Abstract: The adsorption of C and CHx radicals on anatase (001) was studied using DFT within the generalized gradient approximation using the Perde-Burke-Ernzerhof (PBE) functional. We have studied the influence of oxygen vacancies in and at the surface on the adsorption properties of the radicals. For the oxygen vacancies in anatase (001), the most stable vacancy is located at the surface. For this vacancy, the maximal adsorption strength of C and CH decreases compared to the adsorption on the stoichiometric surface, but it increases for CH2 and CH3. If an oxygen vacancy is present in the first subsurface layer, the maximal adsorption strength increases for C, CH, CH2, and CH3. When the vacancy is present in the next subsurface layer, we find that only the CH3 adsorption is enhanced, while the maximal adsorption energies for the other radical species decrease. Not only does the precise location of the oxygen vacancy determine the maximal adsorption interaction, it also influences the adsorption strengths of the radicals at different surface configurations. This determines the probability of finding a certain adsorption configuration at the surface, which in turn influences the possible surface reactions. We find that C preferentially adsorbs far away from the oxygen vacancy, while CH2 and CH3 adsorb preferentially at the oxygen vacancy site. A fraction of CH partially adsorbs at the oxygen vacancy, and another fraction adsorbs further away from the vacancy.

Abstract: Non-thermal plasma (NTP) has shown promising anti-cancer effects, but there is still limited knowledge about the underlying cell death mechanisms induced by NTP and inherent differences between NTP treatment modalities. This study aimed to investigate four major regulated cell death (RCD) pathways, namely apoptosis, pyroptosis, necroptosis, and ferroptosis, in melanoma cancer cells following NTP treatment, and to provide an overview of molecular mechanistic differences between direct and indirect NTP treatment modalities. To discriminate which cell death pathways were triggered after treatment, specific inhibitors of apoptosis, pyroptosis, necroptosis, and ferroptosis were evaluated. RCD-specific molecular pathways were further investigated to validate the findings with inhibitors. Both direct and indirect NTP treatment increased caspase 3/7 and annexin V expression, indicative of apoptosis, as well as lipid peroxidation, characteristic of ferroptosis. Pyroptosis, on the other hand, was only induced by direct NTP treatment, evidenced by increased caspase 1 activity, whereas necroptosis was stimulated in a cell line-dependent manner. These findings highlight the molecular differences and implications of direct and indirect NTP treatment for cancer therapy. Altogether, activation of multiple cell death pathways offers advantages in minimizing treatment resistance and enhancing therapeutic efficacy, particularly in a combination setting. Understanding the mechanisms underlying NTP-induced RCD will enable the development of strategic combination therapies targeting multiple pathways to achieve cancer lethality.

Abstract: Cold atmospheric pressure plasmas are gaining increased interest in the medical sector and clinical trials to treat skin diseases are underway. Plasmas are capable of producing several reactive oxygen and nitrogen species (RONS). However, there are open questions how plasma-generated RONS interact on a molecular level in a biological environment, e.g. cells or cell components. The redox pair glutathione (GSH) and glutathione disulphide (GSSG) forms the most important redox buffer in organisms responsible for detoxification of intracellular reactive species. We apply Raman spectroscopy, mass spectrometry, and molecular dynamics simulations to identify the time-dependent chemical modifications on GSH and GSSG that are caused by dielectric barrier discharge under ambient conditions. We find GSSG, S-oxidised glutathione species, and S-nitrosoglutathione as oxidation products with the latter two being the final products, while glutathione sulphenic acid, glutathione sulphinic acid, and GSSG are rather reaction intermediates. Experiments using stabilized pH conditions revealed the same main oxidation products as were found in unbuffered solution, indicating that the dominant oxidative or nitrosative reactions are not influenced by acidic pH. For more complex systems these results indicate that too long treatment times can cause difficult-to-handle modifications to the cellular redox buffer which can impair proper cellular function.

Abstract: SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c] pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations. Molecular docking studies revealed the importance of hydrophobic and hydrophilic amino acid residues for the stability. The molecular dynamics study examined conformational changes in the enzymes caused by the binding of the substrates and how those changes affected the stability of the protein-drug complex. The average RMSD values of the backbone atoms in compounds 6 and 10 were calculated from 1000 ps to 10000 ps and were found to be 0.13 nm for both compounds. Similarly, the radius of gyration values for compounds 6 and 10 were found to be 1.87 +/- 0.03 nm and 1.86 +/- 0.02 nm, respectively. The work presented here, will be of great help in lead identification and optimization for early drug discovery.

Abstract: Cold atmospheric plasma (CAP) has great potential for sterilization in the food industry, by deactivation of thermophilic bacteria, but the underlying mechanisms are largely unknown. Therefore, we investigate here whether CAP is able to denature/modify protein from thermophilic bacteria. We focus on MTH1880 (MTH) from Methanobacterium thermoautotrophicum as model protein, which we treated with dielectric barrier discharge (DBD) plasma operating in air for 10, 15 and 20 mins. We analysed the structural changes of MTH using circular dichroism, fluorescence and NMR spectroscopy, as well as the thermal and chemical denaturation, upon CAP treatment. Additionally, we performed molecular dynamics (MD) simulations to determine the stability, flexibility and solvent accessible surface area (SASA) of both the native and oxidised protein.

Abstract: There is a growing body of literature that recognizes the importance of plasma treated water (PTW)for inactivation of microorganism. However, very little attention has been paid to the role of reactive nitrogen species (RNS) in deactivation of bacteria. The aim of this study is to explore the role of RNS in bacterial killing, and to develop a plasma system with increased sterilization efficiency. To increase the concentration of reactive oxygen and nitrogen species (RONS) in solution, we have used vapor systems (DI water/HNO3 at different wt%) combined with plasma using N2 as working gas. The results show that the addition of the vapor system yields higher RONS contents. Furthermore, PTW produced by N2 + 0.5 wt% HNO3 vapor comprises a large amount of both RNS and ROS, while PTW created by N2 + H2O vapor consists of a large amount of ROS, but much less RNS. Interestingly, we observed more deactivation of E. Coli with PTW created by N2 + 0.5 wt% HNO3 vapor plasma as compared to PTW generated by the other plasma systems. This work provides new insight into the role of RNS along with ROS for deactivation of bacteria.

Abstract: The aggregation of insoluble amyloid beta (Aβ) peptides in the brain is known to trigger the onset of neurodegenerative diseases, such as Alzheimer’s disease. In spite of the massive number of investigations, the underlying mechanisms to destabilize the Aβ aggregates are still poorly understood. Some studies indicate the importance of oxidation to destabilize the Aβ aggregates. In particular, oxidation induced by cold atmospheric plasma (CAP) has demonstrated promising results in eliminating these toxic aggregates. In this paper, we investigate the effect of oxidation on the stability of an Aβ pentamer. By means of molecular dynamics simulations and umbrella sampling, we elucidate the conformational changes of Aβ pentamer in the presence of oxidized residues, and we estimate the dissociation free energy of the terminal peptide out of the pentamer form. The calculated dissociation free energy of the terminal peptide is also found to decrease with increasing oxidation. This indicates that Aβ pentamer aggregation becomes less favorable upon oxidation. Our study contributes to a better insight in one of the potential mechanisms for inhibition of toxic Aβ peptide aggregation, which is considered to be the main culprit to Alzheimer’s disease.

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In line with these inherent aggressive characteristics, only a subset of patients shows a clinical response to the standard of care therapies, thereby highlighting the need for a more personalized treatment approach. In this study, we comprehensively unraveled the intra-patient response heterogeneity and intrinsic aggressive nature of PDAC on bulk and single-organoid resolution. We leveraged a fully characterized PDAC organoid panel ( N  = 8) and matched our artificial intelligence-driven, live-cell organoid image analysis with retrospective clinical patient response. In line with the clinical outcomes, we identified patient-specific sensitivities to the standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX) using a growth rate-based and normalized drug response metric. Moreover, the single-organoid analysis was able to detect resistant as well as invasive PDAC organoid clones, which was orchestrates on a patient, therapy, drug, concentration and time-specific level. Furthermore, our in vitro organoid analysis indicated a correlation with the matched patient progression-free survival (PFS) compared to the current, conventional drug response readouts. This work not only provides valuable insights on the response complexity in PDAC, but it also highlights the potential applications (extendable to other tumor types) and clinical translatability of our approach in drug discovery and the emerging era of personalized medicine.

Abstract: Bacteria can be inactivated through various physical and chemical means, and these have always been the focus of extensive research. To further improve the methodology for these ends, two types of plasma systems were investigated: nano-second pulsed plasma (NPP) as liquid discharge plasma and an Argon gas-feeding dielectric barrier discharge (Ar-DBD) as a form of surface plasma. To understand the sterilizing action of these two different plasma sources, we performed experiments with Staphylococcus aureus (S. aureus) bacteria (wild type) and multidrug resistant bacteria (Penicillum-resistant, Methicillin-resistant and Gentamicin-resistant). We observed that both plasma sources can inactivate both the wild type and multidrug-resistant bacteria to a good extent. Moreover, we observed a change in the surface morphology, gene expression and β-lactamase activity. Furthermore, we used X-ray photoelectron spectroscopy to investigate the variation in functional groups (C-H/C-C, C-OH and C=O) of the peptidoglycan (PG) resulting from exposure to plasma species. To obtain atomic scale insight in the plasma-cell interactions and support our experimental observations, we have performed molecular dynamics simulations to study the effects of plasma species, such as OH, H2O2, O, O3, as well as O2 and H2O, on the dissociation/formation of above mentioned functional groups in PG.

Abstract: Purified water supply for human use, agriculture and industry is the major global priority nowadays. The advanced oxidation process based on atmospheric pressure non-thermal plasma (NTP) has been used for purification of wastewater, although the underlying mechanisms of degradation of organic pollutants are still unknown. In this study we employ two needle-type atmospheric pressure non-thermal plasma jets, i.e., indirect (ID-APPJ) and direct (D-APPJ) jets operating at Ar feed gas, for the treatment of methylene blue, methyl orange and congo red dyes, for two different times (i.e., 20 min and 30 min). Specifically, we study the decolorization/degradation of all three dyes using the above mentioned plasma sources, by means of UV-Vis spectroscopy, HPLC and a density meter. We also employ mass spectroscopy to verify whether only decolorization or also degradation takes place after treatment of the dyes by the NTP jets. Additionally, we analyze the interaction of OH radicals with all three dyes using reactive molecular dynamics simulations, based on the density functional-tight binding method. This investigation represents the first report on the degradation of these three different dyes by two types of NTP setups, analyzed by various methods, and based on both experimental and computational studies.

Abstract: N-Based fertilisers are paramount to support our still-growing world population. Current industrial N₂fixation is heavily fossil fuel-dependent, therefore, a lot of work is put into the development of fossil-free pathways. Plasma technology offers a fossil-free and flexible method for N₂fixation that is compatible with renewable energy sources. We present here a pulsed plasma jet for direct NO_{<italic>x</italic>}production from air. The pulsed power allows for a record-low energy consumption (EC) of 0.42 MJ (mol N)⁻¹. This is the lowest reported EC in plasma-based N₂fixation at atmospheric pressure thus far. We compare our experimental data with plasma chemistry modelling, and obtain very good agreement. Hence, we can use our model to explain the underlying mechanisms responsible for this low EC. The pulsed power and the corresponding pulsed gas temperature are the reason for the very low EC: they provide a strong vibrational–translational non-equilibrium and promote the non-thermal Zeldovich mechanism. This insight is important for the development of the next generation of plasma sources for energy-efficient NO_{<italic>x</italic>}production.

Abstract: Modeling the oxidation process of silicon nanowires through reactive force field based molecular dynamics simulations suggests that the formation of Si epoxide defects occurs both at the Si/SiOx interface and at the nanowire surface, whereas for flat surfaces, this defect is experimentally observed to occur only at the interface as a result of stress. In this paper, we argue that the increasing curvature stabilizes the defect at the nanowire surface, as suggested by our density functional theory calculations. The latter can have important consequences for the opto-electronic properties of thin silicon nanowires, since the epoxide induces an electronic state within the band gap. Removing the epoxide defect by hydrogenation is expected to be possible but becomes increasingly difficult with a reduction of the diameter of the nanowires.

Abstract: Using reactive molecular dynamics simulations, the melting behavior of nickel-carbon nanoclusters is examined. The phase diagrams of icosahedral and Wulff polyhedron clusters are determined using both the Lindemann index and the potential energy. Formulae are derived for calculating the equilibrium constants and the solid and liquid fractions during a phase transition, allowing more rational determination of the melting temperature with respect to the arbitrary Lindemann value. These results give more insight into the properties of nickel-carbon nanoclusters in general and can specifically be very useful for a better understanding of the synthesis of carbon nanotubes using the catalytic chemical vapor deposition method.

Abstract: Carbon dioxide conversion and utilization has gained significant interest over the years. A novel gas conversion technique with great potential in this area is plasma technology. A lot of research has already been performed, but mostly on pure gases. In reality, N2 will always be an important impurity in effluent
gases. Therefore, we performed an extensive combined experimental and computational study on the effect of N2 in the range of 1–98% on CO2 splitting in dielectric barrier discharge (DBD) plasma. The presence of up to 50% N2 in the mixture barely influences the effective (or overall) CO2 conversion and energy efficiency, because the N2 metastable molecules enhance the absolute CO2 conversion, and this compensates for the lower CO2 fraction in the mixture. Higher N2 fractions, however, cause a drop in the CO2 conversion and energy efficiency. Moreover, in the entire CO2/N2 mixing ratio, several harmful compounds, i.e., N2O and NOx compounds, are produced in the range of several 100 ppm. The reaction pathways for the formation of these compounds are explained based on a kinetic analysis, which allows proposing solutions on how to prevent the formation of these harmful compounds.

Abstract: We studied the transport of copper droplets through an inductively coupled plasma, connected to the sampling cone of a mass spectrometer, by means of a computational model. The sample droplets are followed until they become evaporated. They are inserted as liquid particles from the central inlet and the effects of injection position (i.e. “on” and “off” axis), droplet diameter, as well as mass loading flow rate are investigated. It is shown that more “on-axis” injection of the droplets leads to a more straight path line, so that the droplets move less in the radial direction and are evaporated more on the central axis, enabling a better sample transfer efficiency to the sampler cone. Furthermore, there are optimum ranges of diameters and flow rates, which guarantee the proper position of evaporation along the torch, i.e. not too early, so that the sample can get lost in the torch, and not too late, which reduces the chance of becoming ionized before reaching the sampler.