The optimization and synthesis of new CK2 and CK1 inhibitors are the basis for the development of new therapeutic strategies for the treatment of cancer and neurodegenerative disorders associated with overexpression and abnormal functioning of these enzymes. Triazole derivatives appear to be especially interesting as potential kinase inhibitors. In this context we synthesized a series of 1,2,4-triazolin-5-thione derivatives as CK1γ kinase inhibitors. The antiproliferative activity of synthesized compounds was assessed against cancer cells human lung adenocarcinoma (A549), human hepatoma (HepG2), and human breast adenocarcinoma (MCF-7). Compound 1 exhibited antiproliferative potency against A549 cancer cells and was characterized by a selective antiproliferative effect. Additionally, this compound has high apoptotic activity against A549, HepG2, MCF-7 cells and induced only slight amount of necrotic cells in these cell lines. In order to decipher the mechanism of anticancer activity of the studied compounds PASS software was used and these compounds were assayed for the inhibition of CK1γ and CK2α kinases. The reported series of 1,2,4-triazolin-5-thiones inhibits CK1γ and CK2α kinases in micromolar range. The most active compound shows activity against isoform γ3 which at concentration of 50 μM reduced the kinase activity by 69% while at 100 μM by 80%. CK2α was found to be less susceptible to the effects of the triazoles tested, as the reduction in kinase activity by 29% was observed for compound 15, and by 27% for compound 1 only at the concentration of 100 μM. The inhibition of CK1γ and CK2α kinases was rationalized using molecular docking. Lung cancer is the most common cancer and leading cause of cancer-related deaths worldwide. The first-generation reversible, ATP-competitive inhibitors gefetinib and elotinib showed good clinical responses in lung adenocarcinoma tumors (NSCLC). But almost all patients developed resistance to these inhibitors over time. Such resistance of EGFR inhibitors was frequently linked to the acquired L858R and T790M point mutations in the kinase domain of EGFR. To overcome these resistance problems, the second and the third generation inhibitors have been discovered. FDA approved afatinib, the second generation irreversible inhibitor and osimitinib, the third generation irreversible EGFR inhibitors for the treatments of NSCLC. We identified new covalent quinazoline inhibitors (E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide (6d) and (E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4-(dimethyl-amino)but-2-enamide (6h) that exhibited potent EGFR kinase inhibitory activities on L858R and T790M mutations. The compound 6 h showed selectivity similar to AZD9291 (osimertinib) in mutated and wild type tumor cell lines. In vitro cell assay 6d and 6h were better than afatinib and osimertinib. In vivo antitumor efficacy studies of these compounds were done in NCI-H1975 mice xenografts. A number of new fluorescent nucleic acid binding ligands were synthesized by utilizing the non-specific thiazole orange dye as the basic scaffold for molecular design. Under simple synthetic conditions, the molecular scaffold of thiazole orange bridged with a terminal side-group (phenol or methoxybenzene) becomes more flexible because the newly added ethylene bridge is relatively less rigid than the methylene of thiazole orange. It was found that these molecules showed better selectivity towards G-quadruplex DNA structure in molecular interactions with different type of nucleic acids. The difference in terms of induced DNA-ligand interaction signal, selectivity, and binding affinity of the ligands with the representative nucleic acids including single-stranded DNA, double-stranded DNA, telomere and promoter G4-DNA and ribosomal RNA were investigated. The position of the terminal methoxyl groups was found showing strong influence both on binding affinity and fluorescent discrimination among 19 nucleic acids tested. The ligand with a methoxyl group substituted at the meta-position of the styryl moiety exhibited the best fluorescent recognition performance towards telo21 G4-DNA. A good linear relationship between the induced fluorescent binding signal and the concentration of telo21 was obtained. The comparison of ligand-DNA interaction properties including equilibrium binding constants, molecular docking, G4-conformation change and stabilization ability for G4-structures was also conducted. Two cancer cell lines (human prostate cancer cell (PC3) and human hepatoma cell (hepG2)) were selected to explore the inhibitory effect of the ligands on the cancer cell growth. The IC50 values obtained in the MTT assay for the two cancer cells were found in the range of 3.4-10.8 μM. In this paper, a novel strategy in the application of the parallel factor analysis (PARAFAC) to a four-way voltammetric dataset was improved to evidence the interaction of etoposide (ETO) and calf thymus deoxyribonucleic acid (DNA) to determine the ETO-DNA binding constant. PARAFAC is one of the most commonly used techniques applicable to the decomposition of higher-order data arrays to focus on features of interest and provides a different resolution of the chemical problem of interest. Under optimized conditions, peak current data of a seven-sample set containing DNA in the range of 2.0-90.0 µM in the presence of ETO at a constant concentration (10 µM) at five different pHs were recorded as a function of potential and frequency and then arranged as a four-dimensional array. The characteristic curves of ETO and ETO-DNA complex were monitored from the potential, frequency, pH, and DNA concentration profiles obtained by PARAFAC decomposition of the fourth-order array. The binding constant, which is one of the principal parameters for the estimation of drug-DNA interaction and mechanism, was computed from the DNA concentration profile. The consequence of drug-DNA binding constant (K = 1.26 × 106) indicated that there was a significant interaction between ETO and DNA with the intercalation mechanism. The modeling and simulation of experimental families of current-time (I-t) curves of dimeric voltage-gated proton channels and of proton-conducting voltage sensing domains (VSDs) with a minimum of free parameters requires the movement of protons to be controlled by the rate of increase of the Boltzmann open probability p over time in passing from the holding to the depolarizing potential. Families of I-t curves of protomers and proton-conducting VSDs can be satisfactorily fitted by the use of a single free parameter expressing the rate constant kp for the increase of p over time. Families of I-t curves of dimeric Hv1 channels can be fitted by a model that assumes an initial proton current I1 flowing along the two monomeric units, while they are still operating separately; I1 is gradually replaced by a slower and more potential-dependent current I2 flowing when the two monomers start operating jointly under the control of the coiled-coil domain. Here too, p is assumed to increase over time with a rate constant kp that doubles in passing from I1 to I2, with fit requiring three free parameters. Chord conductance yields erroneously high gating charges when fitted by the Boltzmann function, differently from slope conductance. Co-metabolism is one of the effective approaches to increase the removal of refractory pollutants in microbial fuel cells (MFCs), but studies on the links between the co-substrates and biodegradation remain limited. In this study, four external carbon resources were used as co-substrates for phenol removal and power generation in MFC. The result demonstrated that acetate was the most efficient co-substrate with an initial phenol degradation of 78.8% and the voltage output of 389.0 mV. Polarization curves and cyclic voltammogram analysis indicated that acetate significantly increased the activity of extracellular electron transfer (EET) enzyme of the anodic microorganism, such as cytochrome c OmcA. GC-MS and LC-MS results suggested that phenol was biodegraded via catechol, 2-hydroxymuconic semialdehyde, and pyruvic acid, and these intermediates were reduced apparently in acetate feeding MFC. The microbial community analysis by high-throughput sequencing showed that Acidovorax, Geobacter, and Thauera were predominant species when using acetate as co-substrate. It can be concluded that the efficient removal of phenol was contributed to the positive interactions between electrochemically active bacteria and phenolic degradation bacteria. This study might provide new insight into the positive role of the co-substrate during the treatment of phenolic wastewater by MFC. V.This research presents a novel comprehensive method for optimizing the design of cavitating slit Venturi for a given cavitation intensity. This method is applicable to any cavitation number and can be used to provide the Venturi geometry that is suitable for a specific application. In this paper, cavitating Venturi design process is represented in seven steps. As an example, for the cavitation number of 0.2, geometrical and operational parameters of the Venturi were determined using the proposed seven steps. During the design process, the Venturi discharge coefficient was calculated using computational fluid dynamics (CFD) simulations. Furthermore, Venturi parameters such as inlet pressure, throat area, width, length, height and divergence angle, were optimized by the combination of CFD and Response Surface Methodology (RSM). In addition to calculating the mentioned optimum parameters, other hydraulic parameters of Venturi including discharge coefficient, flowrate, throat velocity, cavitation volume and length were also determined. Finally, the proposed design method in this study was verified by conducting sets of laboratory experiments. OBJECTIVES Sarcopenic obesity (SO) is characterized by the co-occurrence of high adiposity (HA) and low muscle mass (LM) and has been associated with an increased risk for cardiometabolic diseases. The aim of this study was to investigate the association between markers of insulin sensitivity and SO defined by three novel body composition models body composition phenotypes; truncal fat mass-to-appendicular skeletal mass (TrFM/ASM) ratio load capacity; and fat mass-to-fat-free mass (FM/FFM) ratio load capacity. METHODS The study included 314 participants 18 to 65 y of age. Body composition was assessed by dual-energy x-ray absorptiometry. The first model includes four phenotypes low adiposity-high muscle mass (LA-HM), high adiposity-high muscle mass (HA-HM), low adiposity-low muscle mass (LA-LM), and high adiposity-low muscle mass (HA-LM). The second and third load-capacity models stratified participants into three centile groups less then 15th, 15th to 84th and ≥85th. A 2-h oral glucose tolerance test was performed and insulin sensitivity was calculated using the Matsuda Index. Glycated hemoglobin and highly sensitive C-reactive protein also were measured. RESULTS Lower insulin sensitivity was observed in the HA-LM (P less then 0.001) and in the ≥85th centile groups of the TrFM/ASM ratio (P less then 0.001) and the FM/FFM ratio (P = 0.001) compared with the other body composition phenotypes. The HA-LM and ≥85th centile group of the TrFM/ASM ratio model showed significantly higher (P less then 0.001) concentrations of glycated hemoglobin compared with the other phenotypes. CONCLUSIONS SO defined by both the four body composition phenotypes and TrFM/ASM definitions was associated with greater impairment of insulin sensitivity and glycemic control.