12 research outputs found

    Atomic Sn–enabled high-utilization, large-capacity, and long-life Na anode

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    Constructing robust nucleation sites with an ultrafine size in a confined environment is essential toward simultaneously achieving superior utilization, high capacity, and long-term durability in Na metal-based energy storage, yet remains largely unexplored. Here, we report a previously unexplored design of spatially confined atomic Sn in hollow carbon spheres for homogeneous nucleation and dendrite-free growth. The designed architecture maximizes Sn utilization, prevents agglomeration, mitigates volume variation, and allows complete alloying-dealloying with high-affinity Sn as persistent nucleation sites, contrary to conventional spatially exposed large-size ones without dealloying. Thus, conformal deposition is achieved, rendering an exceptional capacity of 16 mAh cm−2 in half-cells and long cycling over 7000 hours in symmetric cells. Moreover, the well-known paradox is surmounted, delivering record-high Na utilization (e.g., 85%) and large capacity (e.g., 8 mAh cm−2) while maintaining extraordinary durability over 5000 hours, representing an important breakthrough for stabilizing Na anode

    Single domain antibody multimers confer protection against rabies infection

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    Post-exposure prophylactic (PEP) neutralizing antibodies against Rabies are the most effective way to prevent infection-related fatality. The outer envelope glycoprotein of the Rabies virus (RABV) is the most significant surface antigen for generating virus-neutralizing antibodies. The small size and uncompromised functional specificity of single domain antibodies (sdAbs) can be exploited in the fields of experimental therapeutic applications for infectious diseases through formatting flexibilities to increase their avidity towards target antigens. In this study, we used phage display technique to select and identify sdAbs that were specific for the RABV glycoprotein from a naïve llama-derived antibody library. To increase their neutralizing potencies, the sdAbs were fused with a coiled-coil peptide derived from the human cartilage oligomeric matrix protein (COMP48) to form homogenous pentavalent multimers, known as combodies. Compared to monovalent sdAbs, the combodies, namely 26424 and 26434, exhibited high avidity and were able to neutralize 85-fold higher input of RABV (CVS-11 strain) pseudotypes in vitro, as a result of multimerization, while retaining their specificities for target antigen. 26424 and 26434 were capable of neutralizing CVS-11 pseudotypes in vitro by 90–95% as compared to human rabies immunoglobulin (HRIG), currently used for PEP in Rabies. The multimeric sdAbs were also demonstrated to be partially protective for mice that were infected with lethal doses of rabies virus in vivo. The results demonstrate that the combodies could be valuable tools in understanding viral mechanisms, diagnosis and possible anti-viral candidate for RABV infection

    Activating a Semiconductor-Liquid Junction via Laser-Derived Dual Interfacial Layers for Boosted Photoelectrochemical Water Splitting

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    The semiconductor liquid junction SCLJ , the dominant place in photoelectrochemical PEC catalysis, determines the interfacial activity and stability of photoelectrodes, whcih directly affects the viability of PEC hydrogen generation. Though efforts dedicated in past decades, a challenge remains regarding creating a synchronously active and stable SCLJ, owing to the technical hurdles of simultaneously overlaying the two advantages. The present work demonstrates that creating an SCLJ with a unique configuration of the dual interfacial layers can yield BiVO4 photoanodes with synchronously boosted photoelectrochemical activity and operational stability, with values located at the top in the records of such photoelectrodes. The bespoke dual interfacial layers, accessed via grafting laser generated carbon dots with phenolic hydroxyl groups LGCDs PHGs , are experimentally verified effective, not only in generating the uniform layer of LGCDs with covalent anchoring for inhibited photocorrosion, but also in activating, respectively, the charge separation and transfer in each layer for boosted charge carrier kinetics, resulting in FeNiOOH LGCDs PHGs MBVO photoanodes with a dual configuration with the photocurrent density of 6.08 mA cm amp; 8722;2 1.23 VRHE, and operational stability up to 120 h 1.23 VRHE. Further work exploring LGCDs PHGs from catecholic molecules warrants the proposed strategy as being a universal alternative for addressing the interfacial charge carrier kinetics and operational stability of semiconductor photoelectrode

    Percentage neutralization of 26424, 26434 and BR 2.3.

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    <p>Neutralization potencies have been calculated in percentage with reference to the decrease in RLUs of the antibody-treated samples as compared to negative control containing CVS-11 pseudotypes alone. Percentage neutralization of samples treated with 26424 and 26434 has been calculated against 6×10<sup>5</sup> RLUs input of CVS-11 pseudotypes (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071383#pone-0071383-g005" target="_blank">Figure 5A</a>), while that for BR 2.3 (control sdAb in monomer format) was calculated against 7×10<sup>3</sup> RLUs of pseudovirus input (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071383#pone-0071383-g005" target="_blank">Figure 5B</a>). HRIG was used as the positive control at similar concentrations of the test samples in all <i>in vitro</i> neutralization assays.</p

    Characterization of sdAb monomer and combodies.

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    <p>(A). Primary structure of monomer and combodies of the sdAbs used in our study are shown. (B) Size-exclusion chromatography of BR 2.3, 26424 and 26434. The size of the monomeric and multimeric sdAbs was analyzed through Sephadex 200 chromatography and the elution positions have been depicted. (C) The size of BR 2.3, 26424 and 26434 has been further confirmed through SDS-PAGE. BR 2.3 elutes as a 14 kDa monomer in both reducing (+DTT) and non-reducing (-DTT) conditions. Combodies 26424 and 26434 elutes as 25 kDa protein in reducing conditions and appears to be more than 130 kDa in non-reducing SDS-PAGE, suggesting pentamerization of the coiled-coil peptide. (D) The monomeric and pentameric sdAbs were further analyzed in Western blot. The purified proteins were run in a 12% SDS-PAGE in both reducing and non-reducing conditions. The antibodies were detected using Mouse anti-<i>myc</i> IgG and HRP-labeled goat anti-mouse IgG followed by chemiluminiscence detection. The figure depicts Western blot for 26434 and BR 2.3.</p

    Schematic illustration of the isolation of sdAbs from naïve llama library through phage display.

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    <p>Whole RABV (inactivated) was used as antigen to screen the phages during bio-panning. Positive control (PC) and negative control (NC) were included in each plate during phage ELISA. The strongest positive clones were selected for subsequent cloning and expression as monomer and multimer (combody) in E.<i>coli</i>.</p

    Neighbor-Joining phylogenetic analysis of the sdAb gene sequences isolated through phage display from naïve llama library.

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    <p>35 strong positive clones (from a total of 1000 clones) were screened for amino acid homology in the complementary determining regions (CDRs) of the sdAb gene. Out of them, 16 sequences could be efficiently cloned and expressed in E.coli expression system. The shaded clones depict the sdAb genes investigated in our study. Combodies, 26424 and 26434, were derived from BR0042 and BR0043 respectively; whereas the monomer, BR 2.3, was derived from BR0002. The tree topology with bootstrap values for 100 replicates is constructed using CLC Sequence Viewer 6.</p

    <i>In vitro</i> neutralization of CVS-11 pseudotypes by 26424, 26434 and BR 2.3.

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    <p>(A) BHK-21 cells were seeded into 96-well plate at 5×10<sup>3</sup> cells per well along with pseudotypes (CVS-11 pseudo) with an input of 6×10<sup>5</sup> RLUs. Wells treated with 26434 and 26424 as well as HRIG (positive control) showed inhibition of infection through decrease in RLUs, indicative of virus neutralization. The neutralization efficiencies with serial dilutions of 26424, 26434 and HRIG are depicted with reference to RLUs. (B) Neutralization assay of BR 2.3, a control sdAb in the monomer format isolated from the same naïve llama library. Lower titer of CVS-11 pseudotypes (7×10<sup>3</sup> RLUs) was used to infect BHK-21 cells. Based on the ability to inhibit luciferase expression of the transduced cells, combodies 26424 and 26434 were able to neutralize 85-fold increased input of CVS-11 pseudotypes as compared to the monovalent BR 2.3. The relative neutralizing ability of 26424, 26434, and BR 2.3 were compared with similar concentrations of HRIG, currently used for post exposure prophylaxis (PEP) in rabies infection. All assays were carried out in triplicates and the graphs represent the average value. Standard deviations (± SD) are indicated by bars.</p

    <i>In vivo</i> lethal challenge of rabies infection.

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    <p>(A) Kaplan–Meier survival curve for mice in post exposure prophylaxis with the sdAb pentamer constructs. Mice were challenged with 2500 LD<sub>50</sub> CVS-24 strain of RABV mixed with 26424 (1.6 IU ml<sup>−1</sup>) and 26434 (0.2 IU ml<sup>−1</sup>) individually on Day 0. Negative control groups received PBS along with vaccine (CVS+Vac) or without vaccine (CVS) whereas positive control received 15.4 IU ml<sup>−1</sup> equine rabies immunoglobulin (ERIG). Vaccination was done on day 0, 3, and 7 in all groups including negative and positive control. Animals were monitored daily for viability and weight change for a total of 28 days. Kaplan–Meier curves are shown by plotting percent survival against days (0 to 28). (B) Percentage death rate of each group after 28 days of observation. Mantel-Cox statistical analysis has been performed for all the groups. 26424 showed statistical significance in survival rate, compared to 26434 (* 0.01</p
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