Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques.

Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.

Review of the Effects and Mechanism of Curcumin in the Treatment of Inflammatory Bowel Disease.

Curcumin is extracted from the rhizomes of Curcuma longa L. It is now widely used in food processing, cosmetics, dyes, etc. Current researching indicates that curcumin has high medical value, including anti-inflammatory, antioxidant, anti-tumor, anti-apoptotic, anti-fibrosis, immune regulation and other effects, and can be used to treat a variety of diseases. Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine including Crohn's disease (CD) and ulcerative colitis (UC). The drug treatment effect is often limited and accompanied by side effects. A large number of basic and clinical studies have shown that curcumin has the effect of treating IBD and also can maintain the remission of IBD. In this review, the research of curcumin on IBD in recent years is summarized in order to provide reference for further research and application of curcumin.

Learning and memory impairment induced by 1,4-butanediol is regulated by ERK1/2-CREB-BDNF signaling pathways in PC12 cells.

1,4-butanediol (1,4-BD) is a known γ-hydroxybutyric acid (GHB) precursor which affects the nervous system after ingestion, leading to uncontrolled behavioral consequences. In the present study, we investigated whether 1,4-BD induces oxidative stress and inflammation in PC12 cells and evaluated the toxic effects of 1,4-BD associates with learning and memory. CCK-8 results revealed a dose-effect relationship between the cell viability of PC12 cells and 1,4-BD when the duration of action was 2 h or 4 h. Assay kits results showed that 1,4-BD decreased the levels of Glutathione (GSH), Glutathione peroxidase (GSH-px), Superoxide dismutase (SOD), Acetylcholine (Ach) and increased the levels of Malondialdehyde (MDA), Nitric oxide (NO) and Acetylcholinesterase (AchE). Elisa kits results indicated that 1,4-BD decreased the levels of synaptophysin I (SYN-1), Postsynaptic density protein-95 (PSD-95), Growth associated protein-43 (GAP-43) and increased the levels of Tumor necrosis factor alpha (TNF-α) and Interleukin- 6 (IL-6). RT-PCR results showed that the mRNA levels of PSD-95, SYN-1 and GAP-43 were significantly decreased. The expression of phosphorylation extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phosphorylation cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) proteins were significantly decreased in PC12 cells by protein blotting. Overall, these results suggest that 1,4-BD may affect synaptic plasticity via the ERK1/2-CREB-BDNF pathway, leading to Ach release reduction and ultimately to learning and memory impairment. Furthermore, oxidative stress and inflammation induced by 1,4-BD may also result in learning and memory deficits. These findings will enrich the toxicity data of 1.4-BD associated with learning and memory impairment.

Dose- and time-effects responses of Nonylphenol on oxidative stress in rat through the Keap1-Nrf2 signaling pathway.

Nonylphenol (NP) is a representative environmental endocrine-disrupting compound that can induce oxidative stress in organisms. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway acts an important role in preventing oxidative stress. The aim of this study was to investigate the influence of oxidative stress caused by NP on Keap1-Nrf2 pathway in rats. Rats were treated with NP (30, 90, 270 mg/kg) for different exposure time (7, 14 and 28 days). The levels of reactive oxygen species (ROS) in serum and glutathione S-transferase (GST), UDP-Glucuronosyl Transferase (UGT) in liver were detected by ELISA kits. Western blot was used to detect Keap1, Nrf2 protein expression in liver and cerebral cortex. The results showed that 28 days of NP exposure significantly increased ROS levels in NPH group. And 14 days exposure to NP significantly enhanced the levels of GST and UGT, while 28 days of exposure showed a suppressive effect. In liver, Keap1 levels was upregulated at 7, 14 and 28 days of NP exposure, while nuclear Nrf2 levels decreased at 7 and 28 days but increased at 14 days. In cerebral cortex, Keap1 and Nrf2 expression increased at 14 days but decreased at 28 days. Besides, with the prolongation of NP exposure time, the GST and UGT levels in NPM and NPH groups were increased firstly and then decreased, while Keap1 and Nrf2 protein levels were constantly decreased in liver and cerebral cortex. In conclusion, the lower dose and shorter exposure time of NP activated the Keap1-Nrf2 pathway that may reduce the damage of oxidative stress, but when further exposed to NP at higher dose and time, the pathway could be inhibited.

Comparative Analysis of Whey Proteins in Human Milk Using a Data-Independent Acquisition Proteomics Approach during the Lactation Period.

Human milk (HM) is the primary source of nutrients and bioactive components that supports the growth and development of infants. However, the proteins present in human milk may change depending on the period of lactation. In this light, the objective of the present study was to evaluate the effect of lactation period on HM utilizing a data-independent acquisition (DIA) approach to identify the differences in HM whey protein proteomes. As part of the study, whey proteins of January, February, and June in human milk were studied. The results identified a total of 1563 proteins in HM whey proteins of which 114 groups were subunits of differentially expressed proteins as revealed by cluster analysis. Protein expression was observed to be affected by the period of lactation with expression levels of plasminogen, thrombospondin-1, and tenascin higher during January, keratin, type I cytoskeletal 9 highest in February, and transcobalamin-1 highest in June. The results of this study contribute to expand our understanding of the human whey proteome but also provide strong evidence for the nutritional difference of HM during different lactation periods.

Effects of nonylphenol administration on serum, liver and testis estrogen metabolism.

PURPOSE: Nonylphenol (NP) is one widely distributed representative of environmental estrogens that disturb reproductive activities, bone metabolism and brain function through interfering diverse signal pathways leading to hormone metabolic dysfunctions, immunologic derangement, and tumorigenesis. Few of previous studies have observed the subacute toxicity on rodents, and little has been focused on the mechanism underneath the toxicities observed. METHODS: The 32 male Sprague-Dawley (SD) rats were randomly divided into four groups, the negative control group (corn oil) NP low, medium and high dose groups [30, 90, 270 mg/(kg·d)]. SD rats administrated with different dosage of NP every other day for 28d. Elisa and RT-PCR was employed to observe estrogen metabolism markers or mRNA expressions. RESULTS: In serum, NP exposure caused testosterone (T) (p < 0.001), progesterone (PROG) (p < 0.05) and estrone (E1) (p < 0.05) increased. In testicle, NP exposure caused T (p < 0.001), PROG (p < 0.05), E1 (p < 0.05), 17ß-estradiol (E2) (p < 0.05) and ERα mRNA (p < 0.01) increased, while P450 aromatizing enzyme (p < 0.001) decreased in NPL and ERß mRNA (p < 0.001) decreased in NPM and NPH. In liver, NP exposure caused 17ß-HSD2 mRNA (p < 0.01) increased, while P450 aromatizing enzyme decreased (p < 0.05). CONCLUSION: NP exposure exhibited general and estrogenic toxicity in rats through disturbing estrogen secretion network and estrogen receptor expression network, inducing abnormal metabolism of estrogen, whether in serum, liver and testicle.

Negative Mood Is Associated with Diet and Dietary Antioxidants in University Students During the Menstrual Cycle: A Cross-Sectional Study from Guangzhou, China.

Postpubescent females may have negative mood or premenstrual syndrome during the menstrual cycle; with the emotional and physical symptoms interfering with their quality of life. Little is known about the relationship of dietary behaviors and dietary antioxidant intake with negative mood or premenstrual syndrome in university students in China; so we explored the relationship between negative mood and dietary behavior in female university students during the three menstrual cycle phases. Random sampling was used to enroll 88 individuals from a university in Guangzhou; China in the study. Data were collected using self-administered questionnaires. Descriptive statistics and multiple logistic regression analyses were performed. During the menstrual phase, tea, black coffee and carbonated beverage intake was higher in the group with a high negative affect scale score than in the low score group (p < 0.05). Likewise; during the premenstrual phase, fresh fruit (banana and red Chinese dates) intake was higher in the group with a high negative affect scale score than in the low-score group (p < 0.05). The logistic regression analysis results showed that negative mood was positively associated with tea, coffee, and carbonated beverage intake during the menstrual phase (ß = 0.21, p = 0.0453, odds ratio = 1.23), and negative mood was positively associated with banana and red Chinese dates intake during the premenstrual phase (ß = 0.59, p = 0.0172, odds ratio = 1.81). Our results suggest that negative mood may be associated with diet and specific food in university postpubescent females.

Semitransparent Fully Air Processed Perovskite Solar Cells.

Semitransparent solar cells are highly attractive for application as power-generating windows. In this work, we present semitransparent perovskite solar cells that employ conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) film as the transparent counter electrode. The PEDOT: PSS electrode is prepared by transfer lamination technique using plastic wrap as the transfer medium. The use of the transfer lamination technique avoids the damage of the CH3NH3PbI3 perovskite film by direct contact of PEDOT: PSS aqueous solution. The semitransparent perovskite solar cells yield a power conversion efficiency of 10.1% at an area of about 0.06 cm(2) and 2.9% at an area of 1 cm(2). The device structure and the fabrication technique provide a facile way to produce semitransparent perovskite solar cells.

Growth, patterning and alignment of organolead iodide perovskite nanowires for optoelectronic devices.

Organolead halide perovskites are becoming intriguing materials applied in optoelectronics. In the present work, organolead iodide perovskite (OIP) nanowires (NWs) have been fabricated by a one step self-assembly method. The controllable NW distributions were implemented by a series of facile techniques: monolayer and small diameter NWs were prepared by precursor concentration tuning; NW patterning was achieved via selected area treatment assisted by a mask; NW alignment was implemented by modified evaporation-induced self-assembly (EISA). The synthesized multifunctional NWs were further applied in photodetectors (PDs) and solar cells as application demos. The PD performances have reached 1.32 AW(-1) for responsivity, 2.5 × 10(12) Jones for detectivity and 0.3 ms for response speed, superior to OIP films and other typical inorganic NW based PD performances. An energy conversion efficiency of ∼2.5% has been obtained for NW film based solar cells. The facile fabrication process, controllable distribution and optoelectronic applications make the OIP NWs promising building blocks for future optoelectronics, especially for low dimensional devices.

p-Type mesoscopic NiO as an active interfacial layer for carbon counter electrode based perovskite solar cells.

Replacement of the ZrO2 insulator layer in the state-of-the-art TiO2/ZrO2/carbon structure by mesoscopic p-type NiO particles led to 39% increase of energy conversion efficiency of hole-conductor-free organometallic perovskite heterojunction solar cells with carbon counter electrodes. In these cells, the light absorber, CH3NH3PbI3, formed instantly inside the pores of the entire TiO2/NiO/carbon layer upon sequential deposition of PbI2 and CH3NH3I. Photoluminescence, impedance spectroscopy and transient photovoltage decay measurements have revealed that introduction of NiO extended the electron lifetime and augmented the hole extraction of the counter electrode. As a result, the photocurrent and open-circuit voltage both increased, resulting in a cell with impressive energy conversion efficiency of 11.4% under AM1.5G conditions.