Uptake of polycyclic aromatic hydrocarbons (PAHs) from PAH-contaminated soils to carrots and Chinese cabbages under the greenhouse and field conditions.

Polycyclic aromatic hydrocarbons (PAHs) with the properties of structural stability, semi-volatility, and hydrophobicity are toxic and persistent in environments; thus, their transport and fate in agroecosystems is essential for reducing PAH accumulation in the edible parts of crops. Here, we cultivated cabbages (Brassica pekinensis L.) and carrots (Daucus carota L.) in PAH-contaminated soils under the greenhouse and field conditions. After harvesting, we observed a 9.5-46% reduction in soil ∑PAH concentrations. There were 37% of bioconcentration factors (BCFbs) > 1 and 93% of translocation factors (TFab) > 1, while low-molecular-weight (LMW) PAHs had higher BCFbs than high-molecular-weight (HMW) PAHs. The PAH concentrations showed significant and positive correlations among soils, the belowground parts, and the aboveground parts. The toxicity equivalent concentration (TEQBaP) followed the order of cabbage (greenhouse) > cabbage (field) > carrot (greenhouse) > carrot (field), suggesting potentially higher health risks in cabbage relative to carrot and vegetables under the greenhouse relative to field condition. Our study suggested growing carrots under field conditions as a management strategy for reducing the risks of vegetables grown in PAH-contaminated soils.

Wild-type IDH1 maintains NSCLC stemness and chemoresistance through activation of the serine biosynthetic pathway.

Tumor-initiating cells (TICs) reprogram their metabolic features to meet their bioenergetic, biosynthetic, and redox demands. Our previous study established a role for wild-type isocitrate dehydrogenase 1 (IDH1WT) as a potential diagnostic and prognostic biomarker for non-small cell lung cancer (NSCLC), but how IDH1WT modulates NSCLC progression remains elusive. Here, we report that IDH1WT activates serine biosynthesis by enhancing the expression of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1), the first and second enzymes of de novo serine synthetic pathway. Augmented serine synthesis leads to GSH/ROS imbalance and supports pyrimidine biosynthesis, maintaining tumor initiation capacity and enhancing gemcitabine chemoresistance. Mechanistically, we identify that IDH1WT interacts with and stabilizes PHGDH and fragile X-related protein-1 (FXR1) by impeding their association with the E3 ubiquitin ligase parkin by coimmunoprecipitation assay and proximity ligation assay. Subsequently, stabilized FXR1 supports PSAT1 mRNA stability and translation, as determined by actinomycin D chase experiment and in vitro translation assay. Disrupting IDH1WT-PHGDH and IDH1WT-FXR1 interactions synergistically reduces NSCLC stemness and sensitizes NSCLC cells to gemcitabine and serine/glycine-depleted diet therapy in lung cancer xenograft models. Collectively, our findings offer insights into the role of IDH1WT in serine metabolism, highlighting IDH1WT as a potential therapeutic target for eradicating TICs and overcoming gemcitabine chemoresistance in NSCLC.

Deciphering the photolysis products and biological concerns of triclosan under UVC and UVA.

Triclosan (TCS) is omnipresent in the environment and has drawn increasing attention due to its potential adverse effects on human health. Direct photolysis of TCS readily occurs, especially in the surface layers of waters that receive abundant ultraviolet radiation during the daytime. However, biological concerns and the identification of toxic products during TCS photolysis have been explored limitedly. Therefore, in the present work, the structural characterization of the photolysis products by UVC and UVA were performed based on the mass spectra and fragmental ions. The results displayed that TCS was more readily eliminated by UVC than UVA, and the product species were completely different when TCS was degraded by UVC and UVA, respectively. Two products, m/z 235 and m/z 252, were produced via reductive dechlorination and nucleophilic substitution with UVC, while three dioxin-like isomer products were generated by dechlorination, cyclization and hydroxylation. Furthermore, the results of biological concerns suggested that the elimination of TCS did not represent the disappearance of biological risks. Specifically, more hazardous and photolysis products were formed during TCS photolysis with ultraviolets. For instance, the dioxin-like isomer products were highly microtoxic and genotoxic, and mildly antiestrogenic. The positive findings highlighted the biological concerns of TCS photolysis by ultraviolet radiation in the aquatic environment.

Molecular signatures of soil-derived dissolved organic matter constrained by mineral weathering.

Dissolved organic matter (DOM) in soils drives biogeochemical cycling and soil functions in different directions depending on its molecular signature. Notably, there is a distinct paucity of information concerning how the molecular signatures of soil DOM vary with different degrees of weathering across wide geographic scales. Herein, we resolved the DOM molecular signatures from 22 diverse Chinese reference soils and linked them with soil organic matter and weathering-related mineralogical properties. The mixed-effects models revealed that the yields of DOM were determined by soil organic carbon content, whereas the molecular signature of DOM was primarily constrained by the weathering-related dimension. The soil weathering index showed a positive effect on the lability and a negative effect on the aromaticity of DOM. Specifically, DOM in highly weathered acidic soils featured more amino sugars, carbohydrates, and aliphatics, as well as less O-rich polyphenols and condensed aromatics, thereby conferring a higher DOM biolability and lower DOM aromaticity. This study highlights the dominance of the weathering-related dimension in constraining the molecular signatures and potential functions of DOM in soils across a wide geographic scale.

Burn Intensity Drives the Alteration of Phenolic Lignin to (Poly) Aromatic Hydrocarbons as Revealed by Pyrolysis Gas Chromatography-Mass Spectrometry (Py-GC/MS).

High-intensity wildfires alter the chemical composition of organic matter, which is expected to be distinctly different from low-intensity prescribed fires. Herein, we used pyrolysis gas chromatography/mass spectrometry (Py-GC/MS), in conjunction with solid-state 13C nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy, to assess chemical alterations from three wildfires and a long-term frequent prescribed fire site. Our results showed that black ash formed under moderate intensity burns contained less aromatic (ArH), polyaromatic hydrocarbon (PAH), and nitrogen-containing compounds (Ntg) but more lignin (LgC) and phenol compounds (PhC), compared to white ash formed under high intensity burns. Both 13C NMR and FT-IR confirmed a higher relative percentage of carboxyl carbon in white ash, indicating the potential for higher water solubility and more mobile carbon, relative to black ash. Compared to wildfires, ash from low-intensity prescribed fire contained less ArH, PAH, and Ntg and more LgC and PhC. Controlled laboratory burning trials indicated that organic matter alteration was sensitive to the burn temperature, but not related to the fuel type (pine vs fir) nor oxygen absence/presence at high burn temperatures. This study concludes that higher burn temperatures resulted in higher (poly)aromatic carbon/nitrogen and lower lignin/phenol compounds.

Lake reclamation alters molecular-level characteristics of lacustrine dissolved organic matter - A study of nine lakes in the Yangtze Plain, China.

In recent decades, the reclamation of lakes has captured 42% of the total lake area of the Yangtze Plain in China and introduced additional pressure on lacustrine water quality. While lacustrine dissolved organic matter (DOM) is critical in regulating biogeochemical processing and aquatic biodiversity, the impact of reclamation on the molecular-level characteristics of lacustrine DOM remains unexplored. Here, the DOM characteristics altered by reclamation practices in the Yangtze Plain lakes were investigated using fluorescence spectroscopy, nuclear magnetic resonance spectroscopy, and Fourier transform ion cyclotron resonance mass spectrometry. Results demonstrated that reclamation not only elevated the quantity (on average +32%) but also altered the characteristics and composition of lacustrine DOM. Compared to the natural water sites close by, reclamation sites did not significantly alter the DOM aromaticity but significantly lowered the average molecular weight and increased the biolability of DOM. The chromophoric DOM and humic-like fluorescent components were remarkably elevated, but not the protein-like fluorescent components. More lipid-like and condensed aromatic-like components were detected in the lacustrine DOM as compared to the lignin-like, carbohydrate-like, and protein-like components, which may be driven by the increased microbial processing. Overall, the significant alteration in characteristics and composition of lacustrine DOM highlights the potential impact of reclamation on the DOM biogeochemical cycle and the environmental quality in aquatic ecosystems.

Impacts of haze on the photobleaching of chromophoric dissolved organic matter in surface water.

Sunlight plays an important role in the photochemical processes of chromophoric dissolved organic matter (CDOM), which is closely related to water self-purification and primary productivity of healthy aquatic ecosystem health. The fine particles of haze, a widespread air pollutant, absorb natural ultraviolet (UV) irradiation and have an unknown degree of influence on the photochemical transformation of CDOM. Here, an in-situ experiment investigating how the amount and composition of CDOM changes under hazy conditions was conducted in Ningbo, southeastern China, a city that frequently suffers from seasonal haze pollution. The results indicated that haze attenuated UV light under different weather conditions. The UV intensities were reduced from 1124.90 ± 91.58 to 510.26 ± 40.26 µW cm-2 and 748.54 ± 101.68 to 316.32 ± 40.48 µW cm-2 on sunny and cloudy days, respectively; these values approached those on rainy days (186.97 ± 28.58 µW cm-2). Consequently, the loss of dissolved organic carbon during the irradiation test was reduced on hazy days (e.g., from 5.63% to 2.59% on sunny/hazy days). The impact of haze on CDOM photobleaching was further assessed by an excitation-emission matrix (EEM) combined with parallel factor (PARAFAC) analysis. On hazy days, the EEM-PARAFAC components were saved from photobleaching to different degrees; and humic-like substances showed a stronger protective effect from haze than protein-like substances because of their higher photosensitivity. Consequently, haze could cause more terrestrial CDOM to remain in surface water. UV intensity played a critical role in the composition characteristics of CDOM. This study identifies the linkage between atmospheric pollution and water quality and demonstrates that long-term and large-scale haze may adversely influence aquatic ecology through pollutant/nutrient accumulation.

Crop selection reduces potential heavy metal(loid)s health risk in wastewater contaminated agricultural soils.

Vegetable crops have varied heavy metal(loid)s accumulation rates from soils to their edible tissues. However, crop selection has been seldom evaluated as a strategy for reducing the health risks of ingesting vegetables grown in soils contaminated by treated wastewater (TWW) irrigation. We cultivated twenty commonly grown vegetables using soils with an approximately 50-year history of TWW irrigation, and their ingestion risks were evaluated by the health risk index (HRI). Results showed that twenty vegetable species had varied abilities in accumulating heavy metal(loid)s from soils to their edible parts (e.g., >100 times of difference for Cd). We found higher potential health risks (HRI > 1) due to As, Cd, and Pb for adults ingesting few vegetable species and all the studied vegetables had negligible health risks (HRI < 1) for Cr, Cu, and Zn. These results suggest that remediation strategies should be targeted towards As, Cd, and Pb removal in agricultural soils in this region. Total HRI > 5 was obtained for ingesting spinach, Chinese lettuce, and Chinese chives, suggesting a high potential of severe health risks. Negligible risks (total HRI < 1) were found for tomato, kidney bean, potato, and cabbage. Our study highlights crop selection as a feasible strategy for ensuring food safety in TWW contaminated farmlands.

Characteristics and chlorine reactivity of biochar-derived dissolved organic matter: Effects of feedstock type and pyrolysis temperature.

Increasing biochar application worldwide may release more biochar-derived dissolved organic matter (BDOM) to the source water for drinking water supply. However, it is unclear how feedstock types and pyrolysis temperatures for biochar production would affect the characteristics and chlorine reactivity of BDOM. Here, we studied the spectroscopic characteristics of BDOM pyrolyzed from pine needle, wheat straw, walnut shells, alfalfa, pig manure, and sludge derived biochars at 300, 500, and 700 °C, as well as the formation potential of disinfection byproducts (DBPs) and their bulk toxicity after BDOM chlorination. The N/C ratio of biochar was higher for N-rich than C-rich feedstocks. Optical analyses indicated that BDOM aromaticity was highest at 700 °C, while the impact of pyrolysis temperature on the molecular weight of BDOM varied greatly among feedstocks. Increasing pyrolysis temperature caused consistently decreased BDOM reactivity toward haloketone formation but did not show consistent impacts on the other DBPs. Among feedstocks, the N-rich sludge showed the highest specific haloacetonitrile formation potential of BDOM at any given pyrolysis temperature. The DBP formation potential from biochar was consistently highest at 300 °C and was higher for N-rich than C-rich feedstocks. The microtoxicity of DBP mixture was highest for the BDOM derived from sludge produced at 300 °C. This study highlights the high variations in characteristics and chlorination reactivity of BDOM with varying feedstocks and pyrolysis temperatures, which implies that more attention should be paid to the environmental impacts of the intensive application of low-temperature biochar from N-rich feedstock such as sludge.

[Effects of Greenhouse and Open-field Cultivation on Heavy Metal Uptake During Carrot Growth].

Clarifying the absorption dynamics of heavy metal(loid)s by crops under different cultivation methods is critical for risk management and control for heavy metal pollution. Here, taking carrots as an example, the pH, cation exchange capacity (CEC), and contents of heavy metals in soil and carrots were analyzed. We compared the absorption and transport characteristics of six metal(loid)s (As, Cd, Cr, Cu, Pb, and Zn) during the three key growth periods under greenhouse and open-field cultivation methods. In addition, the effects of planting methods on carrot biomass and heavy metal content over time were studied, and a health risk assessment was conducted. The results showed that the greenhouse and open-field cultivation methods had the following in common:① As the carrots continuously grew, the metal uptake and biomass in the belowground part (edible part) and the metal(loid) concentrations in the aboveground and belowground parts both showed trends of increasing first and then decreasing or stabilizing. ② The absorption of As, Cd, Cr, and Pb in carrots was mostly accumulated in the aboveground part. ③ The content of Cd in the edible part exceeded the standard, and the total target hazard quotient was>1, indicating potential adverse health risks, most of which were contributed by As and Cd. Compared to that under open-field, the short-term greenhouse cultivation had a harvest time approximately 15 d earlier. The As, Cd, and Pb concentrations in the aboveground part during the seedling and fast-growing periods were significantly lower in the greenhouse than that in the open-field (P<0.05) but did not differ between greenhouse and open-field (except As) at the mature stage. The concentrations of As and Cd in the belowground part of greenhouse carrots were lower in the greenhouse than those of carrots grown in the open-field at the seedling stage (P<0.05). The absorption of As and Cd was decreased significantly from 0 to 95 d (P<0.05), and there was no significant difference in the metal concentration and absorption in the rest of the growth stages. The bioconcentration factors (BCF) of As, Cd, and Pb in the aboveground part in all stages and those of As and Cd in the belowground part in the seedling stage were lower in the greenhouse than that in the open-field. This study emphasizes the possibility of short-term changes in cultivation mode to reduce the risks of metal(loid)s in contaminated farmland vegetables.

Potential use of arbuscular mycorrhizal fungi for simultaneous mitigation of arsenic and cadmium accumulation in rice.

Rice polluted by metal(loid)s, especially arsenic (As) and cadmium (Cd), imposes serious health risks. Numerous studies have demonstrated that the obligate plant symbionts arbuscular mycorrhizal fungi (AMF) can reduce As and Cd concentrations in rice. The behaviours of metal(loid)s in the soil-rice-AMF system are of significant interest for scientists in the fields of plant biology, microbiology, agriculture, and environmental science. We review the mechanisms of As and Cd accumulation in rice with and without the involvement of AMF. In the context of the soil-rice-AMF system, we assess and discuss the role of AMF in affecting soil ion mobility, chemical forms, transport pathways (including the symplast and apoplast), and genotype variation. A potential strategy for AMF application in rice fields is considered, followed by future research directions to improve theoretical understanding and encourage field application.

The m6A demethylase FTO promotes the osteogenesis of mesenchymal stem cells by downregulating PPARG.

N6-methyladenosine (m6A) is the most abundant posttranscriptional methylation modification that occurs in mRNA and modulates the fine-tuning of various biological processes in mammalian development and human diseases. In this study we investigated the role of m6A modification in the osteogenesis of mesenchymal stem cells (MSCs), and the possible mechanisms by which m6A modification regulated the processes of osteoporosis and bone necrosis. We performed systematic analysis of the differential gene signatures in patients with osteoporosis and bone necrosis and conducted m6A-RNA immunoprecipitation (m6A-RIP) sequencing to identify the potential regulatory genes involved in osteogenesis. We showed that fat mass and obesity (FTO), a primary m6A demethylase, was significantly downregulated in patients with osteoporosis and osteonecrosis. During the differentiation of human MSCs into osteoblasts, FTO was markedly upregulated. Both depletion of FTO and application of the FTO inhibitor FB23 or FB23-2 impaired osteogenic differentiation of human MSCs. Knockout of FTO in mice resulted in decreased bone mineral density and impaired bone formation. PPARG, a biomarker for osteoporosis, was identified as a critical downstream target of FTO. We further revealed that FTO mediated m6A demethylation in the 3'UTR of PPARG mRNA, and reduced PPARG mRNA stability in an YTHDF1-dependent manner. Overexpression of PPARG alleviated FTO-mediated osteogenic differentiation of MSCs, whereas knockdown of PPARG promoted FTO-induced expression of the osteoblast biomarkers ALPL and OPN during osteogenic differentiation. Taken together, this study demonstrates the functional significance of the FTO-PPARG axis in promoting the osteogenesis of human MSCs and sheds light on the role of m6A modification in mediating osteoporosis and osteonecrosis.

The novel indomethacin derivative CZ-212-3 exerts antitumor effects on castration-resistant prostate cancer by degrading androgen receptor and its variants.

Androgen receptor (AR) serves as a main therapeutic target for prostate cancer (PCa). However, resistance to anti-androgen therapy (SAT) inevitably occurs. Indomethacin is a nonsteroidal anti-inflammatory drug that exhibits activity against prostate cancer. Recently, we designed and synthesized a series of new indomethacin derivatives (CZ compounds) via Pd (II)-catalyzed synthesis of substituted N-benzoylindole. In this study, we evaluated the antitumor effect of these novel indomethacin derivatives in castration-resistant prostate cancer (CRPC). Upon employing CCK-8 cell viability assays and colony formation assays, we found that these derivatives had high efficacy against CRPC tumor growth in vitro. Among these derivatives, CZ-212-3 exhibited the most potent efficacy against CRPC cell survival and on apoptosis induction. Mechanistically, CZ-212-3 significantly suppressed the expression of AR target gene networks by degrading AR and its variants. Consistently, CZ-212-3 significantly inhibited tumor growth in CRPC cell line-based xenograft and PDX models in vivo. Taken together, the data show that the indomethacin derivative CZ-212-3 significantly inhibited CRPC tumor growth by degrading AR and its variants and could be a promising agent for CRPC therapy.

Coupling sprinkler freshwater irrigation with vegetable species selection as a sustainable approach for agricultural production in farmlands with a history of 50-year wastewater irrigation.

Soil contamination and crop risks of heavy metal(loid)s are widely reported after the long-term irrigation of treated wastewater, causing an adverse influence on agricultural sustainability. Here, we collected soils after 50 years of wastewater irrigation to cultivate cabbage (Brassica pekinensis L.), rape (Brassica chinensis L.), carrots (Daucus carota L.), and potatoes (Solanum tuberosum L.), using surface and sprinkler irrigation with freshwater and wastewater. In general, we found the statistically insignificant influence of short-term freshwater irrigation on the soil and vegetable metal(loid) concentrations. Most of the vegetables had potential adverse health risks with the relatively lower risks in carrots and potatoes, and most of the risks were contributed by As and Cd. Nevertheless, we observed negligible health risks for all studied metal(loid)s in potatoes under the freshwater irrigations. Besides, compared to wastewater irrigations, freshwater irrigations produced lower Cd health risks in all four vegetable species. Sprinkler irrigation with freshwater was a favorable approach for reducing the uptake of metal(loid)s from soils and the metal(loid) concentrations in aboveground parts. Our study highlights the possibility of reducing vegetable metal(loid) risks in contaminated farmlands via a combined approach of coupling the short-term decrease in their levels in irrigation water with vegetable species selection.

Chemodiversity of water-extractable organic matter in sediment columns of a polluted urban river in South China.

Dissolved organic matter (DOM) in sediments of polluted rivers significantly contributes to oxygen consumption and river blackening and odorization. However, the chemodiversity of DOM at different depths or river reaches is poorly known. Here, we studied the storage and molecular-level signatures of water-extractable organic matter (WEOM) in the sediment column (0-100 cm) of the upper, middle, and lower mainstream of Maozhou River (a polluted river in Shenzhen, China, with 40 years of urbanization) using optical spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry. The sediment WEOM level increased from upstream to downstream. The relative abundances of sulfur-containing surfactants in all sediment WEOM were higher than those previously reported for surface water DOM. The WEOM in surface sediment had higher aromaticity, molecular size, and nominal oxidation state of carbon and greater signals from anthropogenic inputs than did deep sediment at the upper and middle mainstream sites. However, these characteristics varied little between surface and deep sediments at the lower mainstream site, probably due to intensive surface water and pore water interactions. The sediment WEOM at 0-40 cm in the middle mainstream showed a greater anthropogenic signature (e.g., more surfactant and dissolved black carbon contributions) than any other sediment. We demonstrate strong anthropogenic impacts on the surface sediment over decades of urbanization.

Antioxidant CPA-type indole alkaloids produced from the deep-sea derived fungus Aspergillus sp. SCSIO 41024.

Twelve indole alkaloids, including α-cyclopiazonic acid (CPA) (1), nine 2-oxo indole CPA derivatives (2-10), and two open-ring indole CPA derivatives (11 and 12), were isolated from the fermentation broth of a deep-sea derived fungus Aspergillus sp. SCSIO 41024. Their structures and absolute configurations were elucidated mainly by using extensive NMR spectroscopic, mass spectrometric and single crystal X-ray diffraction analysis. To the best of our knowledge, the crystallographic data of 3 and 7 were firstly reported, and the absolute configuration of 3 was confirmed for the first time by the single crystal X-ray diffraction analysis. Most isolated compounds were tested for their antimicrobial, antitumor and radical scavenging activities. In addition, compounds 1, 2 and 11 showed moderate antioxidative activity against DPPH with IC50 values of 190.1, 31.9, 228.4 µg/mL, respectively.

Cytotoxic benzopyranone and xanthone derivatives from a coral symbiotic fungus Cladosporium halotolerans GXIMD 02502.

Coral-derived microorganisms have been historically proven to be prolific sources of bioactive secondary metabolites. Twelve benzopyranone and/or xanthone derivatives, including a new benzopyranone with an uncommon carboxyl group at C-8, coniochaetone K (1), were obtained from the Beibu Gulf-derived coral symbiotic fungus Cladosporium halotolerans GXIMD 02502. Their structures were determined by extensive spectroscopic data interpretation and comparison with literature values. The absolute configuration of 1 was accomplished by comparison of specific optical rotation as well as quantum chemical ECD calculations. The in vitro cytotoxicity of compounds 1-12 against two human prostatic cancer cell lines, C4-2B and 22RV1, were evaluated. And compounds 1, 3, 6-8, and 10-11 demonstrated significant cytotoxicity with inhibitions ranging from 55.8% to 82.1% at the concentration of 10 µM.

Long-term biochar addition alters the characteristics but not the chlorine reactivity of soil-derived dissolved organic matter.

Biochar is widely and increasingly applied to farmlands. However, it remains unclear how long-term biochar addition alters the characteristics and chlorine reactivity of soil-derived dissolved organic matter (DOM), an important terrestrial disinfection byproduct (DBP) precursor in watersheds. Here, we analyzed the spectroscopic and molecular-level characteristics of soil-derived DOM and the formation and toxicity of DBP mixtures from DOM chlorination for two long-term (5 and 11 years) biochar addition experimental farmlands. As indicated by spectroscopic indices and Fourier transform ion cyclotron resonance mass spectrometry analyses, 11 years of biochar addition could increase the humic-like and aromatic and condensed aromatic DOM and decrease the microbial-derived DOM, while 5 years of biochar addition at the other site did not. The response of condensed aromatic dissolved black carbon did not increase with increasing cumulative biochar dose but appeared to be affected by biochar aging time. Despite the possible increase in aromatic DOM, biochar addition neither increased the reactivity of DOM in forming trihalomethanes, haloacetonitriles, chloral hydrates, or haloketones nor significantly increased the microtoxicity or genotoxicity of the DBP mixture. This study indicates that biochar addition in watersheds may not deteriorate the drinking water quality via the export of terrestrial DBP precursors like wildfire events.

Chlorination of soil-derived dissolved organic matter: Long term nitrogen deposition does not increase terrestrial precursors of toxic disinfection byproducts.

Terrestrial dissolved organic matter (DOM) in forested watersheds is a known precursor of disinfection byproducts (DBPs) in drinking water. Although the characteristics of terrestrial DOM may change with increasing nitrogen (N) deposition in forests, how these changes alter formation potential and toxicity of DBPs remains unexplored. We analyzed the speciation and toxicity of DBPs from chlorination of DOM derived from soils (O, A, and B horizons) in an experimental temperate forest with 22 years of N addition. With long-term N addition, the DOM reactivity toward the formation of trihalomethanes (from 27.7-51.8 to 22.8-31.1 µg/mg-dissolved organic carbon (DOC)) and chloral hydrate (from 1.25-1.63 to 1.14-1.36 µg/mg-DOC) decreased, but that toward the formation of haloketones increased (from 0.23-0.26 to 0.26-0.33 µg/mg-DOC). The DOM reactivity toward the formation of haloacetonitriles was increased in the deeper soil but reduced in the surface soil. The DBP formation potential of DOM draining from a certain area of forest soils (in µg-DBP/m2-soil) was estimated to be reduced by 20.3% for trihalomethanes and increased by 37.5% for haloketones and have minor changes for haloacetonitriles and chloral hydrate (both <7%). Furthermore, the DBPs from chlorination of the soil-derived DOM showed lowered microtoxicity with N addition possibly due to reduced brominated DBP formation. Overall, this study highlights that N deposition may not increase drinking water toxicity through altering terrestrial DOM characteristics.

sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway.

Doxorubicin (Dox) is an effective chemotherapy drug against a wide range of cancers, including both hematological and solid tumors. However, the serious cardiotoxic effect restricted its clinical application. We previously have illuminated the protective role of canonical Wnt/ß-catenin signaling in Dox-induced cardiotoxicity. Secreted frizzled-related protein 1 (sFRP1) is one of the endogenous inhibitors of both canonical and noncanonical Wnt signaling. In this study, we investigated the relationship between sFRP1 and noncanonical Wnt/PCP-JNK (Wnt/planar cell polarity-c-Jun N-terminal kinase) pathway in Dox-induced cardiotoxicity in vitro and in vivo. We showed that treatment of H9c2 cardiac myoblasts with Dox (1 µM) time-dependently suppressed cell viability accompanied by significantly decreased sFRP1 protein level and increased Wnt/PCP-JNK signaling. Pretreatment with SP600125, the Wnt/PCP-JNK signaling inhibitor, attenuated Dox-induced apoptosis of H9c2 cells. Overexpression of sFRP1 protected H9c2 cells from Dox-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway. After intraperitoneal injection of a cumulative dose of 15 mg/kg Dox, rats displayed significant cardiac dysfunction; their heart showed inhibited Wnt/ß-catenin signaling and activated Wnt/PCP-JNK signaling. These results suggest that sFRP1 may be a novel target for Dox-induced cardiotoxicity.