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Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection byproducts (DBPs) have been widely found in drinking water and are receiving more and more attentions because of their high cytotoxicity, genotoxicity, and developmental toxicity. However, the effects of HNMs exposure on the intestinal tract and intestinal flora remain unknown. This study comprehensively determined the effects of trichloronitromethane, bromonitromethane, and bromochloronitromethane exposure on the intestinal tract and intestinal flora. Results showed that the three HNMs induced intestinal oxidative stress and inflammatory response. Further, HNMs exposure could change the diversities and community structure of intestinal flora, thereby triggering intestinal flora dysbiosis, which might be associated with the intestinal damage such as oxidative stress and inflammation. The intestinal flora dysbiosis was accompanied with mark alterations in function of intestinal flora, such as carbohydrate, lipid, and amino acid metabolisms. This research provides a new insight into studying the toxicity of HNMs exposure based on intestinal flora, which will further improve the health risk assessment of DBPs in drinking water.

Abstract Background Alzheimer's disease (AD) is a prevalent irreversible neurodegenerative condition marked by gradual cognitive deterioration and neuronal loss. The mammalian Ste20-like kinase (MST1)–Hippo pathway is pivotal in regulating cell apoptosis, immune response, mitochondrial function, and oxidative stress. However, the association between MST1 and mitochondrial function in AD remains unknown. Therefore, this study investigates the effect of MST1 on neuronal damage and cognitive impairment by regulating mitochondrial homeostasis in AD. Methods In this study, 4- and 7-month-old 5xFAD mice were selected to simulate the early and middle stages of AD, respectively; age-matched wild-type mice served as controls for comparative analysis. Adeno-associated virus (AAV) was injected into the hippocampus of mice. Four weeks post-injection, cognitive function, neuronal damage indicators, and mitochondrial morphology, dynamics, oxidative stress, ATP, and apoptosis-related indicators were evaluated. Additionally, RNA-sequencing was performed on the hippocampal tissue of 5xFAD mice and MST1-knockdown 5xFAD mice. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on differentially expressed genes to elucidate the potential mechanism of MST1. In vitro studies were performed to investigate the effects of MST1 on SH-SY5Y model cell viability and mitochondrial function and validate the potential underlying molecular mechanisms. Results MST1 overexpression accelerated neuronal degeneration and cognitive deficits in vivo while promoting oxidative stress and mitochondrial damage. Similarly, in vitro, MST1 overexpression facilitated apoptosis and mitochondrial dysfunction. MST1 knockdown and chemical inactivation reduced cognitive decline, mitochondrial dysfunction, and neuronal degeneration. Mechanistically, MST1 regulated the transcription of mitochondrial genes, including MT-ND4L, MT-ATP6, and MT-CO2, by binding to PGC1α. Moreover, MST1 influenced cellular oxidative stress through the PI3K-Akt-ROS pathway, ultimately disrupting mitochondrial homeostasis and mediating cell damage. Conclusions Cumulatively, these results suggest that MST1 primarily regulates mitochondrial DNA transcription levels by interacting with PGC1α and modulates cellular oxidative stress through the PI3K-Akt-ROS pathway, disrupting mitochondrial homeostasis. This discovery can be exploited to potentially enhance mitochondrial energy metabolism pathways by targeting MST1, offering novel potential therapeutic targets for treating AD. Graphical Abstract

Discharge plasmas, recognized as unique platforms for investigating the origins of chemical life, have garnered extensive interest for their potential to simulate prebiotic conditions. This paper embarks on a comprehensive overview of recent advancements in the plasma-enabled synthesis of life’s building blocks, charting the complex environmental parameters believed to have surrounded life’s inception. This discussion elaborates on the fundamental mechanisms of discharge plasmas and their likely role in fostering conditions necessary for the origin of life on early Earth. We consider a variety of chemical reactions facilitated by plasma, specifically the synthesis of vital organic molecules — amino acids, nucleobases, sugars, and lipids. Further, we delve into the impact of plasmas on prebiotic chemical evolution. We expect this review to open new horizons for future investigations in plasma-related prebiotic chemistry that could offer valuable insights for unraveling the mysteries of life's origin.

Abstract Background Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. Methods This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. Results A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW. Conclusion This pilot trial preliminarily confirmed that nebulized inhalation of PAW can alleviate pneumonia in moderate COVID-19 patients with antiviral treatment failure, with no adverse reactions observed. This still needs to be verified by large-scale studies. Trial registration Chinese Clinical Trial Registry; No.: ChiCTR2300078706 (retrospectively registered, 12/15/2023); URL: www.chictr.org.cn .

Malignant melanoma is the most lethal form of skin cancer. As a promising anti-cancer agent, plasma-activated water (PAW) rich in reactive oxygen and nitrogen species (RONS) has shown significant potential for melanoma treatment. However, rapid decay of RONS and inefficient delivery of PAW in conventional injection methods limit its practical applications. To address this issue, here we report a new approach for the production of plasma-activated cryo-microneedles (PA-CMNs) patches using custom-designed plasma devices and processes. Our innovation is to incorporate PAW into the PA-CMNs that are fabricated using a fast cryogenic micro-molding method. It is demonstrated that PA-CMNs can be easily inserted into skin to release RONS and slow the decay of RONS thereby prolonging their bioactivity and effectiveness. The new insights into the effective melanoma treatment suggest that the rich mixture of RONS within PA-CMNs prepared by custom-developed hybrid plasma-assisted configuration induces both ferroptosis and apoptosis to selectively kill tumor cells. A significant inhibition of subcutaneous A375 melanoma growth was observed in PA-CMNs-treated tumor-bearing nude mice without any signs of systemic toxicity. The new approach based on PA-CMNs may potentially open new avenues for a broader range of disease treatments.

The interaction between an atmospheric pressure plasma jet (APPJ) and an aqueous solution has great application prospects in biomedicine and many other fields. Reactive species adjacent to a water surface is critical to the activation of APPJ-treated water, which is affected by both the water evaporation and the admixture of ambient air. In this paper, taking He APPJ as an example, a two-dimensional (2D) cylindrically symmetric fluid model is developed to obtain the spatial distributions of gas components before discharging, and a series of global models are developed for the discharge in the boundary gas layer adjacent to the water surface. The interfacial distributions of reactive species and their fluxes onto the water surface are quantified. It is found that the electron density is 1016–1017 m−3 and it shows an annular distribution in the boundary gas layer. The density distributions of most reactive species there reveal ring-like shapes as well. The dominant cation and anion in such a boundary layer are H3O+ and OH−, respectively. The most abundant metastable is O2(a1Δ), the most abundant reactive oxygen species are H2O2 and OH, and the most abundant reactive nitrogen species are NO and HNO2. The species of H2O2, OH, HO2, and HNO2 are reportedly to have significant biological effects, and in our simulation, their fluxes onto the water surface are remarkable, higher than 1017 m−2 s−1. In addition, the effects of radial gas velocity and water evaporation on the particle flux distributions are also revealed.

The moderate-resolution camera (MoRIC) of the Tianwen-1 orbiter, China’s first Mars exploration mission, is a frame-imaging scheme color camera. However, generating a precise digital elevation model (DEM) from these images faces challenges due to the presence of featureless and repetitive regions on the Martian surface. Traditional photogrammetric methods often struggle to achieve pixel-level resolution in these areas. To address this, we employ a shape from shading (SFS) algorithm that leverages shading patterns to reconstruct fine-scale terrain details, optimizing photogrammetric initial DEM. This paper presents a novel global bisection search algorithm, based on the Pearson correlation coefficient to determine the smoothing parameter, a crucial element in the SFS process. Comparisons with higher-resolution data from the Mars Express high-resolution stereo camera and Mars Reconnaissance Orbiter CTX images validate our approach, highlighting the potential of SFS to significantly enhance the scientific value of Tianwen-1 MoRIC data by generating high-resolution, three-dimensional maps of Mars.

Abstract A continuous risk from microbial infections poses a major environmental and public health challenge. As an emerging strategy for inhibiting bacterial infections, plasma‐activated water (PAW) has proved to be highly effective, environmental‐friendly, and non‐drug resistant to a broad range of microorganisms. However, the relatively short lifetime of reactive oxygen and nitrogen species (RONS) and the high spreadability of liquid PAW inevitably limit its real‐life applications. In this study, plasma‐activated hydrogel (PAH) is developed to act as reactive species carrier that allow good storage and controlled slow‐release of RONS to achieve long‐term antibacterial effects. Three hydrogel materials, including hydroxyethyl cellulose (HEC), carbomer 940 (Carbomer), and acryloyldimethylammonium taurate/VP copolymer (AVC) are selected, and their antibacterial performances under different plasma activation conditions are investigated. It is shown that the composition of the gels plays the key role in determining their biochemical functions after the plasma activation. The antimicrobial performance of AVC is much better than that of PAW and the other two hydrogels, along with the excellent stability to maintain the antimicrobial activity for more than 14 days. The revealed mechanism of the antibacterial ability of the PAH identifies the unique combination of short‐lived species (1O2, ∙OH, ONOO− and O2−) stored in hydrogels. Overall, this study demonstrates the efficacy and reveals the mechanisms of the PAH as an effective and long‐term disinfectant capable of delivering and preserving antibacterial chemistries for biomedical applications.

Abstract Sulphur hexafluoride (SF6) is widely used in gas insulation, and its decomposition products can be used to diagnose potential insulation failures. Quick and accurate detection of decomposition products can help to understand equipment‐operating conditions in time. In this study, the decomposition products of SF6/air gas mixtures under different pulsed discharge voltages were studied. It was found that the main products were SOF2, SO2F2, SO2, CF4 and SOF4, and the yields of SOF2, SO2F2, SO2 and SOF4 increased with the number of discharge pulse. The productive rate of SOF2, SO2 and SOF4 were positively correlated with the discharge voltage, and when the discharge voltage increased from 5 to 15 kV, their yields after 50,000 discharges increased by 49%, 120% and 1100%, respectively. The productive rate of SOF2 and SO2 were positively correlated with the proportion of air in the gas mixtures while that of SOF4 was opposite. When the proportion of air increases from 0% to 90%, their yields after 50,000 discharges became 270%, 3169% and 10% of the originals, respectively. In addition, the productive rate of SO2F2 was not affected by discharge voltage and the proportion of air in the gas mixtures. SO2F2, SOF2, SOF4 and SO2 can be used as the basis for judging the discharge failures and the discharge degree of power equipment.

Infection can hinder the process of wound healing, so it is important to begin antibacterial treatment quickly after a wound forms. Plasma activated water (PAW) can inactivate a variety of common wound infection bacteria. In this study, we compared the effects of PAW prepared with portable surface discharge plasma equipment and medical alcohol on wound healing in a mouse full-thickness skin wound model. The effectiveness of wound healing processes in mice was ranked accordingly: PAW treatment group > medical alcohol treatment group > control group. In order to further understand the mechanism of PAW in promoting wound healing, we tested the expression levels of the pro-inflammatory factors interleukin (IL)-1β and IL-6, the anti-inflammatory factor IL-10, and vascular endothelial growth factor (VEGF). The results showed that PAW promoted the release of pro-inflammatory factors and anti-inflammatory factors from the wounds in mice, which allowed the mice in the treatment group to transition out of the inflammatory period early and enter the next stage of wound healing. The expression level of VEGF in the wounds of mice in the PAW treatment group was higher, which indicates that the microvessels around the wound in the PAW treatment group proliferated faster, and thus the wound healed faster. PAW biosafety experiments showed that PAW did not significantly affect the appearance, morphology, or tissue structure of internal organs, or blood biochemical indicators in mice. In general, PAW prepared via portable devices is expected to become more widely used given its convenience, affordability, and lack of side effects in promoting wound healing.

Due to their good dielectric properties and low global warming potential, C4F7N–CO2 and C4F7N–N2 mixtures have shown promising potential to replace SF6 in high voltage gas insulated equipment. However, during manufacturing, installation, and transportation of power equipment, burs and metal particles can be inevitably left inside, and they can cause corona discharge. Fundamental investigation of the corona discharge mechanism is essential to monitor partial discharge signals in environmentally friendly power equipment. This paper applies the fluid model to investigate the discharge mechanism of C4F7N–CO2 and C4F7N–N2 mixtures in negative point-plane corona discharge. A 2D axisymmetric model combines the drift-diffusion equations for electrons, positive ions, and negative ions and Poisson’s equation to study the process of dynamics. The gas is a mixture of C4F7N (5%, 7%, or 13%) and CO2 or N2 (95%, 93%, or 87%). The rise time of the first discharge pulse in C4F7N–CO2 and C4F7N–N2 mixtures is about 0.1 ns. The interval time between the first and the second pulse in the 5% C4F7N–95%CO2 mixture is about 1.5 times longer than that in the 5% C4F7N–95% N2 mixture. When the C4F7N content is 7% and 13%, the interval time between the first and second pulses in C4F7N–CO2 mixtures is about 2 and 3 times longer than those in C4F7N–N2 mixtures, respectively. The suppression regions in C4F7N–CO2 mixtures are larger than those in corresponding C4F7N–N2 mixtures. The total number of electrons, positive ions, and negative ions in C4F7N–CO2 mixtures is higher than that in C4F7N–N2 mixtures, while the reduced electric field in C4F7N–CO2 mixtures is smaller than that in C4F7N–N2 mixtures.

Abstract Metal–organic frameworks (MOFs) are a class of hybrid materials with many promising applications. In recent years, lots of investigations have been oriented toward applications of MOFs in electronic and photoelectronic devices. While many high-quality reviews have focused on synthesis and mechanisms of electrically conductive MOFs, few of them focus on their photophysical properties. Herein, we provide an in-depth review on photoconductive and photoluminescent properties of conductive MOFs together with their corresponding applications in solar cells, luminescent sensing, light emitting, and so forth. For integration of MOFs with practical devices, recent advances in fabrication of photoactive MOF thin films are also summarized.

Plasma-activated liquid (PAL) can effectively and selectively kill various types of cancer cells both in superficial and deeper tumors. As a promising novel approach to oncotherapy, the safety of PAL is essential in the clinic but has not been thoroughly assessed. In myeloma and blood tumors, the pathogenesis is in the bone marrow cavity. We have therefore evaluated the safety of PAL in New Zealand rabbits by intra-bone marrow injection, and provide a basis of further clinical research and application of PALs. In this study, both a plasma jet and plasma surface were used to treat saline solution, phosphate-buffered solution, and cell culture medium, to produce PAL. Then, oscillograms and optical emission spectra were evaluated to characterize the plasma discharge. Acute toxicity tests and safety evaluation studies were conducted by intra-bone marrow injection of PAL into New Zealand rabbits, while control rabbits received saline only. Body weight, vital organ coefficient, organ appearance, organ histopathology, blood cell and hemoglobin parameters, and blood biochemical indicators were tested on the 30th day after injection. We found that there was no mortality or loss of mobility throughout the experimental period. Acute toxicity tests showed that there were no PAL-related side effects in rabbits receiving the maximum dose of 700 μL PAL. PAL treatments did not affect body weight, organ coefficient, organ appearance, organ histopathology, or blood biochemical indicators. However, the percentage of lymphocytes decreased while the percentage of neutrophil granulocytes increased compared with the control group. In summary, our results indicate that PAL can be safely injected into bone marrow of New Zealand rabbits without significant toxicity.

Abstract Background It was reported that tumor-expressed dickkopf-related (DKK) proteins affect micro-environment. However, the influence of DKK1 on colorectal cancer (CRC) liver oligometastases (CRCLOM) remains unclear. Methods CRC cases after resection of liver oligometastases were enrolled in Sun Yat-Sen University Cancer Center with intact clinical data. Serum DKK1 was detected by ELISA assay. Immunofluorescent staining examination for CD3 and CD8 in slices were also conducted. Results Among 65 patients included, the recurrence-free survival (RFS) and overall survival (OS) were significantly better in the low serum DKK1 group (RFS: P = 0.021; OS: P = 0.043). DKK1 was overexpressed in stage IV CRC patients in TCGA data. The number of CD8+ tumor-infiltrating lymphocytes (TILs) in invasive margin of CRC liver oligometastases was significantly higher in low serum DKK1 group (P = 0.042). Conclusion Elevated serum DKK1 level was associated with poorer RFS and OS, and less CD8+ TILs in invasive margin in CRC liver oligometastases. DKK1 might serve as a supplementalprognostic factor for clinical risk score and a potential target for immunotherapy.

Abstract 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.

Metal–organic frameworks with highly ordered porosity have been studied extensively. In this paper, the effect of framework (pore) disorder on the gas sorption of azole-based isoreticular Cu(II) MOFs with rtl topology and characteristic 1D tubular pore channels is investigated for the first time. In contrast to other isoreticular rtl metal–organic frameworks, the Cu(II) metal–organic framework based on 5-(1H-imidazol-1-yl)isophthalate acid has a crystallographically identifiable disordered framework without open N-donor sites. The framework provides a unique example for investigating the effect of pore disorder on gas sorption that can be systematically evaluated. It exhibits remarkable temperature-dependent hysteretic CO2 sorption up to room temperature, and shows selectivity of CO2 over H2, CH4 and N2 at ambient temperature. The unique property of the framework is its disordered structure featuring distorted 1D tubular channels and DMF-guest-remediated defects. The results imply that structural disorder (defects) may play an important role in the modification of the performance of the material.

Plasma–liquid interaction is a critical area of plasma science, mainly because much remains unknown about the physicochemical processes occurring at the plasma–liquid interface. Besides a lot of experimental studies toward the interaction, a few fluid models have also been reported in recent years. However, the interfacial boundary conditions in the models are different and the Henry’s law constants therein are uncertain; hence, the accuracy and robustness of the simulation results are doubtable. In view of this, three 1D fluid models are developed for the interaction between a plasma jet and deionized water, each of which has a unique interfacial boundary condition as reported in the literature. It is found that the density distribution of reactive species is nearly independent of the interfacial boundary conditions in both the gas and liquid phases, except for that in the interfacial gas layer with a thickness of several tens of micrometers above water. The densities of the reactive species with high Henry’s law constants (H > 104) are much different in such gas layers among the interfacial boundary conditions. Moreover, some Henry’s law constants are changed in the models according to their uncertainty reported in the literature, and only the reactive species with low Henry’s law constants (H < 1) have their aqueous densities following the change. These densities are very low in the plasma-activated water. It could be concluded that the simulation of plasma–liquid interaction is generally independent of the interfacial boundary conditions and the uncertainty in Henry’s law constants.

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.

Background Dickkopf 1 (DKK1) is associated with tumor progression. However, whether DKK1 influences the tumor response to programmed cell death protein 1 (PD-1) blockade in colorectal cancers (CRCs) with deficient mismatch repair (dMMR) or microsatellite instability (MSI) has never been clarified.Methods Tumor tissues from 80 patients with dMMR CRC were evaluated for DKK1 expression and immune status via immunohistochemistry. Serum DKK1 was measured in another set of 43 patients who received PD-1 blockade therapy. CT26 cells and dMMR CRC organoids were cocultured with T cells, and CT26-grafted BALB/c mice were also constructed. T-cell cytotoxicity was assessed by apoptosis assays and flow cytometry. The pathway through which DKK1 regulates CD8+ T cells was investigated using RNA sequencing, and chromatin immunoprecipitation and luciferase reporter assays were conducted to determine the downstream transcription factors of DKK1.Results Elevated DKK1 expression was associated with recurrence and decreased CD8+ T-cell infiltration in dMMR CRCs, and patients with high-serum DKK1 had a poor response to PD-1 blockade. RNA interference or neutralization of DKK1 in CRC cells enhanced CD8+ T-cell cytotoxicity, while DKK1 decreased T-bet expression and activated GSK3β in CD8+ T cells. In addition, E2F1, a downstream transcription factor of GSK3β, directly upregulated T-bet expression. In organoid models, the proportion of apoptotic cells was elevated after individual neutralization of PD-1 or DKK1 and was further increased on combined neutralization of PD-1 and DKK1.Conclusions DKK1 suppressed the antitumor immune reaction through the GSK3β/E2F1/T-bet axis in CD8+ T cells. Elevated serum DKK1 predicted poor tumor response to PD-1 blockade in dMMR/MSI CRCs, and DKK1 neutralization may restore sensitivity to PD-1 blockade.

Abstract Background Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet. Methods In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG analysis we try to figure out the metabolism pathway that was significantly affected by gas plasma treatment. Results By GC-TOF mass-spectrometry, 573 signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we listed all the differential metabolites and further classified into different metabolic pathways. The results showed that beta-alanine metabolism pathway was the most significant change after He gas plasma treatment in myeloma cells. Besides, propanoate metabolism and linoleic acid metabolism should also be concerned during gas plasma treatment of cancer cells. Conclusions Cold atmospheric plasma treatment could significantly alter the metabolite profiling of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the most susceptible to He gas plasma treatment.

Systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are life-threatening due to their strong multidrug resistance, especially since the biofilms formed by MRSA are more difficult to inactivate by antibiotics, causing long term recurrence of infection. Plasma-activated saline (PAS), a derived form of cold atmospheric-pressure plasma, can effectively inactivate bacteria and cancer cells and has been applied to sterilization and cancer treatment. Previous studies have demonstrated that the pretreatment of MRSA with PAS could promote the action of antibiotics. Here, the PAS was used as an antibiotic adjuvant to promote the inactivation of MRSA biofilms by rifampicin and vancomycin, and the combined treatment reduced approximately 6.0-log10 MRSA cells in biofilms. The plasma-activated saline and rifampicin synergistically and effectively reduced the systemic infection in the murine model. The histochemical analysis and the blood hematological and biochemical test demonstrated that the combined treatment with plasma-activated saline and rifampicin improved the blood hematological and biochemical parameters of infected mice by reducing the infection. Therefore, PAS based on plasma technology represents a new strategy for the treatment of infectious disease caused by multidrug-resistant bacteria and alleviating antibiotic resistance.

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.

Reactive oxygen and reactive nitrogen species (RONS) are believed to play a key role in biomedical applications, which means that RONS must reach the target tissue to produce a therapeutic effect. Existing methods (electron spin spectrometry and microplate reading) to determine the RONS concentration are not suitable for experimental real-time measurements because they require adding an indicating reagent to the plasma-treated medium, which may alter the chemical composition of the medium. In this paper, we propose a method to measure the long-lived RONS concentration in plasma-activated water (PAW) by using UV absorption spectroscopy. Based on an analysis and fit of the absorption spectra of standard solutions (H2O2, NaNO2, and NaNO3), we propose a detailed fitting procedure that allows us to calculate the concentrations of simplex H2O2, NO2−, and NO3−. The results show that the pH and the cross reactivity between RONS in PAW correlate strongly with the absorption spectra. To confirm the accuracy of the calculations, we also use a microplate reader and add chemical reagents to measure the concentrations of H2O2, NO2−, and NO3−. The results show that the concentrations calculated by the proposed fitting method are relatively accurate and that the error range is acceptable. Additionally, the time-dependent diffusion of RONS in PAW is measured and analyzed at different depths in the PAW. This fitting approach constitutes a nonintrusive approach to measure RONS at different depths in PAW.

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.

Cold atmospheric plasma (CAP) is a rapidly developed technology that has been widely applied in biomedicine especially in cancer treatment. Due to the generation of various active species in plasma, CAP could induce various tumor cells death and showed a promising potential in cancer therapy. To enhance the biological effects of gas plasma, changing the discharging parameters is the most commonly used method, yet increasing discharging power will lead to a higher possibility of simultaneously damage surrounding tissues. In this study, by adding nontoxic concentration of additional nitrite and nitrate in the medium, we found that anti-tumor effect of CAP treatment was enhanced in the same discharging parameters. By microplate reader and cell flow cytometer we measured several extracellular and intracellular RONS and found that ONOO- was mostly correlated with the enhanced cancer cell killing effect. We proposed that more nitrogen supplies such as nitrite and nitrate could increase the production of RNS especially ONOO- and resulted in a better killing effect to cancer cells. Our results provided a new strategy to enhance the antitumor effect by plasma jet treatment without changing the discharging parameters.

Immunotherapy is reportedly effective in a subset of colorectal cancers (CRCs) with high microsatellite instability (MSI-H). Exploring the expression patterns and clinical values of immunologic molecules is critical in defining the specific responsive candidates. Here, we performed comprehensive molecular profiling of the B7 and TNFR family genes across 6 CRC datasets with over 1,000 patients’ details using cBioPortal TCGA data. About 20% of patients had B7 and TNFR family gene alterations. The frequency of B7 gene mutations (2.2%–5%) were similar to copy number alterations (0.53%–5.46%). TNFR amplifications were relatively more common (5.45–11.32%) than that of B7 (0.09–2.73%). B7 and TNFR gene mRNAs were upregulated in 26% of cases (102/379) and 16% of cases (61/379), respectively. The mRNA levels of B7 and TNFR genes were inversely correlated with promoter methylation status. Clinically, both B7-H3 and TNFSF7 mRNA overexpression were associated with unfavorable clinical outcomes, and the B7-H3 expression was increased gradually in cases with gene amplifications. Moreover, patients with MSI-H had significantly higher PD-L1 or PD-1 expression. Most importantly, in MSI-H group, patients with PD-L1 or PD-1 upregulation had poorer survivals than those with PD-L1/PD-1 downregulation. This is the first study drawing the immune landscapes of the co-stimulator B7 and TNFR families in CRC and showing that MSI-H patients with PD-1/PD-L1 upregulation are associated with poor clinical outcomes, providing potential markers to stratify patients responsive to immune checkpoint therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious nosocomial infections, and recurrent MRSA infections primarily result from the survival of persister cells after antibiotic treatment. Gas plasma, a novel source of ROS (reactive oxygen species) and RNS (reactive nitrogen species) generation, not only inactivates pathogenic microbes but also restore the sensitivity of MRSA to antibiotics. This study further found that sublethal treatment of MRSA with both plasma and plasma-activated saline increased the antibiotic sensitivity and promoted the eradication of persister cells by tetracycline, gentamycin, clindamycin, chloramphenicol, ciprofloxacin, rifampicin, and vancomycin. The short-lived ROS and RNS generated by plasma played a primary role in the process and induced the increase of many species of ROS and RNS in MRSA cells. Thus, our data indicated that the plasma treatment could promote the effects of many different classes of antibiotics and act as an antibiotic sensitizer for the treatment of antibiotic-resistant bacteria involved in infectious diseases.