Sex bias in experimental immune-mediated, drug-induced liver injury in BALB/c mice: suggested roles for Tregs, estrogen, and IL-6.

Immune-mediated, drug-induced liver injury (DILI) triggered by drug haptens is more prevalent in women than in men. However, mechanisms responsible for this sex bias are not clear. Immune regulation by CD4+CD25+FoxP3+ regulatory T-cells (Tregs) and 17β-estradiol is crucial in the pathogenesis of sex bias in cancer and autoimmunity. Therefore, we investigated their role in a mouse model of immune-mediated DILI.To model DILI, we immunized BALB/c, BALB/cBy, IL-6-deficient, and castrated BALB/c mice with trifluoroacetyl chloride-haptenated liver proteins. We then measured degree of hepatitis, cytokines, antibodies, and Treg and splenocyte function.BALB/c females developed more severe hepatitis (p<0.01) and produced more pro-inflammatory hepatic cytokines and antibodies (p<0.05) than did males. Castrated males developed more severe hepatitis than did intact males (p<0.001) and females (p<0.05). Splenocytes cultured from female mice exhibited fewer Tregs (p<0.01) and higher IL-1β (p<0.01) and IL-6 (p<0.05) than did those from males. However, Treg function did not differ by sex, as evidenced by absence of sex bias in programmed death receptor-1 and responses to IL-6, anti-IL-10, anti-CD3, and anti-CD28. Diminished hepatitis in IL-6-deficient, anti-IL-6 receptor α-treated, ovariectomized, or male mice; undetectable IL-6 levels in splenocyte supernatants from ovariectomized and male mice; elevated splenic IL-6 and serum estrogen levels in castrated male mice, and IL-6 induction by 17β-estradiol in splenocytes from naïve female mice (p<0.05) suggested that 17β-estradiol may enhance sex bias through IL-6 induction, which subsequently discourages Treg survival. Treg transfer from naïve female mice to those with DILI reduced hepatitis severity and hepatic IL-6.17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a therapeutic approach to DILI

Study on Verifying the Effectiveness of Non-face-to-face Youth Volunteering in Improving Self-Esteem Among Children of Deaf Adults (CODAs)

The goal of this study is to evaluate the effectiveness of youth volunteering in increasing the self-esteem of hearing children of deaf adults (CODAs), who commonly start taking care of their parents from a young age. To this end, an experimental study based on the non-equal comparison groups design was applied to a experimental group of 4 participants and a control group of 3 participants, selected based on the recommendation from expert social workers from the M General Social Welfare Center in P City. The volunteer programs, conducted non-face-to-face due to COVID-19, were centered on art activities such as drawing one's own dreams, decorating flowers, and customizing pencil cases. Repeated measures analysis of variance (rANOVA) was conducted to verify the effectiveness of volunteering, and the analysis results are as follows. First, in both the experimental group and the control group, CODAs' self esteem increased after the program was carried out. Second, while the growth effect appeared in both groups, the slope of increase in the self-esteem of the experimental group was significantly higher than that of the control group. Accordingly, the effectiveness of volunteering to improve CODAs' self-esteem was verified. This study suggests academic and practical implications based on these findings

Antimicrobial PEGtides: A Modular Poly(ethylene glycol)-Based Peptidomimetic Approach to Combat Bacteria

Despite their high potency, the widespread implementation of natural antimicrobial peptides is still challenging due to their low scalability and high hemolytic activities. Herein, we address these issues by employing a modular approach to mimic the key amino acid residues present in antimicrobial peptides, such as lysine, leucine, and serine, but on the highly biocompatible poly(ethylene glycol) (PEG) backbone. A series of these PEG-based peptides (PEGtides) were developed using functional epoxide monomers, corresponding to each key amino acid, with several possessing highly potent bactericidal activities and controlled selectivities, with respect to their hemolytic behavior. The critical role of the composition and the structure of the PEGtides in their selectivities was further supported by coarse-grained molecular dynamic simulations. This modular approach is anticipated to provide the design principles necessary for the future development of antimicrobial polymers

N-doped graphene quantum sheets on silicon nanowire photocathodes for hydrogen production

Photoelectrochemical hydrogen production from solar energy has been attractingmuch attention in the field of renewable energy technology. The realization of cost-effective hydrogen production by water splitting requires electrolysis or photoelectrochemical cells decorated with highly efficient co-catalysts. A critical requirement for catalysts in photoelectrochemical cells is not only the ability to boost the kinetics of a chemical reaction but also to exhibit durability against electrochemical and photoinduced degradation. In the race to replace previous noble-metal catalysts, the design of carbon-based catalysts represents an important research direction in the search for non-precious, environmentally benign, and corrosion-resistant catalysts. Herein, we suggest graphene quantum sheets as a catalyst for the solar-driven hydrogen evolution reaction on Si nanowire photocathodes. The optimum nanostructures of the Si photocathodes exhibit an enhanced photocurrent and a lower overpotential compared to those of a planar Si surface. This significant enhancement demonstrates how graphene quantum sheet catalysts can be used to produce Si nanowire photocathodes as hydrogen evolution reaction catalysts with high activity

Increased T and B cells are associated with impaired splenic Treg expansion in female BALB/c mice following TFA-S100 immunizations.

<p>Splenocytes were isolated from female mice 2 weeks after TFA-S100 immunizations, stimulated with CYP2E1 (A) or TFA (B) <i>in vitro</i> (10 µg/mL) and analyzed for Tregs as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061186#pone-0061186-g006" target="_blank">Figure 6</a>. CD3+CD25 T cells and B220+ cells were significantly elevated in the same cultures from females when compared to males. (Experiments run in duplicate, n = 3 mice/group, Mann-Whitney <i>U</i>, * = p<0.05, ** = p<0.01, *** = p<0.001).</p

Experimental anesthetic DILI is associated with higher serum antibodies and proinflammatory cytokines in female BALB/c mice.

<p>(A) TFA IgG, IgG1, and IgG2a and S100 IgG1 and IgG2a antibodies were significantly higher in females than in males (values expressed as OD). (B) IL-2, IL-9, IL-12, and IL-17 (pg/g) were significantly higher in livers from females than in those from males. IL-5, IL-6, and IL-13 (pg/g) were significantly higher in spleens from females, but IL-10 was higher in spleens from males. mean ± SEM. *p<0.05, **p<0.01, ***p<0.001.</p

Female BALB/c mice develop more severe experimental anesthetic DILI than do males.

<p>(A) Female mice (n = 8) had significantly more severe hepatitis 3 weeks after TFA-S100/CFA immunizations than did males (n = 7/group). (B) Representative liver sections from female and male mice (H&E, magnification 64×). (C) Numbers of hepatic CD4+, CD8+, NK+, and NKT+ cells were significantly higher in females than in males. mean ± SEM. *p<0.05, **p<0.01, ***p<0.001.</p

IL-6 supplementation diminishes Tregs in TFA-S100 – immunized male and female splenocyte cultures in vitro.

<p>IL-6 supplementation (25 ng/mL) of <i>in vitro</i> splenocyte cultures from female (A) and male (B) TFA-S100-immunized BALB/c mice diminished Tregs in both groups. (Experiments run in duplicate, n = 3 mice/group, Mann-Whitney <i>U</i>, * = p<0.05, ** = p<0.01, *** = p<0.001).</p

Anti-IL-10 antibody diminishes Tregs in TFA-S100 – immunized male and female splenocyte cultures in vitro.

<p>IL-10 blocking antibody (rat anti-mouse, 10 µg/mL), similarly diminished Tregs in female (A) and male (B) BALB/c mice isolated from TFA-S100- immunized mouse splenocytes challenged with CYP2E1 or the TFA (TFA-OVA) (Mann-Whitney <i>U</i>, *p<0.05, **p<0.01, ***p<0.001, experiments run in duplicate, n = 3 mice/group).</p

An electrochemical approach to graphene oxide coated sulfur for long cycle life

Owing to the possibilities of achieving high theoretical energy density and gravimetric capacity, sulfur has been considered as a promising cathode material for rechargeable lithium batteries. However, sulfur shows rapid capacity fading due to the irreversible loss of soluble polysulfides and the decrease in active sites needed for conducting agents. Furthermore, the low electrical conductivity of sulfur hampers the full utilization of active materials. Here we report that graphene oxide coated sulfur composites (GO-S/CB) exhibit improved electrochemical stability as well as enhanced rate performance, evidenced by various electrochemical analyses. The cyclic voltammetry and the galvanostatic cycling analysis revealed that the GO plays key roles in homogenizing the nanocomposite structures of the electrodes, in improving the electrochemical contact, and in minimizing the loss of soluble polysulfide intermediates. An electrochemical impedance spectroscopy analysis also confirms the enhanced structural stability of the GO-S/CB composites after battery operation. As a result, the GO-S/CB exhibited excellent cycle stability and specific capacity as high as similar to 723.7 mA h g(-1) even after 100 cycles at 0.5 C