Pathogenic mycobacterium upregulates cholesterol 25-hydroxylase to promote granuloma development via foam cell formation.

Pathogenic mycobacteria orchestrate the complex cell populations known as granuloma that is the hallmark of tuberculosis. Foam cells, a lipid-rich cell-type, are considered critical for granuloma formation; however, the causative factor in foam cell formation remains unclear. Atherosclerosis is a chronic inflammatory disease characterized by the abundant accumulation of lipid-laden-macrophage-derived foam cells during which cholesterol 25-hydroxylase (CH25H) is crucial in foam cell formation. Here, we show that M. marinum (Mm), a relative of M. tuberculosis, induces foam cell formation, leading to granuloma development following CH25H upregulation. Moreover, the Mm-driven increase in CH25H expression is associated with the presence of phthiocerol dimycocerosate, a determinant for Mm virulence and integrity. CH25H-null mice showed decreased foam cell formation and attenuated pathology. Atorvastatin, a recommended first-line lipid-lowering drug, promoted the elimination of M. marinum and concomitantly reduced CH25H production. These results define a previously unknown role for CH25H in controlling macrophage-derived foam cell formation and Tuberculosis pathology.

Arabinogalactan enhances Mycobacterium marinum virulence by suppressing host innate immune responses.

Arabinogalactan (AG) participates in forming the cell wall core of mycobacteria, a structure known as the mAGP complex. Few studies have reported the virulence of inartificial AG or its interaction with the host immune system. Using clustered regularly interspaced short palindromic repeats interference gene editing technology, conditional Mycobacterium marinum mutants were constructed with a low expression of embA or glfT2 (EmbA_KD or GlfT2_KD), which are separately involved in the biosynthesis of AG arabinose and galactose domains. High-performance gel permeation chromatography and high-performance liquid chromatography assays confirmed that the EmbA_KD strain showed a remarkable decrease in AG content with fragmentary arabinose chains, and the GlfT2_KD strain displayed less reduction in content with cut-down galactose chains. Based on transmission and scanning electron microscopy observations, the cell walls of the two mutants were found to be dramatically thickened, and the boundaries of different layers were more distinct. Phenotypes including the over-secretion of extracellular substances and enhanced spreading motility with a concomitant decreased resistance to ethambutol appeared in the EmbA_KD strain. The EmbA_KD and GlfT2_KD strains displayed limited intracellular proliferation after infecting murine J774A.1 macrophages. The disease progression infected with the EmbA_KD or GlfT2_KD strain significantly slowed down in zebrafish/murine tail infection models as well. Through transcriptome profiling, macrophages infected by EmbA_KD/GlfT2_KD strains showed enhanced oxidative metabolism. The cell survival measured using the CCK8 assay of macrophages exposed to the EmbA_KD strain was upregulated and consistent with the pathway enrichment analysis of differentially expressed genes in terms of cell cycle/apoptosis. The overexpression of C/EBPß and the increasing secretion of proinflammatory cytokines were validated in the macrophages infected by the EmbA_KD mutant. In conclusion, the AG of Mycobacterium appears to restrain the host innate immune responses to enhance intracellular proliferation by interfering with oxidative metabolism and causing macrophage death. The arabinose chains of AG influence the Mycobacterium virulence and pathogenicity to a greater extent.

E3 Ligase FBXW7 Facilitates Mycobacterium Immune Evasion by Modulating TNF-α Expression.

Tumor necrosis factor alpha (TNF-α) is a crucial factor in the control of Mycobacterium tuberculosis (Mtb) infection. Pathogenic mycobacteria can inhibit and/or regulate host cell TNF-α production in a variety of ways to evade antituberculosis (anti-TB) immunity as well as facilitate immune escape. However, the mechanisms by which TNF-α expression in host cells is modulated to the benefit of mycobacteria is still an interesting topic and needs further study. Here, we report that macrophages infected with Mycobacterium marinum (Mm)-a close relative of Mtb-upregulated the expression of E3 ubiquitin ligase FBXW7. Specific silencing FBXW7 with small interfering RNA (siRNA) significantly elevates TNF-α expression and eventually promotes the elimination of intracellular bacteria. In turn, overexpression of FBXW7 in Raw264.7 macrophages markedly decreased TNF-α production. Furthermore, partial inhibition of FBXW7 in an Mm-infected murine model significantly reduced TNF-α tissue content, alleviated tissue damage as well as reduced the bacterial load of mouse tails. Finally, FBXW7 could decrease TNF-α in a K63-linked ubiquitin signaling dependent manner. Taken together, our study uncovered a previously unknown role of FBXW7 in regulating TNF-α dynamics during mycobacterial infection, which provides new insights into understanding the role of FBXW7 in anti-tuberculosis immunity and its related clinical significance.

Superfluorescence of Sub-Band States in C-Plane In0.1Ga0.9N/GaN Multiple-QWs.

Superfluorescence is a collective emission from quantum coherent emitters due to quantum fluctuations. This is characterized by the existence of the delay time (τD) for the emitters coupling and phase-synchronizing to each other spontaneously. Here we report the observation of superfluorescence in c-plane In0.1Ga0.9N/GaN multiple-quantum wells by time-integrated and time-resolved photoluminescence spectroscopy under higher excitation fluences of the 267 nm laser and at room temperature, showing a characteristic τD from 79 ps to 62 ps and the ultrafast radiative decay (7.5 ps) after a burst of photons. Time-resolved traces present a small quantum oscillation from coupled In0.1Ga0.9N/GaN multiple-quantum wells. The superfluorescence is attributed to the radiative recombination of coherent emitters distributing on strongly localized subband states, Ee1→Ehh1 or Ee1→Elh1 in 3nm width multiple-quantum wells. Our work paves the way for deepening the understanding of the emission mechanism in the In0.1Ga0.9N/GaN quantum well at a higher injected carrier density.

Involvement of SIRT1 in amelioration of schistosomiasis-induced hepatic fibrosis by genistein.

Previous study revealed that genistein alleviate the extent of hepatic fibrosis in schistosomiasis-infected mice, however, the potential mechanism is still incomplete. Present study was, therefore, carried out to investigate the underlying mechanism of ameliorating schistosomiasis-induced hepatic fibrosis by genistein. α-smooth muscle actin (α-SMA) expression, as a critical fibrotic marker, was markedly upregulated in Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis, and gradually inhibited by genistein administration in infected mice. Contrary to the changes of α-SMA expression, hepatic SIRT1 expression and activity was greatly inhibited in mice upon S. japonicum infection, and the repression was reversed in liver tissues after receiving 25 mg/kg genistein. 50 mg/kg genistein treatment gave rise to the higher SIRT1 expression and activity than that of the control group. In hepatic stellate cells (HSCs), genistein (5, 10, 20 µM) treatment resulted in the increases of SIRT1 expression and activity in concentration-dependent manner. Moreover, to mimic the fibrogenesis in vivo, macrophage was treated with soluble egg antigen (SEA) to obtain macrophage-conditioned medium (MφCM), which was used to stimulate HSCs. Intriguingly, SIRT1 overexpression decreased fibrosis associated gene expression in HSCs exposed to MφCM or not. Additionally, MφCM gave rise to high levels of α-SMA and p-Smad3 and the increments were reversed upon genistein treatment in HSCs. Furthermore, EX527, SIRT1 specific inhibitor, abrogated the inhibitory effects of genistein on HSCs activation. Together, the results support the notion that the strong elevation of SIRT1 expression and activity may represent a potential mechanism of protection against schistosomiasis-induced hepatic fibrosis by genistein.

Dicyanostilbene-derived two-photon fluorescence probe for lead ions in live cells and living tissues.

A novel two-photon fluorescence probe for Pb(2+) derived from 4-methyl-2,5-dicyano-4'-amino stilbene as a two-photon fluorophore and bis[2-(2-aminophenylsulfanyls)ethyl]amine as a novel Pb(2+) ligand was developed. The probe possesses small molecule size, large two-photon absorption cross-section (1020 GM), noncytotoxic effect, long-wavelength emission at 609 nm, large Stokes shift (209 nm), excellent photostability, moderate water-solubility, good cell-permeability, and pH-insensitivity in the biologically relevant pH range. The probe can selectively detect Pb(2+) ions in live cells and living tissues without interference from other metal ions and the membrane-bound probes, and its quenching constant (K(SV)(TP)) is 7.58×10(5) M(-1).

[Room temperature ultraviolet stimulated emission of ZnO nanocrystals].

The characteristics of the exciton in ZnO is essential to the development of ZnO-based optoelectronic devices, therefore it is critical to study the optical properties of exciton and transition process in ZnO quantum dot. In the present work, zinc oxide nanocrystals were prepared by the sol-gel method. X-ray diffraction (XRD) pattern shows that they have a hexagonal wurtzite structure. The pumping power dependent UV emission and their dynamics were studied, the spontaneous emission of the free exciton and the stimulated emission due to exciton-exciton collision and electron hole plasmon were observed, and the pumping power dependent dynamics was reported for the first time. This is helpful for us to understand the near-band-edge excitonic emission, and might be valuable in the realization of semiconductor UV diode.

A novel europium(III) complex with versatility in excitation ranging from infrared to ultraviolet.

One- and two-photon absorption properties of a novel europium(III) complex containing a hemicyanine cation are investigated in this paper; in which the sensitization wavelength of europium(III), induced by beta-diketonate ligands, is in the ultraviolet range, and the hemicyanine(aminostyrylpyridinium) cation extends the sensitization wavelength of Eu(III) to visible region. Furthermore, under 1.06 microm ultrashort pulse laser excitation, the complex exhibits effective europium(III) luminescence induced by the two-photon absorption of the hemicyanine cation. Therefore, this new europium(III) complex with excitation bands in the near infrared, visible and ultraviolet ranges. Since the 1.06-microm ultrafast laser is one of the most frequently used laser sources and 1.06 microm is an 'optical window' for cells and tissues, the results suggest that this kind of complex has promising applications in deep-penetrating and high quality bioimaging in vivo.