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Pulmonary fibrosis is a devastating lung disease with few therapeutic options. CHIT1 (chitinase 1), an 18 glycosyl hydrolase family member, contributes to the pathogenesis of pulmonary fibrosis through the regulation of TGF-b (transforming growth factor-b) signaling and effector function. Therefore, CHIT1 is a potential therapeutic target for pulmonary fibrosis. This study aimed to identify and characterize a druggable CHIT1 inhibitor with strong antifibrotic activity and minimal toxicity for therapeutic application to pulmonary fibrosis. Extensive screening of small molecule libraries identified the aminoglycoside antibiotic kasugamycin (KSM) as a potent CHIT1 inhibitor. Elevated concentrations of CHIT1 were detected in the lungs of patients with pulmonary fibrosis. In in vivo bleomycin- and TGFb- stimulated murine models of pulmonary fibrosis, KSM showed impressive antifibrotic effects in both preventive and therapeutic conditions. In vitro studies also demonstrated that KSM inhibits fibrotic macrophage activation, fibroblast proliferation, and myofibroblast transformation. Null mutation of TGFBRAP1 (TGF-b-associated protein 1), a recently identified CHIT1 interacting signaling molecule, phenocopied antifibrotic effects of KSM in in vivo lungs and in vitro fibroblasts responses. KSM inhibits the physical association between CHIT1 and TGFBRAP1, suggesting that the antifibrotic effect of KSM is mediated through regulation of TGFBRAP1, at least in part. These studies demonstrate that KSM is a novel CHIT1 inhibitor with a strong antifibrotic effect that can be further developed as an effective and safe therapeutic drug for pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Nano-diamond particles are co-deposited on Ti substrates with metal (Ti/Ni) nanoparticles (NPs) by the electrophoretic deposition (EPD) method combined with a furnace annealing at 800 °C under N2 atmosphere. Modifications of structural and electron field emission (EFE) properties of the metal-doped films are investigated with different metal NPs concentrations. Our results show that the surface characteristics and EFE performances of the samples are first enhanced and then reduced with metal NPs concentration increasing. Both the Ti-doped and Ni-doped nano-diamond composite films exhibit optimal EFE and microstructural performances when the doping quantity is 5 mg. Remarkably enhanced EFE properties with a low turn-on field of 1.38 V/μm and a high current density of 1.32 mA/cm2 at an applied field of 2.94 V/μm are achieved for Ni-doped nano-diamond films, and are superior to those for Ti-doped ones. The enhancement of the EFE properties for the Ti-doped films results from the formation of the TiC-network after annealing. However, the doping of electron-rich Ni NPs and formation of high conductive graphitic phase are considered to be the factor, which results in marvelous EFE properties for these Ni-doped nano-diamond films. [ABSTRACT FROM AUTHOR]

• Ta diffusion layers were prepared by double glow plasma surface alloying technique and its reverse-sputtering process. • Diamond coating exhibits good adhesion on WC-Co with Ta diffusion layer after reverse-sputtering for 60 min. • The barrier effect of cobalt diffusion is enhanced by introducing Ta diffusion layer. To enhance diamond nucleation and adhesion on cemented carbide substrates, the Ta diffusion layers with gradient structure were deposited by the combination with double glow plasma surface alloying technique (DGPSA) and the reverse-sputtering process. The effect of reverse-sputtering times on phase composition and morphology of the Ta surface layers was studied. It was found that both the thickness of the Ta deposition layer and the amount of Ta elements decreased during the removal of the Ta deposition layer. With the reverse-sputtering time increases from 0 to 60 min, the thickness of the Ta deposition layers decreased from 1.6 μm to 0 μm. When the reverse-sputtering time reached 30 min, the as-prepared sample surface exhibited the maximum micro-hardness (3496.3 HV 1.96N). Rockwell C indentation tests were used to investigate the effect of the Ta diffusion layers on the adhesion between the WC-Co substrate and the diamond coating. The results show that diamond coating exhibits good adhesion performance on WC-Co substrate with the Ta diffusion layer after reverse-sputtering for 60 min, indicating that the barrier effect of cobalt diffusion is enhanced by introducing the Ta diffusion layer. [ABSTRACT FROM AUTHOR]