Effect of ferrate pre-oxidation on algae-laden water ultrafiltration: Attenuating membrane fouling and decreasing formation potential of disinfection byproducts.

Effect of ferrate [Fe(VI)] pre-oxidation on improving FeCl3/ultrafiltration (UF) of algae-laden source water was investigated. Fe(VI) disrupted algae cells and the in situ formed ferric (hydr)oxides aggregated with cell debris. Particle size and zeta potential of algae increased by 20% and 55% on average, respectively, after treatment with 0.02 mM of Fe(VI). These variations facilitated the formation of algae-ferric floc. Fe(VI) degraded algal extracellular organic matter into lower molecular weight products (fulvic-like and humic-like substances). Membrane flux, reversible membrane resistance (Rr) and irreversible membrane resistance (Rir) were improved by 51%, 61%, and 52% in Fe(VI) (0.02 mM)/FeCl3/UF treatment group compared with FeCl3/UF treatment after three filtration cycles. Fe(VI)/FeCl3/UF removed more than 10% ~ 34% of the dissolved organic compounds (DOC) and 6% ~ 17% of the total nitrogen (TN) compared with FeCl3/UF. Due to the enhanced removal of DOC and TN, formation potential of 12 kinds of carbonaceous-disinfection byproducts (C-DBPs) and 7 kinds of nitrogenous-disinfection byproducts (N-DBPs) decreased by 32.5% and 22.5%, respectively. Fe(VI) pre-oxidant was effective for alleviating membrane fouling and reducing formation potential of DBPs in algal laden water treatment.

MeCP2 in cholinergic interneurons of nucleus accumbens regulates fear learning.

Methyl-CpG-binding protein 2 (MeCP2) encoded by the MECP2 gene is a transcriptional regulator whose mutations cause Rett syndrome (RTT). Mecp2-deficient mice show fear regulation impairment; however, the cellular and molecular mechanisms underlying this abnormal behavior are largely uncharacterized. Here, we showed that Mecp2 gene deficiency in cholinergic interneurons of the nucleus accumbens (NAc) dramatically impaired fear learning. We further found that spontaneous activity of cholinergic interneurons in Mecp2-deficient mice decreased, mediated by enhanced inhibitory transmission via α2-containing GABAA receptors. With MeCP2 restoration, opto- and chemo-genetic activation, and RNA interference in ChAT-expressing interneurons of the NAc, impaired fear retrieval was rescued. Taken together, these results reveal a previously unknown role of MeCP2 in NAc cholinergic interneurons in fear regulation, suggesting that modulation of neurons in the NAc may ameliorate fear-related disorders.

Enhanced Permanganate Oxidation of Sulfamethoxazole and Removal of Dissolved Organics with Biochar: Formation of Highly Oxidative Manganese Intermediate Species and in Situ Activation of Biochar.

Sulfamethoxazole (SMX) is a broad-spectrum antibiotic and was largely used in breeding industry. The reaction rate of SMX with KMnO4 is slow, and the adsorption efficiency of biochar for SMX was inferior (less than 11% in 30 min). By adding biochar powder into SMX solution with the addition of permanganate, the oxidation ratio of SMX surged to 97% in 30 min, and over 58% of the total organic carbon (TOC) was simultaneously removed. KMnO4 interacted with biochar and resulted in the formation of highly oxidative intermediate manganese species, which transformed SMX into hydrolysis products, oxygen-transfer products, and self-coupling products. Brunauer-Emmett-Teller (BET) analysis showed that surface area, total pore volume, and micropore volume of biochar increased by 32.1%, 36.4%, and 80.6%, respectively, after reaction process. This in situ activation of biochar with KMnO4 enhanced its adsorption capacity and led to great improvement of TOC removal. Besides KMnO4 oxidation, biochar also enhanced TOC removal in Mn(III) oxidation (KMnO4+ bisulfite) and ozonization of SMX. Considering that KMnO4 could react with biochar and result in the formation of intermediate manganese species, while biochar can be simultaneously activated and exhibit high capacity for organic adsorption, the combination of biochar with the chemical/advanced oxidation could be a promising process for the removal of environmental pollutants.

Fluorescent Recognition of 4-Amino-2,6-dinitrotoluene by a Cerium-Based Metal-Organic Tetrahedron.

A cerium-based metal-organic tetrahedron has been developed as a highly selective and sensitive fluorescence sensor for the recognition of 4-amino-2,6-dinitrotoluene (4-ADNT). The redox-active tetrahedron could encapsulate 4-ADNT through weak interaction and spatial stereoselectivity, resulting in an enhanced fluorescence. The tetrahedral sensor Ce-ZPS is capable of realizing fluorescent sensing in urine and in cells and thus has the potential to detect 4-ADNT in organisms.

ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines.

Dysfunction of the noradrenergic (NE) neurons is implicated in the pathogenesis of bipolar disorder (BPD). ErbB4 is highly expressed in NE neurons, and its genetic variation has been linked to BPD; however, how ErbB4 regulates NE neuronal function and contributes to BPD pathogenesis is unclear. Here we find that conditional deletion of ErbB4 in locus coeruleus (LC) NE neurons increases neuronal spontaneous firing through NMDA receptor hyperfunction, and elevates catecholamines in the cerebrospinal fluid (CSF). Furthermore, Erbb4-deficient mice present mania-like behaviors, including hyperactivity, reduced anxiety and depression, and increased sucrose preference. These behaviors are completely rescued by the anti-manic drug lithium or antagonists of catecholaminergic receptors. Our study demonstrates the critical role of ErbB4 signaling in regulating LC-NE neuronal function, reinforcing the view that dysfunction of the NE system may contribute to the pathogenesis of mania-associated disorder.

Sodium chloride exacerbates dextran sulfate sodium-induced colitis by tuning proinflammatory and antiinflammatory lamina propria mononuclear cells through p38/MAPK pathway in mice.

AIM: To investigate the influence of high salt on dextran sulfate sodium (DSS)-induced colitis in mice and explore the underlying mechanisms of this effect. METHODS: DSS and NaCl were used to establish the proinflammatory animal model. We evaluated the colitis severity. Flow cytometry was employed for detecting the frequencies of Th1, macrophages and Tregs in spleen, mesenteric lymph node and lamina propria. The important role of macrophages in the promotion of DSS-induced colitis by NaCl was evaluated by depleting macrophages with clodronate liposomes. Activated peritoneal macrophages and lamina propria mononuclear cells (LPMCs) were stimulated with NaCl, and proteins were detected by western blotting. Cytokines and inflammation genes were analyzed by enzyme-linked immunosorbent assay and RT-PCR, respectively. RESULTS: The study findings indicate that NaCl up-regulates the frequencies of CD11b+ macrophages and CD4+IFN-γ+IL-17+ T cells in lamina propria in DSS-treated mice. CD3+CD4+CD25+Foxp3+ T cells, which can secrete high levels of IL-10 and TGF-ß, increase through feedback in NaCl- and DSS-treated mice. Furthermore, clodronate liposomes pretreatment significantly alleviated DSS-induced colitis, indicating that macrophages play a vital role in NaCl proinflammatory activity. NaCl aggravates peritoneal macrophage inflammation by promoting the expressions of interleukin (IL)-1, IL-6 and mouse inducible nitric oxide synthase. Specifically, high NaCl concentrations promote p38 phosphorylation in lipopolysaccharide- and IFN-γ-activated LPMCs mediated by SGK1. CONCLUSION: Proinflammatory macrophages may play an essential role in the onset and development of NaCl-promoted inflammation in DSS-induced colitis. The underlining mechanism involves up-regulation of the p38/MAPK axis.

Development of a human rotavirus induced diarrhea model in Chinese mini-pigs.

AIM: To establish a new animal model for the research of human rotavirus (HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines. METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and Bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PBS (control), respectively, and fecal samples of pigs from 0 to 7 d post infection (DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. The HRV was tested by real-time PCR (RT-PCR). The sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography. RESULTS: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an age-dependent manner and shed HRV antigen of the same inoculum, as demonstrated by RT-PCR. Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal mini-pigs. Guizhou mini-pigs were more sensitive to HRV than Bamma with respect to RV antigen shedding and clinical diarrhea. CONCLUSION: These results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.

Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus.

Mutations in the X-linked MECP2 gene cause Rett syndrome (RTT), an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain (BF) cholinergic neurons rather than in the caudate putamen of conditional knockout (Chat-Mecp2(-/y)) mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2(-/y) mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2(-/y) mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro.

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1ß, TNF-α, and IL-6 in vitro.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795 percent (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Induction of specific immune response and suppression of fertility by B-cell-epitope-based mimovirus vaccine.

SPINLW1 (previously known as eppin (epididymal protease inhibitor)) is a target under intense scrutiny in the study of male contraceptive vaccines. B-cell-dominant epitopes are now recognized as key parts of the induction of humoral immune responses against target antigens. The generation of robust humoral responses in vivo has become a crucial problem in the development of modern vaccines. In this study, we developed a completely novel B-cell-dominant-epitope-based mimovirus vaccine, which is a kind of virus-size particulate antigen delivery system. The mimovirus successfully self-assembled from a cationic peptide containing a cell-penetrating peptide of TAT49-57 and a plasmid DNA encoding both three SPINLW1 (103-115) copies and adjuvant C3d3. The male mice were immunized with the epitope-based mimovirus vaccine, which resulted in a gradual elevation of specific serum IgG antibody levels. These reached a peak at week 4. Mating for the fertility assay showed that the mimovirus vaccine had accomplished a moderate fertility inhibition effect and investigation into the mechanism of action showed that it did so by interfering with the reproductive function of the sperm but that it did not damage the structures of the testes or cause serum testosterone to decline. Our results suggest an ideal protocol for suppressing fertility in mice by an engineered mimovirus vaccine.

Immunogenicity of a plant-derived edible rotavirus subunit vaccine transformed over fifty generations.

Major efforts have been put forth for the development of effective rotavirus vaccines including transgenic plant vaccines. Previous studies have reported that rotavirus VP7 maintains its neutralizing immunity when it is transformed into the potato genome. The present study was aimed at investigating the hereditary stability of VP7-transformed potatoes over fifty generations. The VP7 gene was stably transcribed and expressed in potato cells as detected by RT-PCR and Western blotting. Humeral and mucosal responses were successfully induced in BALB/c mice fed with the fiftieth generation transformed potato tubers. There were no significant differences in serum IgG and fecal IgA between the mice fed with the first and fiftieth generation potatoes (P>0.05). Profiles of cytokines such as IFN-gamma, IL-2, IL-4, IL-5 and TGF-beta in immunized mice showed a naive T-cells bias to Th1 and Th3 polarization. Moreover, specific CTL responses were also detected in C57BL/6 mice fed with transformed potatoes. This research represents a significant step towards the development of rotavirus vaccines derived from a transgenic plant that can be obtained by long-term and large-scale vegetative reproduction. To our knowledge, this is the first finding regarding vaccines derived from plants that can be propagated for many generations.