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SARS-CoV-2-Host Chimeric RNA-Sequencing Reads Do Not Necessarily Come up Through Malware Integration Into the Number Genetic make-up.
The ionization properties of protein side chains in lipid-bilayer membranes will differ from the canonical values of side chains exposed to an aqueous solution. While the propensities of positively charged side chains of His, Lys, and Arg to release a proton in lipid membranes have been rather well characterized, the propensity for a negatively charged Glu side chain to receive a proton and achieve the neutral state in a bilayer membrane has been less well characterized. Indeed, the ionization of the glutamic acid side chain has been predicted to depend on its depth of burial in a lipid membrane but has been difficult to verify experimentally. To address the issue, we incorporated an interfacial Glu residue at position 4 of a distinct 23-residue transmembrane helix and used 2H NMR to examine the helix properties as a function of pH. We observe that the helix tilt and azimuthal rotation vary little with pH, but the extent of helix unraveling near residues 3 and 4 changes as the Glu residue E4 titrates. Remarkably, the 2H quadrupolar splitting for the side chain of alanine A3 responds to pH with an apparent pK a of 4.8 in 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) and 6.3 in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC), but is unchanged up to pH 8.0 in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in the presence of residue E4. With bilayers composed of alkali-stable ether-linked lipids, the side chain of A3 responds to pH with an apparent pK a of 11.0 in the ether analogue of DOPC. These results suggest that the depth dependence of Glu ionization in lipid-bilayer membranes may be steeper than previously predicted or envisioned.Opportunistic fungal infections caused by Cryptococcus neoformans are a significant source of mortality in immunocompromised patients. They are challenging to treat because of a limited number of antifungal drugs, and novel and more effective anticryptococcal therapies are needed. Ciclopirox olamine, a N-hydroxypyridone, has been in use as an approved therapeutic agent for the treatment of topical fungal infections for more than two decades. It is a fungicide, with broad activity across multiple fungal species. We synthesized 10 N-hydroxypyridone derivatives to develop an initial structure-activity understanding relative to efficacy as a starting point for the development of systemic antifungals. We screened the derivatives for antifungal activity against C. neoformans and Cryptococcus gattii and counter-screened for specificity in Candida albicans and two Malassezia species. Eight of the ten show inhibition at 1-3 μM concentration (0.17-0.42 μg per mL) in both Cryptococcus species and in C. see more albicans, but poor activity in the Malassezia species. In C. neoformans, the N-hydroxypyridones are fungicides, are not antagonistic with either fluconazole or amphotericin B, and are synergistic with multiple inhibitors of the mitochondrial electron transport chain. They appear to function primarily by chelating iron within the active site of iron-dependent enzymes. This preliminary structure-activity relationship points to the need for a lipophilic functional group at position six of the N-hydroxypyridone ring and identifies positions four and six as sites where further substitution may be tolerated. These molecules provide a clear starting point for future optimization for efficacy and target identification.A novel azelaic acid/expanded graphite (AA/EG) phase change composite (PCC) was fabricated as a shape-stabilized phase change material (PCM) for latent heat storage at medium temperatures. The composite exhibited a low supercooling degree and high heat storage capacity. Despite the impregnation of a high quantity of AA (85 wt %) in the porous network of EG, there was no leakage of liquid AA. This was attributed to the capillary forces and surface tension forces. The pure AA exhibited a melting temperature of 108.0 °C, with an intrinsically low supercooling degree of 5.8 °C. The melting temperature of AA in the PCC decreased slightly to 105.8 °C, and there was a significant decrease in the supercooling degree to 1.0 °C. The AA/EG PCC exhibited a high latent heat storage capacity of 162.5 J/g, and there was a significant gap between the decomposition temperature and the phase change temperature range. Therefore, the composite exhibited high thermal stability during operations. The results of an accelerated thermal cycling test (200 cycles) indicated the high cycling durability and chemical stability of the PCC. The thermal conductivity of AA increased by 15.7 times after impregnation in EG, as compared to that of the pure AA, and thus, thermal kinetics of the PCC was improved. The results of a heat storage/release test with 15 g of the PCM revealed that the melting and solidification of the AA/EG PCC were 5.0-fold and 7.4-fold faster, respectively, than those of the pure AA. This was attributed to the high thermal conductivity of the PCC.The organic soluble extractant bis(2,4,4-trimethylpentyl)dithiophosphinic acid, often called Cyanex 301 (HC301), has shown selectivity for preferentially extracting trivalent actinides over the lanthanides in the treatment of used nuclear fuel. To maintain control and efficiency of a separation process using this extractant, it is necessary to accurately know specific parameters of the system, including the concentration of HC301 in the organic phase, at any given time. Here, the ability to quickly determine the concentration of HC301 in n-dodecane was tested by a one-step permanganometric titration in an organic solution using a double-beam UV-vis spectrophotometer. The addition of HC301 in n-dodecane to solutions of KMnO4 was found to decolorize the KMnO4 solutions, but the HC301 was best quantified in terms of decolorization in acetone. This decolorization allowed for the creation of a linear analytical curve relating the amount of KMnO4 consumed to the amount of HC301 added. Cross-validation of this analytical curve reproduced the known amount of HC301 with an average difference of 1.73% and a maximum of 4.03%.MFI-type zeolitic membranes were prepared on the porous α-A2O3 support to investigate the separation properties of dichlorobenzene isomers. The pervaporation tests were performed with unary and binary isomer mixtures at 333 K. The results indicate that the silicalite membranes, irrespective of being synthesized by the templated or template-free method, are permeable for all dichlorobenzene isomers. The pervaporation fluxes of the pure dichlorobenzene isomers decrease in the order p-DCB > o-DCB > m-DCB. For the binary pervaporation system, the dichlorobenzene fluxes are all less than those with a single component due to the binary interactions between DCB isomers and between the DCB isomer and the zeolite membrane. Comparatively, the template-free MFI-type zeolite exhibits higher selectivity for dichlorobenzene isomers due to less inter-crystalline gaps. The separation factors for p-/o-DCB and p-/m-DCB can reach 16.7 and 22.0, respectively.The selectivity of the palladium-catalyzed aroylation and arylation of 1-tributylstannyl glycals with aroyl chlorides was investigated. The selectivity was controlled by the palladium catalyst, and high selectivity was achieved via ligand modification of the palladium catalyst. The reaction catalyzed by Pd(OAc)2 provided aroyl C-glycals with high selectivity, whereas the reaction catalyzed by Pd(PPh3)4 produced aryl C-glycals with diminished selectivity. The scope and limitation of the selectivity in this reaction are discussed.Mesoporous carbon materials have been increasingly studied due to their large specific surface area and good chemical stability. Optimizing their functionality through a doping modification can broaden their application in many fields. Herein, a series of B-doped mesoporous carbon materials are prepared by a convenient hydrothermal synthesis using F127 as the template and boric acid as the boron source. The whole material preparation process meets the requirements of green chemistry. Notably, the prepared carbon materials not only exhibit good electrocatalytic oxygen reduction to hydrogen peroxide in alkaline media but also have an excellent CO2 adsorption capacity (up to 121.34 mg/g) at 303 K and atmospheric pressure. These results show that the prepared samples can be utilized as multifunctional materials for handling a variety of environmental issues.With the aim of developing an improved strategy for the preparation of ethylene-bridged polysilsesquioxanes as thermal insulator materials, this paper describes the synthesis of a crack- and shrinkage-free ethylene-bridged polysilsesquioxane film by the hydrosilylation reaction of hydrodimethyl-silylated oligomethylsilsesquioxane (MSQ-SiH) and dimethylvinyl-silylated oligomethylsilsesquioxane (MSQ-SiVi) in the presence of Karstedt's catalyst. Polysilsesquioxane precursors were prepared by the sol-gel reaction of triethoxymethylsilane and the successive capping reaction with chlorodimethylsilane and chlorodimethylvinylsilane. The obtained ethylene-bridged polysilsesquioxane film showed lower density and thermal diffusivity (1.13 g/cm3 and 1.15 × 10-7 m2/s, respectively) than a polymethylsilsesquioxane film (1.34 g/cm3 and 1.36 × 10-7 m2/s, respectively). As a result of the introduction of the SiCCSi ethylene bridge, the thermal insulation property of the polysilsesquioxane film was enhanced.Accurately determining the spontaneous combustion zone of coal around the borehole plays an important role in preventing borehole accidents. To solve the problem of dividing the hazardous zone of spontaneous combustion in boreholes, a fully coupled model of the gas flow, coal oxidation reaction, and energy transportation is developed in this study. Taking the drainage borehole of the 24130 working face in the No. 10 Coal Mine of the Pingdingshan mining area as an example, the proposed model is used to simulate the seepage velocity field, oxygen concentration field, and temperature field of the coal around the borehole. The simulation results are found to be consistent with the field test results. Based on the simulation results, the coal around the borehole is divided into two areas in the axial direction of the borehole. The intersection of the seepage velocity u ≤ 0.004 m/s and oxygen concentration 7% ≤ C(O2) ≤ 21% are considered the "hazardous zone", and the union of the oxygen concentration C(O2) 0.004 m/s are considered the "safety zone". The influences of various factors inducing spontaneous combustion of coal around the borehole on the hazardous zone are revealed by analyzing the drainage negative pressure, sealing length, and roadway temperature. The results show that reducing the drainage negative pressure and increasing the sealing length can effectively restrain the spontaneous combustion of the borehole and can also help reduce the scope of the hazardous zone of the borehole. Finally, a reasonable arrangement of the predrainage period in the appropriate season can also effectively inhibit the spontaneous combustion of coal around boreholes.Inhibition of the major cyclic adenosine monophosphate-metabolizing enzyme PDE4 has shown potential for the discovery of drugs for cancer, inflammation, and neurodegenerative disorders such as Alzheimer's disease. As a springboard to explore new anti-cancer and anti-Alzheimer's chemical prototypes from rare Annonaceae species, the present study evaluated anti-PDE4B along with antiproliferative and anti-cholinesterase activities of the extracts of the Philippine endemic species Uvaria alba using in vitro assays and framed the resulting biological significance through computational binding and reactivity-based experiments. Thus, the PDE4 B2B-inhibiting dichloromethane sub-extract (UaD) of U. alba elicited antiproliferative activity against chronic myelogenous leukemia (K-562) and cytostatic effects against human cervical cancer (HeLa). The extract also profoundly inhibited acetylcholinesterase (AChE), an enzyme involved in the progression of neurodegenerative diseases. Chemical profiling analysis of the bioactive extract identified 18 putative secondary metabolites.
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