A Herpes Simplex Virus 2 (HSV-2) Glycoprotein D-expressing Nonreplicating Dominant-Negative HSV-2 Virus Vaccine Is Superior to a gD2 Subunit Vaccine against HSV-2 Genital Infection in Guinea Pigs

We recently constructed a novel non-replicating dominant-negative HSV-2 recombinant viral vaccine (CJ2-gD2) capable of expressing various HSV-2 antigens that are dominant targets of HSV-2-specific CD8 T-cell response. Importantly, CJ2-gD2 expresses gD2, the HSV-2 major antigen glycoprotein D, as efficiently as wild-type HSV-2 infection and can lead to a nearly 500-fold reduction in wild-type HSV-2 viral replication in cells co-infected with CJ2-gD2 and wild-type HSV-2. In this report, we show that CJ2-gD2 elicits a strong antibody response to various HSV-2 antigens and is highly effective in the prevention of primary and recurrent HSV-2 genital infection and disease in the immunized guinea pigs. The direct comparison study between CJ2-gD2 and a gD2 subunit vaccine (gD2-alum/MPL) with a formulation akin to a vaccine tested in phase III clinical trials shows that CJ2-gD2 is 8 times more effective than the gD2-alum/MPL subunit vaccine in eliciting an anti-HSV-2 specific neutralizing antibody response and offers significantly superior protection against primary and recurrent HSV-2 genital infections. Importantly, no challenge wild-type HSV-2 viral DNA was detectable in dorsal root ganglia DNA isolated from CJ2-gD2-immunized guinea pigs on day 60 post-challenge. CJ2-gD2 should be an excellent HSV-2 vaccine candidate for protection against HSV-2 genital infection and disease in humans

1-Deoxynojirimycin from Bacillus subtilis improves antioxidant and antibacterial activities of juvenile Yoshitomi tilapia

Background: Juvenile Yoshitomi tilapia is often infected by pathogens and results in low-level survival rate. Bacillus subtilis, as a probiotic, may have beneficial effects on Y. tilapia with compound 1-deoxynojirimycin (DNJ), which has antibacterial activities. The effects of dietary probiotic supplementation on Y. tilapias were evaluated. Results: Juvenile Y. tilapia was fed with B. subtilis for 56 d. Y. tilapia was infected by Aeromonas hydrophila and survival rate was compared. Dietary B. subtilis increased weight gain rate, specific growth, food conversion ratios and food intake rate of Y. tilapia. The diet improved the cumulative survival rate (CSR) of juvenile Y. tilapia when the concentration of B. subtilis was more than 2.05 7 1010 cfu/kg and CSR reached a maximum rate when the concentration of bacillus was 4.23 7 1010 (P < 0.05). Meanwhile, B. subtilis improved total antioxidant capacity (TAC), spleen index, the activities of serum lysozyme, alkaline phosphatase (ALP), superoxide dismutase (SOD) and catalase (CAT) (P b 0.05). In contrast, B. subtilis reduced serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) and C3 complement (P < 0.05). DNJ was isolated from secondary metabolisms and proved to increase the levels of SOD, CAT and reduce the levels of AST, ALT and MDA at cell levels. After A. hydrophila infection, DNJ prevented the reduction in survival rate of Y. tilapia (P < 0.05). Conclusions: 1-Deoxynojirimycin from Bacillus subtilis can be used to improve the growth performance of juvenile Y. tilapia by affecting its antioxidant and antibacterial activities

Comparative efficacy and acceptability of antidepressants, psychological interventions, and their combination for depressive disorder in children and adolescents:protocol for a network meta-analysis

Introduction Depressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents. Methods and analysis We will update the literature search of two previous NMAs for the identification of trials of antidepressant and psychotherapy alone for depressive disorder in children and adolescents. For identification of trials of combination interventions, seven databases (PubMed, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS) will be searched from date of inception. We will also search ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and check relevant reports on the US Food and Drug Administration website for unpublished data. Building on our previous findings in the field, we will include any commonly prescribed oral antidepressants and any manualised or structured psychotherapies, as well as their combinations. Randomised controlled trials assessing any active intervention against active comparator or pill placebo/psychological controls in acute treatment for depressive disorder in children and adolescents will be included. The primary outcomes will be efficacy (mean change in depressive symptoms), and acceptability of treatment (dropout rate due to any cause). The secondary outcomes will be remission rate, tolerability of treatment (dropouts for adverse events), as well as suicide-related outcomes (suicidal behaviour or ideation). We will perform Bayesian NMAs for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. Dissemination This NMA will provide the most up to date and clinically useful information about the comparative efficacy and acceptability of antidepressants, psychological intervention and their combination in the acute treatment of children and adolescents with depressive disorder. This is the newest NMA and therefore these results are very important in terms of evidence-based medicine. The results will be disseminated through peer-reviewed publication. Protocol registration PROSPERO CRD42015020841

Peripheral surgical wounding may induce cognitive impairment through interlukin-6-dependent mechanisms in aged mice

Post-operative cognitive dysfunction (POCD) is associated with morbidity, mortality and increased cost of medical care. However, the neuropathogenesis and targeted interventions of POCD remain largely to be determined. We have found that the peripheral surgical wounding induces an age-dependent Aβ accumulation, neuroinflammation and cognitive impairment in aged mice. Pro-inflammatory cytokine interlukin-6 (IL-6) has been reported to be associated with cognitive impairment in rodents and humans. However, the role of IL-6 in the neuropathogenesis of POCD is unknown. We therefore employed pharmacological (IL-6 antibody) and genetic (knockout of IL-6) approach to investigate whether IL-6 contributed to the peripheral surgical wounding-induced cognitive impairment in aged mice. Abdominal surgery under local anesthesia (peripheral surgical wounding) was established in 18-month-old wild-type and IL-6 knockout mice (n = 6 to 10 in each group). Brain level of IL-6 and cognitive function in the mice were determined by western blot, ELISA at the end of procedure, and Fear Conditioning System at 7 days after the procedure. The peripheral surgical wounding increased the level of IL-6 in the hippocampus of aged wild-type, but not IL-6 knockout mice. IL-6 antibody ameliorated the peripheral surgical wounding-induced cognitive impairment in the aged wild-type mice. Finally, the peripheral surgical wounding did not induce cognitive impairment in the aged IL-6 knockout mice. These data suggested that IL-6 would be a required pro-inflammatory cytokine for the peripheral surgical wounding-induced cognitive impairment. Given this, further studies are warranted to investigate the role of IL-6 in the neuropathogenesis and targeted interventions of POCD

Upconversion Luminescent Humidity Sensors Based on Lanthanide-Doped MOFs

Lanthanide-doped metal-organic frameworks (Y/Yb/Er-MOF) were synthesized by a low-cost solvothermal method. The obtained Y/Yb/Er-MOF shows the cooperative upconversion luminescence of Yb3+ and upconversion luminescence of Er3+ (Yb3+-sensitized) irradiated by a continuous wave 980 nm laser. In order to explore the potential application of Y/Yb/Er-MOF in relative humidity (RH) sensors, the RH responsiveness of Y/Yb/Er-MOF was investigated by measuring the intensity changes of upconversion luminescence. The Y/Yb/Er-MOF possesses two luminescence centers, in which Yb3+ forms emission at 500 nm through the cooperative luminescence effect, and Er3+ achieves 660 nm emission through excited state absorption and successive energy transfer from Yb3+. Hence, the ratio meter luminescence sensor for RH is constructed based on Y/Yb/Er-MOF. The results show that the response of Y/Yb/Er-MOF to RH presents a linear relationship in the range of 11–95%. The cycle stability of Y/Yb/Er-MOF responses to RH was investigated with the intensity changes of upconversion luminescence, and the recovery ratio was more than 93% each time. Therefore, the Y/Yb/Er-MOF is a humidity-sensitive material with great potential for applications such as humidity sensors