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Abstract Nonthermal atmospheric pressure biocompatible plasma (NBP), alternatively called bio-cold plasma, is a partially ionized gas that consists of charged particles, neutral atoms and molecules, photons, an electric field, and heat. Recently, nonthermal plasma-based technology has been applied to bioscience, medicine, agriculture, food processing, and safety. Various plasma device configurations and electrode layouts has fast-tracked plasma applications in the treatment of biological and material surfaces. The NBP action mechanism may be related to the synergy of plasma constituents, such as ultraviolet radiation or a reactive species. Recently, plasma has been used in the inactivation of viruses and resistant microbes, such as fungal cells, bacteria, spores, and biofilms made by microbes. It has also been used to heal wounds, coagulate blood, degrade pollutants, functionalize material surfaces, kill cancers, and for dental applications. This review provides an outline of NBP devices and their applications in bioscience and medicine. We also discuss the role of plasma-activated liquids in biological applications, such as cancer treatments and agriculture. The individual adaptation of plasma to meet specific medical requirements necessitates real-time monitoring of both the plasma performance and the target that is treated and will provide a new paradigm of plasma-based therapeutic clinical systems.

Abstract: Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation. Confocal microscopy, proliferation and surface biotinylation assays, co-immunoprecipitation, and western blotting analysis were used to elucidate the function and trafficking of Mpl mutants. Results showed that Mpl protein bearing the W272R mutation, alone or together with the K39N mutation, lacks detectable surface expression while being strongly colocalized with the endoplasmic reticulum (ER) marker calreticulin. Both WT and K39N-mutated Mpl were found to be signaling competent, but single or double mutants bearing W272R were unresponsive to Tpo. Function of the deficient Mpl receptor could be rescued by using 2 separate approaches: (1) GRASP55 overexpression, which partially restored Tpo-induced signaling of mutant Mpl by activating an autophagy-dependent secretory pathway and thus forcing ER-trapped immature receptors to traffic to the cell surface; and (2) CRISPR-Cas9 gene editing used to repair MPL T814C mutation in transfected cell lines and primary umbilical cord blood–derived CD34+ cells. We demonstrate proof of principle for rescue of mutant Mpl function by using gene editing of primary hematopoietic stem cells, which indicates direct therapeutic applications for CAMT patients.

Cold atmospheric plasma (plasma) has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p < 0.05) by plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

Liquid gallium ion source is experimented upon to determine the current-voltage (I-V) characteristics and angular distribution of the current density at different emitting tip temperatures and surface flow impedances. The flow of impedance of the liquid gallium on the emitting tip influences the I-V slope. Emitting tips which have a rough surface exhibit steep I-V curves. The region near the center has a depression of current density, and exists for various axial locations of the rings.

This letter proposes an approximate waterfill power loading scheme using limited feedback in orthogonal frequency division multiplexing (OFDM) systems. The proposed technique achieves nearly the capacity of optimal waterfill power loading, while significantly reducing feedback by using order information for the subcarrier channel gains. Furthermore, the proposed power loading technique can circumvent the practical shortcomings of previous limited feedback power loading techniques by simply exploiting order mapping and interpolation. The advantages are particularly visible at low SNR or for many subcarriers, both of which will be very common in emerging wireless broadband OFDM standards. [ABSTRACT FROM AUTHOR]

This study reports the experimental findings and plasma delivery approach developed at the Plasma Bioscience Research Center, Korea for the assessment of antitumor activity of dielectric barrier discharge (DBD) for cancer treatment. Detailed investigation of biological effects occurring after atmospheric pressure non-thermal (APNT) plasma application during in vitro experiments revealed the role of reactive oxygen species (ROS) in modulation of the antioxidant defense system, cellular metabolic activity, and apoptosis induction in cancer cells. To understand basic cellular mechanisms, we investigated the effects of APNT DBD plasma on antioxidant defense against oxidative stress in various malignant cells as well as normal cells. T98G glioblastoma, SNU80 thyroid carcinoma, KB oral carcinoma and a non-malignant HEK293 embryonic human cell lines were treated with APNT DBD plasma and cellular effects due to reactive oxygen species were observed. Plasma significantly decreased the metabolic viability and clonogenicity of T98G, SNU80, KB and HEK293 cell lines. Enhanced ROS in the cells led to death via alteration of total antioxidant activity, and NADP+/NADPH and GSH/GSSG ratios 24 hours (h) post plasma treatment. This effect was confirmed by annexin V-FITC and propidium iodide staining. These consequences suggested that the failure of antioxidant defense machinery, with compromised redox status, might have led to sensitization of the malignant cells. These findings suggest a promising approach for solid tumor therapy by delivering a lethal dose of APNT plasma to tumor cells while sparing normal healthy tissues.