Toxocara canis is regarded as the main cause of human toxocarosis but the relative contribution of T. cati is probably underestimated; serological and other diagnostic methods used in most studies of this zoonotic disease do not distinguish between the two parasites. The definitive hosts for T. canis are caniidae. Pups generally have higher infection rates than adult animals and are a major source of eggs in the environment. Humans usually acquire T. canis infection by accidental ingestion of embryonated eggs or encapsulated larvae from the environment or contaminated food, such infections may lead to visceral larva migrans (VLM), ocular larva migrans (OLM) or covert toxocarosis (CT). Although a mixed Th1- and Th2-mediated immunological response, particularly with high levels of IgE and eosinophilia is observed, the underlying mechanisms of molecular and immunopathogenesis for the development of the symptomatic syndromes of VLM, OLM, or of asymptomatic CT are largely unclear. Studies have indicated that immunological defences against various infectious diseases may be highly influenced by complex interactions of environmental and host genetic factors e.g. MHC class I and II, also known as human leucocyte antigen (HLA). Toxocara spp. infections are associated with a polarized CD4(+) Th2 response with high IgE levels and eosinophilia, mediated mainly by HLA class II molecules. Associations have been made between HLA class II and pathological severity and host genetic effects on exposure to infection. Recent research suggests Foxp3(+) CD4(+)CD25(+)-expressing T regulatory (Treg) cells play a role in regulation of the immunopathology of granulomas in experimental toxocaral granulomatous hepatitis and in enhanced expression of TGF-β1, which is an important factor for the local survival and function of Treg observed during T. canis invasion in the mouse small intestine, liver, muscle, and brain. Since the potential susceptibility loci HLA class II molecules, are considered involved in the regulation of a Th2-dominant immunity which is highly controlled by Foxp3(+) CD4(+)CD25(+) Treg cells by stimulation through TGF-β1, which thus provides a beneficial environment to T. canis larvae but severe injuries to local organs. However, TGF-β1 variant Leu10Pro known to be involved in disease severity warrants further elucidation as this too may have a role in the severity of human toxocarosis. Exploration of TGF-β1 polymorphism, Foxp3(+) CD4(+)CD25(+) Treg cells, and MHC polymorphisms may allow insight into the contribution made by environmental and genetic factors in influencing disease syndrome type and severity in humans with toxocarosis.
G-quadruplexes are unusual DNA and RNA secondary structures ubiquitous in a variety of organisms including vertebrates, plants, viruses and bacteria. The folding topology and stability of intramolecular G-quadruplexes are determined to a large extent by their loops. Loop permutation is defined as swapping two or three of these regions so that intramolecular G-quadruplexes only differ in the sequential order of their loops. Over the past two decades, both length and base composition of loops have been studied extensively, but a systematic study on the effect of loop permutation has been missing. In the present work, 99 sequences from 21 groups with different loop permutations were tested. To our surprise, both conformation and thermal stability are greatly dependent on loop permutation. Loop permutation actually matters as much as loop length and base composition on G-quadruplex folding, with effects on Tm as high as 17°C. Sequences containing a longer central loop have a high propensity to adopt a stable non-parallel topology. Conversely, sequences containing a short central loop tend to form a parallel topology of lower stability. In addition, over half of interrogated sequences were found in the genomes of diverse organisms, implicating their potential regulatory roles in the genome or as therapeutic targets. This study illustrates the structural roles of loops in G-quadruplex folding and should help to establish rules to predict the folding pattern and stability of G-quadruplexes.
The chemical-looping gasification (CLG) of coal is a clean and effective technology for syngas generation. Sharing principles with chemical-looping combustion (CLC), CLG also uses oxygen carriers to transfer lattice oxygen to the fuel. Investigations into CLG with different O/C ratios are carried out in a fluidized bed reactor with steam used as the gasification− fluidization medium. The effect of the active component content of the oxygen carrier on the gas selectivity is performed, and reaction mechanisms between the Fe 2 O 3 oxygen carrier and coal with steam as the gasification agent are discussed. Moreover, we also assessed the reactivity of the CaO-decorated iron-based oxygen carrier particles in multicycle reactions. The carbon conversion efficiency is increased from 55.74 to 81% with increasing O/C ratio, whereas the content of H 2 first decreases and then increases. The addition of CaO can increase the carbon conversion efficiency and the gasification rate substantially and reduce the generation rate of H 2 S from 1.89 × 10 −3 to 0.156 × 10 −3 min −1 . Furthermore, X-ray diffraction (XRD) images indicate that the CaO-decorated iron-based oxygen carrier particles were completely regenerated after six redox cycles. Finally, the peak fitting of gasification reaction rate curves is used to explore the reaction mechanism between coal char and the CaOdecorated iron-based oxygen carrier, indicating that the reactions in the CLG include three stages: the complex reactions involved an oxygen carrier, coal char, and steam; the gasification of coal char; and the reduction of Fe 3 O 4 to FeO. The two-segment modified random pore model (MRPM) fits the experiment data well.
Chemical looping combustion (CLC) is an attractive technology for CO2 capture with high energy efficiency. In this article, an Fe2O3/Al2O3 (Fe:Al = 3:1) oxygen carrier was first prepared by the solution combustion approach for the CLC process. The prepared oxygen carrier was characterized by different means. XRD identification has substantiated the necessity of calcinations to synthesize Fe2O3/Al2O3 oxygen carrier. SEM and TEM images showed the regular spherical and cubical shape and abundant porous structure in Fe2O3/Al2O3 oxygen carrier, respectively. Structural characteristics displayed that the pore shape of Fe2O3/Al2O3 particles was heterogeneous. The average pore size and surface area were 64.76 nm and 4.01 m2/g, respectively. Further, H2 temperature programmed reduction (TPR) of Fe2O3/Al2O3 oxygen carrier indicated that the reduction reaction had only one distinct DTG peak with the weight loss rate reaching 4.75 wt %/min. Finally, five cycles of red–ox reaction by alternating with CH4 and air demonstrated that Fe2O3/Al2O3 oxygen carrier had excellent reactivity and sintering resistance and consequently was capable of the CLC process.
A series of isopropanol-bridged carbazole azoles as potential antimicrobial agents were designed and synthesized from commercial carbazoles. Bioassay revealed that 3,6-dichlorocarbazolyl triazole 3f could effectively inhibit the growth of E. faecalis with minimal inhibitory concentration of 2 μg/mL. The active molecule 3f showed lower propensity to trigger the development of resistance in bacteria than norfloxacin and exerted rapidly bactericidal ability. Compound 3f also exhibited low cytotoxicity to normal mammalian RAW264.7 cells. Further mechanism exploration indicated that conjugate 3f was membrane active against E. faecalis and could form 3f−DNA complex by intercalating into DNA of resistant E. faecalis, which might be responsible for its antimicrobial action. Molecular docking showed an efficient binding of triazole derivative 3f with DNA gyrase enzyme through noncovalent interactions.
A series of novel naphthalimide aminothiazoles were developed for the first time and evaluated for their antimicrobial activity. Some prepared compounds possessed good inhibitory activity against the tested bacteria and fungi. Noticeably, the piperazine derivative displayed superior antibacterial activity against MRSA and with MIC values of 4 and 8 μg/mL, respectively, to reference drugs. The most active compound showed low toxicity against mammalian cells with no obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy and efficient membrane permeability. Preliminarily investigations revealed that compound could not only bind with gyrase-DNA complex through hydrogen bonds but could effectively intercalate into MRSA DNA to form -DNA supramolecular complex, which might be responsible for the powerful bioactivity. Further transportation behavior evaluation indicated that molecule could be effectively stored and carried by human serum albumin, and the hydrophobic interactions and hydrogen bonds played important roles in the binding process.
Cofactor hemin is sandwiched between 3′ homodimeric G-quadruplexes, leading to an excellent DNAzyme as a mimic of peroxidase and monooxygenase.
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