A critical feature of Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing the intracellular tubercle bacilli is a key requirement for efficient tuberculosis treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques and lack of validated targets. Here, we present the development of a phenotypic cell-based assay that uses automated confocal fluorescence microscopy for high throughput screening of chemicals that interfere with the replication of M. tuberculosis within macrophages. Screening a library of 57,000 small molecules led to the identification of 135 active compounds with potent intracellular anti-mycobacterial efficacy and no host cell toxicity. Among these, the dinitrobenzamide derivatives (DNB) showed high activity against M. tuberculosis, including extensively drug resistant (XDR) strains. More importantly, we demonstrate that incubation of M. tuberculosis with DNB inhibited the formation of both lipoarabinomannan and arabinogalactan, attributable to the inhibition of decaprenyl-phospho-arabinose synthesis catalyzed by the decaprenyl-phosphoribose 2′ epimerase DprE1/DprE2. Inhibition of this new target will likely contribute to new therapeutic solutions against emerging XDR-TB. Beyond validating the high throughput/content screening approach, our results open new avenues for finding the next generation of antimicrobials.
LiNi0.6Co0.2Mn0.2O2 cathode materials were surface-modified by coating with a dual conductive poly(3,4-ethylenedioxythiophene)-co-poly(ethylene glycol) (PEDOT-co-PEG) copolymer, and their resulting electrochemical properties were investigated. The surface-modified LiNi0.6Co0.2Mn0.2O2 cathode material exhibited a high discharge capacity and good high rate performance due to enhanced transport of Li(+) ions as well as electrons. The presence of a protective conducting polymer layer formed on the cathode also suppressed the growth of a resistive layer and inhibited the dissolution of transition metals from the active cathode materials, which resulted in more stable cycling characteristics than the pristine LiNi0.6Co0.2Mn0.2O2 cathode material at 55 (o)C.
We demonstrate the effectiveness of dual-layer coating of cathode active materials for improving the cycling performance and thermal stability of lithium-ion cells. Layered nickel-rich LiNi0.6Co0.2Mn0.2O2 cathode material was synthesized and double-layer coated with alumina nanoparticles and poly(3,4-ethylenedioxythiophene)-co-poly(ethylene glycol). The lithium-ion cells assembled with a graphite negative electrode and a double-layer-coated LiNi0.6Co0.2Mn0.2O2 positive electrode exhibited high discharge capacity, good cycling stability, and improved rate capability. The protective double layer formed on the surface of LiNi0.6Co0.2Mn0.2O2 materials effectively inhibited the dissolution of Ni, Co, and Mn metals from cathode active materials and improved thermal stability by suppressing direct contact between electrolyte solution and delithiated Li(1-x)Ni0.6Co0.2Mn0.2O2 materials. This effective design strategy can be adopted to enhance the cycling performance and thermal stability of other layered nickel-rich cathode materials used in lithium-ion batteries.
Liquid electrolytes composed of lithium salt in a mixture of organic solvents have been widely used for lithium-ion batteries. However, the high flammability of the organic solvents can lead to thermal runaway and explosions if the system is accidentally subjected to a short circuit or experiences local overheating. In this work, a cross-linked composite gel polymer electrolyte was prepared and applied to lithium-ion polymer cells as a safer and more reliable electrolyte. Mesoporous SiO2 nanoparticles containing reactive methacrylate groups as cross-linking sites were synthesized and dispersed into the fibrous polyacrylonitrile membrane. They directly reacted with gel electrolyte precursors containing tri(ethylene glycol) diacrylate, resulting in the formation of a cross-linked composite gel polymer electrolyte with high ionic conductivity and favorable interfacial characteristics. The mesoporous SiO2 particles also served as HF scavengers to reduce the HF content in the electrolyte at high temperature. As a result, the cycling performance of the lithium-ion polymer cells with cross-linked composite gel polymer electrolytes employing methacrylate-functionalized mesoporous SiO2 nanoparticles was remarkably improved at elevated temperatures.
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