Discovery of novel BRD4-BD2 inhibitors via in silico approaches: QSAR techniques, molecular docking, and molecular dynamics simulations.

Bromodomain-containing protein 4(BRD4) plays an important role in the occurrence and development of various malignant tumors, which has attracted the attention of scientific research institutions and pharmaceutical companies. The structural modification of most currently available BRD4 inhibitors is relatively simple, but the drug effectiveness is limited. Research has found that the inhibition of BD1 may promote the differentiation of oligodendrocyte progenitor cell; however, the inhibition of BD2 will not cause this outcome. Therefore, newly potential drugs which target BRD4-BD2 need further research. Herein, we initially built QSAR models out of 49 compounds using HQSAR, CoMFA, CoMSIA, and Topomer CoMFA technology. All of the models have shown suitable reliabilities (q2 = 0.778, 0.533, 0.640, 0.702, respectively) and predictive abilities (r2pred = 0.716, 0.6289, 0.6153, 0.7968, respectively) for BRD4-BD2 inhibitors. On the basis of QSAR results and the search of the R-group in the topomer search module, we designed 20 new compounds with high activity that showed appropriate docking score and suitable ADMET. Docking studies and MD simulation were carried out to reveal the amino acid residues (Asn351, Cys347, Tyr350, Pro293, and Asp299) at the active site of BRD4-BD2. Free energy calculations and free energy landscapes verified the stable binding results and indicated stable conformations of the complexes. These theoretical studies provide guidance and theoretical basis for designing and developing novel BRD4-BD2 inhibitors.

[Preparation of Iron-Aluminum Modified Diatomite and Its Immobilization in Cadmium-Polluted Soil].

To improve the in-situ immobilization effect of diatomite on cadmium (Cd)-contaminated soil, diatomite was modified by hydroxyl iron-aluminum (Fe-Al). The soil incubation experiments were carried out to investigate the effect of Fe/Al molar ratio, OH/cation of molar ratio, pillaring agent aging time, (Fe+Al)/diatomite ratio, pillaring temperature, and pillaring product aging time on the immobilization of Cd in soils. The changes in properties of diatomite before and after modification were analyzed by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The results showed that:the optimal preparation conditions for modification were:Fe/Al molar ratio=1:8, OH/cation molar ratio 2.0-2.2, pillaring agent aging time=2 d, (Fe+Al)/diatomite ratio=10 mmol·g-1, pillaring temperature=60℃, pillaring product aging time=2 d. The hydroxyl-Fe-Al-modified diatomite significantly reduced the content of exchangeable Cd in soil, and the modification reduced soil exchangeable Cd from 11.83% to 39.52%. The SEM and FTIR analyses of hydroxyl-Fe-Al-modified diatomite revealed increase in the specific surface area of diatomite and the amount of the Si-O-H groups. After modification, the hydroxyl-Fe-Al successfully exchanged into the diatom shell forming available pillars, thus increasing channel spacing and enhancing the microporous surface activity. The modification with hydroxyl-Fe-Al increased the immobilization effect of diatomite on Cd in soil. The modification methods and data from this study will help increase the application of diatomite materials for the immobilization of soil containing heavy metals.

Application of TiO2-organobentonite modified by cetyltrimethylammonium chloride photocatalyst and polyaluminum chloride coagulant for pretreatment of aging landfill leachate.

This study investigated the treatment performance for aging leachate containing refractory organic pollutants by TiO2-organobentonite photocatalyst combined with polyaluminum chloride (PAC) coagulant. TiO2 was immobilized on organobentonite granules as a supporter modified by cetyltrimethylammonium chloride (CTAC). The prepared catalysts were characterized by ESEM, FTIR, and XRD analysis, which showed that TiO2-organobentonite catalyst had uniform coating of TiO2 on support. Chemical oxygen demand (COD) and NH3-N removal rates by combination of TiO2-CTAC2.0 photocatalysis and PAC coagulation were evaluated, optimized, and compared to that by either treatment alone, with respect to TiO2-CTAC2.0 dose, photocatalytic contact time, pH, and PAC dose. Furthermore, higher removal rates (COD 80 %; NH3-N 46 %) were achieved by response surface methodology (RSM) when TiO2-CTAC2.0 photocatalysis was followed by PAC coagulation at optimized conditions. The optimized experimental conditions were TiO2-CTAC2.0 dosage of 5.09 g/L, at pH 5.53, photocatalytic contact time for 180 min, and PAC dosage of 1062 mg/L.

Combination of cathodic reduction with adsorption for accelerated removal of Cr(VI) through reticulated vitreous carbon electrodes modified with sulfuric acid-glycine co-doped polyaniline.

Improving the reduction kinetics is crucial in the electroreduction process of Cr(VI). In this study, we developed a novel adsorption-electroreduction system for accelerated removal of Cr(VI) by employing reticulated vitreous carbon electrode modified with sulfuric acid-glycine co-doped polyaniline (RVC/PANI-SA-GLY). Firstly, response surface methodology confirmed the optimum polymerization condition of co-doped polyaniline for modifying electrodes (Aniline, sulfuric acid and glycine, respectively, of 0.2 mol/L, 0.85 mol/L, 0.93 mol/L) when untraditional dopant glycine was added. Subsequently, RVC/PANI-SA-GLY showed higher Cr(VI) removal percentages in electroreduction experiments over RVC electrode modified with sulfuric acid doped polyaniline (RVC/PANI-SA) and bare RVC electrode. In contrast to RVC/PANI-SA, the improvement by RVC/PANI-SA-GLY was more significant and especially obvious at more negative potential, lower initial Cr(VI) concentration, relatively less acidic solution and higher current densities, best achieving 7.84% higher removal efficiency with entire Cr(VI) eliminated after 900 s. Current efficiencies were likewise enhanced by RVC/PANI-SA-GLY under quite negative potentials. Fourier transform infrared (FTIR) and energy dispersive spectrometer (EDS) analysis revealed a possible adsorption-reduction mechanism of RVC/PANI-SA-GLY, which greatly contributed to the faster reduction kinetics and was probably relative to the absorption between protonated amine groups of glycine and HCrO4(-). Eventually, the stability of RVC/PANI-SA-GLY was proven relatively satisfactory.

A novel approach for improving the drying behavior of sludge by the appropriate foaming pretreatment.

Foaming pretreatment has long been recognized to promote drying materials with sticky and viscous behaviors. A novel approach, CaO addition followed by appropriate mechanical whipping, was employed for the foaming of dewatered sludge at a moisture content of 80-85%. In the convective drying, the foamed sludge at 0.70 g/mL had the best drying performance at any given temperature, which saved 35-41% drying time for reaching 20% moisture content compared with the non-foamed sludge. Considering the maximum foaming efficiency, the optimal CaO addition was found at 2.0 wt%. For a better understanding of the foaming mechanisms, the foamability of sludge processed with other pretreatment methods, including NaOH addition (0-3.0 wt%) and heating application (60-120 °C), were investigated while continuously whipping. Their recovered supernatant phases were characterized by pH, surface tension, soluble chemical oxygen demand (sCOD), protein concentration, polysaccharide concentration and spectra of excitation-emission matrices (EEM). These comparative studies indicated that the sludge foaming was mainly derived from the decreased surface tension by the surfactants and the promoted foam persistence by the protein derived compounds. Further, a comprehensive analysis of the sludge drying characteristics was performed including the surface moisture evaporation, the effective moisture diffusivity and the micromorphology of dried sludge. The results indicated that the drying advantages of foamed sludge were mainly attributed to the larger evaporation surface in a limited drying area and the more active moisture capillary movement through the liquid films, which resulted in longer constant evaporation rate periods and better effective moisture diffusivity, respectively.