Potent Neutralization of Influenza A Virus by a Single-Domain Antibody Blocking M2 Ion Channel Protein

Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH) libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses

Elasto-Plastic Behaviour of Transversely Isotropic Cellular Materials with Inner Gas Pressure

The fabrication process of cellular materials, such as foaming, usually leads to cells elongated in one direction, but equiaxed in a plane normal to that direction. This study is aimed at understanding the elasto-plastic behaviour of transversely isotropic cellular materials with inner gas pressure. An idealised ellipsoidal-cell face-centred-cubic foam that is filled with gas was generated and modelled to obtain the uniaxial stress–strain relationship, Poisson’s ratio and multiaxial yield surface. The effects of the elongation ratio and gas pressure on the elasto-plastic properties for a relative density of 0.5 were investigated. It was found that an increase in the elongation ratio caused increases in both the elastic modulus and yield stress for uniaxial loading along the cell elongation direction, and led to a tilted multiaxial yield surface in the mean stress and Mises equivalent stress plane. Compared to isotropic spheroidal-cell foams, the size of the yield surface of the ellipsoidal-cell foam is smaller for high-stress triaxiality, but larger for low-stress triaxiality, and the yield surface rotates counter-clockwise with the Lode angle increasing. The gas pressure caused asymmetry of the uniaxial stress–strain curve (e.g., reduced tensile yield stress), and it increased the nominal plastic Poisson’s ratio for compression, but had the opposite effect for tension. Furthermore, the gas pressure shifted the yield surface towards the negative mean stress axis with a distance equal to the gas pressure. The combined effects of the elongation ratio and gas pressure are complicated, particularly for the elasto-plastic properties in the plane in which the cells are equiaxed

Advances and challenges in 2D MXenes: from structures to energy storage and conversions

Since the discovery of Ti3C2 in 2011, a class of 2D transition metal carbides and nitrides, called MXene, has received increasing attention. So far, about 30 different kinds of MXenes with clear structure and properties exist and more MXenes are theoretically predicted. As a consequence of their excellent metal conductivity, unique in-plane anisotropy, attractive optical, mechanical, and thermal properties, MXenes show great potential for many applications. This review highlights the fundamentals, synthesis, and properties of MXenes, and focuses on applications of MXenes in supercapacitors, batteries, sensors, electromagnetic shielding/absorption and catalysis. Finally, we point out the controversies, challenges, and future opportunities in MXenes

Xiaoyao Kangai Jieyu Fang, a Chinese Herbal Formulation, Ameliorates Cancer-Related Depression Concurrent with Breast Cancer in Mice via Promoting Hippocampal Synaptic Plasticity

Diagnosis with breast cancer is a major life event that elicits increases in depressive symptoms for up to 50% of women. Xiaoyao Kangai Jieyu Fang (XYKAJY) is derived from a canonical TCM formula, Xiaoyao San (XYS), which has a history of nearly 1000 years for treating depression. The aim of this study was to investigate whether XYKAJY alleviates depression-like behavior and breast tumor proliferation in breast cancer mice then explore the mechanisms underlying its action on HPA axis and hippocampal plasticity further. XYKAJY was treated at the high dose of 1.95 g/mL and 0.488 g/mL, after 21 days of administration. Different behaviors, monoamine neurotransmitters, tumor markers, and the index of HPA axis were detected to evaluate depressive-like symptoms of breast cancer mice. Also, the pathological changes of the tumor, hippocampus, and the expressions of GR, NR2A, NR2B, CAMKII, CREB, and BDNF were detected. In this study, XYKAJY formulation significantly improved the autonomic behavior, reduced the incubation period of feeding, and reversed the typical depressive-like symptoms in breast cancer mice. Also, it reduced the content of CORT, ACTH, CRH, and CA125, CA153, CEA in the blood, protected the pathological changes of the hippocampus and tumor, upregulated the expression of GR, CREB, and BDNF in the hippocampus, and significantly decreased the expression of NR2A, NR2B, and CaMKII. These results provide direct evidence that XYKAJY effectively alleviates depression-like behaviors and tumor proliferation in vehicle mice with ameliorates hippocampus synaptic plasticity dysfunctions

M2-7A protects M2-expressing cells from pH-induced cell mortality.

<p>M2wt-T-REx-293 cells (A) and M2mu-T-REx-293 cells (B) were induced by tetracycline for 24 h, incubated with M2-7A, amantadine, or control VHH 6D (in PBS, pH 7.4) for 30 min at 37°C, and then treated with pH 5.8 PBS containing antibodies or amantadine for 3 h. Cells were maintained in complete medium for another 24 h and then assayed using Cell Counting Kit-8 according to the provider's instruction.</p

Kinetic rate and dissociation constants of M2-7A and 14C2 to the full length M2 protein.

<p>Kinetic rate and dissociation constants of M2-7A and 14C2 to the full length M2 protein.</p

Immunofluorescent staining of influenza infected cells.

<p>MDCK cells were infected with A/Puerto Rico/8/34 at an MOI of 1 for 2 h, cultured for 24 h, and fixed with 10% paraformaldehyde. The infected cells were then incubated with control VHH 6D, M2-7A, and 14C2 antibodies then stained with either FITC-rabbit-anti-His IgG (6D and M2-7A) or FITC-goat-anti-mouse IgG (14C2).</p

Schematic flow chart for the assembly of the synthetic oligonucleotides.

<p>Synthetic VHH genes were generated by PCR extension of oligonucleotides represented by oligo1-5 (FR1, CDR1-FR2, CDR2-FR3, FR3, CDR3-FR4), forward and reverse primers. The final PCR products were purified from agarose gels, digested sequentially with <i>Sfi</i>I and <i>Not</i>I, and cloned into the pCANTAB 5 E phagmid vector.</p

Binding properties of M2-7A.

<p>(A) Purified influenza virus (A/Puerto Rico/8/34), 10 µg/ml, (B) Recombinant full length M2 protein, 1 µg/ml, (C) 23-mer synthetic peptide of M2e conjugated to KLH, 1 µg/ml, were coated on ELISA wells and incubated with M2-7A ,14C2 (murine anti-M2 antibody), or 6D (control VHH). The assay was done as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028309#s2" target="_blank">Methods</a>. Secondary antibodies used: HRP-labeled goat anti-his for M2-7A and 6D; HRP-labeled goat anti-mouse for 14C2.</p