An accumulation of reactive oxygen species (ROS) in cardiomyocytes can induce pro-arrhythmogenic late Na+ currents by removing the inactivation of voltage-gated Na+ channels including the tetrodotoxin (TTX)-resistant cardiac α-subunit Nav1.5 as well as TTX-sensitive α-subunits like Nav1.2 and Nav1.3. Here, we explored oxidant-induced late Na+ currents in mouse cardiomyocytes and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as in HEK 293 cells expressing Nav1.2, Nav1.3, or Nav1.5. Na+ currents in mouse cardiomyocytes and hiPSC-CMs treated with the oxidant chloramine T (ChT) developed a moderate reduction in peak current amplitudes accompanied by large late Na+ currents. While ChT induced a strong reduction in peak current amplitudes but only small persistent currents on Nav1.5, both Nav1.2 and Nav1.3 produced increased peak current amplitudes and large persistent currents following oxidation. TTX (300 nM) blocked ChT-induced late Na+ currents significantly stronger as compared to peak Na+ currents in both mouse cardiomyocytes and hiPSC-CMs. Similar differences between Nav1.2, Nav1.3, and Nav1.5 regarding ROS sensitivity were also evident when oxidation was induced with UVA-light (380 nm) or the cysteine-selective oxidant nitroxyl (HNO). To conclude, our data on TTX-sensitive Na+ channels expressed in cardiomyocytes may be relevant for the generation of late Na+ currents following oxidative stress.

Legionella is an opportunistic waterborne pathogen that causes Legionnaires\' disease. It poses a significant public health risk, especially to vulnerable populations in health care facilities. It is ubiquitous in manufactured water systems and is transmitted via inhalation or aspiration of aerosols/water droplets generated from water fixtures (e.g., showers and hand basins). As such, the effective management of premise plumbing systems (building water systems) in health care facilities is essential for reducing the risk of Legionnaires\' disease. Chemical disinfection is a commonly used control method and chlorine-based disinfectants, including chlorine, chloramine, and chlorine dioxide, have been used for over a century. However, the effectiveness of these disinfectants in premise plumbing systems is affected by various interconnected factors that can make it challenging to maintain effective disinfection. This systematic literature review identifies all studies that have examined the factors impacting the efficacy and decay of chlorine-based disinfectant within premise plumbing systems. A total of 117 field and laboratory-based studies were identified and included in this review. A total of 20 studies directly compared the effectiveness of the different chlorine-based disinfectants. The findings from these studies ranked the typical effectiveness as follows: chloramine > chlorine dioxide > chlorine. A total of 26 factors were identified across 117 studies as influencing the efficacy and decay of disinfectants in premise plumbing systems. These factors were sorted into categories of operational factors that are changed by the operation of water devices and fixtures (such as stagnation, temperature, water velocity), evolving factors which are changed in-directly (such as disinfectant concentration, Legionella disinfectant resistance, Legionella growth, season, biofilm and microbe, protozoa, nitrification, total organic carbon(TOC), pH, dissolved oxygen(DO), hardness, ammonia, and sediment and pipe deposit) and stable factors that are not often changed(such as disinfectant type, pipe material, pipe size, pipe age, water recirculating, softener, corrosion inhibitor, automatic sensor tap, building floor, and construction activity). A factor-effect map of each of these factors and whether they have a positive or negative association with disinfection efficacy against Legionella in premise plumbing systems is presented. It was also found that evaluating the effectiveness of chlorine disinfection as a water risk management strategy is further complicated by varying disinfection resistance of Legionella species and the form of Legionella (culturable/viable but non culturable, free living/biofilm associated, intracellular replication within amoeba hosts). Future research is needed that utilises sensors and other approaches to measure these key factors (such as pH, temperature, stagnation, water age and disinfection residual) in real time throughout premise plumbing systems. This information will support the development of improved models to predict disinfection within premise plumbing systems. The findings from this study will inform the use of chlorine-based disinfection within premise plumbing systems to reduce the risk of Legionnaires disease.

As an eco-friendly and sustainable energy, solar energy has great application potential in water treatment. Herein, simulated sunlight was for the first time utilized to activate monochloramine for the degradation of environmental organic microcontaminants. Various microcontaminants could be efficiently degraded in the simulated sunlight/monochloramine system. The average innate quantum yield of monochloramine over the wavelength range of simulated sunlight was determined to be 0.068 mol/Einstein. With the determined quantum yield, a kinetic model was established. Based on the good agreement between the simulated and measured photolysis and radical contributions to the degradation of ibuprofen and carbamazepine, the major mechanism of monochloramine activation by simulated sunlight was proposed. Chlorine radical (Cl∙) and hydroxyl radical (HO∙) were major radicals responsible for microcontaminant degradation in the system. Moreover, the model facilitated a deep investigation into the effects of different reaction conditions (pH, monochloramine concentration, and water matrix components) on the degradation of ibuprofen and carbamazepine, as well as the roles of the involved radicals. The differences between simulated and measured degradation data of each microcontaminant under all conditions were less than 10 %, indicating the strong reliability of the model. The model could also make good prediction for microcontaminant degradation in the natural sunlight/monochloramine system. Furthermore, the formation of disinfection byproducts (DBPs) was evaluated at different oxidation time in simulated sunlight/monochloramine with and without post-chloramination treatment. In real waters, organic components showed more pronounced suppression on microcontaminant degradation efficiency than inorganic ions. This study provided a systematic investigation into the novel sunlight-induced monochloramine activation system for efficient microcontaminant degradation, and demonstrated the potential of the system in practical applications.

The presence of CECs in aquatic systems has raised significant concern since they are potentially harmful to the environment and human health. Eliminating CECs has led to the development of alternatives to treat wastewater, such as advanced oxidation processes (AOPs). The ultraviolet-mediated activation of monochloramine (UV/NH2Cl) is a novel and relatively unexplored AOPs for treating pollutants in wastewater systems. This process involves the production of amino radicals (•NH2) and chlorine radicals (Cl•) from the UV irradiation of NH2Cl. Studies have demonstrated its effectiveness in mitigating various CECs, exhibiting advantages, such as the potential to control the amount of toxic disinfection byproducts (TDBPs) formed, low costs of reagents, and low energy consumption. However, the strong influence of operating parameters in the degradation efficiency and existence of NH2Cl, the lack of studies of its use in real matrices and techno-economic assessments, low selectivity, and prolonged treatment periods must be overcome to make this technology more competitive with more mature AOPs. This review article revisits the state-of-the-art of the UV/NH2Cl technology to eliminate pharmaceutical and personal care products (PPCPs), micropollutants from the food industry, pesticides, and industrial products in aqueous media. The reactions involved in the production of radicals and the influence of operating parameters are covered to understand the formation of TDBPs and the main challenges and limitations of the UV/NH2Cl to degrade CECs. This review article generates critical knowledge about the UV/NH2Cl process, expanding the horizon for a better application of this technology in treating water contaminated with CECs.

This work comprehensively demonstrates the ability of heterotrophic bacteria, isolated from a chloraminated system, to decay chloramine. This study non-selectively isolated 62 cultures of heterotrophic bacteria from a water sample (0.002 mg-N/L nitrite and 1.42 mg/L total chlorine) collected from a laboratory-scale reactor system; most of the isolates (93.3%) were Mycobacterium sp. Three species of Mycobacterium and one species of Micrococcus were inoculated to a basal inorganic medium with initial concentrations of acetate (from 0 to 24 mg-C/L) and 1.5 mg/L chloramine. Bacterial growth coincided with declines in the concentrations of chloramine, acetate, and ammonium. Detailed experiments with one of the Mycobacterium sp. isolates suggest that the common mechanism of chloramine loss is auto-decomposition likely mediated by chloramine-decaying proteins. The ability of the isolates to grow and decay chloramine underscores the important role of heterotrophic bacteria in the stability of chloramine in water-distribution systems. Existing strategies based on controlling nitrification should be augmented to include minimizing heterotrophic bacteria.

Nitrification is a serious water-quality issue in chloraminated engineered water systems (EWSs). Nitrification is often remediated by a chlorine burn (i.e., a free‑chlorine conversion), a short-term switch from chloramination to chlorination in EWSs. Opportunistic pathogens (OPs) are the dominant infectious agents in EWSs. However, the responses of OPs to a chlorine burn are unknown. This study for the first time assessed how a chlorine burn affected OPs in a full-scale EWS. We determined the impact of a 1.5-month chlorine burn on four dominant OPs (Legionella, Mycobacterium, Pseudomonas, and Vermamoeba vermiformis) in a representative full-scale chloraminated EWS in the United States. Legionella and Mycobacterium were the most abundant OPs. In the water main, the summed concentration of the four OPs during the chlorine burn [3.27 ± 1.58 log10(GCN·L-1); GCN: genome or gene copy number] was lower (p ≤ 0.001) than before the burn [4.83 ± 0.50 log10(GCN·L-1)]. After the burn, the summed concentration increased to 4.27 ± 0.68 log10(GCN·L-1), comparable to before the burn (p > 0.05), indicating a transient effect of the chlorine burn in the water main. At the residential sites, the summed concentrations of the four OPs were comparable (p > 0.05) at 5.50 ± 0.84, 5.27 ± 1.44, and 5.08 ± 0.71 log10(GCN·L-1) before, during, and after the chlorine burn, respectively. Therefore, the chlorine burn was less effective in suppressing OP (re)growth in the premise plumbing. The low effectiveness might be due to more significant water stagnation and disinfectant residual decay in the premise plumbing. Indeed, for the entire sampling period, the total chlorine residual concentration in the premise plumbing (1.8 mg Cl2·L-1) was lower than in the water main (2.4 mg Cl2·L-1). Consequently, for the entire sampling period, the summed concentration of the four OPs in the premise plumbing [5.26 ± 1.08 log10(GCN·L-1)] was significantly higher (p < 0.001) than in the water main [4.04 ± 1.25 log10(GCN·L-1)]. In addition, the chlorine burn substantially increased the levels of disinfection by-products (DBPs) in the water main. Altogether, a chlorine burn is transient or even ineffective in suppressing OP (re)growth but raises DBP concentrations in chloraminated EWSs. Therefore, the practice of chlorine burns to control nitrification should be optimized, reconsidered, or even replaced.

This study investigated degradation behaviors of a nonsteroidal anti-inflammatory drug Nabumetone (NMT) and its major metabolite 6-methoxy-2-naphthylacetic acid (MNA) in the coupling process of ultraviolet and monochloramine (UV/NH2Cl). The second-order rate constants of the contaminants reacting with reactive radicals (HO•, Cl•, Cl2•⁻, and CO3•⁻) were determined by laser flash photolysis experiments. HO• and Cl• contributed predominantly with 52.3% and 21.7% for NMT degradation and 60.8% and 22.3% for MNA degradation. The presence of chlorides retarded the degradation of NMT, while promoted the destruction of MNA, which was ascribed to the photosensitization effects of MNA under UV irradiation. Density functional theory (DFT) calculations revealed that radical adduct formation (RAF) was dominant pathway for both HO• and Cl• reacting with the contaminants, and hydrogen atom transfer (HAT) preferred to occur on side chains of NMT and MNA. NMT reacted with NO2• through single electron transfer (SET) with the second-order rate constant calculated to be 5.35 × 107 (mol/L)-1 sec-1, and the contribution of NO2• was predicted to be 13.0% of the total rate constant of NMT in pure water, which indicated that NO2• played a non-negligible role in the degradation of NMT. The acute toxicity and developmental toxicity of NMT were enhanced after UV/NH2Cl treatment, while those of MNA were alleviated. The transformation products of both NMT and MNA exhibited higher mutagenicity than their parent compounds. This study provides a deep understanding of the mechanism of radical degradation of NMT and MNA in the treatment of UV/NH2Cl.

Chlorine-resistant bacteria (CRB) in drinking water treatment plants (DWTPs) jeopardize water quality and pose a potential risk to human health. However, the specific response of CRB to chlorination and chloramination remains uncharacterized. Therefore, we analyzed 16 S rRNA sequencing data from water samples before and after chlorination and chloramination taken between January and December 2020. Proteobacteria and Firmicutes dominated all finished water samples. After chloramination, Acinetobacter, Pseudomonas, Methylobacterium, Ralstonia, and Sphingomonas were the dominant CRB, whereas Ralstonia, Bacillus, Acinetobacter, Pseudomonas, and Enterococcus were prevalent after chlorination. Over 75% of the CRB e.g. Acinetobacter, Pseudomonas, Bacillus, and Enterococcus were shared between the chlorination and chloramination, involving potentially pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Notably, certain genera such as Faecalibacterium, Geobacter, and Megasphaera were enriched as strong CRB after chloramination, whereas Vogesella, Flavobacterium, Thalassolituus, Pseudoalteromonas, and others were enriched after chlorination according to LEfSe analysis. The shared CRB correlated with temperature, pH, and turbidity, displaying a seasonal pattern with varying sensitivity to chlorination and chloramination in cold and warm seasons. These findings enhance our knowledge of the drinking water microbiome and microbial health risks, thus enabling better infectious disease control through enhanced disinfection strategies in DWTPs.

This paper highlights the potential to effectively inhibit nitrification and restore chloramine levels using a low copper concentration in a biofilm-affected (surface-to-volume ratio 16 m-1) continuous-flow laboratory-scale chloraminated system. High nitrite and low chloramine containing tanks are always recovered with chlorine \"burn\" by water utilities. The \"burn\" is not only costly and operationally complex, but also compromises the water quality, public health, and customer relations. A laboratory system comprising five reactors connected in series was operated. Each reactor simulated conditions typically encountered in full-scale systems. Low amount of copper (0.1-0.2 mg-Cu L-1) was dosed once per day into nitrified reactors. At any given time, only one reactor was dosed with copper. Not only inhibition of nitrification, chloramine decay associated with bulk water, biofilm and sediments also improved. However, the improvement was quicker and more significant when the influent to the reactor contained a high chloramine and a low nitrite concentration. Ammonia oxidising microbes exhibited resilience when exposed to low copper and chloramine concentrations for an extended period. Chloramine decay due to planktonic microbes and chemical reactions in bulk water decreased more rapidly than decay attributed to biofilm and sediments. The concept \"biostable residual chlorine\" explained how copper and chloramine can inhibit nitrification. Once nitrification was inhibited, the chloramine supplied from upstream effectively continued to suppress downstream nitrification, and this effect lasted more than 50 days even at 22 °C. The findings could be used to develop short-term copper dosing strategies and prevent negative impacts of nitrification and breakpoint chlorination.

Chloramination is an effective strategy for eliminating pathogens from drinking water and repressing their regrowth in water distribution systems. However, the inevitable release of NH4+ potentially promotes nitrification and associated ammonia-oxidizing bacteria (AOB) contamination. In this study, AOB (Nitrosomona eutropha) were isolated from environmental water and treated with two disinfection stages (chloramine disinfection and chloramine residues) to investigate the occurrence mechanisms of AOB in chloramination. The results showed that N. eutropha had considerable resistance to monochloramine compared to Escherichia coli, whose inactivation rate constant was 19.4-fold lower. The higher resistance was attributed to high levels of extracellular polymer substances (EPS) in AOB, which contribute to AOB surviving disinfection and entering the distribution system. In AOB response to the chloramine residues stage, the respiratory activity of N. eutropha remained at a high level after three days of continuous exposure to high chloramine residue concentrations (0.5-1.5 mg/L). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) suggested that the mechanism of N. eutropha tolerance involved a significantly high expression of the intracellular oxidative stress-regulating (sodB, txrA) and protein-related (NE1545, NE1546) genes. Additionally, this process enhanced EPS secretion and promoted biofilm formation. Adhesion predictions based on the XDLVO theory corroborated the trend of biofilm formation. Overall, the naturally higher resistance contributed to the survival of AOB in primary disinfection; the enhanced antioxidant response of surviving N. eutropha accompanied by biofilm formation was responsible for their increased resistance to the residual chloramines.