Occurrence, removal, and prioritization of organic micropollutants in four full-scale wastewater treatment plants in Korea.

This study investigated the occurrence, removal rate, and potential risks of 43 organic micropollutants (OMPs) in four municipal wastewater treatment plants (WWTPs) in Korea. Results from two-year intensive monitoring confirmed the presence of various OMPs in the influents, including pharmaceuticals such as acetaminophen (pain relief), caffeine (stimulants), cimetidine (H2-blockers), ibuprofen (non-steroidal anti-inflammatory drugs- NSAIDs), metformin (antidiabetics), and naproxen (NSAIDs) with median concentrations of >1 µg/L. Some pharmaceuticals (carbamazepine-anticonvulsants, diclofenac-NSAIDs, propranolol-ß-blockers), corrosion inhibitors (1H-benzotriazole-BTR, 4-methyl-1H-benzotriazole-4-TTR), and perfluorinated compounds (PFCs) were negligibly removed during WWTP treatment. The OMP concentrations in the influents and effluents were mostly lower in August than those of other months (p-value <0.05) possibly due to wastewater dilution by high precipitation or enhanced biodegradation under high-temperature conditions. The anaerobic-anoxic-oxic process (A2O) with a membrane bioreactor exhibited higher OMP removal than other processes, such as A2O with sedimentation or the conventional activated sludge process (p-value <0.05). Pesticides (DEET and atrazine), corrosion inhibitors (4-TTR and BTR), and metformin were selected as priority OMPs in toxicity-driven prioritization, whereas PFCs were determined as priority OMPs given their persistence and bioaccumulation properties. Overall, our results contribute to an important database on the occurrence, removal, and potential risks of OMPs in Korean WWTPs.

In vitro bioanalytical assessment of the occurrence and removal of bioactive chemicals in municipal wastewater treatment plants in Korea.

Effluents of wastewater treatment plants (WWTPs) contain various organic micropollutants, some of which can exert negative effects on the quality of receiving waters or drinking water sources. This study monitored two full-scale WWTPs in Korea for the occurrence and removal of bioactive chemicals for a one-year period using a battery of in vitro bioassays as a complementary approach to chemical analysis. Bioassays covering different endpoints were employed, such as hormone receptor activation (AR and ERα), xenobiotic metabolism (PAH and PXR), oxidative stress response (Nrf2), and cytotoxicity. The WWTP influents showed AR, ERα, and PAH activities at ng/L - µg/L and PXR and Nrf2 activities at µg/L - mg/L as bioanalytical equivalent concentrations of a reference compound for each bioassay. These bioactivities decreased along with the WWTP treatment train, with significant removals achieved by the secondary biological treatment processes. Cytotoxicity was observed only for some municipal wastewater (M-WWTP) influents but was below the limit of quantification for most cases. The influent and effluent bioactivities observed in this study were mostly comparable to those reported in other WWTPs in the literature. Comparison of the bioactivities with the effect-based trigger (EBT) values indicates that the impact of WWTP effluents on receiving water quality was low for most endpoints. For Nrf2, however, further investigation is required to evaluate the observed high bioactivities compared with the current EBT. The observed ERα activity could partly be explained by the presence of some steroid estrogens. Overall, our results contribute to an important database for the concentrations and removal efficiencies of bioactive chemicals in WWTPs and demonstrate bioassays as a useful tool for urban water quality monitoring.

Application of Nucleotide-Based Kinetic Modeling Approaches to Predict Antibiotic Resistance Gene Degradation during UV- and Chlorine-Based Wastewater Disinfection Processes: From Bench- to Full-Scale.

This study investigated antibiotic resistance gene (ARG) degradation kinetics in wastewaters during bench- and full-scale treatment with UV light and chlorine─with the latter maintained as free available chlorine (FAC) in low-ammonia wastewater and converted into monochloramine (NH2Cl) in high-ammonia wastewater. Twenty-three 142-1509 bp segments (i.e., amplicons) of seven ARGs (blt, mecA, vanA, tet(A), ampC, blaNDM, blaKPC) and the 16S rRNA gene from antibiotic resistant bacteria (ARB) strains Bacillus subtilis, Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were monitored as disinfection targets by qPCR. Rate constants for ARG and 16S rRNA gene amplicon degradation by UV, FAC, and NH2Cl were measured in phosphate buffer and used to expand and validate several recently developed approaches to predict DNA segment degradation rate constants based solely on their nucleotide contents, which were then applied to model ARG degradation during bench-scale treatment in buffer and wastewater matrixes. Kinetics of extracellular and intracellular ARG degradation by UV and FAC were well predicted up to ∼1-2-log10 elimination, although with decreasing accuracy at higher levels for intracellular genes, while NH2Cl yielded minimal degradation under all conditions (agreeing with predictions). ARB inactivation kinetics varied substantially across strains, with intracellular gene degradation lagging cell inactivation in each case. ARG degradation levels observed during full-scale disinfection at two wastewater treatment facilities were consistent with bench-scale measurements and predictions, where UV provided ∼1-log10 ARG degradation, and chlorination of high-ammonia wastewater (dominated by NH2Cl) yielded minimal ARG degradation.

Elimination efficiency of synthetic musks during the treatment of drinking water with ozonation and UV-based advanced oxidation processes.

This study investigated the reaction kinetics and elimination efficiency of eleven synthetic musks during ozonation and UV254nm-based, advanced oxidation processes. The synthetic musks containing olefin moieties with electron-donating alkyl substituents such as octahydro tetramethyl naphthalenyl ethanone (OTNE) and ambrettolide (AMBT) showed high reactivity toward ozone (k ≥ 3.7 × 105 M-1 s-1) and free available chlorine (FAC) (k = 9.2 - 88 M-1 s-1), while all other synthetic musks were less ozone reactive (k = 0.3 - 560 M-1 s-1) and FAC-refractory. All synthetic musks showed high •OH reactivity (k > 5 × 109 M-1 s-1), except musk ketone (MK) (k = 2.3 × 109 M-1 s-1). In concordance with the kinetic information, OTNE and AMBT were efficiently eliminated (>97%) in simulated ozone treatments of drinking water at a specific ozone dose of 0.5 gO3/gDOC. The elimination levels of the other synthetic musks were below 50% at 0.5 gO3/gDOC. The fluence-based UV photolysis rate constant of the synthetic musks was determined to be (0.2 - 2.7) × 10-3 cm2/mJ. The elimination levels of synthetic musks during UV alone treatment ranged from 7 to 81% at a UV fluence of 500 mJ/cm2. The addition of 10 mg/L H2O2 (UV/H2O2) significantly enhanced the elimination of most synthetic musks (achieving >90% elimination at 500 mJ/cm2), indicating that the •OH reaction was mainly responsible for their elimination. The addition of 10 mg/L FAC (UV/FAC) also significantly enhanced the elimination of olefinic and aromatic synthetic musks (>90%), for which the reaction with ClO• was mainly responsible. For MK and two alkyl synthetic musks, their elimination during UV/FAC treatment was still limited (28 - 64%) and was mainly achieved by UV photolysis or reaction with •OH. In summary, this study substantiates the chemical kinetics approach as a helpful tool for predicting or interpreting the elimination of micropollutants during oxidative water treatment.

Degradation Kinetics of Antibiotic Resistance Gene mecA of Methicillin-Resistant Staphylococcus aureus (MRSA) during Water Disinfection with Chlorine, Ozone, and Ultraviolet Light.

Degradation kinetics of antibiotic resistance genes (ARGs) by free available chlorine (FAC), ozone (O3), and UV254 light (UV) were investigated in phosphate buffered solutions at pH 7 using a chromosomal ARG (mecA) of methicillin-resistant Staphylococcus aureus (MRSA). For FAC, the degradation rates of extracellular mecA (extra-mecA) were accelerated with increasing FAC exposure, which could be explained by a two-step FAC reaction model. The degradation of extra-mecA by O3 followed second-order reaction kinetics. The degradation of extra-mecA by UV exhibited tailing kinetics, which could be described by a newly proposed kinetic model considering cyclobutane pyrimidine dimer (CPD) formation, its photoreversal, and irreversible (6-4) photoproduct formation. Measured rate constants for extra-mecA increased linearly with amplicon length for FAC and O3, or with number of intrastrand pyrimidine doublets for UV, which enabled prediction of degradation rate constants of extra-mecA amplicons based on sequence length and/or composition. In comparison to those of extra-mecA, the observed degradation rates of intracellular mecA (intra-mecA) were faster for FAC and O3 at low oxidant exposures but significantly slower at high exposures for FAC and UV. Differences in observed extra- and intracellular kinetics could be due to decreased DNA recovery efficiency and/or the presence of MRSA aggregates protected from disinfectants.

Phosphorylation of p53 Serine 15 Is a Predictor of Survival for Patients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with a poor prognosis. Several commonly investigated immunohistochemical markers in resected HCC have potential prognostic value, but the prognostic utility of p53 expression in HCC has remained elusive. Aim: To evaluate the prognostic value of p53 and p53 phosphorylation at serine 15 (p53 Ser15-P) in patients with HCC. Methods: Surgically resected tumors from 199 HCC patients were analyzed for p21, p53, p53 Ser15-P, and proliferating cell nuclear antigen (PCNA) expression using immunohistochemistry. Results: Stratifying by the expression of p53 Ser15-P (P = 0.016), but not by p53 (P = 0.301), revealed significantly different survival outcomes in patients with HCC. Moreover, our analysis demonstrated that patients who were PCNA-positive and p53 Ser15-P-negative had significantly worse survival outcomes (P = 0.001) than patients who were PCNA-positive and p53 Ser15-P-positive. Conclusions: P53 Ser15-P is associated with poor outcomes in patients with HCC, and this prognostic marker is useful for predicting the survival of patients with PCNA-positive HCC.

Secretion of IL-1ß from imatinib-resistant chronic myeloid leukemia cells contributes to BCR-ABL mutation-independent imatinib resistance.

Some cases of chronic myelogenous leukemia are resistant to tyrosine kinase inhibitors (TKIs) independently of mutation in BCR-ABL, but the detailed mechanism underlying this resistance has not yet been elucidated. In this study, we generated a TKI-resistant CML cell line, K562R, that lacks a mutation in BCR-ABL. Interleukin-1ß (IL-1ß) was more highly expressed in K562R than in the parental cell line K562S, and higher levels of IL-1ß contributed to the imatinib resistance of K562R. In addition, IL-1ß secreted from K562R cells affected stromal cell production of CXCL11, which in turn promoted migration of K562R cells into the stroma. Thus, elevated IL-1ß production from TKI-resistant K562R cells may contribute to TKI resistance by increasing cell viability and promoting cell migration.