Design of Trehalose-Based Amide/Sulfonamide C-type Lectin Receptor Signaling Compounds

Mincle agonists have been shown to induce inflammatory cytokine production, such as tumor necrosis factor-alpha (TNF) and promote the development of a Th1/Th17 immune response that might be crucial to development of effective vaccination against pathogens such as Mycobacterium tuberculosis. As an expansion of our previous work, a library of 6,6′-amide and sulfonamide α,α-d -trehalose compounds with various substituents on the aromatic ring was synthesized efficiently in good to excellent yields. These compounds were evaluated for their ability to activate the human C-type lectin receptor Mincle by the induction of cytokines from human peripheral blood mononuclear cells. A preliminary structure–activity relationship (SAR) of these novel trehalose diamides and sulfonamides revealed that aryl amide-linked trehalose compounds demonstrated improved activity and relatively high potency cytokine production compared to the Mincle ligand trehalose dibehenate adjuvant (TDB) and the natural ligand trehalose dimycolate (TDM) inducing dose-dependent and human-Mincle-specific stimulation in a HEK reporter cell line.     

Comparative study of the phenolics,antioxidant and metagenomic composition of novel soy whey-based beverages produced using three different water kefir microbiota

Water kefir microbiota was used to develop novel soy whey-based beverages that have antioxidant activity. In the present study, comparative phenolics, antioxidant and metagenomic composition of the soy whey beverages fermented using three different water kefir microbiota, named WKFS-A, WKFS-B and WKFS-C were investigated. WKFS-B beverage had the highest concentrations of isoflavone aglycones (208.73 ± 2.78 mg L⁻¹) and phenolic acids (132.33 ± 3.41 mg L⁻¹) compared with WKFS-A (193.88 ± 1.15 mg L⁻¹) and (91.73 ± 2.34 mg L⁻¹) and WKFS-C (160.63 ± 1.76 mg L⁻¹) and (97.13 ± 2.63 mg L⁻¹), respectively. The WKFS-B also showed higher DPPH and ABTS radical scavenging activity and ferric reducing antioxidant power compared with WKFS-A and WKFS-C beverages. Microbial species diversity index analysis showed that a higher concentration of isoflavone aglycones, phenolic acids and increased antioxidant activity in the WKFS-B beverage correlates with the higher relative abundance of Lactobacillus genus. This study thus revealed that Lactobacillus dominated water kefir microbiota produces soy whey beverages with high phenolic acids, isoflavone aglycones and antioxidant activity.     

Boosted hydrogen evolution activity from Sr doped ZnO/CNTs nanocomposite as visible light driven photocatalyst

CNTs were decorated onto Sr doped ZnO nanoparticles to construct an efficient photocatalyst via a facile sol-gel method. The as-fabricated Sr doped ZnO/CNTs with recyclability exhibits Sr and CNTs content dependent hydrogen evolution activit under visible light illumination. The Sr doped ZnO/CNTs photocatalyst shows the highest hydrogen evolution rate of 2732.2 μmolh^?1g^?1, which is 33.7 and 2.83 times higher than pure ZnO and Sr doped ZnO photocatalysts, respectively. The improved hydrogen evolution activity of Sr doped ZnO/CNTs is primarily assigned to high surface area, Sr doping and construction of heterojunction, which can extend the light absorption, decrease the optical band gap and improve the charge separation. Moreover, the underlying photocatalytic mechanism is proposed on the basis of Mott-Schottky study and explains the interfacial charge transfer process from ZnO to CNTs and Sr. This work open new strategies to synthesize CNTs based nanocomposite for hydrogen evolution.     

Rational Optimization of Dihydropyrimidinone-Quinoline Hybrids as Plasmodium falciparum Glutathione Reductase Inhibitors

A series of dihydropyrimidinone-based antimalarial compounds were designed and synthesised based on the previously identified amide-based quinoline hybrids which showed good resistance reversal ability against the resistant strain of Plasmodium falciparum. The aromatic ring on the dihydropyrimidinone of the original hits was exchanged for a methyl group to bring the molecular weights below 500 Da and also determine the effect of the aromatic ring count on the resistance reversal ability of the hybrids. Apart from the previously used amide bond, the hybrid linker was also extended to the triazole linker. Although the triazole linker is synthetically easier to access, the use of an amide linker seems to have an activity advantage. The synthesised compounds in addition to the previously identified hits were subjected to molecular docking particularly targeting the orthosteric site of Plasmodium falciparum glutathione reductase (PfGR) protein. The ligand with the best binding interaction was rationally optimised to increase its suitability as a competitive inhibitor against the cofactor of the PfGR. Two of the optimised ligands showed better binding affinities than the cofactor while one of the two ligands displayed hydrophobically packed correlated hydrogen-bond which is very important in maintaining the ligand stability within the protein. In silico ADME predictions of the synthesised compounds indicate that these compounds possess good pharmacokinetic properties.     

Comparison of chlorination and chloramination practices on microbial inactivation efficiencies within a scaled‐up water distribution network using central composite design

Disinfection practices reduce the incidence of water‐borne diseases but may result in formation of disinfection byproducts (DBPs) in raw water that are reported to be carcinogenic. Central composite design (CCD) was employed in the present study for optimization of disinfectant dose and contact time with the rationale to evaluate if an optimal balance could be achieved between minimal DBPs formation and effective microbial inactivation with either free or combined chlorine in treated water within a lab‐scale prototype network to simulate real water distribution network conditions. After a series of experimental runs based upon design of experiments (DoE) by CCD, dose was found to be the most significant factor (P < 0.01) in determining DBPs formation in both disinfectant’s applications. Where, contact time significantly (P < 0.01) affected bacterial inactivation in chlorination experiments, in contrast, dose was effective in chloramination experiments. Thus, it was concluded that the optimal balance may be achieved in the water networks with the help of multifactorial optimization when disinfectant dose was maintained near 3 mg/L as applied chlorine dose in both disinfection cases, while contact time was 62 and 155 min for chlorine and chloramine, respectively.     

Multilayer Partially Homomorphic Encryption Text Steganography (MLPHE-TS): A Zero Steganography Approach

Wireless Personal Communications - This paper presents a Multilayer Partially Homomorphic Encryption Text Steganography, an invisible approach for covert communication. Existing text-based schemes...     

Building a text collection for Urdu information retrieval

Urdu is a widely spoken language in the Indian subcontinent with over 300 million speakers worldwide. However, linguistic advancements in Urdu are rare compared to those in other European and Asian languages. Therefore, by following Text Retrieval Conference standards, we attempted to construct an extensive text collection of 85 304 documents from diverse categories covering over 52 topics with relevance judgment sets at 100 pool depth. We also present several applications to demonstrate the effectiveness of our collection. Although this collection is primarily intended for text retrieval, it can also be used for named entity recognition, text summarization, and other linguistic applications with suitable modifications. Ours is the most extensive existing collection for the Urdu language, and it will be freely available for future research and academic education.