Self-Assembly of an Anionic [Cu5I8]3- Supramolecular Cluster Driven by Ion-Pair Interaction and Catalytic Properties.

The rational design and controlling synthesis of an anionic cuprous iodide supramolecular cluster with high nuclearity through noncovalent interactions remains a significant challenge. Herein, a cationic organic ligand (L1)3+ was driven by anion-cation ion-pair electrostatic interaction to induce free cuprous iodide to aggregate into an anionic supramolecular cluster, [(Cu5I8)3-(L1)3+] (C1). Moreover, five copper(I) atoms bind with eight iodides through multiply bridged Cu-I bonds associated with intramolecular cuprophilic interactions in this butterfly-shaped cluster core. Supramolecular cluster C1 exhibited a solid-state emission at 380 nm and an emission at 405 nm in acetonitrile at room temperature, respectively. Interestingly, this unprecedented cuprous iodide cluster demonstrated a good catalytic performance for azide-alkyne cycloaddition reaction (CuAAC) and the catalytic yield can be up to 80% for eight different substrates at 80 °C. Furthermore, the density functional theory (DFT) calculation revealed that the thermodynamic-dependent cycloaddition reaction underwent a four-step pathway with an overall energy barrier of -43.6 kcal mol-1 on the basis of intermediates monitored by mass spectrum.

Generation of a human haploid neural stem cell line for genome-wide genetic screening.

BACKGROUND: Haploid embryonic stem cells (haESCs) have been established in many species. Differentiated haploid cell line types in mammals are lacking due to spontaneous diploidization during differentiation that compromises lineage-specific screens. AIM: To derive human haploid neural stem cells (haNSCs) to carry out lineage-specific screens. METHODS: Human haNSCs were differentiated from human extended haESCs with the help of Y27632 (ROCK signaling pathway inhibitor) and a series of cytokines to reduce diploidization. Neuronal differentiation of haNSCs was performed to examine their neural differentiation potency. Global gene expression analysis was con-ducted to compare haNSCs with diploid NSCs and haESCs. Fluorescence activated cell sorting was performed to assess the diploidization rate of extended haESCs and haNSCs. Genetic manipulation and screening were utilized to evaluate the significance of human haNSCs as genetic screening tools. RESULTS: Human haESCs in extended pluripotent culture medium showed more compact and smaller colonies, a higher efficiency in neural differentiation, a higher cell survival ratio and higher stability in haploidy maintenance. These characteristics effectively facilitated the derivation of human haNSCs. These human haNSCs can be generated by differentiation and maintain haploidy and multipotency to neurons and glia in the long term in vitro. After PiggyBac transfection, there were multiple insertion sites in the human haNSCs' genome, and the insertion sites were evenly spread across all chromosomes. In addition, after the cells were treated with manganese, we were able to generate a list of manganese-induced toxicity genes, demonstrating their utility as genetic screening tools. CONCLUSION: This is the first report of a generated human haploid somatic cell line with a complete genome, proliferative ability and neural differentiation potential that provides cell resources for recessive inheritance and drug targeted screening.

A validated UPLC-MS/MS method for quantitative determination of a potent neuroprotective agent Sarsasapogenin-AA13 in rat plasma: Application to pharmacokinetic studies.

Sarsasapogenin-AA13(AA13), a sarsasapogenin derivative, exhibited good neuroprotective and anti-inflammatory activities in vitro and therapeutic effects on learning and memory dysfunction in amyloid-ß-injected mice. A sensitive UPLC-MS/MS method was developed and validated to quantitatively determine AA13 in rat plasma and was further applied to evaluate the pharmacokinetic behaviour of AA13 in rats that were administered AA13 intravenously and orally. This method was validated to exhibit excellent linearity in the concentration range of 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL for AA13 in rat plasma. Intra-day accuracy for AA13 was in the range of 90-114%, and inter-day accuracy was in the range of 97-103 %. The relative standard deviation of intra-day and inter-day assay was less than 15%. After a single oral administration of AA13 at the dose of 25 mg/kg, Cmax of AA13 was 1266.4 ± 316.1 ng/mL. AUC0-48 h was 6928.5 ± 1990.1 h·ng/mL, and t1/2 was 10.2 ± 0.8 h. Under intravenous administration of AA13 at a dosage of 250 µg/kg, AUC0-48 h was 785.7 ± 103.3 h⋅ng/mL, and t1/2 was 20.8 ± 7.2 h. Based on the results, oral bioavailability (F %) of AA13 in rats at 25 mg/kg was 8.82 %.

Terahertz modulator based on insulator-metal transition in photonic crystal waveguide.

A terahertz modulator based on the insulator-metal transition (IMT) in a photonic crystal waveguide (PCW) coated by vanadium dioxide (VO2) film is proposed. The numerical simulations show that a dielectric state and a metallic state with quite different photonic band structures and transmission properties in the proposed PCW are reciprocally converted because of the IMT of VO2, and the pass-bands of this PCW are greatly shifted from 0.68 to 0.8 and 1.02 to 1.25 THz to 0.8-1.45 THz. This PCW significantly enhances the modulation depth and sensitivity compared with bare VO2 film. Extensive investigation demonstrates that the thickness of VO2 film greatly affects the IMT process in the PCW, and limits the ultimate modulation depth of the device. The proposed modulation scheme will be of great significance for potential THz applications.

Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice.

Asthma, a chronic inflammatory disorder of the airways, is coordinated by Th2 cells in both human asthmatics and animal models of allergic asthma. It has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma. In the present study, BALB/c mice were infected with bisexual and unisexual (male) S. japonicum, respectively, prior to ovalbumin (OVA) sensitization and challenge. Compared to mice with OVA sensitization/challenge alone, S. japonicum infection led to a significant decrease of eosinophil accumulation in bronchoalveolar lavage fluid (BALF) collected 48 h postchallenge, as well as to a marked reduction in inflammatory cell infiltration around the airways and pulmonary blood vessels. Compared to OVA-immunized uninfected mice, the level of OVA-specific serum IgE as well as interleukin (IL)-4 and IL-5 in BALF were reduced, but IL-10 was strongly elevated in mice with preexisting S. japonicum infection prior to OVA immunization. These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma.

[Suppression effect of different stage antigens of Schistosoma japonicum on airway inflammation in a murine model of asthma].

OBJECTIVE: To investigate the effect of antigens of different stage Schistosoma japonicum on airway inflammation in a murine model of asthma. METHODS: 48 female BALB/c mice were randomly divided into eight groups. Mice in group A were given normal saline of equal volume as control. Group B was asthma model which was established by intraperitoneal and intranasal challenge with OVA. Mice in groups C, D and E were immunized with soluble egg antigen (SEA), soluble male worm antigen (SWA), and schistosomulum antigen (SSA) respectively 4 times in a week interval, followed by OVA sensitization as in group B 1 week after the final immunization. Mice in groups F, G, and H were immunized with SEA, SWA, and SSA respectively but sensitized and challenged with saline instead of OVA. 48 hours after asthma was induced, the mice were sacrificed. Leukocytes and eosinophils were counted in bronchoalveolar lavage fluid (BALF). The level of IL-5, IL-10 and IFN-gamma in BALF was detected. Pathologic changes in lung tissues were observed. RESULTS: Inflammation cells, especially eosinophils, appeared in airways of mice in groups B, C, D and E, but with much less number in groups C, D and E. No inflammation cells were seen in airways of group A mice. The number of leukocytes, eosinophils and level of IL-5 in BALF of group B [(98.4 +/- 16.1) x 10(4)/ml, (17.6 +/- 4.3) x 10(4)/ml, (197.9 +/- 36.5) pg/ml respectively] were significantly higher than those of group A [(8.2 +/- 1.1) x 10(4)/ml, (0.02 +/- 0.01) x 10(4)/ ml, (12.3 +/- 7.4) pg/ml], however the levels of IL-10 and IFN-gamma were significantly lower than that of group A (P < 0.05). The number of leukocytes, especially eosinophils, in BALF of groups C, D and E was significantly lower than that of group B. The level of IL-5 in BALF of groups C, D and E was significantly reduced, while that of IL-10 and IFN-gamma in BALF of the 3 groups was significantly higher than group B (P < 0.05). CONCLUSIONS: The immunization with S. japonicum antigens can effectively modulate the level of cytokines and inhibit the eosinophil infiltration and airway inflammation in asthmatic mice.

[Up-expression of PD-1-PD-L induced by immunization with SEA and SMWA of Schistosoma japonicum in mice].

OBJECTIVE: To explore the expression of PD-1-PD-L pathway of mice immunized with soluble egg antigen (SEA) or soluble male worm antigen (SMWA) of Schistosoma japonicum. METHODS: Eighteen BALB/c mice were randomly divided into three groups named as control group (A), SEA immunized group (B) and SMWA immunized group (C). Mice in groups B and C were subcutaneously immunized weekly with SEA (50 microg) and SMWA (50 microg) of S. japonicum respectively. After 4 times immunization, the expression of programmed death-1 (PD-1), programmed death-ligand1 (PD-L1) and PD-L2 in splenic cells was measured with flow cytometer. The expression of IL-4 and IFN-gamma in cultural suspension of splenic cells was detected by sandwich-ELISA after stimulation with ConA. RESULTS: The expression ratio of PD-1, PD-L1 and PD-L2 was extremely low in the control group, but increased after the immunization with SEA and SMWA. The expression ratio of PD-1 was (8.24 +/- 1.31)% in SEA immunized mice, higher than the mice immunized by SMWA [(6.08 +/- 1.28)%]. PD-L2 was much more elevated in SEA immunized mice [(5.26 +/- 1.73)%] while PD-L1 more significantly increased with SMWA immunization [(10.82 +/- 2.33)%]. In addition, the up-expression of PD-L1 was associated with the level of IFN-gamma and the expression of PD-L2 was associated with IL-4 secretion. CONCLUSION: The expression of PD-1-PDL was up-regulated in BALB/c mice immunized by SEA or SMWA of S. japonicum.

[Production and identification of chicken egg yolk antibodies against soluble egg antigen of Schistosoma japonicum].

OBJECTIVE: To produce and purify egg yolk immunoglobulin against soluble egg antigen (SEA) of Schistosoma japonicum, and evaluate its specificity and sensitivity. METHODS: 25-week old hen was intravenously and subcutaneously immunized with SEA of Schistosoma japonicum for 4 times. Each hen was first immunized with 60 microg SEA and subsequent injections were performed at 10-day intervals with 30 microg SEA. IgY was extracted from eggs of hen 35 d after the first inoculation by WD (water-dilution) method, eggs from non-immunized hen were used as negative control. The protein concentration of IgY was measured by BCA method, and IgY was analyzed by SDS-PAGE and Western blotting. SEA-based ELISA was used to evaluate the specificity and sensitivity of the IgY. RESULTS: 61 mg IgY was extracted from one egg. The results of SDS-PAGE and Western blotting demonstrated that the IgY contained one major protein band with molecular weight of 130,000 and could be recognized by SEA. Specific IgY could be immediately detected by SDS-PAGE and ELISA in the eggs laid by the hens from 10 days after the first immunization. On day 31 after the primary immunization, the antibody titer reached 1:1 600. 2.4 ng/ml SEA was detected by IgY based-sandwich ELISA, which indicated a high sensitivity of the purified IgY. CONCLUSION: Anti-SEA IgY with high specificity and sensitivity has been obtained and purified.