Search

Background Multiple sclerosis (MS), as a neurodegenerative disorder, exhibits inflammation and oxidative stress hallmarks. Objective The research aims to know any disturbances in haematological parameters and antioxidant system of relapsing-remitting multiple sclerosis (RRMS) patients in the Kurdish population. Methods A case-control research meeting following the McDonald criterion was conducted on 100 RRMS patients and 100 controls. Results Lipid peroxidation products of malondialdehyde (MDA), erythrocyte sedimentation rate (ESR), and total leucocyte counts (TLCs) were increased significantly, but copper (Cu+2) and superoxide dismutase (SOD) were decreased significantly while nitric oxide metabolites (NOx) and lymphocyte were not changed significantly if compared with that of controls. Conclusion Findings from our study revealed that some defects were detected in haematological profiles in the Kurdish population and disturbance of immunological parameters. In addition, the utilization of Cu+2 supplement as an effective modality for RRMS patients may be beneficial.

Metallo-β-lactamases (MBLs) are an emerging cause of bacterial antibiotic resistance by hydrolysing all classes of β-lactams except monobactams, and the MBLs are not inhibited by clinically available serine-β-lactamase inhibitors. Two of the most commonly encountered MBLs in clinical isolates worldwide – the New Delhi metallo-β-lactamase (NDM-1) and the Verona integron-encoded metallo-β-lactamase (VIM-2) – are included in this study. A series of several NH-1,2,3-triazoles was prepared by a three-step protocol utilizing Banert cascade reaction as the key step. The inhibitor properties were evaluated in biochemical assays against the MBLs VIM-2, NDM-1 and GIM-1, and VIM-2 showed IC50 values down to nanomolar range. High-resolution crystal structures of four inhibitors in complex with VIM-2 revealed hydrogen bonds from the triazole inhibitors to Arg228 and to the backbone of Ala231 or Asn233, along with hydrophobic interactions to Trp87, Phe61 and Tyr67. The inhibitors show reduced MIC in synergy assays with Pseudomonas aeruginosa and Escherichia coli strains harbouring VIM enzymes. The obtained results will be useful for further structural guided design of MBL inhibitors.

Accepted manuscript version, licensed CC BY-NC-ND 4.0. " . Published version available in European Journal of Medicinal Chemistry. 135:159-173. Bacterial resistance is compromising the use of β-lactam antibiotics including carbapenems. The main resistance mechanism against β-lactams is hydrolysis of the β-lactam ring mediated by serine- or metallo-β-lactamases (MBLs). Although several inhibitors of MBLs have been reported, none has been developed into a clinically useful inhibitor. Mercaptocarboxylic acids are among the most prominent scaffolds reported as MBL inhibitors. In this study, the carboxylate group of mercaptocarboxylic acids was replaced with bioisosteric groups like phosphonate esters, phosphonic acids and NH-tetrazoles. The influence of the replacement on the bioactivity and inhibitor binding was evaluated. A series of bioisosteres of previously reported inhibitors was synthesized and evaluated against the MBLs VIM-2, NDM-1 and GIM- 1. The most active inhibitors combined a mercapto group and a phosphonate ester or acid, with two/three carbon chains connecting a phenyl group. Surprisingly, also compounds containing thioacetate groups instead of thiols showed low IC50 values. High-resolution crystal structures of three inhibitors in complex with VIM-2 revealed hydrophobic interactions for the diethyl groups in the phosphonate ester (inhibitor 2b), the mercapto bridging the two active site zinc ions, and tight stacking of the benzene ring to the inhibitor between Phe62, Tyr67, Arg228 and His263. The inhibitors show reduced enzyme activity in Escherichia coli cells harboring MBL. The obtained results will be useful for further structural guided design of MBL inhibitors.

The objectives of the present study were (1) to monitor the pattern of excretion of aflatoxinM1 in urine after its conversion from aflatoxinB1 and (2) to observe the effects of different levels of aflatoxinB1 in feed on serum concentrations of key metabolites glucose, total protein, cholesterol and urea as indicators of metabolic status. Nili-Ravi buffalo heifers (n = 12) of similar age and weight were randomly distributed to four groups. Animals in Groups A, B and C were offered a contaminated cottonseed cake-based concentrate ration at 0.5%, 1.0% and 1.5% of bodyweight, respectively. Control animals in Group D were fed with aflatoxinB1-free green fodder. Based on the level of contamination of the concentrate ration with aflatoxinB1 (554 µg/kg), Groups A, B and C consumed 953, 2022, 3202 µg of aflatoxinB1 daily. Feed samples were analysed at Romer Laboratories Pty Ltd, Singapore by high performance liquid chromatography. AflatoxinM1 quantification in urine samples was conducted using a competitive enzyme-linked immunosorbent assay with kits supplied by Helica Biosystems, Inc., USA. Serum samples were analysed for concentrations of glucose, total protein, cholesterol and urea using clinical chemistry kits provided by Human diagnostics (HUMAN, Biochemica und Diagnostica mbH, Germany). Carry-over rate of aflatoxinM1 in urine for Groups A, B and C was 15.51%, 15.44% and 14.04% of aflatoxinB1 while there was no detectable aflatoxinM1 in the urine of the control group (D). There was no significant difference in the concentrations of serum glucose, total protein and cholesterol between treatment groups. However, the concentration of serum urea was significantly higher (P < 0.05) in the group offered the highest level of aflatoxinB1-contaminated concentrate. This result suggests that mycotoxicosis may compromise protein metabolism and accretion in affected animals. This leaves open the possibility that high concentrations of aflatoxins in milk may ultimately affect the health status of human milk consumers.

The production performance of multiparous lactating Sahiwal cows (n = 24) was evaluated according to both milking frequency and method. Selected animals were randomly divided into four groups containing six animals each under a completely randomized design. Cows in groups A & B were milked by the hand milking method three times per day, respectively. Similarly, cows in groups C & D were milked by the machine milking method two and three times per day, respectively. All animals were maintained under uniform feeding and management conditions. Dry matter intake was high in animal groups milked three times per day, and it remained unchanged between the hand and machine milking methods. Milk yield was higher (P 0.05) among the treatment groups. Collectively, the results show that milking three times per day instead of twice at 8-hour intervals can enhance milk yield in Sahiwal cows using both hand and machine milking methods.

Here, we report a new post-synthesis modification strategy for functionalizing reduced graphene aerogels (rGAs) towards an exceptional CO2 separation performance. 1-N-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) was impregnated on a rGA, prepared by reducing GA at 700 degrees C, at various ionic liquid (IL) loadings of 5, 10, 30, and 50 wt%. The resulting composites were characterized in deep detail by X-ray photoelectron spectroscopy, X-ray diffraction, N-2 physical adsorption measurements, scanning electron microscopy, Fourier transform infrared and Raman spectroscopies, and thermogravimetric analysis. Results indicated the presence of interactions between the rGA surface and the anion of the IL, potentially improving the CO2 affinity. Volumetric gas adsorption measurements using these materials showed that the deposition of [BMIM][PF6] on rGA surface at an IL loading of 50 wt% boosts the CO2/CH4 selectivity by more than 20-times, exceeding an absolute value of 120, a remarkably higher CO2/CH4 selectivity compared to that of other functionalized materials under similar operating conditions. Tunability of both the IL structure and the surface characteristics of rGA offer a tremendous degree of flexibility for the rational design of these IL/rGA composites towards high performance in gas separation applications., Scientific and Technological Research Council of Turkey (TÜBİTAK); Koç University Seed Fund Program; HEC-Pakistan Scholarship; TARLA; METU Prof. Dr. Mustafa N. Parlar Education and Research Foundation's 2019 Research Incentive Award

1-ethyl-3-methylimidazolium diethyl phosphate ([EMIM][DEP]) was incorporated into copper benzene-1,3,5-tricarboxylate, CuBTC. Consequences of molecular interactions on the CO2 separation performance of CuBTC were investigated. Scanning electron microscopy and X-ray diffraction results showed that the surface morphology and crystal structure of CuBTC remained intact upon the incorporation of the ionic liquid (IL); and the results of thermogravimetric analysis and infrared spectroscopy indicated the presence of interactions between the anion of the IL and the open metal sites of CuBTC. Gas adsorption measurements for the pristine CuBTC and IL-incorporated CuBTC were performed at 25 °C in a pressure range of 0.1–1 bar. Data showed that ideal CO2/CH4 and CO2/N2 selectivities of IL-incorporated CuBTC were 1.6- and 2.4-times higher compared to those of the pristine CuBTC at 0.01 bar, respectively. Moreover, for the CO2/CH4:50/50 and CO2/N2:15/85 mixtures, the corresponding selectivities were improved by more than 1.5- and 1.9-times compared to that of pristine CuBTC at 0.01 bar, respectively., Scientific and Technological Research Council of Turkey (TÜBİTAK); 1001- Scientific and Technological Research Projects Funding Program; European Union (EU); Horizon 2020; European Research Council (ERC) Research and Innovation Programme; COSMOS; Koç University Seed Fund Program; TARLA; HEC Pakistan Scholarship; METU Mustafa Parlar Foundation of Science and Education Incentive Award

Here, we present a new concept of a core-shell type ionic liquid/metal organic framework (IL/MOF) composite. A hydrophilic IL, 1-(2-hydroxyethyl)-3-methylimidazolium dicyanamide, [HEMIM][DCA], was deposited on a hydrophobic zeolitic imidazolate framework, ZIF-8. The composite exhibited approximately 5.7 times higher CO2 uptake and 45 times higher CO2/CH4 selectivity at 1 mbar and 25 degrees C compared to the parent MOF. Characterization showed that IL molecules deposited on the external surface of the MOF, forming a core (MOF)-shell (IL) type material, in which IL acts as a smart gate for the guest molecules., Scientific and Technological Research Council of Turkey (TÜBİTAK); European Union (EU); H2020; European Research Council (ERC)-2017 Starting Grant; Koç University Seed Fund Program; Turkish Academy of Sciences (TÜBA)-GEBIP Award; TARLA; HEC Pakistan Scholarship

In this work, we propose a computational methodology based on the state-of-the-art molecular simulations of IL/CuBTC composites composed of ILs having the same cation, 1-n-butyl-3-methylimidazolium ([BMIM](+)), and various anions. Using grand canonical Monte Carlo (GCMC) simulations, we predicted CO2, CH4, and N-2 uptakes of seven different IL/CuBTC composites and compared the simulation results with our experimental gas uptake measurements to select the most appropriate force field that best represents the experimental results. Motivated from the good agreement between experiments and simulations, we applied the same method to estimate the gas adsorption in two new IL/CuBTC composites which have been synthesized and characterized for the first time in this work. Molecular simulations accurately predicted the experimental gas uptakes of newly synthesized IL/ CuBTC composites, validating the transferability of our approach to different types of IL-incorporated CuBTC samples. We also provided a detailed analysis of binary gas mixture separation performances of IL/CuBTC composites and self-diffusion coefficients of gases in the composites performing GCMC and molecular dynamics simulations, respectively. Results showed that IL/CuBTC composites have higher CO2/CH4, CO2/N-2, and CH4/N-2 selectivities than those of CuBTC, demonstrating a broad potential of these composites for CO2 separation from natural gas and flue gas mixtures. The combination of experiments and molecular simulations that we described in this study will be useful to efficiently screen various IL/MOF composites to unlock their full potential for gas separation applications., European Union (European Union); Horizon 2020; European Research Council (ERC); ERC-2017-Starting Grant; Scientific and Technological Research Council of Turkey (TÜBİTAK); 1001-Scientific and Technological Research Projects Funding Program; Koç University Seed Fund Program

[BMIM][PF6] and its methylated form, [BMMIM][PF6] were incorporated into CuBTC to examine the effect of methylation of ionic liquids (ILs) on the gas separation performance of the corresponding IL/metal–organic framework (MOF) composites., 1-N-Butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF6], and its methylated form, 1-N-butyl-2,3-dimethylimidazolium hexafluorophosphate, [BMMIM][PF6], were incorporated into CuBTC to examine the effect of methylation of ionic liquids (ILs) on the gas separation performance of the corresponding IL/metal–organic framework (MOF) composites. Spectroscopic analysis revealed that the interactions of the methylated ILs with CuBTC were weaker compared to those of its non-methylated counterpart. Gas uptake measurements illustrated that this difference in the interactions influences the gas separation performance of the composites. Accordingly, the CO2/N2: 15/85 and CH4/N2: 50/50 selectivities increased by 37% and 60% for [BMMIM][PF6]/CuBTC and 34% and 50% for [BMIM][PF6]/CuBTC, respectively, compared to the corresponding selectivities of pristine CuBTC at 1000 mbar. The results revealed another structural parameter controlling the performance of the IL/MOF composites, a novel type of material with rapidly expanding application areas.

Ionic liquid (IL)-incorporated metal organic frameworks (MOFs) are promising materials for gas adsorption and separation processes. In this work, 1-n-butyl-3-methylimidazolium thiocyanate ([BMIM][ SCN]) was incorporated in a zeolitic imidazolate framework (ZIF-8) to examine the adsorption and separation of different gases. X-ray diffraction (XRD) and scanning electron microscopy (SEM) results confirmed that ZIF-8 retains its structural integrity in the IL-incorporated sample. The Brunauer-Emmett-Teller (BET) surface area and pore volume of the IL-incorporated sample decreased significantly indicating the IL confinement into the MOF. Results of thermogravimetric analysis (TGA) demonstrate changes in the decomposition temperatures of both bulk IL and pristine ZIF-8 when the IL was incorporated into the MOF pores. Fourier transform infrared (FTIR) spectroscopy was performed to confirm the presence of interactions and successful incorporation of IL into MOF. Gas adsorption isotherms of CO2, CH4, and N-2 were measured for pristine ZIF-8 and IL-incorporated ZIF-8. The uptake amounts for each gas decreased as compared to their values on pristine ZIF-8, however, the decrease in the CO2 uptake was less compared to CH4 and N-2. The IL-incorporated sample exhibited approximately 2.6-times higher ideal selectivity for CO2/CH4 and four-times higher ideal selectivity for CO2/N-2 at 1 mbar than their corresponding values for pristine ZIF-8. These results indicate that IL-MOF combinations offer a huge potential for gas separations., Scientific and Technological Research Council of Turkey (TÜBİTAK) 1001-Scientific and Technological Research Projects Funding Program; European Union (EU) H2020; European Research Council (ERC)-2017 Starting Grant; Koç University Seed Fund Program

We investigated the influences of the changes in the electronic structure and size of the anion of an imidazolium ionic liquid (IL) on gas adsorption and separation performance of the IL/ZIF-8 (zeolitic imidazolate framework) composites. We studied four different imidazolium ILs having the same cation, 1-n-butyl-3-methylimidazolium, [BMIM]+, with anions having structures allowing a systematic comparison of the changes in the electronic structure and size. To examine the influence of changes in the electronic structure, we considered anions representing the fluorination on the anion, methanesulfonate, [MeSO3]−, and trifluoromethanesulfonate, [CF3SO3]−. To investigate the change in the anion size, methyl sulfate, [MeSO4]−, and octyl sulfate, [OcSO4]−, were studied. Characterization of IL/ZIF-8 composites demonstrated successful incorporation of each IL in ZIF-8 without causing any detectable changes in the crystal structure and morphology of ZIF-8. Thermogravimetric analysis and infrared (IR) spectroscopy indicated the presence of direct interactions between ILs and ZIF-8, which directly control gas separation performance of the composite. Gas adsorption measurements illustrated that incorporation of ILs significantly improves the gas separation performance of the pristine ZIF-8. [BMIM][MeSO4]/ZIF-8 composite had 3.3- and 1.8-times higher CO2/N2 and CH4/N2 selectivities compared to ZIF-8, respectively, at 1 bar. When the IL has a fluorinated anion, CO2/CH4 selectivity improved 3-times compared to its non-fluorinated counterpart. Upon the incorporation of IL with a small anion, IL/ZIF-8 composite showed higher CO2/N2 and CH4/N2 selectivities compared to the composite having an IL with a bulky anion. These results will contribute in guiding rational design of IL/MOF composites for different gas separations., Scientific and Technological Research Council of Turkey (TÜBİTAK); 1001- Scientific and Technological Research Projects Funding Program; ERC-2017 -Starting Grant; European Research Council (ERC); European Union (European Union); Horizon 2020; Koç University Seed Fund Program; HEC-Pakistan Scholarship