammals. However, the regulatory role of the serotonin system in fish immunity remains unclear. In this study, various serotonergic markers in Nile tilapia (Oreochromis niloticus) were identified and characterized. The involvement of the serotonin system during bacterial infection was investigated. Moreover, the expression characteristics and specific functions of serotonergic markers within Nile tilapia immune cells were also assessed. Overall, 22 evolutionarily conserved serotonergic marker genes in Nile tilapia were cloned and characterized. Transcriptional levels of these molecules were most abundant in the brain, and their transcripts were induced during Streptococcus agalactiae infection. Nevertheless, few serotonergic markers exist on Nile tilapia immune cells, and no distinct immunomodulation effect was observed during an immune response. The present study lays a theoretical foundation for further investigation of the immunological mechanisms in fish as well as the evolution of the serotonin system in animals

Development of 230 GHz finline SIS mixers for next-generation large array receivers and HARP instrument upgrade

In pursuit of advancing large array receiver capabilities and enhancing the 16-element Heterodyne Array Receiver Program (HARP) instrument on the James Clerk Maxwell Telescope (JCMT), we have successfully fabricated 230 GHz finline superconductor-insulator-superconductor (SIS) mixers. These mixers are critical for assessing the potential and prospective for the HARP instrument’s upgrade. Unlike the existing HARP’s mixer, we replace the probe antenna with an end-fire unilateral finline as the waveguide to planar circuit transition. This mixer design is expected to operate from about 160–260 GHz (approximately 47% bandwidth), and the mixer chips’ current-voltage (I-V) curves have been characterized, showing promising results with a quality factor (Rsg/Rn) exceeding 9.3. Evaluation of the double-sideband (DSB) receiver noise temperature (Trx) is currently underway. Once successfully characterised, our immediate aim is to scale the mixer to operate at HARP’s frequency range near 345 GHz to achieve similar broad RF bandwidth performance. Ongoing simulations are currently being conducted for the design of the 345 GHz finline mixer. This work marks a crucial step toward enhancing HARP receiver performance with better sensitivity and wider Intermediate Frequency (IF) bandwidth, enabling higher-frequency observations, and expanding the scientific potential of the JCMT and its collaborative partners

The Convergence Rate on a Quadrature of a Fourier Integral with Symmetrical Jacobi Weight for an Analytical Function

In this paper, through complex analysis, the convergence rate is given on a quadrature of a Fourier integral with symmetrical Jacobi weight. The interpolation nodes of this quadrature formula are expressed by the frequency, and the coefficients can be expressed by the Bessel function. When the frequency is close to 0, the nodes are close to those in the Gauss quadrature. When the frequency tends to infinity, the nodes tend symmetrically to the two ends of the integrand. The higher the frequency is, the higher the accuracy of this quadrature will be. Numerical examples are provided to illustrate the theoretical results