Tuftelin1 drives experimental pulmonary fibrosis progression by facilitating stress fiber assembly.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with unknown etiology, characterized by sustained damage repair of epithelial cells and abnormal activation of fibroblasts, the underlying mechanism of the disease remains elusive. METHODS: To evaluate the role of Tuftelin1 (TUFT1) in IPF and elucidate its molecular mechanism. We investigated the level of TUFT1 in the IPF and bleomycin-induced mouse models and explored the influence of TUFT1 deficiency on pulmonary fibrosis. Additionally, we explored the effect of TUFT1 on the cytoskeleton and illustrated the relationship between stress fiber and pulmonary fibrosis. RESULTS: Our results demonstrated a significant upregulation of TUFT1 in IPF and the bleomycin (BLM)-induced fibrosis model. Disruption of TUFT1 exerted inhibitory effects on pulmonary fibrosis in both in vivo and in vitro. TUFT1 facilitated the assembly of microfilaments in A549 and MRC-5 cells, with a pronounced association between TUFT1 and Neuronal Wiskott-Aldrich syndrome protein (N-WASP) observed during microfilament formation. TUFT1 can promote the phosphorylation of tyrosine residue 256 (Y256) of the N-WASP (pY256N-WASP). Furthermore, TUFT1 promoted transforming growth factor-ß1 (TGF-ß1) induced fibroblast activation by increasing nuclear translocation of pY256N-WASP in fibroblasts, while wiskostatin (Wis), an N-WASP inhibitor, suppressed these processes. CONCLUSIONS: Our findings suggested that TUFT1 plays a critical role in pulmonary fibrosis via its influence on stress fiber, and blockade of TUFT1 effectively reduces pro-fibrotic phenotypes. Pharmacological targeting of the TUFT1-N-WASP axis may represent a promising therapeutic approach for pulmonary fibrosis.

Visualize intracellular ß-galactosidase using an asymmetric near-infrared fluorescent probe with a large Stokes shift.

ß-galactosidase (ß-Gal) is an important biomarker of cell senescence and primary ovarian cancer. Therefore, it is of great significance to construct a near-infrared fluorescent probe with deep tissue penetration and a high signal-to-noise ratio for visualization of ß-galactosidase in biological systems. However, most near-infrared probes tend to have small Stokes shifts and low signal-to-noise ratios due to crosstalk between excitation and emission spectra. Using d-galactose residues as specific recognition units and near-infrared dye TJ730 as fluorophores, a near-infrared fluorescence probe SN-CR with asymmetric structure was developed for the detection of ß-Gal. The probe has a fast reaction equilibrium time (<12 min) with ß-Gal, excellent biocompatibility, near-infrared emission (738 nm), low detection limit (0.0029 U/mL), and no crosstalk between the excitation spectrum and emission spectrum (Stokes shifts 142 nm) of the probe. Cell imaging studies have shown that SN-CR can visually trace ß-Gal in different cells and distinguish ovarian cancer cells from other cells.

Bidirectional relationship between sexual arousal and (sex-related) disgust.

Sexual stimuli provoke both sexual arousal and disgust, and the coaction between these emotions determines sexually behavioral outcomes. The current research includes two experiments to explore the bidirectional relationship between sexual arousal toward erotic stimuli and disgust induced by sexual body fluids. Study 1 presented 234 participants (117 women) with sexual body (vs. neutral) fluids followed by erotic stimuli, and Study 2 presented 235 participants (117 women) with erotic (vs. neutral) videos followed by sexual body fluids (and a non-sex-related stimulus). Study 1 showed that exposure to sexual body fluids reduced sexual arousal and the likelihood of sexual engagement toward erotic stimuli in participants with high sexual disgust sensitivity but increased sexual arousal and the likelihood of sexual engagement in participants with low sexual disgust sensitivity, while Study 2 suggested that men exposed to erotic (vs. neutral) stimuli reported lower disgust, stronger sexual arousal state, and higher willingness to interact with the sexual body fluids. There was no relationship between subjective feelings of sexual arousal and disgust in these experiments, while the balance of sexual arousal and disgust toward sexual body fluids and erotic stimuli had a positive association. Also, exposure to erotic stimuli had no effect on reactions to generally disgusting stimulus, but feelings of sexual arousal toward erotic stimuli were positively associated with disgust induced by generally disgusting fluid. These findings suggest that Behavior Immune System regulates disgust to establish a balance between benefit and cost related to sex as well as provide insight into the process underlying sexual dysfunctions.

Dichlorido(2,9-diprop-oxy-1,10-phenanthroline-κN,N')cadmium(II).

In the title complex, [CdCl(2)(C(18)H(20)N(2)O(2))], the Cd(II) ion is coordinated by two N atoms from a bis-chelating 2,9-diprop-oxy-1,10-phenanthroline ligand and two Cl atoms in a distorted tetra-hedral environment. The two Cd-Cl bond distances are significantly different from each other and the N-Cd-N bond angle is acute. In the crystal structure, there are π-π stacking inter-actions between symmetry-related phenanthroline ring systems, with a centroid-centroid distance of 3.585 (3) Å.

catena-Poly[[(2,9-dieth-oxy-1,10-phen-anthroline-κN,N')cadmium(II)]-di-µ-dicyan-amido-κN:N].

In the title polymer, [Cd(C(2)N(3))(2)(C(16)H(16)N(2)O(2))](n), the Cd(II) ion is coordinated by two N atoms from one 2,9-dieth-oxy-1,10-phenanthroline mol-ecule and four N atoms from four symmetry-related dicyanamide ions in a distorted octa-hedral geometry. In the 2,9-dieth-oxy-1,10-phenanthroline ligand, the O and C atoms of the eth-oxy groups are located almost in the plane defined by the phenanthroline ring system. Two dicyanamide ions bridge two Cd(II) ions, which are located on a twofold axis, forming a one-dimensional zigzag chain along the [001] direction. The 2,9-dieth-oxy-1,10-phenanthroline mol-ecules act as bidentate terminal ligands. There are π-π inter-actions between polymeric chains, characterized by a centroid-centroid distance of 3.7624 (2) Šbetween the phenanthroline rings of two neighbouring chains.