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Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical‐genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl‐2‐keto‐b‐D‐erythro‐pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography‐mass spectrometry (LC‐MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment. [ABSTRACT FROM AUTHOR]

Advancing the study of membrane associated proteins and their interactions is dependent on accurate membrane models. While a variety of membrane models for high‐resolution membrane protein study exist, most do not reflect the diversity of lipids found within biological membranes. In this work, we have developed native reverse micelles (nRMs) formulated with lipids from multiple eukaryotic sources, which encapsulate proteins and enable them to interact as they would with a biological membrane. Diverse formulations of nRMs using soy lecithin, porcine brain lipids, or bovine heart lipids combined with n‐dodecylphosphocholine were developed and characterized by dynamic light scattering and 31P‐NMR. To optimize protein encapsulation, ubiquitin was used as a standard and protein NMR verified minimal changes to its structure. Peripheral membrane proteins, which bind reversibly to membranes, were encapsulated and include glutathione peroxidase 4 (GPx4), phosphatidylethanolamine‐binding protein 1 (PEBP1), and fatty acid binding protein 4 (FABP4). All three proteins showed anticipated interactions with the membrane‐like inner surface of the nRMs as assessed by protein NMR. The nRM formulations developed here allow for efficient, high‐resolution study of membrane interacting proteins up to and beyond ~21 kDa, in a more biologically relevant context compared to other non‐native membrane models. The approach outlined here may be applied to a wide range of lipid extracts, allowing study of a variety of membrane associated proteins in their specific biological context. [ABSTRACT FROM AUTHOR]

Two novel complexes, [Cu (L)(H2O)]⋅H2O (1) and [Mn (H2O)6] ⋅L ⋅H2O (2) (L = 1,4‐bis (pyrazol‐1‐yl) terephthalic acid), were synthesized under hydrothermal conditions. They were characterized using elemental analysis, infrared spectroscopy and single‐crystal X‐ray diffraction. Intramolecular weak interactions, such as hydrogen bonds, and intermolecular interactions play important roles in the construction of the complexes. The interaction of these complexes with fish sperm DNA (FS‐DNA) was monitored and binding constants were determined using UV–visible spectroscopy, which revealed their ability to bind to FS‐DNA, with binding constants for the two complexes of 1.88 × 104 M−1 (1) and 1.06 × 104 M−1 (2). Viscosity experiments further demonstrated the binding of the complexes to DNA. The complexes were further studied using gel electrophoresis assay with supercoiled plasmid pBR322 DNA. In addition, anticancer activities of the metal complexes investigated through MTT assays in vitro indicated good cytotoxic activity against cancer cell lines. Flow cytometry and apoptosis experiments showed that these complexes induced apoptosis of two different cancer cell lines (HeLa and KB cells), demonstrating a significant cancer cell inhibitory rate. Finally, a further molecular docking technique was employed to confirm the binding of the complexes towards the molecular target DNA. [ABSTRACT FROM AUTHOR]

Nuclear factor-kappaB (NF-κB) is an important transcriptional factor and regulates a variety of pathophysiologic process involved in cell survival and death. This study aimed to assess the effects of NF-κB p65 subunit knockdown in suppression of nude mouse lung tumour cell xenografts and understands the underlying molecular events. A nude mouse Lewis lung carcinoma cell xenograft model was established, and the mice were intraperitoneally injected with NF-κB p65 small interfering RNA (siRNA) and sacrificed after 2weeks of tumour cell injection. Tumour xenografts were harvested for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Western blot and quantitative reverse transcription-polymerase chain reaction analyses. Results found that compared to the phosphate-buffered saline (PBS)-treated or the negative control (NC) siRNA-treated mice tumour xenograft weight and volume were significantly decreased in the NF-κB p65 siRNA-treated mice. The TUNEL positive (apoptosis) cells in xenograft sections were 45 ± 5 in PBS and 38 ± 3 in NC siRNA but increased to 271 ± 11 in p65 siRNA-treated mice. Compared to the PBS or the NC mice, levels of Bcl-2 mRNA and protein in tumour xenografts were significantly downregulated in p65 siRNA-treated mice. Knockdown of NF-κB p65 subunit expression can significantly inhibit the growth of nude mouse Lewis tumour cell xenografts by inducing tumour cell apoptosis and downregulating pro-apoptotic protein Bcl-2 expression. Targeting NF-κB p65 subunit expression as a potential therapeutic strategy needs further evaluation in treating human lung cancer. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Four metal-organic coordination polymers [Cd(4-bpcb)1.5Cl2(H2O)] ( 1), [Cd(4-bpcb)0.5(mip)(H2O)2] ·3H2O ( 2), [Co(4-bpcb)(oba)(H2O)2] ( 3), and [Ni(4-bpcb)(oba)(H2O)2] ( 4) [4-bpcb = N, N′-bis(4-pyridinecarboxamide)-1, 4-benzene, H2mip = 5-methylisophthalic acid, and H2oba = 4, 4′-oxybis(benzoic acid)] were synthesized under hydrothermal conditions and characterized by single-crystal X-ray diffraction, elemental analyses, IR spectroscopy, powder X-ray diffraction, and TG analysis. In complex 1, two Cl- anions serve as bridges to connect two Cd-(μ1-4-bpcb) subunits forming a dinuclear unit, which are further linked by μ2-bridging 4-bpcb to generate 1D zigzag chain. Complex 2 shows a 2D 63 network constructed by [Cd-mip] n zigzag chains and μ2-bridging 4-bpcb ligands. Complexes 3 and 4 are isostructural 2D (4, 4) grid networks derived from [ M-oba] n ( M = Co, Ni) zigzag chains and [ M-(4-bpcb)] n linear chains. The 1D chains for 1 and the 2D networks for 2- 4 are finally extended into 3D supramolecular architectures by hydrogen bonding interactions. The roles of dicarboxylates and central metal ions on the assembly and structures of the target compounds were discussed. Moreover, the thermal stabilities, photoluminescent properties, and photocatalytic activities of complexes 1- 4 and the electrochemical properties of complexes 3 and 4 were investigated. [ABSTRACT FROM AUTHOR]

Four CoII/MnII coordination compounds, namely, [Co(dpq)(L1)(H2O)1.5] ( 1), [Co(dpq)(L2)(H2O)2] ·H2O ( 2), [Mn2(dpq)2(L2)2] ·2H2O ( 3), and [Mn(dpq)(L3)] ( 4) [H2L1 = 5-methylisophthalic acid, H2L2 = 5-hydroxyisophthalic acid, and H2L3 = bis(sulfanediyl) thiadiazole diacetic acid] were obtained from hydrothermal reactions of dipyrido [3,2-d:2′,3′-f]quinoxaline (dpq) and three structurally related mixed dicarboxylate ligands. Single crystal X-ray diffraction analysis reveals that compound 1 consists of a dinuclear CoII cluster linked by two carboxylate groups from different L1 anions and a coordination water molecule. Compound 2 is a dimeric structure based on a pair of L2 anions and two CoII ions. Both compounds are finally extended into three dimensional (3D) supramolecular networks by hydrogen bonding and π-π stacking interactions. In compound 3, two MnII ions are linked by a pair of carboxylate groups to form a bimetallic unit, which is extended by pairs of L2 anions to generate a 1D wave-like band. The adjacent bands are linked by hydrogen bonding interactions forming a 2D supramolecular architecture. Compound 4 is a (4,4)-connected 2D network based on L3 linkers and dinuclear MnII units connected by two carboxylate groups. The effects of metal ions and dicarboxylates with different spacers on the architectures of the title compounds were discussed. Moreover, the electrochemical behavior of compounds 1 and 2, magnetic properties of compounds 1, 3, and 4, and photoluminescent properties of compounds 1- 4 were investigated. [ABSTRACT FROM AUTHOR]

Three coordination compounds with dimensions from 0D to 2D, namely, [Co(bppdca)2(HL1)2] ( 1) [Co(bppdca)(L2)(H2O)] ·2H2O ( 2) and [Co(bppdca)(L3)] ·3H2O ( 3) [bppdca = N, N′-bis(pyridine-3-yl)pyridine-2,6-dicarboxamide, H2L1 = 2,5-pyridinedicarboxylic acid, H2L2 = 4,4′-oxybisbenzoic acid, H2L3 = 2-carboxymethylsulfanyl nicotinic acid] were hydrothermally synthesized and structurally characterized. Single crystal X-ray diffraction analysis reveals that complex 1 is a discrete 0D complex, in which the bppdca ligand and the H2L1 act as the terminal groups to coordinate with the CoII ions. In coordination polymer 2, two bppdca ligands coordinate in anti configuration with two CoII ions to generate a 28-membered Co2(bppdca)2 loop, which is further extended into 1D ladder-like double chain by pairs of L2 ligands. In 3, the CoII ions are linked by bppdca ligands to generate 1D wave-like chain, which is further connected by the L3 to form a 2D network. Finally, the coordination compounds 1- 3 are extended into 3D supramolecular frameworks through the hydrogen bonding interactions. The CoII ions and the bppdca ligands in the title coordination compounds exhibit different coordination characters and conformations. The effect of organic dicarboxylates with different rigidity and length on the structures of CoII coordination compounds was investigated. In addition, the fluorescence and electrochemical behaviors of coordination compounds 1- 3 were reported. [ABSTRACT FROM AUTHOR]

Three new metal-organic complexes [Ni2(dpq)2(L1)2(H2O)5] ·H2O ( 1), [Pb2(dpq)2(L1)2] ·H2O ( 2), and [Pb(dpq)(L2)] ( 3) (dpq = dipyrido[3,2-d:2′3′-f]quinoxaline, H2L1 = 1,1′-biphenyl-2, 2′-dicarboxylic acid, H2L2 = 2-carboxymethylsulfanyl nicotinic acid) were synthesized under hydrothermal conditions and structurally characterized by elemental analyses, IR, and single-crystal X-ray diffraction analyses. X-ray analysis reveals that complex 1 has a semi-cycling dinuclear unit, which is extended into a 3D supramolecular architecture by hydrogen bonding and π-π stacking interactions. Complex 2 is an unusual 0D + 1D cocrystal of dinuclear units and left-/right-handed helical chains, which are ultimately packed into a 3D supramolecular structure through hydrogen bonding interactions. Complex 3 shows a 2D network bridged by L2 anions, which is finally extended into a 3D supramolecular structure through π-π stacking interactions. The diverse structures of complexes 1- 3 indicate that the central metal ions and the dicarboxylates have significant effects on the final structures. Moreover, the thermal stabilities, the photoluminescent properties of complexes 1- 3 and the electrochemical property of complex 1 were also investigated. [ABSTRACT FROM AUTHOR]

A correction to the article "Syntheses, Structures, and Properties of Three Metal-Organic Complexes with Different Dimensionality Based on Dipyrido quinoxaline and Different Dicarboxylates" is presented.