The underlying molecular mechanism of ciliated epithelium dysfunction and TGF-ß signaling in children with congenital pulmonary airway malformations.

The aim of this study was to investigate the variation in gene expression in the complete transcripts of Congenitalpulmonary airwaymalformation (CPAM) of the lung using Next Generation Sequencing (NGS) technology. There were 20 cases involving children with CPAM were used for selection of study sample. NGS was used to establish RNA-Seq libraries for the two groups of samples separately, and both groups were conducted to differential expression analysis and Gene Ontology (GO) functional enrichment analysis. The pathways of the differential genes were analyzed to find the enriched target pathways. A total of 592 genes were expressed with significant differences (CPAM vs. normal tissue, P < 0.05). GO functional analysis of DEGs indicated that abnormal ciliary function played a role in the development of CPAM. Subsequently, analysis of these genes pathways showed the TGF-ß signaling pathway was significantly enriched. Finally, the results of immunohistochemical analysis of some DEGs showed that a significant reduction in the expression of SMAD6, a gene related to the TGF-ß signaling pathway, led to abnormal activation of the pathway. TGF-ß signaling pathway involved in the evolution of the disease obtained by DEGs enrichment pathway analysis. SMAD6, a gene involved in this pathway, might be a potential biomarker for the diagnosis and treatment of CPAM.

Targeted Antibacterial Strategy Based on Reactive Oxygen Species Generated from Dioxygen Reduction Using an Organoruthenium Complex.

Pathogenic microorganisms pose a serious threat to global public health due to their persistent adaptation and growing resistance to antibiotics. Alternative therapeutic strategies are required to address this growing threat. Bactericidal antibiotics that are routinely prescribed to treat infections rely on hydroxyl radical formation for their therapeutic efficacies. We developed a redox approach to target bacteria using organotransition metal complexes to mediate the reduction of cellular O2 to H2O2, as a precursor for hydroxyl radicals via Fenton reaction. We prepared a library of 480 unique organoruthenium Schiff-base complexes using a coordination-driven three-component assembly strategy and identified the lead organoruthenium complex Ru1 capable of selectively invoking oxidative stress in Gram-positive bacteria, in particular methicillin-resistant Staphylococcus aureus, via transfer hydrogenation reaction and/or single electron transfer on O2. This strategy paves the way for a targeted antimicrobial approach leveraging on the redox chemistry of organotransition metal complexes to combat drug resistance.

Harnessing Endogenous Formate for Antibacterial Prodrug Activation by in cellulo Ruthenium-Mediated Transfer Hydrogenation Reaction.

The abundance and evolving pathogenic behavior of bacterial microorganisms give rise to antibiotic tolerance and resistance which pose a danger to global public health. New therapeutic strategies are needed to keep pace with this growing threat. We propose a novel approach for targeting bacteria by harnessing formate, a cell metabolite found only in particular bacterial species, to activate an antibacterial prodrug and selectively inhibit their growth. This strategy is premised on transfer hydrogenation reaction on a biorthogonal substrate utilizing native formate as the hydride source as a means of uncaging an antibacterial prodrug. Using coordination-directed 3-component assembly to prepare a library of 768 unique Ru-Arene Schiff-base complexes, we identified several candidates that efficiently reduced sulfonyl azide functional group in the presence of formate. This strategy paves the way for a new approach of targeted antibacterial therapy by exploiting unique bacterial metabolites.

Alveolar soft part sarcoma: Clinicopathological analysis and imaging results.

Alveolar soft part sarcoma (ASPS) is a rare, malignant, soft-tissue tumor that accounts for ~1.2% of all soft-tissue sarcomas. Due to its low incidence, clinicians often overlook the diagnosis. However, it is difficult to form an accurate diagnosis prior to surgery due to the lack of experience in imaging diagnosis. The present study reviewed the pathological images, and the computed tomography and magnetic resonance imaging data of 6 ASPS cases in order to investigate the clinicopathological and imaging characteristics of the tumor. The present study indicated that the magnetic resonance imaging (MRI) appearances of ASPS are nonspecific, but malignancy may be determined to a certain degree, which may aid in diagnosis prior to surgery and provides information for treatment guidance.