Plasma-enhanced microbial electrolytic disinfection: Decoupling electro- and plasma-chemistry in plasma-electrolyzed oxidizing water using ion-exchange membranes.

Pathogenic microorganisms pose a global threat to public health and environment. Common antibacterial chemicals produce toxic residues, inevitably harming the environment. Electrolyzed oxidizing water (EOW), a promising environment-friendly alternative disinfectant, still lacks effective production processes, sufficient bactericidal efficacy and stability, while the enabling physico-chemical mechanisms remain unclear. Here, we report, for the first time, an effective hybrid plasma electrochemical EOW production process and reveal the mechanisms by combining nonthermal plasmas and a two-chamber electrochemical cell separated by a cation exchange membrane (CEM) for decoupling the chemical reactions during the plasma treatment of water. Experimental results demonstrate that combined chlorine (chloramine) was the main chlorine product in the plasma-enhanced EOW (P-EOW) without a membrane, owing to the consumption of free chlorine  (Cl2, HOCl, ClO-) by plasma-generated reactive nitrogen species. With a CEM in the plasma electrolysis system and through controlling the plasma discharge polarity, the production of free chlorine and other reactive species can be selectively controlled, with the highest concentration of free chlorine obtained in the negative plasma-enhanced EOW (NP-EOW). According to the transportation of cations by the CEM, the high concentrations of free chlorine may be attributed to the higher consuptions of H+ in cathode cell of negative plasma. The study of antibacterial ability of EOW produced under different conditions revealed that Staphylococcus aureus cells were best inactivated by the NP-EOW with CEM, which is mainly attributed to the higher concentration of free chlorine. This study demonstrates the feasibility of plasma-enhanced microbial electrolytic disinfection and offers new insights into the fundamental aspects of P-EOW chemistries for the future development of sustainable, efficient, and cost-effective multipurpose sustainable chemical technologies for water research and treatment.

Cold Atmospheric Plasma Ameliorates Skin Diseases Involving Reactive Oxygen/Nitrogen Species-Mediated Functions.

Skin diseases are mainly divided into infectious diseases, non-infectious inflammatory diseases, cancers, and wounds. The pathogenesis might include microbial infections, autoimmune responses, aberrant cellular proliferation or differentiation, and the overproduction of inflammatory factors. The traditional therapies for skin diseases, such as oral or topical drugs, have still been unsatisfactory, partly due to systematic side effects and reappearance. Cold atmospheric plasma (CAP), as an innovative and non-invasive therapeutic approach, has demonstrated its safe and effective functions in dermatology. With its generation of reactive oxygen species and reactive nitrogen species, CAP exhibits significant efficacies in inhibiting bacterial, viral, and fungal infections, facilitating wound healing, restraining the proliferation of cancers, and ameliorating psoriatic or vitiligous lesions. This review summarizes recent advances in CAP therapies for various skin diseases and implicates future strategies for increasing effectiveness or broadening clinical indications.

In Vivo Metabolic Analysis of the Anticancer Effects of Plasma-Activated Saline in Three Tumor Animal Models.

In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in vivo. In addition, based on an ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) analysis of tumor cell metabolism, the glycerophospholipid metabolic pathway was the most susceptible metabolic pathway to PAS treatment in melanoma in vitro and in vivo. Furthermore, PAS also inhibited cell proliferation in vivo in oral tongue squamous-cell cancer and non-small-cell lung cancer. There were few toxic side effects in the three animal models, and the treatment was deemed safe to use. In the future, plasma-activated liquids may serve as a potential therapeutic approach in the treatment of cancer.

Trident cold atmospheric plasma blocks three cancer survival pathways to overcome therapy resistance.

Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer survival pathways are susceptible to disturbances in cellular reactive oxygen species (ROS) and may therefore be disrupted by exogenous ROS. Here, we explore whether trident cold atmospheric plasma (Tri-CAP), a gas discharge with exceptionally low-level ROS, could inhibit multiple cancer survival pathways together in a murine cell line model of therapy-resistant chronic myeloid leukemia (CML). We show that Tri-CAP simultaneously disrupts three cancer survival pathways of redox deregulation, glycolysis, and proliferative AKT/mTOR/HIF-1α signaling in this cancer model. Significantly, Tri-CAP blockade induces a very high rate of apoptotic death in CML cell lines and in primary CD34+ hematopoietic stem and progenitor cells from CML patients, both harboring the therapy-resistant T315I mutation. In contrast, nonmalignant controls are minimally affected by Tri-CAP, suggesting it selectively targets resistant cancer cells. We further demonstrate that Tri-CAP elicits similar lethality in human melanoma, breast cancer, and CML cells with disparate, resistant mechanisms and that it both reduces tumor formation in two mouse models and improves survival of tumor-bearing mice. For use in patients, administration of Tri-CAP may be extracorporeal for hematopoietic stem cell transplantation therapy, transdermal, or through its activated solution for infusion therapy. Collectively, our results suggest that Tri-CAP represents a potent strategy for disrupting cancer survival pathways and overcoming therapy resistance in a variety of malignancies.

Oxygen harvesting from carbon dioxide: simultaneous epoxidation and CO formation.

Due to increasing concentrations in the atmosphere, carbon dioxide has, in recent times, been targeted for utilisation (Carbon Capture Utilisation and Storage, CCUS). In particular, the production of CO from CO2 has been an area of intense interest, particularly since the CO can be utilized in Fischer-Tropsch synthesis. Herein we report that CO2 can also be used as a source of atomic oxygen that is efficiently harvested and used as a waste-free terminal oxidant for the oxidation of alkenes to epoxides. Simultaneously, the process yields CO. Utilization of the atomic oxygen does not only generate a valuable product, but also prevents the recombination of O and CO, thus increasing the yield of CO for possible application in the synthesis of higher-order hydrocarbons.

Plasma-activated thermosensitive biogel as an exogenous ROS carrier for post-surgical treatment of cancer.

Post-surgical residual tumor cells are the primary cause of relapse and progression of cancer but unfortunately, there are limited therapeutic options. In this work, a fillable plasma-activated biogel is produced on a thermosensitive biogel [(Poly-DL-lactide)-(poly-ethylene glycol)-(poly-DL-lactide), PLEL] with the aid of a discharge plasma for local post-operative treatment of cancer. In vivo data show that the plasma-activated PLEL biogel (PAPB) eliminates residual tumor tissues after removal surgery and also inhibits in situ recurrence while showing no evident systemic toxicity. Moreover, the PAPB possesses excellent storage capability, allows for slow release of plasma-generated reactive oxygen species (ROS), and exhibits good ROS-mediated anticancer effects in vitro. Our results reveal that the novel plasma-activated biogel is an effective therapeutic agent for local post-operative treatment of cancer.

Low-Temperature Gas Plasma Combined with Antibiotics for the Reduction of Methicillin-Resistant Staphylococcus aureus Biofilm Both In Vitro and In Vivo.

Biofilm infections in wounds seriously delay the healing process, and methicillin-resistant Staphylococcus aureus is a major cause of wound infections. In addition to inactivating micro-organisms, low-temperature gas plasma can restore the sensitivity of pathogenic microbes to antibiotics. However, the combined treatment has not been applied to infectious diseases. In this study, low-temperature gas plasma treatment promoted the effects of different antibiotics on the reduction of S. aureus biofilms in vitro. Low-temperature gas plasma combined with rifampicin also effectively reduced the S. aureus cells in biofilms in the murine wound infection model. The blood and histochemical analysis demonstrated the biosafety of the combined treatment. Our findings demonstrated that low-temperature gas plasma combined with antibiotics is a promising therapeutic strategy for wound infections.

Cold Atmospheric-Pressure Plasma Caused Protein Damage in Methicillin-Resistant Staphylococcus aureus Cells in Biofilms.

Biofilms formed by multidrug-resistant bacteria are a major cause of hospital-acquired infections. Cold atmospheric-pressure plasma (CAP) is attractive for sterilization, especially to disrupt biofilms formed by multidrug-resistant bacteria. However, the underlying molecular mechanism is not clear. In this study, CAP effectively reduced the living cells in the biofilms formed by methicillin-resistant Staphylococcus aureus, and 6 min treatment with CAP reduced the S. aureus cells in biofilms by 3.5 log10. The treatment with CAP caused the polymerization of SaFtsZ and SaClpP proteins in the S. aureus cells of the biofilms. In vitro analysis demonstrated that recombinant SaFtsZ lost its self-assembly capability, and recombinant SaClpP lost its peptidase activity after 2 min of treatment with CAP. Mass spectrometry showed oxidative modifications of a cluster of peaks differing by 16 Da, 31 Da, 32 Da, 47 Da, 48 Da, 62 Da, and 78 Da, induced by reactive species of CAP. It is speculated that the oxidative damage to proteins in S. aureus cells was induced by CAP, which contributed to the reduction of biofilms. This study elucidates the biological effect of CAP on the proteins in bacterial cells of biofilms and provides a basis for the application of CAP in the disinfection of biofilms.

Successful Treatment of Vitiligo with Cold Atmospheric Plasma‒Activated Hydrogel.

Vitiligo shows insufficient response to current therapies largely owing to T-lymphocyte dysfunction, abnormal inflammatory activation, and excessive oxidative stress in lesions. Cold atmospheric plasma (CAP) possesses pleiotropic antioxidant and anti-inflammatory properties and may offer an improvement to current treatment options. In this study, the efficacy and safety of CAP were investigated in a mouse model of vitiligo and a randomized and controlled trial of patients with active focal vitiligo. Skin biopsies showed that topical treatment of vitiligo-like lesions on mouse dorsal skin by CAP restored the distribution of melanin. In addition, CAP treatment reduced the infiltration of CD11c+ dendritic cells, CD3+ T cells, and CD8+ T cells; inhibited the release of CXCL10 and cytokine IFN-γ; and enhanced cellular resistance to oxidative stress and excessive immune response by enhancing the expression of the transcription factor NRF2 and attenuating the activity of inducible nitric oxide synthase. In a randomized and controlled trial, CAP treatment achieved partial and complete repigmentation in 80% and 20% of vitiligo lesions, respectively, without hyperpigmentation in surrounding areas or other adverse events during the treatment period and its follow-up period. In conclusion, CAP offers a promising option for the management of vitiligo.

Effect of He Plasma Jet Versus Surface Plasma on the Metabolites of Acute Myeloid Leukemia Cells.

Cold atmospheric plasma, including plasma jet and surface plasma, can promote the apoptosis of cancer cells without causing significant damage to surrounding normal cells, which was hopeful to be applied to the clinical cancer therapy. However, experimental plasma devices used directly to clinical experiments has challenges in technology and methods, especially the difference in killing tumor cells efficiency of these two common plasma sources. Therefore, it is great necessity to explore the differences in treating tumors between different plasma sources. This paper achieved good killing efficiency by using two kinds of cold atmospheric plasma generating devices, namely plasma jet and surface plasma treatment along acute myeloid leukemia (AML). The results showed that the He plasma jet kills leukemia cells more efficiently than surface plasma with the same voltage and frequency and the same time. By GC-TOFMS and metabolomics analysis, this paper compared the differential metabolites of leukemia cells treated by two plasma devices and the key metabolic pathways closely related to differential metabolites. Simultaneously, we found alanine, aspartate and glutamate metabolism was most correlated with a key differential metabolite, glutamine. It was found that the glutaminase activity of He plasma jet group was lower than that of surface plasma group, which might be a reason for He plasma jet group to kill tumor cells better. It was also worth noting that relative quantity of glucose metabolites of plasma jet treatment group was lower than that of surface plasma treatment group. This study provides the basis for clinical trials for future.

The Antitumor Effects of Plasma-Activated Saline on Muscle-Invasive Bladder Cancer Cells In Vitro and In Vivo Demonstrate Its Feasibility as a Potential Therapeutic Approach.

Muscle-invasive bladder cancer (MIBC) is a fast-growing and aggressive malignant tumor in urinary system. Since chemotherapy and immunotherapy are only useable with a few MIBC patients, the clinical treatment of MIBC still faces challenges. Here, we examined the feasibility of plasma-activated saline (PAS) as a fledgling therapeutic strategy for MIBC treatment. Our data showed that plasma irradiation could generate a variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in saline. In vivo tests revealed that pericarcinomatous tissue injection with PAS was effective at preventing subcutaneous bladder tumor growth, with no side effects to the visceral organs after long-term administration, as well as having no obvious influence on the various biochemistry indices of the blood in mice. The in vitro studies indicated that adding 30% PAS in cell culture media causes oxidative damage to the bladder transitional cells T24 and J82 through enhancing the intracellular ROS level, and eventually induces cancer cells' apoptosis by activating the ROS-mediated Fas/CD95 pathway. Therefore, for an intracavity tumor, these initial observations suggest that the soaking of the tumor tissue with PAS by intravesical perfusion may be a novel treatment option for bladder cancer.

Plasma-activated water: An alternative disinfectant for S protein inactivation to prevent SARS-CoV-2 infection.

SARS-CoV-2 is a highly contagious virus and is causing a global pandemic. SARS-CoV-2 infection depends on the recognition of and binding to the cellular receptor human angiotensin-converting enzyme 2 (hACE2) through the receptor-binding domain (RBD) of the spike protein, and disruption of this process can effectively inhibit SARS-CoV-2 invasion. Plasma-activated water efficiently inactivates bacteria and bacteriophages by causing damage to biological macromolecules, but its effect on coronavirus has not been reported. In this study, pseudoviruses with the SARS-CoV-2 S protein were used as a model, and plasma-activated water (PAW) effectively inhibited pseudovirus infection through S protein inactivation. The RBD was used to study the molecular details, and the RBD binding activity was inactivated by plasma-activated water through the RBD modification. The short-lived reactive species in the PAW, such as ONOO-, played crucial roles in this inactivation. Plasma-activated water after room-temperature storage of 30 days remained capable of significantly reducing the RBD binding with hACE2. Together, our findings provide evidence of a potent disinfection strategy to combat the epidemic caused by SARS-CoV-2.

Effects of Plasma-Activated Water on Skin Wound Healing in Mice.

Cold atmospheric plasma (CAP) has been widely used in biomedicine during the last two decades. While direct plasma treatment has been reported to promote wound healing, its application can be uneven and inconvenient. In this study, we first activated water with a portable dielectric barrier discharge plasma device and evaluated the inactivation effect of plasma-activated water (PAW) on several kinds of bacteria that commonly infect wounds. The results show that PAW can effectively inactivate these bacteria. Then, we activated tap water and examined the efficacy of PAW on wound healing in a mouse model of full-thickness skin wounds. We found that wound healing in mice treated with PAW was significantly faster compared with the control group. Histological analysis of the skin tissue of mice wounds showed a significant reduction in the number of inflammatory cells in the PAW treatment group. To identify the possible mechanism by which PAW promotes wound healing, we analyzed changes in the profiles of wound bacteria after PAW treatment. The results show that PAW can significantly reduce the abundance of wound bacteria in the treatment group. The results of biochemical blood tests and histological analysis of major internal organs in the mice show that PAW had no obvious side effects. Taken together, these results indicate that PAW may be a new and effective method for promoting wound healing without side effects.

Effect of cold atmospheric plasma treatment on the metabolites of human leukemia cells.

BACKGROUND: Acute myeloid leukemia (AML) is a typically fatal malignancy and new drug and treatment need to be developed for a better survival outcome. Cold atmospheric plasma (CAP) is a novel technology, which has been widely applied in biomedicine, especially in various of cancer treatment. However, the changes in cell metabolism after CAP treatment of leukemia cells have been rarely studied. METHODS: In this study, we investigated the metabolite profiling of plasma treatment on leukemia cells based on Gas Chromatography Tandem Time-of-Flight Mass Spectrometry (GC-TOFMS). Simultaneously, we conducted a series of bioinformatics analysis of metabolites and metabolic pathways with significant differences after basic data analysis. RESULTS: 800 signals were detected by GC-TOF mass-spectrometry and then evaluated using PCA and OPLS-DA. All the differential metabolites were listed and the related metabolic pathways were analyzed by KEGG pathway. The results showed that alanine, aspartate and glutamate metabolism had a significant change after plasma treatment. Meanwhile, d-glutamine and d-glutamate metabolism were significantly changed by CAP. Glutaminase activity was decreased after plasma treatment, which might lead to glutamine accumulation and leukemia cells death. CONCLUSIONS: We found the above two metabolic pathways vulnerable to plasma treatment, which might result in leukemia cells death and might be the cornerstone of further exploration of plasma treatment targets.

Discharge Plasma-Activated Saline Protects Against Abdominal Sepsis by Promoting Bacterial Clearance.

AIM: The aim of the present study was to investigate the effect of cold atmospheric discharge plasma-activated saline (DPAS) on abdominal sepsis. METHODS: For in vitro research, Methicillin-resistant Staphylococcus aureus (MRSA) was treated with DPAS, and the survival was detected. For in vivo research, male C57BL/6 mice were induced to sepsis by cecal ligation and puncture (CLP) and were randomly allocated into saline and DPAS control groups, CLP group, and low or high doses of DPAS (CLP + DPAS 5 and CLP + DPAS 10) groups. In experiment 1, mice were monitored for 120 h to conduct a Kaplan-Meier survival curve analysis. In experiment 2, blood, peritoneal fluid, and lung and intestinal tissues in experimental groups were collected at 4, 8, and 24 h after the CLP/sham operation to determine the severity of sepsis. RESULTS: In vitro results showed that DPAS significantly inhibited MRSA proliferation. In vivo results showed that both low and high doses of DPAS could significantly improve septic survival in the mice. DPAS treatment also significantly attenuated the lung and intestine histopathological injuries; lung wet/dry ratio; inflammatory reaction; bacterial load in the peritoneal cavity, blood, and lungs; HMGB1 and NF-κB p65 expression levels; cell apoptosis in the lung and intestine. However, there was no difference between CLP + DPAS 5 and CLP + DPAS 10 groups. CONCLUSION: In conclusion, DPAS had markedly protective effects on abdominal sepsis in mice, and the potential mechanism was associated with the ability of reactive species in DPAS to promote bacterial clearance, inhibit the inflammatory response and cell apoptosis.

Efficacy of low-temperature plasma-activated gas disinfection against biofilm on contaminated GI endoscope channels.

BACKGROUND AND AIMS: It has been increasingly recognized that the safety of GI endoscopes needs to be improved by addressing the small margin of safety of high-level disinfectants (HLDs) and the failure of HLDs to clear multidrug-resistant organisms and biofilms. There is also an unmet need for effective low-temperature sterilization techniques that have a clear pathway for U.S. Food and Drug Administration clearance. Here, we report the results of our investigation of a novel argon plasma-activated gas (PAG) for disinfection and potentially sterilization of biofilm-contaminated endoscopic channels. METHODS: Test polytetrafluoroethylene channel segments were contaminated with 4-, 24- and 48-hour luminal biofilms of methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, or Escherichia coli and were treated by PAG flowing for up to 9 minutes. After PAG treatment, inactivation and dispersal of luminal bacterial biofilms and their regrowth in 48 hours were evaluated. Reactive species induced by PAG were measured with colorimetric probes and electron spin resonance spectrometry. Surface morphology and elemental composition of PAG-treated channel material were analyzed with scanning electron microscopy. RESULTS: PAG treatment for 9 minutes led to more than 8 log reduction of viable cells and dispersal of 24- and 48-hour luminal biofilms of all 3 bacteria and to suppression of their regrowth, whereas it resulted in little morphologic abnormalities in channel material. Ozone concentration of PAG fell to below .01 ppm within 30 seconds of switching off the plasma. PAG-treated deionized water was acidified with numerous types of reactive species, each with a concentration some 3 orders of magnitude or more below its bacterial inhibition concentration. CONCLUSIONS: PAG is capable of effectively and rapidly disinfecting luminal bacterial biofilms and offers an alternative to the step of HLDs and/or ethylene oxide in the endoscope reprocessing procedure with safety to personnel and environment.

Cold atmospheric plasma induces apoptosis of melanoma cells via Sestrin2-mediated nitric oxide synthase signaling.

Cold atmospheric plasma (CAP) represents a promising therapy for selectively cancer killing. However, the mechanism of CAP-induced cancer cell death remains unclear. Here, we identified the tumor necrosis factor-family members, especially Fas, and overloaded intracellular nitric oxide participated in CAP induced apoptosis in A375 and A875 melanoma cell lines, which was known as extrinsic apoptosis pathway. This progress was mediated by antagonistic protein of reactive oxygen species, Sestrin2. The over expression of Sestrin2 induced by plasma treatment resulted in phosphorylation of p38 mitogen-activated protein kinase (MAPK), followed by increased expression of nitric oxide synthase (iNOS), Fas and Fas ligand. Depletion of Sestrin2 reduced iNOS and Fas expression, which was associated with reduction of plasma-induced apoptosis. In contrast, inhibition of iNOS activity and phosphorylation of p38 did not alter Sestrin2 expression in plasma-treated melanoma cells. Taken together, cold atmospheric plasma increases Sestrin2 expression and further activates downstream iNOS, Fas and p38 MAPK signaling to induce apoptosis of melanoma cell lines. These findings suggest a previously unrecognized mechanism in melanoma cells response to cold atmospheric plasma therapy.

Mechanism of Virus Inactivation by Cold Atmospheric-Pressure Plasma and Plasma-Activated Water.

Viruses cause serious pathogenic contamination that severely affects the environment and human health. Cold atmospheric-pressure plasma efficiently inactivates pathogenic bacteria; however, the mechanism of virus inactivation by plasma is not fully understood. In this study, surface plasma in argon mixed with 1% air and plasma-activated water was used to treat water containing bacteriophages. Both agents efficiently inactivated bacteriophages T4, Φ174, and MS2 in a time-dependent manner. Prolonged storage had marginal effects on the antiviral activity of plasma-activated water. DNA and protein analysis revealed that the reactive species generated by plasma damaged both nucleic acids and proteins, consistent with the morphological examination showing that plasma treatment caused the aggregation of bacteriophages. The inactivation of bacteriophages was alleviated by the singlet oxygen scavengers, demonstrating that singlet oxygen played a primary role in this process. Our findings provide a potentially effective disinfecting strategy to combat the environmental viruses using cold atmospheric-pressure plasma and plasma-activated water.IMPORTANCE Contamination with pathogenic and infectious viruses severely threatens human health and animal husbandry. Current methods for disinfection have different disadvantages, such as inconvenience and contamination of disinfection by-products (e.g., chlorine disinfection). In this study, atmospheric surface plasma in argon mixed with air and plasma-activated water was found to efficiently inactivate bacteriophages, and plasma-activated water still had strong antiviral activity after prolonged storage. Furthermore, it was shown that bacteriophage inactivation was associated with damage to nucleic acids and proteins by singlet oxygen. An understanding of the biological effects of plasma-based treatment is useful to inform the development of plasma into a novel disinfecting strategy with convenience and no by-product.

Antimicrobial Efficacy and Safety of a Novel Gas Plasma-Activated Catheter Lock Solution.

Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans in mature biofilms were reduced by 6 to 8 orders of magnitude with a PAD lock for 60 min. Subsequent 24-h incubation of PAD-treated samples resulted in no detectable regrowth of viable bacteria or fungi. As a comparison, the use of a minocycline-EDTA-ethanol lock solution for 60 min led to regrowth of bacteria and fungi, up to 107 to 109 CFU/ml, in 24 h. The PAD lock solution had minimal impact on human umbilical vein endothelial cell viability, whereas the minocycline-EDTA-ethanol solution elicited cell death in nearly half of human endothelial cells. Additionally, PAD treatment caused little topological change to catheter materials. In conclusion, PAD represents a novel antibiotic-free, noncytotoxic lock solution that elicits rapid and broad-spectrum eradication of biofilm-laden microbes and shows promise for the prevention and treatment of intravascular catheter infections.

Cold atmospheric-pressure plasma induces DNA-protein crosslinks through protein oxidation.

Reactive oxygen and nitrogen species (ROS and RNS) generated by cold atmospheric-pressure plasma could damage genomic DNA, although the precise types of these DNA damage induced by plasma are poorly characterized. Understanding plasma-induced DNA damage will help to elucidate the biological effect of plasma and guide the application of plasma in ROS-based therapy. In this study, it was shown that ROS and RNS generated by physical plasma could efficiently induce DNA-protein crosslinks (DPCs) in bacteria, yeast, and human cells. An in vitro assay showed that plasma treatment resulted in the formation of covalent DPCs by activating proteins to crosslink with DNA. Mass spectrometry and hydroperoxide analysis detected oxidation products induced by plasma. DPC formation were alleviated by singlet oxygen scavenger, demonstrating the importance of singlet oxygen in this process. These results suggested the roles of DPC formation in DNA damage induced by plasma, which could improve the understanding of the biological effect of plasma and help to develop a new strategy in plasma-based therapy including infection and cancer therapy.