Evaluating a river's ecological health: A multidimensional approach.

Evaluating the health of river surface water is essential, as rivers support significant biological resources and serve as vital drinking water sources. While the Water Quality Index (WQI) is commonly employed to evaluate surface water quality, it fails to consider biodiversity and does not fully capture the ecological health of rivers. Here we show a comprehensive assessment of the ecological health of surface water in the lower Yangtze River (LYR), integrating chemical and biological metrics. According to traditional WQI metrics, the LYR's surface water generally meets China's Class II standards. However, it also contains 43 high-risk emerging contaminants; nitrobenzenes are found at the highest concentrations, representing 25-90% of total detections, while polycyclic aromatic hydrocarbons present the most substantial environmental risks, accounting for 81-93% of the total risk quotient. Notably, the plankton-based index of biological integrity (P-IBI) rates the ecological health of the majority of LYR water samples (59.7%) as 'fair', with significantly better health observed in autumn compared to other seasons (p < 0.01). Our findings suggest that including emerging contaminants and P-IBI as additional metrics can enhance the traditional WQI analysis in evaluating surface water's ecological health. These results highlight the need for a multidimensional assessment approach and call for improvements to LYR's ecological health, focusing on emerging contaminants and biodiversity rather than solely on reducing conventional indicators.

Effects of sulfamonomethoxine and trimethoprim co-exposures at different environmentally relevant concentrations on microalgal growth and nutrient assimilation.

In aquaculture around the world, sulfamonomethoxine (SMM), a long-acting antibiotic that harms microalgae, is widely employed in combination with trimethoprim (TMP), a synergist. However, their combined toxicity to microalgae under long-term exposures at environmentally relevant concentrations remains poorly understood. Therefore, we studied the effects of SMM single-exposures and co-exposures (SMM:TMP=5:1) at concentrations of 5 µg/L and 500 µg/L on Chlorella pyrenoidosa within one aquacultural drainage cycle (15 days). Photosynthetic activity and N assimilating enzyme activities were employed to evaluate microalgal nutrient assimilation. Oxidative stress and flow cytometry analysis for microalgal proliferation and death jointly revealed mechanisms of inhibition and subsequent self-adaptation. Results showed that exposures at 5 µg/L significantly inhibited microalgal nutrient assimilation and induced oxidative stress on day 7, with a recovery to levels comparable to the control by day 15. This self-adaptation and over 95 % removal of antibiotics jointly contributed to promoting microalgal growth and proliferation while reducing membrane-damaged cells. Under 500 µg/L SMM single-exposure, microalgae self-adapted to interferences on nutrient assimilation, maintaining unaffected growth and proliferation. However, over 60 % of SMM remained, leading to sustained oxidative stress and apoptosis. Remarkably, under 500 µg/L SMM-TMP co-exposure, the synergistic toxicity of SMM and TMP significantly impaired microalgal nutrient assimilation, reducing the degradation efficiency of SMM to about 20 %. Consequently, microalgal growth and proliferation were markedly inhibited, with rates of 9.15 % and 17.7 %, respectively, and a 1.36-fold increase in the proportion of cells with damaged membranes was observed. Sustained and severe oxidative stress was identified as the primary cause of these adverse effects. These findings shed light on the potential impacts of antibiotic mixtures at environmental concentrations on microalgae, facilitating responsible evaluation of the ecological risks of antibiotics in aquaculture ponds.

Microalgae enhanced co-metabolism of sulfamethoxazole using aquacultural feedstuff components: Co-metabolic pathways and enzymatic mechanisms.

The application of antibiotics in freshwater aquaculture leads to increased contamination of aquatic environments. However, limited information is available on the co-metabolic biodegradation of antibiotics by microalgae in aquaculture. Feedstuffs provide multiple organic substrates for microalgae-mediated co-metabolism. Herein, we investigated the co-metabolism of sulfamethoxazole (SMX) by Chlorella pyrenoidosa when adding main components of feedstuff (glucose and lysine). Results showed that lysine had an approximately 1.5-fold stronger enhancement on microalgae-mediated co-metabolism of SMX than glucose, with the highest removal rate (68.77% ± 0.50%) observed in the 9-mM-Lys co-metabolic system. Furthermore, we incorporated reactive sites predicted by density functional theory calculations, 14 co-metabolites identified by mass spectrometry, and the roles of 18 significantly activated enzymes to reveal the catalytic reaction mechanisms underlying the microalgae-mediated co-metabolism of SMX. In lysine- and glucose-treated groups, five similar co-metabolic pathways were proposed, including bond breaking on the nucleophilic sulfur atom, ring cleavage and hydroxylation at multiple free radical reaction sites, together with acylation and glutamyl conjugation on electrophilic nitrogen atoms. Cytochrome P450, serine hydrolase, and peroxidase play crucial roles in catalyzing hydroxylation, bond breaking, and ring cleavage of SMX. These findings provide theoretical support for better utilization of microalgae-driven co-metabolism to reduce sulfonamide antibiotic residues in aquaculture.

Mutation breeding of high-stress resistant strains for succinic acid production from corn straw.

The production of succinic acid from corn stover is a promising and sustainable route; however, during the pretreatment stage, byproducts such as organic acids, furan-based compounds, and phenolic compounds generated from corn stover inhibit the microbial fermentation process. Selecting strains that are resistant to stress and utilizing nondetoxified corn stover hydrolysate as a feedstock for succinic acid production could be effective. In this study, A. succinogenes CICC11014 was selected as the original strain, and the stress-resistant strain A. succinogenes M4 was obtained by atmospheric and room temperature plasma (ARTP) mutagenesis and further screening. Compared to the original strain, A. succinogenes M4 exhibited a twofold increase in stress resistance and a 113% increase in succinic acid production when hydrolysate was used as the substrate. By conducting whole-genome resequencing of A. succinogenes M4 and comparing it with the original strain, four nonsynonymous gene mutations and two upstream regions with base losses were identified. KEY POINTS: • A high-stress-resistant strain A. succinogenes M4 was obtained by ARTP mutation •  The production of succinic acid increased by 113% • The mutated genes of A. succinogenes M4 were detected and analyzed.

Gastrointestinal Degradation and Toxicity of Disinfection Byproducts in Drinking Water Using In Vitro Models and the Roles of Gut Microbiota.

Disinfection byproducts (DBPs) in drinking water are mainly exposed to the human body after oral ingestion and degradation in the gastrointestinal tract. The role of gastrointestinal degradation in the toxic effects of DBPs still needs further investigation. In this study, the degradation of five categories of DBPs (22 DBPs) in the stomach and small intestine was investigated based on a semicontinuous steady-state gastrointestinal simulation system, and 22 DBPs can be divided into three groups based on their residual proportions. The degradation of chloroacetonitrile (CAN), dibromoacetic acid (DBAA), and tetrabromopyrrole (FBPy) was further analyzed based on the Simulator of the Human Intestinal Microbial Ecosystem inoculating the gut microbiota, and approximately 60% of CAN, 45% of DBAA, and 80% of FBPy were degraded in the stomach and small intestine, followed by the complete degradation of remaining DBPs in the colon. Meanwhile, gastrointestinal degradation can reduce oxidative stress-mediated DNA damage and apoptosis induced by DBPs in DLD-1 cells, but the toxicity of DBPs did not disappear with the complete degradation of DBPs, possibly because of their interferences on gut microbiota. This study provides new insights into investigating the gastrointestinal toxic effects and mechanisms of DBPs through oral exposure.

Correlations among Antibiotic Resistance Genes, Mobile Genetic Elements and Microbial Communities in Municipal Sewage Treatment Plants Revealed by High-Throughput Sequencing.

Municipal sewage treatment plants (MSTPs) are environmental pools for antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs), which is cause for growing environmental-health concerns. In this study, the effects of different wastewater treatment processes on microbial antibiotic resistance in four MSTPs were investigated. PCR, q-PCR, and molecular cloning integrally indicated that the tetracycline resistance (tet) genes significantly reduced after activated-sludge treatment. Illumina high-throughput sequencing revealed that the broad-spectrum profile of ARGs and mobile element genes (MGEs) were also greatly decreased by one order of magnitude via activated sludge treatment and were closely associated with each other. Correlations between ARGs and bacterial communities showed that potential ARB, such as Acinetobacter, Bacteroides, and Cloaibacterium, were removed by the activated-sludge process. Sedimentation processes cannot significantly affect the bacterial structure, resulting in the relative abundance of ARGs, MGEs, and ARB in second-clarifier effluent water being similar to activated sludge. A comprehensive study of ARGs associated with MGEs and bacterial structure might be technologically guided for activated sludge design and operation in the MSTPs, to purposefully control ARGs carried by pathogenic hosts and mobility.

Salt tolerance evolution facilitates antibiotic resistome in soil microbiota: Evidences from dissemination evaluation, hosts identification and co-occurrence exploration.

Salinity is considered as one of the vital factors affecting the profiles of antibiotic resistance genes (ARGs) in soils, whereby its roles in shaping the antibiotic resistome were still poorly understood. Here, metagenomic analysis was conducted to track the ARGs distributions and dissemination in soils during salt accumulation and desalinization processes. Neutral-salt accumulation for 45 and 90 days significantly increased the relative abundances of ARGs and mobile genetic elements (MGEs) carrying antibiotic resistance contigs (ARCs). The ARGs within antibiotic efflux and target protection families primarily carried by Streptomyces, Nocardioides, Rhodanobacter and Monashia were largely enriched by salinity. The ARGs subtypes of the resistance-nodulation-division (RND) family, ATP-binding cassette (ABC) family, rRNA methyltransferase and other efflux were closely associated with MGEs, contributing to the enrichment of ARGs. Moreover, the ARGs subtypes and transposons were genetically linked with the salt-tolerance mechanisms of organic osmolyte transporters and K+ uptake proteins on the same ARC, demonstrating the coselection of ARGs and halotolerant genes. Furthermore, the antibiotic resistome could recover to a normal state after the prolonged incubation by alleviating salt stress. Nevertheless, the acquisition of ARGs by opportunistic pathogens after salt treatment was increased, serving to prioritize further efforts on the health risks correlated with resistance propagation and human exposure in saline soils.

Structural and functional alterations of intestinal flora in mice induced by halonitromethanes exposure.

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

CENPL, ISG20L2, LSM4, MRPL3 are four novel hub genes and may serve as diagnostic and prognostic markers in breast cancer.

As a highly prevalent disease among women worldwide, breast cancer remains in urgent need of further elucidation its molecular mechanisms to improve the patient outcomes. Identifying hub genes involved in the pathogenesis and progression of breast cancer can potentially help to unveil mechanism and also provide novel diagnostic and prognostic markers. In this study, we integrated multiple bioinformatic methods and RNA in situ detection technology to identify and validate hub genes. EZH2 was recognized as a key gene by PPI network analysis. CENPL, ISG20L2, LSM4, MRPL3 were identified as four novel hub genes through the WGCNA analysis and literate search. Among these, many studies on EZH2 in breast cancer have been reported, but no studies are related to the roles of CENPL, ISG20L2, MRPL3 and LSM4 in breast cancer. These four novel hub genes were up-regulated in tumor tissues and associated with cancer progression. The receiver operating characteristic analysis and Kaplan-Meier survival analysis indicated that these four hub genes are promising candidate genes that can serve as diagnostic and prognostic biomarkers for breast cancer. Moreover, these four newly identified hub genes as aberrant molecules in the maintenance of breast cancer development, their exact functional mechanisms deserve further in-depth study.

Prognostic Significance of Autophagy-Relevant Gene Markers in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a common malignant solid tumor with an extremely low survival rate after relapse. Previous investigations have shown that autophagy possesses a crucial function in tumors. However, there is no consensus on the value of autophagy-associated genes in predicting the prognosis of CRC patients. This work screens autophagy-related markers and signaling pathways that may participate in the development of CRC, and establishes a prognostic model of CRC based on autophagy-associated genes. METHODS: Gene transcripts from the TCGA database and autophagy-associated gene data from the GeneCards database were used to obtain expression levels of autophagy-associated genes, followed by Wilcox tests to screen for autophagy-related differentially expressed genes. Then, 11 key autophagy-associated genes were identified through univariate and multivariate Cox proportional hazard regression analysis and used to establish prognostic models. Additionally, immunohistochemical and CRC cell line data were used to evaluate the results of our three autophagy-associated genes EPHB2, NOL3, and SNAI1 in TCGA. Based on the multivariate Cox analysis, risk scores were calculated and used to classify samples into high-risk and low-risk groups. Kaplan-Meier survival analysis, risk profiling, and independent prognosis analysis were carried out. Receiver operating characteristic analysis was performed to estimate the specificity and sensitivity of the prognostic model. Finally, GSEA, GO, and KEGG analysis were performed to identify the relevant signaling pathways. RESULTS: A total of 301 autophagy-related genes were differentially expressed in CRC. The areas under the 1-year, 3-year, and 5-year receiver operating characteristic curves of the autophagy-based prognostic model for CRC were 0.764, 0.751, and 0.729, respectively. GSEA analysis of the model showed significant enrichment in several tumor-relevant pathways and cellular protective biological processes. The expression of EPHB2, IL-13, MAP2, RPN2, and TRAF5 was correlated with microsatellite instability (MSI), while the expression of IL-13, RPN2, and TRAF5 was related to tumor mutation burden (TMB). GO analysis showed that the 11 target autophagy genes were chiefly enriched in mRNA processing, RNA splicing, and regulation of the mRNA metabolic process. KEGG analysis showed enrichment mainly in spliceosomes. We constructed a prognostic risk assessment model based on 11 autophagy-related genes in CRC. CONCLUSION: A prognostic risk assessment model based on 11 autophagy-associated genes was constructed in CRC. The new model suggests directions and ideas for evaluating prognosis and provides guidance to choose better treatment strategies for CRC.

Recovery of gut microbiota in mice exposed to tetracycline hydrochloride and their correlation with host metabolism.

Antibiotics can disturb the gut microbial community and host metabolism. However, their recovery after antibiotics exposure needs to be characterized, and the correlation between gut microbiota and host metabolism remains unclear. In this study, mice were exposed to 0.5, 1.5 and 10 g/L tetracycline hydrochloride (TET) for 2 weeks, then recovered without TET for another 2 weeks. The results showed that 2-week TET exposure changed microbial community and functions in the mouse gut, and increased abundance of antibiotic resistance genes (ARGs), especially in the 10 g/L TET group. After a 2-week recovery, these changes could only be recovered to the control level in the 0.5 g/L TET exposure group, except for ARGs. Besides gut microbiota, TET exposure also changed metabolic profiles in mouse urine. The 2-week recovery significantly reduced changes in metabolic profiles. Some altered metabolites were found to have a very high correlation with gut microbial community and functions, indicating that TET exposure might induce certain changes in urinary metabolic profiles by altering the gut microbiota. The results from this study suggest that the influences of low-level TET exposure are reversible, except for ARGs, which should be paid more attention. During the application of TET, their dosage should be effectively considered and controlled.

Effect of salinity on mature wastewater treatment biofilm microbial community assembly and metabolite characteristics.

The response mechanism of wastewater treatment biofilms to salt stress has not yet been fully established. The aim of this study was to reveal the comprehensive biological effects of salinity on biofilm microbial community and metabonomic characteristics. The study assessed performance at a range of sodium chloride (NaCl) concentrations of 0.6, 14 and 20 g/L. Biofilm coverage rate decreased significantly with increasing NaCl concentrations. High NaCl concentrations resulted in more compact and smoother biofilm morphologies. NaCl concentrations affected bacterial community variation at the class and genus level, with Gammaproteobacteria being the most dominant Proteobacteria, exhibiting NaCl tolerance at concentrations ranging from 0 to 20 g/L. Also, NaCl sensitive or tolerant species were identified, such as Pseudomonas and Planococcus, respectively. Dominant metabolites in wastewater treatment biofilms belonging to nucleotide, lipid, vitamin, amino acid and carbohydrate metabolism pathways decreased with increasing NaCl concentrations. High concentrations of NaCl regulated cell motility, transcription and membrane transport functions. In particular, the activity of ABC transporters were up-regulated at NaCl concentrations of 0.6 g/L and down-regulated at higher salinity concentrations. In addition, transcription machinery were inhibited under the stress of 14 g/L NaCl. These findings further our understanding of the short-term adaption mechanisms of wastewater treatment biofilms to high NaCl concentration environments.

Formation of iodinated trihalomethanes and haloacetic acids from aromatic iodinated disinfection byproducts during chloramination.

Iodinated disinfection byproducts (DBPs) are widely present in disinfected drinking waters and wastewater effluents, and they have drawn increasing concern owing to their high toxicity. To date, the reported iodinated DBPs mainly include aliphatic and aromatic ones, and iodinated trihalomethanes (THMs) and haloacetic acids (HAAs) are the most commonly detected aliphatic iodinated DBPs in disinfected waters. In this study, the formation of iodinated THMs and HAAs from aromatic iodinated DBPs during chloramination was investigated. The decomposition kinetics of the aromatic iodinated DBPs and the formation of iodinated THMs and HAAs were studied, the formation pathways of iodinated THMs and HAAs from the aromatic iodinated DBPs were explored, the factors affecting the formation were examined, and the toxicity change was evaluated. The results revealed that four aromatic iodinated DBPs (2,4,6-triiodophenol, 3,5-diiodo-4-hydroxybenzaldehyde, 3,5-diiodosalicylic acid, and 2,6-diiodo-4-nitrophenol) all underwent transformation to form triiodomethane (TIM), monoiodoacetic acid (MIAA), and diiodoacetic acid (DIAA) during chloramination. The decomposition of the aromatic iodinated DBPs all followed a pseudo-first-order decay during chloramination, and the rank order of the decomposition rate constants was as follows: 2,4,6-triiodophenol > 3,5-diiodo-4-hydroxybenzaldehyde ≥ 3,5-diiodosalicylic acid > 2,6-diiodo-4-nitrophenol. Several polar iodinated intermediates were detected and identified (e.g., 2,6-diiodo-1,4-benzoquinone and iodobutenedioic acid) during chloramination of 2,4,6-triiodophenol, based on which the formation pathways of TIM, MIAA, and DIAA from 2,4,6-triiodophenol during chloramination were proposed and further validated. The results also revealed that monochloramine dose, pH, temperature, and short free chlorine contact time all affected the formation of TIM, MIAA, and DIAA from 2,4,6-triiodophenol during chloramination. The cytotoxicity order of the eight iodinated DBPs was MIAA > 2,6-diiodo-4-nitrophenol > 2,4,6-triiodophenol > 2,6-diiodo-1,4-benzoquinone > DIAA ≥ 3,5-diiodosalicylic acid >3,5-diiodo-4-hydroxybenzaldehyde > TIM. The toxicity of the chloraminated 2,4,6-triiiodophenol sample first decreased and then increased over time due to the transformation.

Rapid and complete dehalogenation of halonitromethanes in simulated gastrointestinal tract and its influence on toxicity.

Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection byproducts in drinking water and wastewater are receiving attentions due to their high toxicity. This study applied a simulator of the human gastrointestinal tract to determine the dehalogenation processes of trichloronitromethane, bromonitromethane and bromochloronitromethane for the first time. Influence of digestion process of HNMs on gut microbiota and hepatotoxicity was further analyzed. Results showed that the three HNMs were rapidly and completely dehalogenated in the gastrointestinal tract, especially in the stomach (2 h retention Time) and small intestine (4 h retention Time). Mucin, cysteine, pancreatin and bile salts in the digestive juice played major roles in the dehalogenation process. HNMs and their dehalogenation products in the resulting fluids of stomach induced the highest toxicity followed by those in intestine and colon, exhibiting dose-dependent effects. Although most HNMs were degraded in the stomach and small intestine, residual HNMs entered into colon changed the microbial community. Abundance of several genera, such as Bacteroides, Lachnospiraceae_unassigned and Lactobacillus had high correlation with exposure concentration of HNMs. This study sheds new light on dehalogenation and toxic processes of HNMs by oral exposure, which provides basic data for their human health risk assessment.

Foxp3 is correlated with VEGF-C expression and lymphangiogenesis in cervical cancer.

BACKGROUND: Recent observations revealed Foxp3 participated in the development of cervical cancer. Furthermore, Foxp3 has a vital function in the lymphatic metastasis of cervical cancer. However, it is unclear whether Foxp3 is correlated with lymphangiogenesis of cervical cancer. METHODS: In this experiment, expression of Foxp3 and VEGF-C was detected in 50 cervical cancer samples by immunohistochemistry. In addition, we evaluated the association between Foxp3 and VEGF-C expression and lymphangiogenesis of cervical cancer evaluated by lymphatic vessel density. RESULTS: These data demonstrate Foxp3 is positively correlated with VEGF-C expression. Furthermore, Foxp3 is associated with lymphangiogenesis of cervical cancer. CONCLUSIONS: These results revealed Foxp3 play an important role in lymphangiogenesis of cervical cancer. TRIAL REGISTRATION: Gunagdong Medical University, PJ2013049.

Transformation among Aromatic Iodinated Disinfection Byproducts in the Presence of Monochloramine: From Monoiodophenol to Triiodophenol and Diiodonitrophenol.

Aromatic iodinated disinfection byproducts (DBPs) are a newly identified category of highly toxic DBPs. Among the identified aromatic iodinated DBPs, 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol have shown relatively widespread occurrence and high toxicity. In this study, we found that 4-iodophenol underwent transformation to form 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol in the presence of monochloramine. The transformation pathways were investigated, the decomposition kinetics of 4-iodophenol and the formation of 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol were studied, the factors affecting the transformation were examined, the toxicity change during the transformation was evaluated, and the occurrence of the proposed transformation pathways during chloramination of source water was verified. The results revealed that 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol, which could account for 71.0% of iodine in the transformed 4-iodophenol, were important iodinated transformation products of 4-iodophenol in the presence of monochloramine. The transformation pathways of 4-iodophenol in the presence of monochloramine were proposed and verified. The decomposition of 4-iodophenol in the presence of monochloramine followed a pseudo-second-order decay. Various factors including monochloramine dose, pH, temperature, nitrite concentration, and free chlorine contact time (before chloramination) affected the transformation. The cytotoxicity of the chloraminated 4-iodophenol samples increased continuously with contact time. The proposed transformation pathways occurred during chloramination of source water.

Comparative toxicity of chloro- and bromo-nitromethanes in mice based on a metabolomic method.

Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection byproducts have been widely found in drinking water. In vitro test found HNMs could induce higher cytotoxicity and genotoxicity than trihalomethanes and haloacetic acids. However, data on toxic effect from in vivo experiment is limited. In this study, bromonitromethane (BNM), bromochloronitromethane (BCNM) and trichloronitromethane (TCNM) were chosen as target HNMs, and exposed to mice for 30 d. Hepatic toxicity and serum metabolic profiles were determined to reveal toxic effects and mechanisms of the three HNMs. Results showed the three HNMs significantly decreased relative liver weight, indicating liver is one of the target organs. Further, the three HNMs exposure damaged hepatic antioxidant defense system, and increased oxidative DNA damage. Nuclear magnetic resonance based metabolomics analysis found amino acid metabolism and carbohydrate metabolism were disturbed by HNMs exposure. Some metabolites in these metabolisms are related to oxidative stress and damage. Combined with above results, BNM had the highest toxicity, followed by BCNM and TCNM, indicating bromo-HNMs had higher toxicity than chloro-HNMs. Induction of oxidative stress is one of the toxicity mechanisms of HNMs. This study firstly provides the insight into in vivo toxicity of HNMs and their underlying mechanisms based on metabolomics methods, which is very useful for their health risk assessment in drinking water.

Differential toxicity of arsenic on renal oxidative damage and urinary metabolic profiles in normal and diabetic mice.

Diabetes is a common metabolic disease, which might influence susceptibility of the kidney to arsenic toxicity. However, relative report is limited. In this study, we compared the influence of inorganic arsenic (iAs) on renal oxidative damage and urinary metabolic profiles of normal and diabetic mice. Results showed that iAs exposure increased renal lipid peroxidation in diabetic mice and oxidative DNA damage in normal mice, meaning different effects of iAs exposure on normal and diabetic individuals. Nuclear magnetic resonance (NMR)-based metabolome analyses found that diabetes significantly changed urinary metabolic profiles of mice. Oxidative stress-related metabolites, such as arginine, glutamine, methionine, and ß-hydroxybutyrate, were found to be changed in diabetic mice. The iAs exposure altered amino acid metabolism, lipid metabolism, carbohydrate metabolism, and energy metabolism in normal and diabetic mice, but had higher influence on metabolic profiles of diabetic mice than normal mice, especially for oxidative stress-related metabolites and metabolisms. Above results indicate that diabetes increased susceptibility to iAs exposure. This study provides basic information on differential toxicity of iAs on renal toxicity and urinary metabolic profiles in normal and diabetic mice and suggests that diabetic individuals should be considered as susceptible population in toxicity assessment of arsenic.

Comprehensive insights into microcystin-LR effects on hepatic lipid metabolism using cross-omics technologies.

Microcystin-LR (MC-LR) can induce hepatic tissue damages and molecular toxicities, but its effects on lipid metabolism remain unknown. This study investigated the effects of MC-LR exposure on mice lipid metabolism and uncovered the underlying mechanism through metabonomic, transcriptomic and metagenomic analyses after administration of mice with MC-LR by gavage for 28 d. Increased liver weight and abdominal fat weight, and evident hepatic lipid vacuoles accumulation were observed in the mice fed with 0.2mg/kg/d MC-LR. Serum nuclear magnetic resonance analysis showed that MC-LR treatment altered the levels of serum metabolites including triglyceride, unsaturated fatty acid (UFA) and very low density lipoprotein. Digital Gene Expression technology was used to reveal differential expression of hepatic transcriptomes, demonstrating that MC-LR treatment disturbed hepatic UFA biosynthesis and activated peroxisome proliferator-activated receptor (PPAR) signaling pathways via Pparγ, Fabp1 and Fabp2 over-expression. Metagenomic analyses of gut microbiota revealed that MC-LR exposure also increased abundant ratio of Firmicutes vs. Bacteroidetes in gut and altered biosynthetic pathways of various microbial metabolic and pro-inflammatory molecules. In conclusion, oral MC-LR exposure can induce hepatic lipid metabolism disorder mediated by UFA biosynthesis and PPAR activation, and gut microbial community shift may play an important role in the metabolic disturbance.

Influences of graphene on microbial community and antibiotic resistance genes in mouse gut as determined by high-throughput sequencing.

Graphene is a promising candidate as an antibacterial material owning to its bacterial toxicity. However, little information on influence of graphene on gut microbiota is available. In this study, mice were exposed to graphene for 4 weeks, and high-throughput sequencing was applied to characterize the changes in microbial community and antibiotic resistance genes (ARGs) in mouse gut. The results showed that graphene exposure increased biodiversity of gut microbiota, and changed their community. The 1 µg/d graphene exposure had higher influences on the gut microbiota than 10 µg/d and 100 µg/d graphene exposures, which might be due to higher aggregation of high-level graphene. The influence of graphene on gut microbiota might attribute to that graphene could induce oxidative stress and damage of cell membrane integrity. The results were verified by the increase of ratio of Gram-negative bacteria. Outer membrane of Gram-negative bacteria could reduce the membrane damage induced by graphene and make them more tolerance to graphene. Further, we found that graphene exposure significantly increased the abundance and types of ARGs, indicating a potential health risk of graphene. This study firstly provides new insight to the health effects of graphene on gut microbiota.