The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host's immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections

The impact of intrauterine and extrauterine weight gain in premature infants on later body composition

Background: The impact of intrauterine and extrauterine growth on later insulin resistance and fat mass (FM) in very low birth weight (VLBW) infants is not well established. The aim of our study was to evaluate the effects of intrauterine and early/late extrauterine growth on later insulin resistance and body composition in VLBW infants from 6 months’ corrected age (CA) to 36 months. Methods: Prospective measurements of body composition by dual-energy X-ray absorptiometry and insulin resistance by homeostasis model assessment insulin resistance (HOMA-IR) along with other fasting plasma biochemistries were made in 95 VLBW infants at 6, 12, 18, and 24 months’ CA and 36 months’ postnatal age. Mixed-effect models were used to evaluate the effects of age, sex, maturation status, and Δweight SD score on percentage FM (PFM), FM index (FMI), fat-free mass index (FFMI), and HOMA-IR. Results: PFM and FMI were negatively associated with a decrease in weight–SD scores from birth to 36 weeks’ postmenstrual age (PMA; P=0.001) and from 36 weeks’ PMA to 6 months’ CA (P=0.003). PFM and FMI were higher in AGA than in small for gestational age (SGA) infants. HOMA-IR was not associated with the Δweight–SD scores in either period. Conclusions: Catch-down growth in terms of weight is associated with persistently lower adiposity but not insulin resistance up to 36 months of age

Bedaquiline loaded lipid nanoparticles: a promising candidate for TB treatment

Four different kinds of Lipid Nanoparticles (LNP) encapsulating bedaquiline have been tested in order to evaluate the possibility to decrease adverse effects of this very efficient and recent antibiotic. The parameters that are studied among these different types of LNP are the surface charge as well as targeting of macrophages through trimannose groups grafted to the surface. It was found that these nanocarriers could encapsulate bedaquiline with a very high loading efficiency, exhibited a very good colloidal stability in storage conditions as well as in biological media, and an excellent compatibility with animal cells. Finally, first in vivo evaluation showed that these carriers are able to accumulate strongly in the lungs and that the almost neutral ones without targeting ligands could be the best candidate for tuberculosis treatment

Optical spectroscopy of Pr3+ in M+Bi(XO4)2, M+ = Li or Na and X = W or Mo, locally disordered single crystals

NaBi(WO4)(2) (NBW), NaBi(MoO4)(2) (NBMo) and LiBi(MoO4)(2) (LBMo) single crystals grown by the Czochralski technique have been doped up to a praseodymium concentration of [Pr] approximate to 1 x 10(20) Cm-3 in the crystal. 10 K polarized optical absorption and photoluminescence measurements have been used to determine the energy position of 32, 39 and 36 Pr 3, Stark levels in NBW, NBMo and LBMo crystals, respectively. These energy levels were labelled with the appropriate irreducible representations corresponding to a C-2 local symmetry of an average optical centre. Single-electron Hamiltonians including free-ion and crystal field interactions have been used in the fitting of experimental energy levels and in the simulation of the full sequence of the 4f(2) Pr3+ configuration. 300 K absorption spectra of different (2S+1)LjPr(3+) multiplets were determined and used in the context of the Judd-Ofelt theory and for the calculation of the D-1(2)-related emission cross sections of this average Pr3+ centre. Non-radiative electron relaxation from the P-3(0) level feeds the D-1(2) multiplet. This latter level efficiently decays radiatively to the ground H-3(4) multiplet but still there is a significant rate of radiative decay to the D-1(2) --> F-3(3) praseodymium laser channel. For [Pr] greater than or equal to 2 x 10(19) cm(-3), non-radiative electric dipole-dipole Pr pair energy transfer limits the radiative yield.This work was supported by CICyT (Spain) under project MAT2002-4603-COS-S. PIXE measurements were performed within the CSIC (Spain)–GRICE (Portugal) cooperation agreement. AM is supported by CONACyT (Mexico) grant No 128118.Peer reviewe

Charge Transport and Sensitized 1.5 μm Electroluminescence Properties of Full Solution-Processed NIR-OLED based on Novel Er(III) Fluorinated β‑Diketonate Ternary Complex

Solution-processed near-infrared organic light-emitting diodes (NIR-OLEDs) with structure glass/indium–tin oxide/poly­(3,4-ethylenedioxythiophene)-poly­(styrene sulfonate)/Er-complex/Ca/Al based on a novel Er­(III) complex, [Er­(tfnb)₃(bipy)] (Htfnb = 4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedione and bipy = 2,2′-bipyridine) have been manufactured and their properties have been studied. A complete quenching of the organic ligand visible emission is shown, and only the sensitized 1.5 μm electroluminesce from Er­(III) results. From the electrical characteristic we present the mobility dependence on applied voltage using a numerical model, comparing it to poly­(9,9-dioctylfluorene), a commercial semiconducting polymer with optical properties close to those of the molecular ligands. The synthesis of the novel complex together with a detailed analysis of its structure elucidated by XRD, ¹H NMR, Raman, and Fourier-transform infrared spectroscopies is presented. A wide-ranging characterization of its photophysical properties in terms of absorption and steady and transient photoluminescence is used to investigate the energy-transfer process from the organic ligand to the central Er­(III) ion