The translocator protein ligands as mitochondrial functional modulators for the potential anti-Alzheimer agents.

Small molecule modulators of mitochondrial function have been attracted much attention in recent years due to their potential therapeutic applications for neurodegenerative diseases. The mitochondrial translocator protein (TSPO) is a promising target for such compounds, given its involvement in the formation of the mitochondrial permeability transition pore in response to mitochondrial stress. In this study, we performed a ligand-based pharmacophore design and virtual screening, and identified a potent hit compound, 7 (VH34) as a TSPO ligand. After validating its biological activity against amyloid-ß (Aß) induced mitochondrial dysfunction and in acute and transgenic Alzheimer's disease (AD) model mice, we developed a library of analogs, and we found two most active compounds, 31 and 44, which restored the mitochondrial membrane potential, ATP production, and cell viability under Aß-induced mitochondrial toxicity. These compounds recovered learning and memory function in acute AD model mice with improved pharmacokinetic properties.

Electrospun tecophilic/gelatin nanofibers with potential for small diameter blood vessel tissue engineering.

Tissue engineering techniques particularly using electrospun scaffolds have been intensively used in recent years for the development of small diameter vascular grafts. However, the development of a completely successful scaffold that fulfills multiple requirements to guarantee complete vascular regeneration remains challenging. In this study, a hydrophilic and compliant polyurethane namely Tecophilic (TP) blended with gelatin (gel) at a weight ratio of 70:30 (TP(70)/gel(30)) was electrospun to fabricate a tubular composite scaffold with biomechanical properties closely simulating those of native blood vessels. Hydrophilic properties of the composite scaffold induced non-thrombogenicity while the incorporation of gelatin molecules within the scaffold greatly improved the capacity of the scaffold to serve as an adhesive substrate for vascular smooth muscle cells (SMCs), in comparison to pure TP. Preservation of the contractile phenotype of SMCs seeded on electrospun TP(70)/gel(30) was yet another promising feature of this scaffold. The nanostructured TP(70)/gel(30) demonstrated potential feasibility toward functioning as a vascular graft.

Peptide functionalized polyhydroxyalkanoate nanofibrous scaffolds enhance Schwann cells activity.

Interactions between Schwann cells (SCs) and scaffolds are important for tissue development during nerve regeneration, because SCs physiologically assist in directing the growth of regenerating axons. In this study, we prepared electrospun scaffolds combining poly (3-hydroxybutyrate) (PHB) and poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) functionalized with either collagen I, H-Gly-Arg-Gly-Asp-Ser-OH (GRGDS), H-Tyr-Ile-Gly-Ser-Arg-NH2 (YIGSR), or H-Arg-Asn-Ile-Ala-Glu-Ile-Ile-Lys-Asp-Ile-OH (p20) neuromimetic peptides to mimic naturally occurring ECM motifs for nerve regeneration. Cells cultured on fibrous mats presenting these biomolecules showed a significant increase in metabolic activity and proliferation while exhibiting unidirectional orientation along the orientation of the fibers. Real-time PCR showed cells cultured on peptide-modified scaffolds had a significantly higher neurotrophin expression compared to those on untreated nanofibers. Our study suggests that biofunctionalized aligned PHB/PHBV nanofibrous scaffolds may elicit essential cues for SCs activity and could serve as a potential scaffold for nerve regeneration. From the clinical editor: Nanotechnology-based functionalized scaffolds represent one of the most promising approaches in peripheral nerve recovery, as well as spinal cord recovery. In this study, bio-functionalized and aligned PHB/PHBV nanofibrous scaffolds were found to elicit essential cues for Schwann cell activity, therefore could serve as a potential scaffold for nerve regeneration.

Destructive adsorption of Diazinon pesticide by activated carbon nanofibers containing Al2O3 and MgO nanoparticles.

We report the destructive adsorption of Diazinon pesticide by porous webs of activated carbon nanofibers containing Al2O3 and MgO nanoparticles. The results show that, the presence of Al2O3 and MgO nanoparticles in the activated carbon nanofibers increases the amount of destructively adsorbed Diazinon pesticide by activated carbon nanofibers. Moreover, type, amount, and specific surface area of metal oxide nanoparticles affect the adsorption rate as well as the total destructively adsorbed Diazinon. Liquid chromatography proved the degradation of Diazinon by chemical reaction with Al2O3 and MgO nanoparticles. Liquid chromatography-mass spectrometry showed that the main product of reaction between Diazinon and the metal oxides is 2-isopropyl-6-methyl-4-pyrimidinol with less toxicity than Diazinon.

Prevalence of antibiotic use for diarrhea among 1.3 million under-five years children: A multicounty retrospective analysis from 2006-2018.

BACKGROUND: This paper aims to estimate the prevalence of antibiotic use for diarrhea among under-five children (u5c) in low- and middle-income countries (LMICs) using data from 112 Demographic Health Surveys (DHS) conducted between 2006 and 2018. The focus is on understanding the extent of antibiotic usage for managing diarrhea, a condition characterized by frequent loose or watery bowel movements that can lead to severe dehydration. METHODS AND FINDINGS: A cross-sectional study design was employed in the DHS. The prevalence of antibiotic use for diarrhea among under-five children was estimated by analyzing DHS data from 2006 to 2018 and using the R statistical programming language. Out of a total of 12,69,944 children under five included in this study, 1,80,067 children had diarrhea and 19,502 children had bloody diarrhea. The overall prevalence of diarrhea estimated at ~14% (prevalence = 0.142; 95% CI = 0.141, 0.142). Among the children with diarrhea, 47,755 child received antibiotic treatment, resulting a prevalence of ~27% (prevalence = 0.27, 95% CI = 0.26, 0.27) globally. Central Asia had the highest prevalence of antibiotic use at ~55% (prevalence = (967/1748) = 0.55, 95% CI = 0.52, 0.59), followed by the Europe region with a prevalence of ~44% (prevalence = (5483/12502) = 0.44, 95% CI = 0.43, 0.45). In the South East and Central Asia region, DHS conducted between 2006 and 2018, showed the highest prevalence of antibiotic use in DHS 2007 (~44%), DHS 2012 (~49%), DHS 2016 (~40%) and DHS 2017 (~65%). The linear trend analysis showed an upward trend for using antibiotic of diarrhea in the South East and Central Asia region. CONCLUSIONS: The Central Asia region had the highest proportion of antibiotic use, with an estimated prevalence of ~55% (95% CI = 0.52, 0.59). The Europe region followed closely with a prevalence of ~44% (95% CI = 0.43, 0.45). The South East Asia region had the lowest prevalence of antibiotic use estimated at ~23% (95% CI = 0.22, 0.24), with a gradual increasing trend.

Fiber nonlinearity compensation for OFDM super-channels using optical phase conjugation.

We experimentally demonstrate that mid-link optical phase conjugation (OPC) effectively compensates fiber nonlinearity in coherent optical OFDM super-channels. The OPC was produced by pump × subcarrier degenerate four-wave-mixing in a 1-km highly nonlinear fiber. The nonlinear threshold for the 10 × 80-km 604.7-Gb/s 16-QAM test system was increased by 4.8 dB. The performance at the optimum power was only improved by 0.2 dB because the OPC module produces a 1.6 dB penalty for the back-to-back system. FWM theory shows that the 'noise' processes of OPC modules utilizing χ3 nonlinearities could be reduced by increasing the pump power, which will improve back-to-back performance with the OPC module.

Study on hydraulic spray atomizing system as a new resource-efficient dyeing-finishing method for wool fabric.

This study introduces hydraulic spray (HS) atomizing system as new resource-efficient continuous dyeing-finishing method for wool fabric. Here, wool fabric was dyed and finished by using commercial dyes and finishes through either one-step or two-steps HS method. Results obtained from color strength (K/S), color difference (ΔECMC) and color fastness analysis presented the apprehension of HS method in dyeing of wool fabric with different GSM and dyes. Finishing performance of wool fabric was measured through water contact angle analysis. Analysis shows that, the finishing performance of HS method were substantial to reach water contact angle as high as 145° while maintaining high fastness to wash and abrasion. Between one-step and two-steps HS method, one-step method showed better performance with high resource efficiency compared to two-steps method. Results from statistical analysis shows no statistical significance of fabric weight, type of dyes, and finishes to the performance of new HS method which is crucial for true-scale industrial implementation and scaling up of this process. The findings of this report are of great importance as it presents a greener alternative to the conventional resource-intensive dyeing-finishing methods of wool fabric.

Alkynylation of benzotriazole with silylethynyliodonium triflates. Regioselective synthesis of 2-ethynyl-2H-benzotriazole derivatives.

Phenyl(trimethylsilylethynyl)iodonium and tert-butyldimethylsilylethynyl(phenyl)iodonium triflates were applied to alkynylation of benzotriazole. Treatment of the silylethynyliodonium triflates with the potassium salt of benzotriazole ion in (t)BuOH and CH(2)Cl(2) gave 2-(trimethylsilylethynyl)-2H-1,2,3-benzotriazole and 2-(tert-butyldimethylsilylethynyl)-2H-1,2,3-benzotriazole in 74% and 76% yields, respectively. The regioisomers, 1-silylethynyl-1H-1,2,3-benzotriazole derivatives, were minor. In both cases of the silyl-substitued ethynyliodonium salts, novel regioselective alkynylation of benzotriazole at the 2 position was observed.

Computational approach to the identification of novel Aurora-A inhibitors.

Aurora kinase A has been emerging as a key therapeutic target for the design of anticancer drugs. For the purpose of finding biologically active and novel compounds and providing new ideas for drug-design, we performed virtual screening using commercially available databases. A three-dimensional common feature pharmacophore model was developed with the HipHop program provided in the Catalyst software package, and this model was used as a query for screening the databases. A recursive partitioning (RP) model was developed as a filtering system, which was able to classify active and inactive compounds. Eventually, a step-wise virtual screening procedure was conducted by applying the common feature pharmacophore and the RP model in succession to discover novel potent Aurora-A inhibitors. A total of 68 compounds were selected for testing of their in vitro anticancer activities against various human cancer cell lines. Based on the activity data, we have identified fifteen compounds that warrant further investigation. Several compounds have a high inhibition rate (above 80% at 10 µM) and a GI50 lower than 5 µM for the cell lines DU145 and HT29. Enzyme assay for these compounds identified hits with micro molar activity. Compound C11 has the highest activity (IC50 = 5.09 µM). The hits obtained from this screening scheme could be potential drug candidates after further optimization.

An overview on biocatalysts immobilization on textiles: Preparation, progress and application in wastewater treatment.

The immobilization of biocatalysts or other bioactive components often means their transformation from a soluble to an insoluble state by attaching them to a solid support material. Various types of fibrous textiles from both natural and synthetic sources have been studied as suitable support material for biocatalysts immobilization. Strength, inexpensiveness, high surface area, high porosity, pore size, availability in various forms, and simple preparation/functionalization techniques have made textiles a primary choice for various applications. This led to the concept of a new domain called-biocatalysts immobilization on textiles. By addressing the growing advancement in biocatalysts immobilization on textile, this study provides the first detailed overview on this topic based on the terms of preparation, progress, and application in wastewater treatment. The fundamental reason behind the necessity of biocatalysts immobilized textile as well as the potential preparation methods has been identified and discussed. The overall progress and performances of biocatalysts immobilized textile have been scrutinized and summarized based on the form of textile, catalytic activity, and various influencing factors. This review also highlighted the potential challenges and future considerations that can enhance the pervasive use of such immobilized biocatalysts in various sustainable and green chemistry applications.

Epidemiology of Cryptococcus gattii, British Columbia, Canada, 1999-2007.

British Columbia, Canada, has the largest reported population of Cryptococcus gattii-infected persons worldwide. To assess the impact of illness, we retrospectively analyzed demographic and clinical features of reported cases, hospitalizations, and deaths during 1999-2007. A total of 218 cases were reported (average annual incidence 5.8 per million persons). Most persons who sought treatment had respiratory illness (76.6%) or lung cryptococcoma (75.4%). Persons without HIV/AIDS hospitalized with cryptococcosis were more likely than those with HIV/AIDS to be older and admitted for pulmonary cryptococcosis. The 19 (8.7%) persons who died were more likely to be older and to have central nervous system disease and infection from the VGIIb strain. Although incidence in British Columbia is high, the predominant strain (VGIIa) does not seem to cause greater illness or death than do other strains. Further studies are needed to explain host and strain characteristics for regional differences in populations affected and disease outcomes.

Development of a multifunctional graphene/Fe-loaded polyester textile: robust electrical and catalytic properties.

A graphene/Fe loaded polyester fabric (PET) with robust electrical and catalytic properties has been successfully developed for the first time via a simple coating-incorporation method using hyperbranched poly(amidoamine) (PAMAM) dendrimer as the binder. Both graphene oxide (GO/rGO) and zerovalent iron (Fe0) nanoparticles were loaded on the polyester fabric surface before and after chemical grafting of PAMAM. Full characterization of fabrics before and after modifications has been performed by sessile droplet goniometry, ζ-potential, K/S coating evenness, SEM, XPS, FTIR, TGA and DSC analyses. The results showed successful and uniform coating of GO/rGO and loading of Fe0 on PET and also showed the correlation between the type of chemical moiety responsible for uniform GO coating, high Fe0 loading and their electrical and catalytic activities. Sheet resistance (Rsh) analysis was carried out to measure the conductivity of the samples. The lowest Rsh (corresponding to high conductivity) was found in PET-PAM-rGO-Fe0 (0.74 ± 0.13 kΩ sq-1) followed by PET-rGO-Fe0 (1.32 ± 0.18 kΩ sq-1), PET-PAM-rGO (2.96 ± 0.08 kΩ sq-1) and PET-rGO (3.41 ± 0.34 kΩ sq-1). Furthermore, Fe0-loaded samples were found to be effective in the catalytic removal of toxic water pollutants (crystal violet dye) with ∼99% removal of pollutants in around one hour, as observed by UV-vis spectroscopy. The relatively high electrical conductivity and catalytic activity of PET-PAM-rGO-Fe0 are related to the role played by PAMAM in the uniform rGO coating and high Fe0 loading. These findings are of great importance as they allow envisaging the development of multifunctional textiles for combined smart and green chemistry application.

Statistical modeling and optimization of heterogeneous Fenton-like removal of organic pollutant using fibrous catalysts: a full factorial design.

This work focuses on the optimization of heterogeneous Fenton-like removal of organic pollutant (dye) from water using newly developed fibrous catalysts based on a full factorial experimental design. This study aims to approximate the feasibility of heterogeneous Fenton-like removal process and optionally make predictions from this approximation in a form of statistical modeling. The fibrous catalysts were prepared by dispersing zerovalent iron nanoparticles on polyester fabrics (PET) before and after incorporation of either polyamidoamine (PAMAM, -NH2) dendrimer, 3-(aminopropyl) triethoxysilane (APTES, -Si-NH2) or thioglycerol (SH). The individual effect of two main factors [pH (X1) and concentration of hydrogen peroxide-[H2O2]µl (X2)] and their interactional effects on the removal process was determined at 95% confidence level by an L27 design. The results indicated that increasing the pH over 5 decreases the dye removal efficiency whereas the rise in [H2O2]µl until equilibrium point increases it. The principal effect of the type of catalysts (PET-NH2-Fe, PET-Si-NH2-Fe, and PET-SH-Fe) did not show any statistical significance. The factorial experiments demonstrated the existence of a significant synergistic interaction effect between the pH and [H2O2]µl as expressed by the values of the coefficient of interactions and analysis of variance (ANOVA). Finally, the functionalization of the resultant fibrous catalysts was validated by electrokinetic and X-ray photoelectron spectroscopy analysis. The optimization made from this study are of great importance for rational design and scaling up of fibrous catalyst for green chemistry and environmental applications.

Modification of fibrous membrane for organic and pathogenic contaminants removal: from design to application.

In this study, a flexible multifunctional fibrous membrane for heterogeneous Fenton-like removal of organic and pathogenic contaminants from wastewater was developed by immobilizing zerovalent iron nanoparticles (Fe-NPs) on an amine/thiol grafted polyester membrane. Full characterization of the resulting polyester membranes allowed validation of successful grafting of amine/thiol (NH2 or SH) functional groups and immobilization of Fe-NPs (50-150 nm). The Fenton-like functionality of iron immobilized fibrous membranes (PET-Fe, PET-Si-NH2-Fe, PET-NH2-Fe, and PET-SH-Fe) in the presence of hydrogen peroxide (H2O2) was comparatively studied in the removal of crystal violet dye (50 mg L-1). The effect of pH, amount of iron and H2O2 concentration on dye removal was systematically investigated. The highest dye removal yield reached 98.87% in 22 min at a rate constant 0.1919 min-1 (R 2 = 95.36) for PET-SH-Fe providing 78% toxicity reduction assessed by COD analysis. These membranes could be reused for up to seven repeated cycles. Kinetics and postulated mechanism of colour removal were proposed by examining the above results. In addition, the resultant membranes showed substantial antibacterial activity against pathogenic bacteria (Staphylococcus epidermidis, Escherichia coli) strains studied through disc diffusion-zone inhibitory and optical density analysis. These findings are of great importance because they provide a prospect of textile-based flexible catalysts in heterogeneous Fenton-like systems for environmental and green chemistry applications.

The thickness of electrospun poly (epsilon-caprolactone) nanofibrous scaffolds influences cell proliferation.

Nanofibrous scaffolds have morphological similarities to native extracellular matrix and have been considered as candidate scaffolds in tissue engineering. However, there is no report on the effect of the thickness of nanofibrous scaffold on cell behavior. In this study poly (epsilon-caprolactone) (PCL) nanofibrous scaffolds with thicknesses of 0.1 and 0.6 mm were fabricated by electrospinning. Properties of PCL nanofibrous scaffolds were measured by contact angle and air permeability measurements while the morphology of the nanofibers was observed by SEM. Mouse embryonal carcinoma stem cells (P19), monkey epithelial kidney cells (Vero), Chinese hamster ovary cells (CHO) and mouse mesenchymal stem cells (MSCs) were seeded on PCL nanofibrous scaffolds with thicknesses of 0.1 and 0.6 mm. Air permeability measurements showed that air permeability decreases with the increase in the thickness of nanofibrous scaffolds, and contact angle measurements revealed a contact angle of 118 degrees for electrospun PCL nanofibers. The MTT assays showed that the proliferation of the cells was influenced by the thickness of the nanofibrous scaffold. Scaffolds with a thickness of 0.6 mm were found to provide a better substrate for cell proliferation, possibly due to more dimensional stability. Therefore, regardless of cell origin, thicker scaffolds provide a better substrate for cell proliferation, possibly due to the higher dimensional stability and tightness of thicker scaffolds.

Surface modification of polyester fabric using plasma-dendrimer for robust immobilization of glucose oxidase enzyme.

Robust immobilization of glucose oxidase (GOx) enzyme was achieved on poly(ethylene terephthalate) nonwoven fabric (PN) after integration of favourable surface functional groups through plasma treatments [atmospheric pressure-AP or cold remote plasma-CRP (N2 + O2)] and/or chemical grafting of hyperbranched dendrimers [poly-(ethylene glycol)-OH or poly-(amidoamine)]. Absorption, stability, catalytic behavior of immobilized enzymes and reusability of resultant fibrous bio-catalysts were comparatively studied. Full characterization of PN before and after respective modifications was carried out by various analytical, instrumental and arithmetic techniques. Results showed that modified polyester having amine terminal functional groups pledged better surface property providing up to 31% enzyme loading, and 81% active immobilized enzymes. The activity of the enzyme was measured in terms of interaction aptitude of GOx in a given time to produce hydrogen peroxide using colorimetric assay. The immobilized GOx retained 50% of its original activity after being reused six (06) times and exhibited improved stability compared with the free enzyme in relation to temperature. The reaction kinetics, loading efficiency, leaching, and reusability analysis of enzyme allowed drawing a parallel to the type of organic moiety integrated during GOx immobilization. In addition, resultant fibrous bio-catalysts showed substantial antibacterial activity against pathogenic bacteria strains (Staphylococcus epidermidis and Escherichia coli) in the presence of oxygen and glucose. These results are of great importance because they provide proof-of-concept for robust immobilization of enzymes on surface-modified fibrous polyester fabric for potential bio-industrial applications.

Iron-loaded amine/thiol functionalized polyester fibers with high catalytic activities: a comparative study.

Dispersion of iron nanoparticles (Fe-NPs) was achieved on polyester fabrics (PET) before and after the incorporation of dendrimers (PAMAM), 3-(aminopropyl) triethoxysilane (APTES) or thioglycerol (SH). The catalytic activity of the resulting materials (PET-Fe, PET-PAMAM-Fe, PET-APTES-Fe and PET-SH-FE) was comparatively investigated in the degradation of 4-nitrophenol (4-NP) and methylene-blue (MB). Full characterization through diverse instrumental methods allowed correlating the type of the organic moiety incorporated with the Fe content, catalytic properties and stability. The highest 4-NP degradation yield reached 99.6% in 12 min for PET-SH-Fe. The catalytic activity was explained in terms of reactant interaction with Fe-NPs. The 1st order reaction kinetics and pseudo-1st order adsorption kinetics provide evidence of the key role of reactant adsorption. These findings allow envisaging the preparation of fiber-based catalysts for potential uses in environmental and green chemistry.

A ternary nanofibrous scaffold potential for central nerve system tissue engineering.

In the present research, a ternary polycaprolactone (PCL)/gelatin/fibrinogen nanofibrous scaffold for tissue engineering application was developed. Through this combination, PCL improved the scaffold mechanical properties; meanwhile, gelatin and fibrinogen provided more hydrophilicity and cell proliferation. Three types of nanofibrous scaffolds containing different fibrinogen contents were prepared and characterized. Morphological study of the nanofibers showed that the prepared nanofibers were smooth, uniform without any formation of beads with a significant reduction in nanofiber diameter after incorporation of fibrinogen. The chemical characterization of the scaffolds confirmed that no chemical reaction occurred between the scaffold components. The tensile test results of the scaffolds showed that increasing in fibrinogen content led to a decrease in mechanical properties. Furthermore, adipose-derived stem cells were employed to evaluate cell-scaffold interaction. Cell culture results indicated that higher cell proliferation occurred for the higher amount of fibrinogen. Statistical analysis was also carried out to evaluate the significant difference for the obtained results of water droplet contact angle and cell culture. Therefore, the results confirmed that PCL/gel/fibrinogen scaffold has a good potential for tissue engineering applications including central nerve system tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2394-2401, 2018.

Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function against Aß-induced neurotoxicity.

Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine group. A series of SVH07 analogues were synthesized and their effects on the mitochondrial membrane potential and ATP production were determined by using neuronal cells under Aß-induced toxicity. Among these analogues, compound 26 significantly recovered mitochondrial membrane depolarization and ATP production. In vitro binding assays indicated that SVH07 and 26 showed high affinities to TSPO with the IC50 values in a nanomolar range. We believe that compound 26 is a promising lead compound for the development of TSPO-targeted mitochondrial functional modulators with therapeutic potential in AD.

Synthesis of polyester urethane urea and fabrication of elastomeric nanofibrous scaffolds for myocardial regeneration.

Fabrication of bioactive scaffolds is one of the most promising strategies to reconstruct the infarcted myocardium. In this study, we synthesized polyester urethane urea (PEUU), further blended it with gelatin and fabricated PEUU/G nanofibrous scaffolds. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and X-ray diffraction were used for the characterization of the synthesized PEUU and properties of nanofibrous scaffolds were evaluated using scanning electron microscopy (SEM), ATR-FTIR, contact angle measurement, biodegradation test, tensile strength analysis and dynamic mechanical analysis (DMA). In vitro biocompatibility studies were performed using cardiomyocytes. DMA analysis showed that the scaffolds could be reshaped with cyclic deformations and might remain stable in the frequencies of the physiological activity of the heart. On the whole, our study suggests that aligned PEUU/G 70:30 nanofibrous scaffolds meet the required specifications for cardiac tissue engineering and could be used as a promising construct for myocardial regeneration.