Predicting leachate impact on groundwater using electrical conductivity and oxidation-reduction potential measurements: An empirical and theoretical approach.

This study developed innovative predictive models of groundwater pollution using in situ electrical conductivity (EC) and oxidation-reduction potential (ORP) measurements at livestock carcass burial sites. Combined electrode analysis (EC and ORP) and machine learning techniques efficiently and accurately distinguished between leachate and background groundwater. Two models-empirical and theoretical-were constructed based on a supervised classification framework. The empirical model constructs a classifier with high accuracy, sensitivity, and specificity, utilizing the comprehensive in situ EC and ORP measurements. The theoretical model with only two end members achieves comparable performance by simulating the leachate-groundwater interactions using a geochemical mixing model. Besides enhancing the early detection capabilities, our approach considerably reduces the reliance on extensive hydrochemical analyses, thus streamlining the monitoring process. Moreover, the use of field parameters was found to proactively identify potential pollution incidents, enhancing the efficiency of groundwater monitoring strategies. Our approach is applicable to various waste disposal sites, indicating its extensive potential for environmental monitoring and management.

Using isometric log-ratio in compositional data analysis for developing a groundwater pollution index.

This study introduces a novel groundwater pollution index (GPI) formulated through compositional data analysis (CoDa) and robust principal component analysis (RPCA) to enhance groundwater quality assessment. Using groundwater quality monitoring data from sites impacted by the 2010-2011 foot-and-mouth disease outbreak in South Korea, CoDa uncovers critical hydrochemical differences between leachate-influenced and background groundwater. The GPI was developed by selecting key subcompositional parts (NH4+-N, Cl-, and NO3--N) using RPCA, performing the isometric log-ratio (ILR) transformation, and normalizing the results to environmental standards, thereby providing a more precise and accurate assessment of pollution. Validated against government criteria, the GPI has shown its potential as an alternative assessment tool, with its reliability confirmed by receiver operating characteristic curve analysis. This study highlights the essential role of CoDa, especially the ILR -transformation, in overcoming the limitations of traditional statistical methods that often neglect the relative nature of hydrochemical data. Our results emphasize the utility of the GPI in significantly advancing groundwater quality monitoring and management by addressing a methodological gap in the quantitative assessment of groundwater pollution.

A supervised machine learning approach to discriminate the effect of carcass leachate on shallow groundwater quality around on-farm livestock mortality burial sites.

The evaluation of leachate leakage at livestock mortality burial sites is challenging, particularly when groundwater is previously contaminated by agro-livestock farming. Supervised machine learning was applied to discriminate the impacts of carcass leachate from pervasive groundwater contamination in the following order: data labeling, feature selection, synthetic data generation, and classification. Physicochemical data of 359 water samples were collected from burial pits (LC), monitoring wells near pits (MW), pre-existing shallow household wells (HW), and background wells with pervasive contamination (BG). A linear classification model was built using two representative groups (LC and BG) affected by different pollution sources as labeled data. A classifier was then applied to assess the impact of leachate leakage in MW and HW. As a result, leachate impacts were observed in 40% of MW samples, which indicates improper construction and management of some burial pits. Leachate impacts were also detected in six HW samples, up to 120 m downgradient, within one year. The quantitative decision-making tool to diagnose groundwater contamination with leachate leakage can contribute to ensuring timely responses to leakage. The proposed machine learning approach can also be used to improve the environmental impact assessment of water pollution by improper disposal of organic waste.

Nitrate sources, timing, and pathways of a permeable volcanic aquifer system with mixed land use in Jeju Island, South Korea.

The occurrence of various N-related human activities increases the difficulty in distinguishing the major sources of NO3- contamination in groundwater, especially in areas with mixed land uses. In addition, the estimation of the timing and pathways of NO3- is necessary to better understand the processes of NO3- contamination in the subsurface aquifer system. This study applied environmental tracers, such as stable isotopes and age tracers (δ15N and δ18O of NO3-, δ11B, chlorofluorocarbons, and 3H), to elucidate the sources, timing, and pathways of NO3- contamination in the groundwaters of the Hanrim area, which has suffered from illegal disposal of livestock wastes since the 1980s, and also characterizes them based on mixed N-contaminant sources such as chemical fertilizers and sewage. The combined use of δ15N and δ11B overcame the limitation of using only NO3- isotopes for the identification of overlapping sources of N and successfully identified the major source of N as livestock wastes. The lumped parameter model (LPM) estimated the binary mixing of the young (age: 23-40 years, NO3-N: 2.55-15.10 mg/L) and old (age: >60 years, NO3-N: <3 mg/L) groundwaters, and explained their age mixing behaviors. The young groundwater was highly affected by livestock-derived N loading during 1987-1998, which coincides with the period of improper dumping of livestock wastes. Furthermore, the young groundwater with elevated NO3-N followed the historical NO3-N curves with younger ages (6 and 16 years) than those derived from the LPM, suggesting the possibility of faster inflows of livestock wastes through the permeable volcanic structures. This study demonstrated that a comprehensive understanding of NO3- contamination processes can be achieved using environmental tracer methods, which enables the efficient management of groundwater resources in areas with multiple N sources.

Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma.

PURPOSE: The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC. MATERIALS AND METHODS: Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed. RESULTS: PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035). CONCLUSION: Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

SGLT2 inhibition ameliorates nano plastics-induced premature endothelial senescence and dysfunction.

Nano plastics (NPs) have been a significant threat to human health and are known to cause premature endothelial senescence. Endothelial senescence is considered one of the primary risk factors contributing to numerous cardiovascular disorders. Recent studies have suggested that inhibition of sodium glucose co-transporter (SGLT2) ameliorates endothelial senescence and dysfunction. Therefore, our study intends to explore the role of SGLT2 in NPs-induced endothelial senescence and dysfunction. Porcine coronary artery and its endothelial cells were treated with NPs in the presence or absence of Enavogliflozin (ENA), a SGLT2 inhibitor and then SGLTs expression, senescence markers and vascular function were evaluated. NPs significantly up-regulated SGLT2 and ENA significantly decreased NPs-induced senescence-associated-ß-gal activity, cell-cycle arrest, and senescence markers p53 and p21 suggesting that inhibition of SGLT2 prevents NPs-induced endothelial senescence. In addition, ENA decreased the formation of reactive oxygen species with the downregulation of Nox2, and p22phox. Furthermore, SGLT2 inhibition also up regulated the endothelial nitric oxide synthase expression along with improving vascular function. In conclusion, premature endothelial senescence by NPs is, at least in part, associated with SGLT2 and it could be a potential therapeutic target for preventing and/or treating environmental pollutants-induced cardiovascular disorders mediated by endothelial senescence and dysfunction.

Multi-Filter Clustering Fusion for Feature Selection in Rotating Machinery Fault Classification.

In the fault classification process, filter methods that sequentially remove unnecessary features have long been studied. However, the existing filter methods do not have guidelines on which, and how many, features are needed. This study developed a multi-filter clustering fusion (MFCF) technique, to effectively and efficiently select features. In the MFCF process, a multi-filter method combining existing filter methods is first applied for feature clustering; then, key features are automatically selected. The union of key features is utilized to find all potentially important features, and an exhaustive search is used to obtain the best combination of selected features to maximize the accuracy of the classification model. In the rotating machinery examples, fault classification models using MFCF were generated to classify normal and abnormal conditions of rotational machinery. The obtained results demonstrated that classification models using MFCF provide good accuracy, efficiency, and robustness in the fault classification of rotational machinery.

Inhibition of Hepatic Stellate Cell Activation Suppresses Tumorigenicity of Hepatocellular Carcinoma in Mice.

Transdifferentiation (or activation) of hepatic stellate cells (HSCs) to myofibroblasts is a key event in liver fibrosis. Activated HSCs in the tumor microenvironment reportedly promote tumor progression. This study analyzed the effect of an inhibitor of HSC activation, retinol-binding protein-albumin domain III fusion protein (R-III), on protumorigenic functions of HSCs. Although conditioned medium collected from activated HSCs enhanced the migration, invasion, and proliferation of the hepatocellular carcinoma cell line Hepa-1c1c7, this effect was not observed in Hepa-1c1c7 cells treated with conditioned medium from R-III-exposed HSCs. In a subcutaneous tumor model, larger tumors with increased vascular density were formed in mice transplanted with Hepa-1c1c7+HSC than in mice transplanted with Hepa-1c1c7 cells alone. Intriguingly, when Hepa-1c1c7+HSC-transplanted mice were injected intravenously with R-III, a reduction in vascular density and extended tumor necrosis were observed. In an orthotopic tumor model, co-transplantation of HSCs enhanced tumor growth, angiogenesis, and regional metastasis accompanied by increased peritumoral lymphatic vessel density, which was abolished by R-III. In vitro study showed that R-III treatment affected the synthesis of pro-angiogenic and anti-angiogenic factors in activated HSCs, which might be the potential mechanism underlying the R-III effect. These findings suggest that the inhibition of HSC activation abrogates HSC-induced tumor angiogenesis and growth, which represents an attractive therapeutic strategy.

Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma.

Adenylate kinase 5 (AK5) belongs to the adenylate kinase family that catalyses reversible phosphate transfer between adenine nucleotides, and it is related to various energetic signalling mechanisms. However, the role of AK5 in colorectal cancer (CRC) has not been reported. In this study, AK5 was significantly hypermethylated in CRC compared to adjacent normal tissues (P < 0.0001) and normal tissues (P = 0.0015). Although the difference in mRNA expression was not statistically significant in all of them, the selected 49 cases of CRC tissues with AK5 hypermethylation with the cut off value of 40% showed a significant inverse correlation with mRNA expression (P = 0.0003). DNA methylation of AK5 promoter significantly decreased and AK5 expression recovered by 5-aza-2'-deoxycytidine, DNA methyltransferase inhibitor in CRC cell lines. In addition, AK5 promoter activity significantly decreased due to DNA methyltransferase, and it increased due to 5-aza. Moreover, AK5 regulated the phosphorylated AMPK and mTOR phosphorylation and inhibited the cell migration and cell invasion in CRC cell lines. Furthermore, low AK5 expression is associated with poor differentiation (P = 0.014). These results demonstrate that the AK5 promoter is frequently hypermethylated and induced methylation-mediated gene down-regulation. AK5 expression regulates AMPK/mTOR signalling and may be closely related to metastasis in colorectal adenocarcinoma.

Albumin inhibits the nuclear translocation of Smad3 via interleukin-1beta signaling in hepatic stellate cells.

Activation of quiescent hepatic stellate cells (HSCs) to myofibroblasts plays a key role in liver fibrosis. We had previously shown that albumin and its derivative, R-III (a retinol-binding protein-albumin domain III fusion protein), inhibited HSC activation by sequestering retinoic acid (RA) and that R-III administration reduced carbon tetrachloride (CCl4)-induced liver fibrosis. In this study, we aimed to elucidate the mechanism of action of albumin downstream of RA sequestration. Nuclear factor-κB p65 was evenly distributed in the cytoplasm in activated mouse HSCs, whereas albumin expression or R-III treatment (albumin/R-III) caused the nuclear translocation of p65, probably via RA sequestration, resulting in a dramatic increase in interleukin-1beta (IL-1ß) expression. Albumin/R-III in turn induced the phosphorylation of Smad3 at the linker region, inhibiting its nuclear import in an IL-1ß-dependent manner. Consistent with the in vitro results, the level of IL-1ß mRNA expression was higher in CCl4/R-III-treated livers than in CCl4-treated livers. These findings reveal that albumin/R-III inhibits the transforming growth factor-ß-Smad3 signaling as well as the retinoic acid receptor-mediated pathway, which probably contributes to the inhibition of HSC activation, and suggest that R-III may be an anti-fibrotic drug candidate.

In situ field method for evaluating biodegradation potential of BTEX by indigenous heterotrophic denitrifying microorganisms in a BTEX-contaminated fractured-rock aquifer.

Generally different anaerobic degradation potentials for benzene, toluene, ethylbenzene and xylene isomers (BTEX) has been reported due to site specific conditions, such as the indigenous microbial population, electron acceptors (EA) available and concentrations of each BTEX compound. It was of interest to estimate relative biodegradation potential of each BTEX compound during enhanced anaerobic bioremediation of a BTEX-contaminated aquifer. In this study, an in situ method for assessing the degradation potentials of each BTEX compound present as a mixture under NO3-injecting conditions by performing a series of single-well push-pull tests and well-to-well tests (WWTs) was developed. During the 1st and 2nd WWTs, biological heterotrophic dissimilative NO3- denitrification was confirmed by simultaneous detection of both NO2- and N2O and significant production of CO2 during the NO3- degradation. The biodegradation fractions of NO3- injected during the 1st and 2nd WWTs were 1.7% and 5.0%, respectively, with 7.18 and 8.85 mmol N/L/day of in situ zero-order denitrification rate coefficients. The concentrations of benzene, ethylbenzene, and xylenes measured were similar to values calculated when considering only dilution, but the measured concentrations of toluene were significantly lower than the values calculated were. These results indicate that in situ method presented in the study successfully evaluate anaerobic biodegradation potential of individual BTEX compounds by indigenous heterotrophic denitrifying microorganisms.

Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. METHODS: Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. RESULTS: Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070-3.455, P = 0.029). CONCLUSIONS: Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Total Synthesis of Cyclopiamide A Using Palladium-Catalyzed Domino Cyclization.

Total synthesis of cyclopiamide A was accomplished using a palladium-catalyzed domino cyclization. Three rings in the tetracyclic skeleton of cyclopiamide A were constructed in a one-step domino reaction incorporating double carbopalladation and C-H activation.

Evaluating a new injection method of liquid/gas mixture spray injection via performing long-term in situ bioremediation tests.

During in situ bioremediation, continuous injection of growth substrates such as carbon sources, electron donors, or electron acceptors inevitably results in microbial growth, resulting in biological clogging in an aquifer. Therefore, for successful bioremediation, development of a new injection method is needed to reduce or alleviate this clogging problem. In this study, we carried out field tracer tests using single-well push-pull tests (SWPPTs), single-well natural gradient drift tests (SWNGDTs), and long-term in situ well-to-well tests to develop and evaluate a new method of liquid/gas mixture spray injection. The effectiveness of the new method was evaluated by estimating the factors as follow: longitudinal dispersivity (αL), radius of influence (RI), shear stress on the surface of aquifer particles (σ), biofilm-shear-loss rate (Rs), and the ratio of volume occupied by cells grown to the original pore volume. At the tested site, the liquid/gas mixture spray injection method turned out to have several advantages compared to the traditional solution injection method: 1) transport of solute to a larger proportion of an aquifer by a factor of 1.3-1.7, 2) application of higher shear stress onto the surface of soil particles by a factor of 4.2-5.0, 3) faster biofilm sloughing rates by a factor of 2.3-2.6, 4) reduction in the ratio of the volume occupied by microorganisms to total pore volume (Volmicrobes/Volpore), and 5) efficient trichloroethylene (TCE) dechlorination for a period of 550 days without any injection problems. This new injection method showed positive effects on the hydrogeological and physical characteristics of the system, thus alleviating the biological clogging problem.

Efficacy of in situ well-based denitrification bio-barrier (WDB) remediating high nitrate flux in groundwater near a stock-raising complex.

This study assessed the feasibility of an in situ well-based denitrification bio-barrier (WDB) for managing groundwater contaminated with high-strength nitrate. To evaluate the efficacy of WDB using fumarate as a carbon source and/or electron donor, three sequential single-well push-pull tests (SWPPTs) were conducted at six test sites. The values of the isotope enrichment factor (ɛ) ranging from -6.5‰ to -22.6‰ and the detection and degradation of nitrite and nitrous oxide confirmed complete in situ denitrification of nitrate to nitrogen gas. The ratio of the first-order rate coefficient of fumarate to nitrate (k1,fum/k1,NO3) was obtained to estimate the amount and frequency of fumarate injection for the effective design of WDB. At three sites, the ratios ranged from 0.67 to 0.80, while the other two sites showed higher ratios of 2.97 and 2.20 than the theoretical values and significant amounts of sulfate reduction, theoretically equivalent to 6.5% of total fumarate consumption. Considering the theoretical mole ratio of fumarate to nitrate of 0.98, the amount and frequency of fumarate injection is site specific. During the operating WDB, the average annual nitrate mass degraded (95% CI) was 2.2 ± 1.0 kg N/yr/well. The amount of N reduced by one well of WDB is equivalent to treating 110 m3 of groundwater at 30 mg N/L to the level of 10 mg N/L for one year. WDB would be an effective remediation option for managing high nitrate flux in groundwater.

Nationwide groundwater monitoring around infectious-disease-caused livestock mortality burials in Korea: Superimposed influence of animal leachate on pre-existing anthropogenic pollution.

A foot-and-mouth disease (FMD) outbreak during 2010 affected the entire country of South Korea and approximately 3.4 million swine and bovine mortalities were disposed of at approximately 4800 on-farm burial sites for a few months following the first outbreak. Furthermore, outbreaks of avian influenza (AI) have struck Korea consistently since 2014. Public concern regarding the deterioration of the surrounding environment has been raised aiming at the enormous infected animal carcass burials. On behalf of the Ministry of Environment (ME) of the Korean government, we conducted groundwater monitoring at approximately 3000 wells around the burial sites for 7 years from 2011 to 2017. The baseline groundwater already had enriched levels of nitrogen and chloride compounds masking the influence of leachate with the pre-existing anthropogenic contamination. Based on the trend analysis, most monitoring wells had no significant trends in NO3-N and Cl implying that an abrupt degradation in water quality was not expected across the country. Increasing proportions of total coliform detection in the groundwater of the majority of provinces will cause potential damage to human health around the carcass burial sites. Wells showing frequent upward and downward trends near the carcass burial pits were targeted for principal component analysis (PCA) and the results showed that NH4-N, TOC, Cl, and K could be indicators distinguishing the sole impacts of animal leachate on the groundwater. Analyses of the nationwide monitoring data indicated possibly delayed and prolonged impacts of the widespread burials of livestock mortalities on the groundwater environment. The finding provides realistic insight regarding how to manage the mass burial of livestock mortalities to protect groundwater resources.

Biogenic Hematite from Bacteria: Facile Synthesis of Secondary Nanoclusters for Lithium Storage Capacity.

Ferrihydrite, or iron(III) (oxyhydr)oxide (Fe(OH)3), a representative scavenger of environmentally relevant toxic elements, has been repurposed as a low-cost and scalable precursor of well-developed hematite (α-Fe2O3) secondary nanoclusters with a hierarchically structured morphology for lithium-ion anode materials. Here, we report that the bacteria Clostridium sp. C8, isolated from a methane-gas-producing consortium, can synthesize self-assembled secondary hematite nanoclusters (∼150 nm) composed of small nanoparticles (∼15 nm) through the molecular structural rearrangement of amorphous ferrihydrite under mild conditions. The biogenic hematite particles, wrapped with graphene oxide reduced in situ by the reducing bacteria Shewanella sp. HN-41 via one-pot synthesis, deliver an excellent reversible capacity of ∼1000 mA h g-1 after 100 cycles at a current density of 1 A g-1. Furthermore, the heat-treated hematite/rGO exhibits a capacity of 820 mA h g-1 at a high current density of 5 A g-1 and a reversible capacity of up to 1635 mA h g-1 at a current density of 100 mA g-1. This study provides an easy, eco-efficient, and scalable microbiological synthetic route to produce hierarchical hematite/rGO secondary nanoclusters with potential as high-performance Li-ion anode materials.

Estimating bioaugmentation efficacy of TCE dechlorination using long-term field well-to-well tests in a highly recharged and TCE-contaminated aquifer.

This study demonstrates a combined field method accurately assessing the extent of trichloroethylene (TCE) reductive dechlorination activity and the mass fraction of its by-products. A combined method of injecting a known concentration of 1,1,2-trichloro-2-fluoroethene (TCFE) as a TCE bio-surrogate and a data processing technique of forced mass balance (FMB), considering the sorption effect on the mass fraction of chloroethene was evaluated by performing soil column and field bioaugmentation tests. In the soil column test, the FMB resulted in the mass fraction of 6% TCE, 48.3% cis-1,2-dichloroethene, 18.5% vinyl chloride and 27.2% ethylene. In the field bioaugmentation test, TCFE showed equivalent dechlorination pathways of TCE. The mass fractions estimated by FMB were very similar to those observed in the soil column bioaugmentation tests: 4.5% TCFE, 57.1% 1,2-dichloro-1-fluoroethene, 12% 1-chloro-1-fluoroethene and 26.4% fluoroethene (FE). The FMB method gave ∼50% higher mass fraction for more chlorinated ethenes (i.e., TCFE) and ∼10% lower mass fraction of less chlorinated ethenes (i.e., FE) than those considering only the aqueous concentrations of chlorofluoroethenes. A combined method of TCFE and FMB that could accurately estimate both the extent of dechlorination activities and mass distribution of TCE reductive dechlorination would be highly useful.

Adsorption and Incorporation of Arsenic to Biogenic Lepidocrocite Formed in the Presence of Ferrous Iron during Denitrification by Paracoccus denitrificans.

We demonstrate adsorption and partial incorporation of arsenic, in its soluble form, either as arsenite or arsenate into lepidocrocite (γ-FeOOH), which was formed through nitrite-driven Fe(II) oxidation by Paracoccus denitrificans under nitrate-reducing conditions. Fe and As K-edge XANES and radial distribution functions of Fourier-transformed EXAFS spectra showed that portions of As were found to be incorporated in the biogenic lepidocrocite, in addition to higher portions of adsorbed As. We suggest that denitrifying bacteria such as Paracoccus denitrificans, studied here, could facilitate decrease of aqueous arsenic As(III) and/or As(V) through indirect Fe(II) oxidation to solid phase iron minerals, here as lepidocrocite, by the denitrification product nitrite in the presence of nitrate, ferrous iron, and arsenic, under certain environmental conditions where these materials could be found, such as in As-contaminated paddy soils and wetlands.

Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells.

BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells. RESULTS: MTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co. Hinokitiol reduced DNA methyltransferase 1 (DNMT1) and ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression in HCT-116 cells. In addition, the expression of ten-eleven translocation protein 1 (TET1), a known DNA demethylation initiator, was increased by hinokitiol treatment. ELISA and FACS data showed that hinokitiol increased the 5-hydroxymethylcytosine (5hmC) level in the both colon cancer cells, but 5-methylcytosine (5mC) level was not changed. Furthermore, hinokitiol significantly restored mRNA expression of O6-methylguanine DNA methyltransferase (MGMT), carbohydrate sulfotransferase 10 (CHST10), and B-cell translocation gene 4 (BTG4) concomitant with reduction of methylation status in HCT-116 cells. CONCLUSIONS: These results indicate that hinokitiol may exert DNA demethylation by inhibiting the expression of DNMT1 and UHRF1 in colon cancer cells.