Demographic variables of the study group.

<p>Demographic variables of the study group.</p

Relationship between cortisol metrics and the negative affect symptom clusters.

<p>S1 = cortisol level before the cognitive tasks; S2 = cortisol level during the cognitive tasks; Mean = mean value of the three cortisol samples.</p><p>Relationship between cortisol metrics and the negative affect symptom clusters.</p

Scatter plot of correlation between negative affect symptom and (a) the log-transformed first cortisol sample (LogS1); (b) the second cortisol sample (LogS2); and (c) the mean cortisol sample during the cognitive tasks.

<p>Scatter plot of correlation between negative affect symptom and (a) the log-transformed first cortisol sample (LogS1); (b) the second cortisol sample (LogS2); and (c) the mean cortisol sample during the cognitive tasks.</p

Cortisol levels at three time points (S1/S2/S3) during the cognitive tasks (nmol/L).

<p>S1 = cortisol level before the cognitive tasks; S2 = cortisol level during the cognitive tasks; S3 = cortisol level after the cognitive tasks; Mean = mean value of the three cortisol samples; AUC_g = area under the curve with reference to the ground; SD = standard deviation.</p><p>Cortisol levels at three time points (S1/S2/S3) during the cognitive tasks (nmol/L).</p

Descriptive statistics of PCL-5 and symptom clusters, CESD, and trauma exposure scores.

<p>PCL-5 = PTSD Checklist for DSM-5; IN = intrusion; AV = avoidance; NA = negative affect; AN = anhedonia; DA = dysphoric arousal; AA = anxious arousal; SD = standard deviation; CESD = Center for Epidemiological Studies Depression Scale; TE = trauma exposure.</p><p>Descriptive statistics of PCL-5 and symptom clusters, CESD, and trauma exposure scores.</p

<i>N</i>′-Nitro-2-hydrocarbylidenehydrazinecarboximidamides: Design, Synthesis, Crystal Structure, Insecticidal Activity, and Structure–Activity Relationships

A novel series of acyclic imine-substituted nitenpyram analogues were designed and synthesized from nitroaminoguanidine, and their structures were confirmed using X-ray diffraction crystallography. Preliminary bioassays showed that the target molecules exhibited good activities against aphids in laboratory (<i>Myzus persicae</i> Sulzer) and field trials (<i>M. persicae</i> Sulzer and <i>Brevicoryne brassicae</i> Linnaeus). Comparative molecular field analysis and comparative molecular similarity indices analysis were employed to develop a three-dimensional quantitative structure–activity relationship model that describes the insecticidal activity of 21 neonicotinoid derivatives. Simple synthesis, low cost, and good insecticidal activity have made this series of compounds become very promising candidates for future commercial pesticides

<i>N</i>′-Nitro-2-hydrocarbylidenehydrazinecarboximidamides: Design, Synthesis, Crystal Structure, Insecticidal Activity, and Structure–Activity Relationships

A novel series of acyclic imine-substituted nitenpyram analogues were designed and synthesized from nitroaminoguanidine, and their structures were confirmed using X-ray diffraction crystallography. Preliminary bioassays showed that the target molecules exhibited good activities against aphids in laboratory (<i>Myzus persicae</i> Sulzer) and field trials (<i>M. persicae</i> Sulzer and <i>Brevicoryne brassicae</i> Linnaeus). Comparative molecular field analysis and comparative molecular similarity indices analysis were employed to develop a three-dimensional quantitative structure–activity relationship model that describes the insecticidal activity of 21 neonicotinoid derivatives. Simple synthesis, low cost, and good insecticidal activity have made this series of compounds become very promising candidates for future commercial pesticides

Discovery of Rhodanine Inhibitors Targeting <i>Of</i> ChtI Based on the π‑Stacking Effect and Aqueous Solubility

The application of some reported inhibitors against the chitinolytic enzyme Of ChtI was limited due to their unsatisfactory insecticidal activities. Hence, we first performed a synergetic design strategy combining the π-stacking effect with aqueous solubility to find novel rhodanine analogues with inhibitory activities against Of ChtI. Novel rhodanine compounds IAa–f and IBa–f have weak aqueous solubility, but they (IAd: Ki = 4.0 μM; IBd: Ki = 2.2 μM) showed better inhibitory activities against Of ChtI and comparable insecticidal efficiency toward Ostrinia furnacalis compared to the high aqueous solubility compounds IIAa–f and IIBa–f (IIAd: Ki = 21.6 μM; IIBd: Ki = 14.3 μM) without a large conjugate plane. Further optimized compounds IIIAa–j with a conjugate plane as well as a higher aqueous solubility exhibited similar good inhibitory activities against Of ChtI (IIIAe: Ki = 2.4 μM) and better insecticidal potency (IIIAe: mortality rate of 63.33%) compared to compounds IAa–f and IBa–f, respectively. Molecular docking studies indicated that the conjugate planarity with the π-stacking effect for rhodanine analogues is responsible for their enzyme inhibitory activity against Of ChtI. This study provides a new strategy for designing insect chitinolytic enzyme inhibitors as insect growth regulators for pest control

Soluble MOG35-55/I-A^b Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells

<div><p>The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosuppression can be induced by using MHC-peptide complexes as specific TCR ligand(s) that interact with autoreactive T cells in the absence of co-stimulation. In this study, a soluble divalent MOG35-55/I-A^b fusion protein (MOG35-55/I-A^b dimer) was constructed to specifically target the autoreactive CD4⁺ T cells in the EAE mouse. Intraperitoneal administration of the MOG35-55/I-A^b dimer significantly delayed and ameliorated EAE symptoms by reducing EAE-related inflammation in the mouse CNS and reducing encephalitogenic Th1 and Th17 cells in the peripheral lymphoid organs. We observed that dimer intervention at a concentration of 1.2 nM suppressed MOG35-55 peptide-specific 2D2 transgenic T cells (2D2 T cells) proliferation by over 90% after <em>in vitro</em> activation with MOG35-55 peptide. The mechanisms involved in this antigen-specific dimer-mediated suppression were found to be downregulated TCR-CD3 expression as well as upregulated expression of membrane-bound TGF-β (mTGF-β) and IL-10 suppressive cytokines by the autoreactive CD4⁺ T cells. Collectively, our data demonstrates that soluble divalent MHC class II molecules can abrogate pathogenic T cells in EAE. Furthermore, our data suggests that this strategy may provide an efficient and clinically useful option to treat autoimmune diseases.</p> </div

MOG35-55/I-A^b dimer delays onset and reduces severity of EAE <i>in vivo</i>.

<p>Female C57BL/6 wild-type mice were immunized with MOG35-55 to induce paralyzed EAE. PBS, excess MOG35-55 peptide, Mulv env145-158/I-A^b dimer (1 µg per mouse) or MOG35-55/I-A^b dimer (1 µg per mouse) was administered i.p. starting at day 9 post-immunization. Treatments lasted 4 days. (A) Data are expressed as mean clinical scores ± SD (n = 10 for PBS and MOG35-55/I-A^b dimer-treated groups, n = 8 for excess MOG35-55 and Mulv env145-158/I-A^b dimer-treated groups). Black arrows indicate i.p. injection. The mean clinical score in MOG35-55/I-A^b dimer-treated group is lowest (<i>P<</i>0.05), whereas there is no difference among PBS, excess MOG35-55 and Mulv env145-158/I-A^b dimer-treated groups. (B–C) Spinal cord sections obtained from the above four groups at day 25 post-immunization were analyzed for degree of inflammation by H&E and for demyelination by LFB (original magnification 200×). (B) The MOG35-55/I-A^b dimer-treated group showed minimal inflammatory cell infiltration and demyelination. One representative sample from each group is depicted. (C) Semi-quantitative analyses of inflammation and demyelination in spinal cords from four groups were conducted. Histopathological scores were determined as described in <i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047435#s4" target="_blank">Materials and Methods</a></i> and are presented as mean ± SD from 4 mice. Data presented are representative of two independent experiments. Differences between groups were assessed by Mann-Whitney U test. *, <i>P<</i>0.05; **, <i>P<</i>0.01 and n.s., nonsignificant.</p