Complement regulatory protein Crry deficiency contributes to the antigen specific recall response in experimental autoimmune myasthenia gravis

Abstract Background Myasthenia gravis (MG) and animal model of experimental autoimmune myasthenia gravis (EAMG) is the most common autoimmune disorder of neuromuscular transmission. The disease is caused by the breakdown of the acetylcholine receptor (AChR) which is largely due to complement activation at the neuromuscular junction (NMJ). Limited knowledge exists to the extent that complement receptor 1-related gene/protein y deficiency (Crry −/−) modulates the adaptive immune response and EAMG outcome. Methods Mouse EAMG was induced by s.c. administrations of purified acetylcholine receptor (AChR) to Crry −/− and age- matched WT (C57BL/6) mice. Disease severity was assessed by clinical score assessment and muscle grip strength measurements. Serum complement activity was determined by hemolytic assay. ELISA was used to detect the level of AChR specific antibodies. Splenic cells were analyzed for T and B cells subsets distribution, release of cytokines and AChR specific recall responses. Deposition of complement components at the NMJ was assessed by immunofluorescence staining. Results In comparison to WT EAMG, Crry −/− EAMG mice showed signs of augmented muscle weakness but differences, except for one time point, were not statistically significant. Serum complement activity was reduced in Crry −/− EAMG mice and no substantial changes in deposition of C3, C3b/iC3b and C5b-9 (MAC) at the NMJ between WT EAMG and Crry −/− EAMG mice were detected. Lack of Crry affected adaptive immune response. Crry −/− EAMG mice showed increases in the number of AChR specific splenic T-cells secreting IFN-γ and IL-4. Production of complement fixing antibodies (IgG2b, IgG2c) was also augmented. More Th1, Th2 and Th17 cytokines were released into the bloodstream of Crry −/− EAMG mice. Conclusions Data suggest that Crry deficiency modulates the adaptive immune response in EAMG, but its effect on disease outcome is limited. This was due to the generally lower serum complement level caused by increased C3 turnover. Modulation of complement activity with soluble or membrane bound regulators of complement activity represents a potentially effective approach to modify autoimmune processes in MG and EAMG.</p

Intersection control with connected and automated vehicles: a review

Purpose: This paper aims to review the studies on intersection control with connected and automated vehicles (CAVs). Design/methodology/approach: The most seminal and recent research in this area is reviewed. This study specifically focuses on two categories: CAV trajectory planning and joint intersection and CAV control. Findings: It is found that there is a lack of widely recognized benchmarks in this area, which hinders the validation and demonstration of new studies. Originality/value: In this review, the authors focus on the methodological approaches taken to empower intersection control with CAVs. The authors hope the present review could shed light on the state-of-the-art methods, research gaps and future research directions

Protective effects of 4, 5-O-dicaffeoylquinic acid against mouse sepsis via down-regulation of TNF-α, IL-6 and IL-8

Purpose: To investigate the protective effects of 4, 5-O-dicaffeoylquinic acid (DCQA) isolated from Xanthium sibiricum Patr. against mouse sepsis caused by cecal ligation/puncture (CLP) in vivo, as well as the molecular mechanisms of action involved.Methods: DCQA (7.5, 15, and 30 mg/kg/day) were administered to the mice with sepsis and the survival rate was obtained. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were examined by enzyme-linked immunosorbent assay (ELISA). Subsequently, the lipopolysaccharide (LPS) neutralizing ability of DCQA (2, 4, and 8 μg/mL) was measured using limulus amebocyte lysate (LAL) test in vitro. Furthermore, the effect of DCQA (10, 20, and 40 μg/mL) on mRNA expression of TNF-α, IL-6, and IL-8 in LPS (100 ng/mL)-treated RAW 264.7 cells was assessed using quantitative real time-polymerase chain reaction (RT-qPCR) assay.Results: DCQA significantly improved the survival rate of mice with sepsis caused by CLP (35, 50, and 65 %, respectively vs. 15 % for control, p &lt; 0.05). LPS levels fell on co-incubation with DCQA in vitro. Moreover, ELISA and RT-qPCR results revealed that DCQA treatment lowered tendency in the mRNA expression of TNF-α, IL-6, and IL-8 (p &lt; 0.01).Conclusion: DCQA exhibits protective effects against sepsis in mice mediated by downregulating TNF-α, IL-6, and IL-8. Further studies, in animals and humans are requied to determine the safety and efficacy of DCQA in both animal and clinical management of sepsis. Keywords: Xanthium sibiricum, 4,5-O-Dicaffeoylquinic acid, Sepsis, Cecal ligation and puncture, Lipopolysaccharide, TNF-α, IL-6, IL-

Effects of Cations and PH on Antimicrobial Activity of Thanatin and s-Thanatin against _Escherichia coli_ ATCC25922 and _B. subtilis_ ATCC 21332

Thanatin and s-thanatin were insect antimicrobial peptides which have shown potent antimicrobial activities on a variety of microbes. In order to investigate the effect of cations and pH on the activity of these peptides against Gram-negative bacteria and Gram-positive bacteria, the antimicrobial activities of both peptides were studied in increasing concentrations of monovalent cations (K^+^ and Na^+^), divalent cations (Ca^2+^ and Mg^2+^) and H^+^. The NCCLS broth microdilution method showed that both peptides were sensitive to the presence of cations. The divalent cations showed more antagonized effect on the activity against Gram-negative bacteria than the monovalent cations, since the two peptides lost the ability to inhibit bacterial growth at a very low concentration. In addition, the activities of both peptides tested were not significantly affected by pH. Comparing to studies of other antibacterial peptide activities, our data support a hypothesis that positive ions affect the sensitivity to cation peptides

2,4-Di-tert-butyl-6-[1-(3,5-di-tert-butyl-2-hydroxy­phen­yl)eth­yl]phenyl 4-methyl­benzene­sulfonate

The title compound, C37H52O4S, was obtained by the reaction of 6,6′-(ethane-1,1-di­yl)bis­(2,4-di-tert-butyl­phenol) and 4-methyl­benzene-1-sulfonyl chloride. The mol­ecular conformation is stabilized by an intra­molecular O—H⋯O hydrogen bond. Two of the tert-butyl groups are disordered over two sets of sites with occupancies 0.530 (15)/0.470 (15) and 0.615 (11)/0.385 (11)

Superconducting Quantum Computing: A Review

Over the last two decades, tremendous advances have been made for constructing large-scale quantum computers. In particular, the quantum processor architecture based on superconducting qubits has become the leading candidate for scalable quantum computing platform, and the milestone of demonstrating quantum supremacy was first achieved using 53 superconducting qubits in 2019. In this work, we provide a brief review on the experimental efforts towards building a large-scale superconducting quantum computer, including qubit design, quantum control, readout techniques, and the implementations of error correction and quantum algorithms. Besides the state of the art, we finally discuss future perspectives, and which we hope will motivate further research.Comment: Updated version, Typos corrected, New references added, New discussions adde

Stability studies of ZnO and AlN thin film acoustic wave devices in acid and alkali harsh environments

Surface acoustic wave (SAW) devices based on piezoelectric thin-films such as ZnO and AlN are widely used in sensing, microfluidics and lab-on-a-chip applications. However, for many of these applications, the SAW devices will inevitably be used in acid or alkali harsh environments, which may cause their early failures. In this work, we investigated the behavior and degradation mechanisms of thin film based SAW devices in acid and alkali harsh environments. Results show that under the acid and alkali attacks, chemical reaction and corrosion of ZnO devices are very fast (usually within 45 s). During the corrosion, the crystalline orientation of the ZnO film is not changed, but its grain defects are significantly increased and the grain sizes are decreased. The velocity of ZnO-based SAW devices is decreased due to the formation of porous structures induced by the chemical reactions. Whereas an AlN thin-film based SAW device does not perform well in acid–alkali conditions, it might be able to maintain a normal performance without obvious degradation for more than ten hours in acid or alkali solutions. This work could provide guidance for the applications of both ZnO or AlN-based SAW devices in acid/alkali harsh environments