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Objective: This study aimed to investigate the effect of plasma‐activated Ringer's lactate solution (PAL) on oral squamous cell carcinoma (OSCC) cells and carcinogenic processes with a particular focus on iron and collagenous matrix formation. Materials and Methods: We used three OSCC cell lines, one keratinocyte cell line, and two fibroblast lines, and cell viability assays, immunoblotting, flow cytometry, and transmission electron microscopy were performed to evaluate the effect and type of cell death. The effect of PAL treatment on lysyl oxidase (LOX) expression was investigated in vitro and in vivo. Tamoxifen‐inducible Mob1a/b double‐knockout mice were used for the in vivo experiment. Results: PAL killed OSCC cells more effectively than the control nontumorous cells and suppressed cell migration and invasion. Ferroptosis occurred and the protein level of LOX was downregulated in cancer cells in vitro and in vivo. Additionally, PAL improved the survival rate of mice and suppressed collagenous matrix formation. Conclusions: We demonstrated that PAL specifically kills OSCC cells and that ferroptosis occurs in vitro and in vivo. Furthermore, PAL can prevent carcinogenesis and improve the survival rate of oral cancer, especially tongue cancer, by changing collagenous matrix formation via LOX suppression. [ABSTRACT FROM AUTHOR]

One of the goals of systems biology is to reverse engineer in a comprehensive fashion the arrow diagrams of signal transduction systems. An important tool for ordering pathway components is genetic epistasis analysis, and here we present a strategy termed Alternative Inputs (AIs) to perform systematic epistasis analysis. An alternative input is defined as any genetic manipulation that can activate the signaling pathway instead of the natural input. We introduced the concept of an “AIs-Deletions matrix” that summarizes the outputs of all combinations of alternative inputs and deletions. We developed the theory and algorithms to construct a pairwise relationship graph from the AIs-Deletions matrix capturing both functional ordering (upstream, downstream) and logical relationships (AND, OR), and then interpreting these relationships into a standard arrow diagram. As a proof-of-principle, we applied this methodology to a subset of genes involved in yeast mating signaling. This experimental pilot study highlights the robustness of the approach and important technical challenges. In summary, this research formalizes and extends classical epistasis analysis from linear pathways to more complex networks, facilitating computational analysis and reconstruction of signaling arrow diagrams.

Designing the shape and size of a cell is an interesting challenge for synthetic biology. Prolonged exposure to the mating pheromone α-factor induces an unusual morphology in yeast cells: multiple mating projections. The goal of this work was to reproduce the multiple projections phenotype in the absence of α-factor using a gain-of-function approach termed “Alternative Inputs (AIs)”. An alternative input is defined as any genetic manipulation that can activate the signaling pathway instead of the natural input. Interestingly, none of the alternative inputs were sufficient to produce multiple projections although some produced a single projection. Then, we extended our search by creating all combinations of alternative inputs and deletions that were summarized in an AIs-Deletions matrix. We found a genetic manipulation (AI-Ste5p ste2Δ) that enhanced the formation of multiple projections. Following up this lead, we demonstrated that AI-Ste4p and AI-Ste5p were sufficient to produce multiple projections when combined. Further, we showed that overexpression of a membrane-targeted form of Ste5p alone could also induce multiple projections. Thus, we successfully re-engineered the multiple projections mating morphology using alternative inputs without α-factor.

Dimolybdenum complexes bearing 3,3′′′-(1,1′:3′,1′′:3′′,1′′′-quaterphenylene)-bridged pyridine-based PNP-type pincer ligand are designed and prepared according to DFT calculations on the cleavage step of dinitrogen-bridged dimolybdenum complexes bearing polyphenylene-bridged pyridine-based PNP-type pincer ligands. The dimolybdenum complexes are found to work as effective catalysts toward ammonia formation from dinitrogen with samarium diiodide as a reductant and water as a proton source under ambient reaction conditions. [ABSTRACT FROM AUTHOR]