A number of prior studies have demonstrated that the DNA-binding and gene transfection efficacies of cationic amphiphiles crucially depend on their various structural parameters including hydrophobic chain lengths, headgroup functionalities, and the nature of the linker-functionality used in tethering the polar headgroup and hydrophobic tails. However, to date addressing the issue of linker orientation remains unexplored in liposomal gene delivery. Toward probing the influence of linker orientation in cationic lipid mediated gene delivery, we have designed and synthesized two structurally isomeric remarkably similar cationic amphiphiles 1 and 2 bearing the same hydrophobic tails and the same polar headgroups connected by the same ester linker group. The only structural difference between the cationic amphiphiles 1 and 2 is the orientation of their linker ester functionality. While lipid 1 showed high gene transfer efficacies in multiple cultured animal cells, lipid 2 was essentially transfection incompetent. Findings in both transmission electron microscopic and dynamic laser light scattering studies revealed no significant size difference between the lipoplexes of lipids 1 and 2. Findings in confocal microscopic and fluorescence resonance energy transfer (FRET) experiments, taken together, support the notion that the remarkably higher gene transfer efficacies of lipid 1 compared to those of lipid 2 presumably originate from higher biomembrane fusogenicity of lipid 1 liposomes. Differential scanning calorimetry (DSC) and fluorescence anisotropy studies revealed a significantly higher gel-to-liquid crystalline temperature for the lipid 2 liposomes than that for lipid 1 liposomes. Findings in the dye entrapment experiment were also consistent with the higher rigidity of lipid 2/cholesterol (1:1 mole ratio) liposomes. Thus, the higher biomembrane fusibility of lipid 1 liposomes than that of lipid 2 liposomes presumably originates from the more rigid nature of lipid 2 cationic liposomes. Taken together, the present findings demonstrate for the first time that even as minor a structural variation as linker orientation reversal in cationic amphiphiles can profoundly influence DNA-binding characteristics, membrane rigidity, membrane fusibility, cellular uptake, and consequently gene delivery efficacies of cationic liposomes.
We previously discovered that coating solid surfaces with long-chained linear N-dodecyl,N-methyl-polyethylenimine makes them bactericidal and virucidal. In the present study, focusing on the use of this microbicidal paint to kill airborne Escherichia coli and Staphylococcus aureus, we have systematically investigated the dependence of this effect on the concentration and mode of application of the hydrophobic polycation, the number of coats, the nature of the solvent, and the presence of a dye in such paint. In addition, the latter's ability to be regenerated after use, stability upon repeated washings, and mammalian toxicity has been evaluated.
Meticulous surface engineering of layered structures toward new functionalities is a demanding challenge to the scientific community.Here, we introduce defects on varied MoS 2 surfaces by suitable doping of nitrogen atoms in a sulfur-rich reaction environment, resulting in stable and scalable phase conversion. The experimental characterizations along with the theoretical calculations within the framework of density functional theory establish the impact of nitrogen doping on stabilization of defects and reconstruction of the 2H to 1T phase. The as-synthesized MoS 2 samples exhibit excellent dye removal capacity in the dark, facilitated by a synergistic effect of reactive oxygen species (ROS) generation and adsorption. Positron annihilation spectroscopy and electron paramagnetic resonance studies substantiate the role of defects and associated sulfur vacancies toward ROS generation in the dark. Further, on the basis of its ample ROS generation in the dark and in the light, the commendable antimicrobial activity of the prepared MoS 2 samples against fungal pathogen Alternaria alternata has been demonstrated. Thus, the present study opens up a futuristic avenue to develop newer functional materials through defect engineering by suitable dopants toward superior performances in environment issues.
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and results in innumerable deaths across the world. The emergence of multidrug-resistant and extremely drug-resistant tuberculosis strains and its coinfection with HIV has made tuberculosis more difficult to treat. Therefore, new antimycobacterial agent(s) for both therapy and disinfection are urgently required. In this context the present study describes the antibacterial property of long-chain fatty alcohols against mycobacteria. The antimycobacterial activities of alcohols with chain length ranging from C(5) to C(13) were examined against Mycobacterium smegmatis mc(2) 155 and M. tuberculosis H(37)R(v). The best activity was found with one with a C(10) chain length. This bactericidal activity can partly be attributed to its ability to damage the robust and complex cell envelope of Mycobacteria. Moreover, our study reveals the ability of decanol to attenuate biofilm formation by M. smegmatis. This knowledge can be used to develop new therapeutics and disinfectants against mycobacteria.
This study compared the effectiveness and side-effects of intra-operative fentanyl with fentanyl and morphine for elective adenotonsillectomy in a double-blind study, in 60 children randomly allocated to receive either intravenous fentanyl 1 microg x kg(-1) intra-operatively or intramuscular morphine 100 microg x kg(-1) at induction. All children received a standard anaesthetic induction with intravenous fentanyl 1 microg x kg(-1) and propofol 4-5 mg x kg(-1) and maintenance with oxygen, nitrous oxide and isoflurane. Pain scores, emetic episodes and supplemental morphine requirements were recorded for 24 h postoperatively. The overall incidence of postoperative vomiting was high in both groups: 70% in the fentanyl group and 78% in the morphine group. The incidence of postoperative vomiting was lower in the fentanyl group (p < 0.03) in the first 4 h, but similar by 24 h. Children who received morphine at any time in the first 24 h had more median (range) episodes of vomiting [2 (0-7)] than children receiving fentanyl only [l (0-3); p < 0.03]. Administration of rescue anti-emetics, pain scores in recovery and pain scores over the next 24 h were similar between the two groups.
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