Polyoxometalate/laccase-mediated oxidative polymerization of catechol for textile dyeing

The synergistic effect between polyoxometalates (POMs), namely K₅[SiW₁₁V^VO₄₀]·11H₂O and H₅[PMo₁₀V^V ₂O₄₀]·13H₂O and laccase from ascomycete Myceliophthora thermophila has been employed for the first time in oxidative polymerization of catechol. Such a laccase-mediator system allowed the formation of a relatively high molecular weight polycatechol as confirmed by size exclusion chromatography and electrospray ionization mass spectrometry (ESI-MS) (3990 Da when using K₅[SiW₁₁V^VO₄₀]·11H₂O and 3600 Da with H₅[PMo₁₀V^V ₂O₄₀]·13H₂O). The synthesized polymers were applied as dyes for the dyeing of flax fabrics. The color intensity of flax fabrics colored with polymer solutions was evaluated by diffuse reflectance spectrophotometry via k/s measurements (+10% of fixation ratio). A new synthetic process allowed a dyeing polymer, provided upon flax coloration, better color fixation and color resistance when compared to that obtained by conventional synthesis with laccase solely or with addition of organic mediator (1-hydroxybenzotriazole).     

<Emphasis Type="Italic">Spirosoma metallicus</Emphasis> sp. nov., isolated from an automobile air conditioning system

A Gram-stain-negative and orangish yellow-pigmented bacterial strain, designated PR1014K^T, was isolated from an automobile evaporator core collected in Korea. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain PR1014K^T was related with the members of the genus Spirosoma (94.7–90.2%) and closely related with Spirosoma lacussanchae CPCC 100624^T (94.7%), Spirosoma knui 15J8-12^T (94.3%), and Spirosoma soli MIMBbqt12^T (93.3%). The strain grew at 15–40°C (optimum, 25°C), pH 6.5–7.0 (optimum, 6.5) and 0–1% (w/v) NaCl (optimum, 0%). The predominant fatty acids were summed feature 3 (C_16:1 ω7c and/or C_16:1 ω6c), C_16:0, iso-C_15:0, C_16:1 ω5c, and iso-C_17:0 3-OH. The major menaquinone was MK-7. The polar lipid profile of the strain indicated that the presence of one phosphatidylethanolamine, one unidentified aminolipid, two unidentified aminophospholipids, and three unidentified lipids. The DNA G+C content of the strain was 47.4 mol%. On the basis of the phenotypic, genotypic and chemotaxonomic characteristics, strain PR1014K^T represents a novel species in the genus Spirosoma, for which the name Spirosoma metallicus sp. nov. (=KACC 17940^T =NBRC 110792^T) is proposed.     

The effects of the new guidance ‘take your sleeping pills 7 h before your wake-up time’: a pilot study

The aim of this study is to investigate the effectiveness and practicality of the newly proposed guidance to take hypnotics 7 h before one’s usual wake-up time, compared to the conventional guidance to do so 30 min before bedtime. Subjects with primary insomnia who were not satisfied with their hypnotics were included between November 2014 and October 2015. Participants were instructed to take their own sleeping pills 7 h before their usual wake-up times, and sleep-related time variables and symptom questionnaires were assessed at baseline and after 2 weeks. Among 32 subjects, 23 patients were successfully followed up. Adhering to the said 7-h instruction, 73.9 % (n = 17) were satisfied with their sleeping pills. Mean hypnotics administration time was significantly delayed from 9:32 p.m. ± 0:58 to 10:55 p.m. ± 0:46 (p < 0.001), duration from pills to wake-up time (PTW) was shortened from 9.0 ± 1.1 to 7.1 ± 0.8 h (p < 0.001), and sleep latency (p = 0.023) was significantly shortened. Scores of ISI and PSQI significantly improved (p < 0.001), and the improvements of ISI and PSQI were positively correlated with the shortened sleep latency (r = 0.49, p < 0.05) and PTW (r = 0.54, p < 0.05), respectively. Advising patients to take hypnotics about 7 h before their usual wake-up time could increase the level of satisfaction with their original medication as is. In incorporating concepts of cognitive-behavioral therapy, this recommendation may serve as a simple but considerably useful guidance on the proper timing for taking prescribed sleeping pills.

     

Synthesis and biological evaluation of triazolothienopyrimidine derivatives as novel HIV-1 replication inhibitors

We identified a novel class of triazolothienopyrimidine (TTPM) compounds as potent HIV-1 replication inhibitors during a high-throughput screening campaign that evaluated more than 200,000 compounds using a cell-based full replication assay. Herein, we report the optimization of the antiviral activity in a cell-based assay system leading to the discovery of aryl-substituted TTPM derivatives (38, 44, and 45), which exhibited significant inhibition of HIV-1 replication with acceptable safety margins. These novel and potent TTPMs could serve as leads for further development.     

A novel 3,4-dihydropyrimidin-2(1H)-one: HIV-1 replication inhibitors with improved metabolic stability

Following the previous SAR of a novel dihydropyrimidinone scaffold as HIV-1 replication inhibitors a detailed study directed towards optimizing the metabolic stability of the ester functional group in the dihydropyrimidinone (DHPM) scaffold is described. Replacement of the ester moiety by thiazole ring significantly improved the metabolic stability while retaining antiviral activity against HIV-1 replication. These novel and potent DHPMs with bioisosteres could serve as advanced leads for further optimization.     

<Emphasis Type="Italic">Flavisolibacter carri</Emphasis> sp. nov., isolated from an automotive air-conditioning system

A Gram-stain negative, aerobic, non-motile, rod-shaped and yellow bacterium, designated TX0651^T, was isolated from an automotive air-conditioning system. Phylogenetically, the strain groups with the members of the genus Flavisolibacter and exhibits high 16S rRNA gene sequence similarities with Flavisolibacter ginsenosidimutans Gsoil 636^T (97.4%), Flavisolibacter ginsengiterrae Gsoil 492^T (96.3%) and Flavisolibacter ginsengisoli Gsoil 643^T (96.2%). DNA–DNA relatedness between TX0651^T and F. ginsenosidimutans KCTC 22818^T and F. ginsengiterrae KCTC 12656^T were determined to be less than 40%. The low levels of DNA–DNA relatedness identifies the strain TX0651^T as a novel species in the genus Flavisolibacter. The major cellular fatty acids were identified as iso-C_15:0, summed feature 3 (C_16:1 ω7c and/or C_16:1 ω6c), iso-C_15:1 G and iso-C_17:0 3-OH. The predominant respiratory quinone was identified as MK-7. The polar lipids were found to be comprised of phosphatidylethanolamine, unidentified amino-glycophospholipids, an unidentified aminophospholipid, an unidentified amino lipid and unidentified lipids. The DNA G+C content of the strain was determined to be 31.2 mol%. On the basis of the phenotypic, genotypic and chemotaxonomic characteristics, strain TX0651^T should be classified in a novel species in the genus Flavisolibacter, for which the name Flavisolibacter carri sp. nov. (=?KACC 19014^T?=?KCTC 52836^T?=?NBRC 111784^T) is proposed.     

Positional scanning of natural product hispidol’s ring-B: discovery of highly selective human monoamine oxidase-B inhibitor analogues downregulating neuroinflammation for management of neurodegenerative diseases

Multifunctional molecules might offer better treatment of complex multifactorial neurological diseases. Monoaminergic pathways dysregulation and neuroinflammation are common convergence points in diverse neurodegenerative and neuropsychiatric disorders. Aiming to target these diseases, polypharmacological agents modulating both monoaminergic pathways and neuroinflammatory were addressed. A library of analogues of the natural product hispidol was prepared and evaluated for inhibition of monoamine oxidases (MAOs) isoforms. Several molecules emerged as selective potential MAO B inhibitors. The most promising compounds were further evaluated in vitro for their impact on microglia viability, induced production of proinflammatory mediators and MAO-B inhibition mechanism. Amongst tested compounds, 1p was a safe potent competitive reversible MAO-B inhibitor and inhibitor of microglial production of neuroinflammatory mediators; NO and PGE₂. In-silico study provided insights into molecular basis of the observed selective MAO B inhibition. This study presents compound 1p as a promising lead compound for management of neurodegenerative disease.     

Interplay between soluble CD74 and macrophage-migration inhibitory factor drives tumor growth and influences patient survival in melanoma

Soluble forms of receptors play distinctive roles in modulating signal-transduction pathways. Soluble CD74 (sCD74) has been identified in sera of inflammatory diseases and implicated in their pathophysiology; however, few relevant data are available in the context of cancer. Here we assessed the composition and production mechanisms, as well as the clinical significance and biological properties, of sCD74 in melanoma. Serum sCD74 levels were significantly elevated in advanced melanoma patients compared with normal healthy donors, and the high ratio of sCD74 to macrophage-migration inhibitory factor (MIF) conferred significant predictive value for prolonged survival in these patients (p = 0.0035). Secretion of sCD74 was observed primarily in melanoma cell lines as well as a THP-1 line of macrophages from monocytes and primary macrophages, especially in response to interferon-γ (IFN-γ). A predominant form that showed clinical relevance was the 25-KDa sCD74, which originated from the 33-KDa isoform of CD74. The release of this sCD74 was regulated by either a disintegrin and metalloproteinase-mediated cell-surface cleavage or cysteine-protease-mediated lysosomal cleavage, depending on cell types. Both recombinant and THP-1 macrophage-released endogenous sCD74 suppressed melanoma cell growth and induced apoptosis under IFN-γ stimulatory conditions via inhibiting the MIF/CD74/AKT-survival pathway. Our findings demonstrate that the interplay between sCD74 and MIF regulates tumor progression and determines patient outcomes in advanced melanoma.Subject terms: Melanoma, Prognostic markers