Pathogenic Roles of MicroRNA in the Development of Asthma

Asthma is a common and chronic inflammatory disease. Pathogenic mechanism underlying asthma is complicated. The inflammatory reactions in asthma have been recognized to involve mast cells, eosinophils, lymphocytes (T cells, B cells), macrophages, and dendritic cells. MicroRNA (miRNA, miR) is a group of small noncoding RNAs with 21–25 nucleotides (nt) in length, which impact biologic responses through the regulation of mRNA transcription and/or translation. MicroRNAs are related to developmental processes of many immunologic diseases. Most studies showed that regulation of miRNAs to their targeting genes appears to play an important role in the development of asthma. This chapter has discussed altered expression of miRNAs in cells and tissues from patients with asthma, in order to better understand the mechanics of pathogenesis of asthma. In addition, the regulation of miRNAs as a novel therapeutic approach will require a deeper understanding of their function and mechanism of action

Manipulation of magnetic topological textures via perpendicular strain and polarization in van der Waals magnetoelectric heterostructure

Multi-functional manipulation of magnetic topological textures such as skyrmions and bimerons in energy-efficient ways is of great importance for spintronic applications, but still being a big challenge. Here, by first-principles calculations and atomistic simulations, the creation and annihilation of skyrmions/bimerons, as key operations for the reading and writing of information in spintronic devices, are achieved in van der Waals magnetoelectric CrISe/In2Se3 heterostructure via perpendicular strain or electric field without external magnetic field. Besides, the bimeron-skyrmion conversion, size modulation and the reversible magnetization switching from in-plane to out-of-plane could also be realized in magnetic-field-free ways. Moreover, the topological charge and morphology can be precisely controlled by a small magnetic field. The strong Dzyaloshinskii-Moriya interaction and tunable magnetic anisotropy energy in a wide window are found to play vital roles in such energy efficient multi-functional manipulation, and the underlying physical mechanisms are elucidated. Our work predicts the CrISe/In2Se3 heterostructure being an ideal platform to address this challenge in spintronic applications, and theoretically guides the low-dissipation multi-functional manipulation of magnetic topological textures.Comment: 7 pages, 5 figure

Aqueous Organic Batteries Using the Proton as a Charge Carrier

Benefiting from the merits of low cost, nonflammability, and high operational safety, aqueous rechargeable batteries have emerged as promising candidates for large-scale energy-storage applications. Among various metal-ion/non-metallic charge carriers, the proton (H+) as a charge carrier possesses numerous unique properties such as fast proton diffusion dynamics, a low molar mass, and a small hydrated ion radius, which endow aqueous proton batteries (APBs) with a salient rate capability, a long-term life span, and an excellent low-temperature electrochemical performance. In addition, redox-active organic molecules, with the advantages of structural diversity, rich proton-storage sites, and abundant resources, are considered attractive electrode materials for APBs. However, the charge-storage and transport mechanisms of organic electrodes in APBs are still in their infancy. Therefore, finding suitable electrode materials and uncovering the H+-storage mechanisms are significant for the application of organic materials in APBs. Herein, the latest research progress on organic materials, such as small molecules and polymers for APBs, is reviewed. Furthermore, a comprehensive summary and evaluation of APBs employing organic electrodes as anode and/or cathode is provided, especially regarding their low-temperature and high-power performances, along with systematic discussions for guiding the rational design and the construction of APBs based on organic electrodes

Proficiency testing of maternal serum prenatal screening in second trimester in China, 2015

Introduction: Prenatal screening and diagnosis is important for the detection of birth defects and genetic diseases. The nationwide proficiency testing (PT) of maternal serum prenatal screening in second trimester in China has been launched since 2003 and partly reflected the performance of screening laboratories. This study analysed the 2015 PT results to examine the performance of clinical laboratories and different platforms. Materials and methods: Fifteen lyophilized samples with different concentrations divided into three panels, were distributed to 613 clinical laboratories in 2015. Acceptable performance was defined as scores more than 80% of acceptable responses with the evaluation criterion of ± 30%. The robust coefficient of variation (CV) was also analysed. Chi-square (?2) test was used to compare the acceptable performance while Kruskal-Wallis test and Mann-Whitney test were applied to compare the robust CV among analytes and mainstream platforms. Results: Overall, 605, 61, 214, 416, 303 laboratories submitted effective results for alpha fetoprotein (AFP), total human chorionic gonadotropin (t-hCG), ß-hCG, unconjugated estriol (uE3) and free ß-hCG. The acceptable performances of AFP (µg/L), AFP (KIU/L), t-hCG, ß-hCG, uE3, and free ß-hCG were 98.45%, 99.24%, 95.58%, 98.72%, 94.50%, and 98.66%, respectively. The ?2 test indicated significant differences existed in the acceptable performances among different analytes and platforms for uE3. Kruskal-Wallis test and Mann-Whitney test suggested the robust CV differed significantly in different analytes and platforms. Conclusions: The majority of results were acceptable. However, further effort is needed to achieve the standardization and harmonization among analytes and various platforms, particularly for uE3

MicroRNA 27b-3p Modulates SYK in Pediatric Asthma Induced by Dust Mites

The PI3K-AKT pathway is known to regulate cytokines in dust mite-induced pediatric asthma. However, the underlying molecular steps involved are not clear. In order to clarify further the molecular steps, this study investigated the expression of certain genes and the involvement of miRNAs in the PI3K-AKT pathway, which might affect the resultant cytokine-secretion. in-vivo and in-vitro ELISA, qRT-PCR and microarrays analyses were used in this study. A down-expression of miRNA-27b-3p in dust mite induced asthma group (group D) was found by microarray analysis. This was confirmed by qRT-PCR that found the miRNA-27b-3p transcripts that regulated the expression of SYK and EGFR were also significantly decreased (p < 0.01) in group D. The transcript levels of the SYK and PI3K genes were higher, while those of EGFR were lower in the former group. Meanwhile, we found significant differences in plasma concentrations of some cytokines between the dust mite-induced asthma subjects and the healthy controls. On the other hand, this correlated with the finding that the transcripts of SYK and its downstream PI3K were decreased in HBE transfected with miRNA-27b-3p, but were increased in HBE transfected with the inhibitor in vitro. Our results indicate that the differential expression of the miRNAs in dust mite-induced pediatric asthma may regulate their target gene SYK and may have an impact on the PI3K-AKT pathway associated with the production of cytokines. These findings should add new insight into the pathogenesis of pediatric asthma

Identification of the ortho-Benzoquinone Intermediate of 5-O- Caffeoylquinic Acid In Vitro and In Vivo: Comparison of Bioactivation under Normal and Pathological Situations □ S

ABSTRACT: 5-O-Caffeoylquinic acid (5-CQA) is one of the major bioactive ingredients in some Chinese herbal injections. Occasional anaphylaxis has been reported for these injections during their clinical use, possibly caused by reactive metabolites of 5-CQA. This study aimed at characterizing the bioactivation pathway(s) of 5-CQA and the metabolic enzyme(s) involved. After incubating 5-CQA with GSH and NADPH-supplemented human liver microsomes, two types of GSH conjugates were characterized: one was M1-1 from the 1,4-addition of GSH to ortho-benzoquinone intermediate; the other was M2-1 and M2-2 from the 1,4-addition of GSH directly to the ␣,␤-unsaturated carbonyl group of the parent. The formation of M1-1 was cytochrome P450 (P450)-mediated, with 3A4 and 2E1 as the principal catalyzing enzymes, whereas the formation of M2-1 and M2-2 was independent of NADPH and could be accelerated by cytosolic glutathione transferase. In the presence of cumene hydroperoxide, M1-1 formation increased 6-fold, indicating that 5-CQA can also be bioactivated by P450 peroxidase under oxidizing conditions. Furthermore, M1-1 could be formed by myeloperoxidase in activated human leukocytes, implying that 5-CQA bioactivation is more likely to occur under inflammatory conditions. This finding was supported by experiments on lipopolysaccharideinduced inflammatory rats, where a greater amount of M1-1 was detected. In S-adenosyl methionine-and GSH-supplemented human S9 incubations, M1-1 formation decreased by 80% but increased after tolcapone-inhibited catechol-O-methyltransferase (COMT) activity. In summary, the high reactivities of the orthobenzoquinone metabolite and ␣,␤-unsaturated carbonyl group of 5-CQA to nucleophiles have been demonstrated. Different pathological situations and COMT activities in patients may alter the bioactivation extent of 5-CQA