Fish skin mucosal surface becomes a barrier of antibiotic resistance genes under apramycin exposure.

Antibiotic resistance genes (ARGs) are a kind of emerging environmental contamination, and are commonly found in antibiotic application situations, attracting wide attention. Fish skin mucosal surface (SMS), as the contact interface between fish and water, is the first line of defense against external pollutant invasion. Antibiotics are widely used in aquaculture, and SMS may be exposed to antibiotics. However, what happens to SMS when antibiotics are applied, and whether ARGs are enriched in SMS are not clear. In this study, Zebrafish (Danio rerio) were exposed to antibiotic and antibiotic resistant bacteria in the laboratory to simulate the aquaculture situation, and the effects of SMS on the spread of ARGs were explored. The results showed that SMS maintained the stability of the bacterial abundance and diversity under apramycin (APR) and bacterial exposure effectively. Until 11 days after stopping APR exposure, the abundance of ARGs in SMS (mean value was 3.32 × 10-3 copies/16S rRNA copies) still did not recover to the initial stage before exposure, which means that enriched ARGs in SMS were persistently remained. Moreover, non-specific immunity played an important role in resisting infection of external contamination. Besides, among antioxidant proteins, superoxide dismutase showed the highest activity. Consequently, it showed that SMS became a barrier of antibiotic resistance genes under APR exposure, and ARGs in SMS were difficult to remove once colonized. This study provided a reference for understanding the transmission, enrichment process, and ecological impact of antibiotics and ARGs in aquatic environments.

Exploring the dynamics of antibiotic resistome on plastic debris traveling from the river to the sea along a representative estuary based on field sequential transfer incubations.

The environmental risks arising from ubiquitous microplastics or plastic debris (PD) acting as carriers of antibiotic resistance genes (ARGs) have attracted widespread attention. Enormous amounts of plastic waste are transported by rivers and traverse estuaries into the sea every year. However, changes in the antibiotic resistome within the plastisphere (the biofilms formed on PD) as PD travels through estuaries are largely unknown. In this study, we performed sequential migration incubations for PD along Haihe Estuary to simulate the natural process of PD floating from rivers to the ocean. Metagenomic sequencing and analysis techniques were used to track microbial communities and antibiotic resistome on migrating PD and in seawater representing the marine environment. The total relative gene copies of ARGs on traveling PD remained stable. As migration between greatly varied waters, additional ARG subtypes were recruited to the plastisphere. Above 80 % ARG subtypes identified in the plastisphere were persistent throughout the migration, and over 30 % of these persistent ARGs were undetected in seawater. The bacterial hosts composition of ARGs on PD progressively altered as transported downstream. Human pathogenic bacteria carrying ARGs (HPBs-ARG) exhibited decreasing trends in abundance and species number during transfer. Individual HPBs-ARG persisted on transferred PD and were absent in seawater samples, comprising Enterobacter cloacae, Klebsiella pneumoniae, Mycobacterium tuberculosis, and Vibrio parahaemolyticus. Based on all detected ARGs and HPBs-ARG, the Projection Pursuit model was applied to synthetically evaluate the potential risks of antibiotic resistance on migrating PD. Diminished risks on PD were observed upon the river-to-sea journey but consistently remained significantly higher than in seawater. The potential risks posed to marine environments by drifting PD as dispersal vectors for antibiotic resistance deserve greater attention. Our results provide initial insights into the dynamics or stability of antibiotic resistome on PD crossing distinct aquatic systems in field estuaries.

Correction: Cyanobacterial extracellular antibacterial substances could promote the spread of antibiotic resistance: impacts and reasons.

Correction for 'Cyanobacterial extracellular antibacterial substances could promote the spread of antibiotic resistance: impacts and reasons' by Rui Xin et al., Environ. Sci.: Processes Impacts, 2023, 25, 2139-2147, https://doi.org/10.1039/D3EM00306J.

Exploring the potential of a new marine bacterium associated with plastisphere to metabolize dibutyl phthalate and bis(2-ethylhexyl) phthalate by enrichment cultures combined with multi-omics analysis.

Phthalic acid esters (PAEs) plasticizers are virulent endocrine disruptors that are mixed into plastics while fabricating and can filter out once they release into the surrounding environments. Plastic surfaces serve as new habitats for microorganisms, referred to as 'plastisphere'. Previous metagenomic investigations of the 'plastisphere' indicated that marine plastic surfaces may harbor microbes that degrade PAEs plasticizers. To our knowledge, the potential of microorganisms in the marine 'plastisphere' to metabolize PAEs is poorly understood. In this study, by screening the natural microbial community on plastic debris that had been deployed in situ for up to 20 months, a novel marine bacterium, Microbacterium esteraromaticum DEHP-1, was successfully isolated, which could degrade and mineralize 10-200 mg/L dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP). According to the results of gas chromatography-mass spectrometry (GC-MS) and whole genome mining of strain DEHP-1, we found that strain DEHP-1 may metabolize DBP by successive removal of the ester side chain by esterase 2518 to produce mono-butyl phthalate (MBP) and phthalic acid (PA), whereas the degradation of DEHP may take place by the direct action of monooxygenase 0132 on the fatty acid side chain of the DEHP molecule to produce di-n-hexyl phthalate (DnHP) and DBP, and then the subsequent hydrolysis of DBP by de-esterification to PA and finally into the tricarboxylic acid (TCA) cycle. Non-targeted metabolomics results showed that intracellular degradation of PAEs did not happen. However, exposure to PAEs was found to significantly affect pathways such as arginine and proline, riboflavin, glutathione and lysine degradation. Therefore, the intracellular metabolic behavior of strain DEHP-1 exposed to PAEs was proposed for the first time. This study sheds light on the metabolic capacity and strategies of bacteria in the marine 'plastisphere' to effectively degrade PAEs and highlights the importance of marine microbes in mitigating plastic poisonousness.

Role of traveling microplastics as bacterial carriers based on spatial and temporal dynamics of bacterial communities.

Microplastics (MPs) are considered as distinct substrates for bacterial colonization, they can carry bacterial communities to travel around environments. The bacterial communities on traveling MPs prefer to be gradually consistent with those on local MPs that were always in the same environment, and this process of change in the bacterial communities on traveling MPs was called 'localization'. However, the dynamics of localization process and their influencing factors are still unclear. Therefore, we simulated the MPs migration process along the water flow direction in the estuary. We used quantitative analysis to study the dynamics of bacterial communities on the migrated MPs. We found the localization characteristics depended on the differences between the former and latter environments, as well as the preexisting bacteria. The localization degree was higher when the former and latter environments were similar. In most cases, compared with the first cultivation of pristine MPs, the time for localization was shorter. Moreover, although the entire bacterial communities tended to be localized, the preexisting bacteria on the migrated MPs had selective effects on subsequent bacterial colonization. Furthermore, the preexisting bacteria on MPs could set up the connections with the bacteria that existed at the latter site, and the stability of the entire bacterial communities on the migrated MPs increased with time. Overall, our findings indicated that the localization characteristics of bacterial communities on traveling MPs were related to the precultured time and environmental differences, which were helpful to understand the colonized bacteria transportation and MPs ecological effects.

Fluoride exposure and prevalence of osteochondroma in drinking water Endemic fluorosis areas of Heilongjiang Province, China: a cross-sectional study.

To investigate the relationship between fluoride exposure and Osteochondroma (OC) prevalence, a cross-sectional study was conducted in drinking water endemic fluorosis areas of Heilongjiang Province, China. Our study first reported that the prevalence of OC was 2.3% in drinking water endemic fluorosis areas of Heilongjiang Province, China, and no difference in gender. Logistic regression analysis found that compared to 1st quartile participants, the prevalence of OC was 73% lower in the 2nd quartile participants of WF (Water fluoride), and 3.4 times higher among the 2nd quartile UF (Urinary fluoride) participants. Our study suggests that 0.259-0.420 mg/L of WF may be considered an appropriate level for reducing OC prevalence, while UF (≥0.750 mg/L) could slightly increase the prevalence of OC. In summary, the link between fluoride and OC prevalence is complicated and needs to be further investigated in a cohort population.

Cyanobacterial extracellular antibacterial substances could promote the spread of antibiotic resistance: impacts and reasons.

Many studies have shown that antibiotic resistance genes (ARGs) can be facilitated by a variety of antibacterial substances. Cyanobacteria are photosynthetic bacteria that are widely distributed in the ocean. Some extracellular substances produced by marine cyanobacteria have been found to possess antibacterial activity. However, the impact of these extracellular substances on ARGs is unclear. Therefore, we established groups of seawater microcosms that contained different concentrations (1000, 100, 10, 1, 0.1, 0.01, and 0 µg mL-1) of cyanobacterial extracellular substances (CES), and tracked the changes of 17 types of ARGs, the integron gene (intI1), as well as the bacterial community at different time points. The results showed that CES could enrich most ARGs (15/17) in the initial stage, particularly at low concentrations (10 and 100 µg mL-1). The correlation analysis showed a positive correlation between several ARGs and intI1. It is suggested that the abundance of intI1 increased with CES may contribute to the changes of these ARGs, and co-resistance of CES may be the underlying reason for the similar variation pattern of some ARGs. Moreover, the results of qPCR and high-throughput sequencing of 16S rRNA showed that CES had an inhibitory impact on the growth of bacterial communities. High concentrations of CES were found to alter the structure of bacterial communities. Co-occurrence networks showed that bacteria elevated in the high concentration group of CES and might serve as the potential hosts for a variety of ARGs. In general, marine cyanobacteria could play an important role in the global dissemination of ARGs and antibiotic-resistant bacteria (ARBs).

Biofilms retard the desorption of benzo(a)pyrene from polyethylene pellets in the marine environment.

Microplastics are emerging as vectors for the transport hydrophobic organic compounds (HOCs) in aquatic environments, however, their impact is poorly understood due to the lack of field studies. In this study, the pristine and benzo(a)pyrene (B[a]P) adsorbed polyethylene (PE) pellets were placed at Haihe Estuary (Tianjin, China) for 80 days to investigate desorption behavior. Combining laboratory and in situ experiments, this study firstly verified that the intra-particle diffusion was the rate-limiting step for the desorption process of B[a]P from PE microplastics under different environmental conditions. By hindering the desorption and modifying MPs surface, biofilm might play a key role in desorption process, leading to the apparent hysteresis of the field desorption process at our time scale. Potential degradation of the polymer and B[a]P by biofilms, however, would support continuing desorption. The study explored the interaction of biofilm and MPs-contaminants mixture and its implications for the environmental fate of HOCs.

A novel marine bacterium Exiguobacterium marinum a-1 isolated from in situ plastisphere for degradation of additive-free polypropylene.

As the ecological niche most closely associated with polymers, microorganisms in the 'plastisphere' have great potential for plastics degradation. Microorganisms isolated from the 'plastisphere' could colonize and degrade commercial plastics containing different additives, but the observed weight loss and surface changes were most likely caused by releasing the additives rather than actual degradation of the plastics itself. Unlike commercial plastics that contain additives, whether marine microorganisms in the 'plastisphere' have adapted to additive-free plastics as a surface to colonize and potentially degrade is not yet known. Herein, a novel marine bacterium, Exiguobacterium marinum a-1, was successfully isolated from mature 'plastisphere' that had been deployed in situ for up to 20 months. Strain a-1 could use additive-free polypropylene (PP) films as its primary energy and carbon source. After strain a-1 was incubated with additive-free PP films for 80 days, the weight of films decreased by 9.2%. The ability of strain a-1 to rapidly form biofilms and effectively colonize the surface of additive-free PP films was confirmed by Scanning Electron Microscopy (SEM), as reflected by the increase in roughness and visible craters on the surface of additive-free PP films. Additionally, the functional groups of -CO, -C-H, and -OH were identified on the treated additive-free PP films according to Fourier Transform Infrared (FTIR). Genomic data from strain a-1 revealed a suite of key genes involved in biosurfactant synthesis, flagellar assembly, and cellular chemotaxis, contributing to its rapid biofilm formation on hydrophobic polymer surfaces. In particular, key enzymes that may be responsible for the degradation of additive-free PP films, such as glutathione peroxidase, cytochrome p450 and esterase were also recognized. This study highlights the potential of microorganisms present in the 'plastisphere' to metabolize plastic polymers and points to the intrinsic importance of the new strain a-1 in the mitigation of plastic pollution.

Metagenomic insights into the potential risks of representative bio/non-degradable plastic and non-plastic debris in the upper and lower reaches of Haihe Estuary, China.

As vectors for microorganisms and genetic elements, vast amounts of solid wastes, including plastics and non-plastics, enter oceans through estuaries globally. The heterogeneity of microbiomes developed on different types of plastic and non-plastic matrices and their potential environmental risks in field estuarine regions have not been fully explored. Here, microbial communities, antibiotic resistance genes (ARGs), virulence factors (VFs), and mobile genetic elements (MGEs) on substrate debris (SD) covering non-biodegradable plastics, biodegradable plastics, and non-plastics were first comprehensively characterized based on metagenomic analyzes (substrate identity). These selected substrates were field-exposed at both ends of the Haihe Estuary, China (geographic location). For substrate identity: conspicuously diverse functional gene profiles on different substrates were obtained; the relative gene copies of ARGs, VFs, and MGEs on non-biodegradable plastics were highest at both locations; non-biodegradable plastic matrices recruited the most abundant unique ARGs from ambient waters; the relative abundance of potential bacterial hosts carrying multiple ARGs and VFs (BH-AV) was much higher on non-biodegradable plastic surfaces than on the other two substrates, especially in the coastal water environment. For geographic locations: more abundant specific ARGs, VFs, and MGEs were significantly enriched on SD from the upper estuary; the average relative abundance of identified BH-AV on SD from the upper estuary was 1.99-7.14 folds from the lower estuary. Finally, the results of the Projection Pursuit Regression model verified the higher comprehensive potential risks arising from non-biodegradable plastics (substrate identity) and SD from the upstream of the estuary (geographic location). Based on comparative analysis, our results alert us to pay particular attention to ecological risks triggered by conventional non-biodegradable plastics in rivers and coastal environments and highlight the microbiological risk from terrestrial solid waste to the downstream marine environment.

Effect of Fluoride on the Expression of 8-Hydroxy-2'-Deoxyguanosine in the Blood, Kidney, Liver, and Brain of Rats.

Excessive exposure of fluoride not only leads to damage on bone, but also has an adverse effect on soft tissues. Oxidative DNA damage induced by fluoride is thought to be one of the toxic mechanisms of fluoride effect. However, the dose-response of fluoride on oxidative DNA damage is barely studied in organisms. This study investigated the concentration of fluoride in rat blood, kidney, liver, and brain as well as the dose-time effect of fluoride on the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the above tissues. Rats were exposed to 0 mg/L, 25 mg/L, 50 mg/L, and 100 mg/L of fluorine ion and treated for one and three months. The results showed that the accumulation of fluoride in soft tissues was very different. At the first month, blood fluoride was increased, liver and brain fluoride showed a U-shaped change, and kidney fluoride was not significant. At the third month, blood fluoride was altered with an inverted U-shaped change, kidney and brain fluoride increased, but liver fluoride decreased. Both the exposure concentration and the time of exposure had a significant effect on the expression of 8-OHdG in the above tissues. However, the effect patterns of fluoride on these tissues were notably different at different times. At the first month of fluoride treatment, blood, kidney, and liver 8-OHdG decreased with the increasing fluoride concentration. At the third month, blood 8-OHdG showed a U-shaped change, but kidney 8-OHdG altered with an inverted U-shaped change. Liver 8-OHdG increased, while brain 8-OHdG decreased at the third month. Correlation analysis showed that only blood 8-OHdG was significantly inversely correlated with blood fluoride and dental fluorosis grade in both the first and third months. Liver 8-OHdG was negatively and significantly correlated with liver fluoride. There was a weak but nonsignificant correlation between kidney and brain 8-OHdG and fluoride in both tissues. Additionally, blood 8-OHdG was positively correlated with kidney and liver 8-OHdG at the first month and positively correlated with brain 8-OHdG at the third month. Taken together, our data suggests that concentration and time of fluoride exposure had a significant effect on 8-OHdG, but the effect patterns of fluoride on 8-OHdG were different in the tissues, which suggests that the impact of fluoride on 8-OHdG may be a tissue-specific, as well as a non-monotonic positive correlation.

Field based studies on aging characteristics of pristine and aged plastic debris in a coastal environment, Bohai Bay, China.

The coastal environment has become a sink of plastic due to the strong impact of plastic waste input from land. Plastics entering a coastal environment usually experience aging on land. However, few previous studies used aged plastics to study plastic aging in seawater, and the aging characteristics of aged plastics in a coastal environment are unclear. In our study, a ten-week investigation of the aging characteristics of pristine and pre-aged polypropylene plastic debris was conducted in Bohai Bay, China. During ten-week field exposure, more biofilms formed on the surfaces of pre-aged plastic debris than pristine plastic debris. However, no significant differences were found in the physicochemical properties (surface chemistry, hydrophobicity, and crystallinity) between pristine and pre-aged plastic debris. In addition, the results of redundancy analysis (RDA) illustrated that temperature was a key factor influencing the aging characteristics of plastic debris. Our research suggests that the aging history can affect the density of plastic debris by affecting the adhesion of the biofilm, which may influence the fate of plastic debris. In a coastal environment, plastic debris at different aging stages with the same initial chemical composition had basically similar changes in physicochemical properties in the short term.

Effect of Fluoride in Drinking Water on Fecal Microbial Community in Rats.

Intestinal nutrition has a close association with the onset and development of fluorosis. Intestinal microbes play a major role in intestinal nutrition. However, the effect of fluoride on intestinal microbes is still not fully understood. This study aimed to evaluate the dose-response of fluoride on fecal microbes as well as the link between fluorosis and fecal microbes. The results showed that fluoride did not significantly alter the diversity of fecal microbiota, but richness estimators (ACE and Chao) increased first, and then decreased with the increase of water fluoride. At the genus level, 150 mg/L fluoride significantly reduced the abundances of Roseburia and Clostridium sensu stricto, and 100 mg/L and 150 mg/L fluoride obviously increased the abundances of Unclassified Ruminococcaceaes and Unclassified Bdellovibrionales, respectively. The correlation analysis showed fluoride exposure had a negative association with Roseburia and Turicibacter and was positively associated with Pelagibacterium, Unclassified Ruminococcaceae, and Unclassified Bdellovibrionales. Dental fluorosis was negatively associated with Clostridium sensu stricto, Roseburia, Turicibacter, and Paenalcaligenes and had a positive association with Pelagibacterium, Unclassified Ruminococcaceae, and Unclassified Bdellovibrionales. In conclusion, this study firstly reports fluoride in drinking water has a remarkable biphasic effect on fecal microbiota in rats, and some bacteria are significantly associated with fluoride exposure and dental fluorosis. These results indicate the gut microbiota may play an important role in fluorosis, and some bacteria are likely to be developed as biomarkers for fluorosis.

Association Between Osteoarthritis and Water Fluoride Among Tongyu Residents, China, 2019: a Case-Control of Population-Based Study.

Fluoride is an environmental chemical that has adverse effects on articular cartilage, probably increasing osteoarthritis (OA) risk. However, this association still needs more epidemiological evidence to clarify. The aim of this study was to determine the relationships between chronic fluoride exposure and OA risk among the residents living in Tongyu County, China, 2019, with a frequency-matched case-control study (186 OA patients and 186 healthy participants). The results showed that urinary fluoride (UF) (2.73 ± 1.18 mg/L) was significantly higher in OA patients compared to the controls (2.35 ± 1.24 mg/L) (p < 0.002). After adjustment, the odds ratios (ORs) with 95% confidence intervals (95% CIs) between the OA risk and fluoride were calculated by the unconditional logistic regression. In full sample analysis, a 1 mg/L increase in UF level was associated with a 27% higher risk of OA (1.06-1.52, p = 0.008), and 4th quarter's participants were associated with higher risk when compared to 1st quarter (OR: 2.46, 95% CI: 1.34-4.57, p = 0.003). In stratified analysis, compared to 1st quarter, 4th quarter's participants were 4 times more likely to have OA (1.86-8.82, p < 0.001) in the non-obese group and 7.7 times more likely to have OA (2.58-25.05, p < 0.001) among adults ≤ 60 years. In conclusion, excessive exposure of water fluoride may increase OA risk, and could have more impact on the specific population such as non-obese, and adult aged ≤ 60 years.

Colonization characteristics of bacterial communities on plastic debris: The localization of immigrant bacterial communities.

The unique characteristics of bacterial communities on plastic debris and microplastics in the environment have been widely studied in recent years. However, due to the randomness of sampling, it is hard to identify whether the unique characteristics of bacterial communities on plastic debris is due to the plastics as substrate itself, or the accumulation and transportation by plastics. Therefore, the ecological effects of bacterial communities on plastic debris, including the species invasion, are still not clear. To investigate such issue, we took the Haihe Estuary (Tianjin, China) as an example, and designed a strategy to sample and redeploy randomly collected environmental plastic debris for 6 weeks, thus the variation of bacterial communities on plastic debris could be assessed. At the same time, commercial experimental plastic debris was used as the control group to monitor the growth of local bacterial communities on plastics in the cultivation environment. Our study discussed the bacterial communities on the environmental plastic debris from three aspects, including colonization characteristics, taxonomic analysis and molecular metabolism estimation. We found that the bacterial communities on environmental plastic debris tended to show local characteristics, which were less affected by their original characteristics. Therefore, the results reminded us that the ecological risks of bacterial communities on plastics, which were brought by the transportation of plastic debris in the environment, may not be as serious as it was expected previously.

Effect of fluoride in drinking water on the level of 5-methylcytosine in human and rat blood.

DNA methylation is an epigenetic modification of genome that is involved in many human diseases. Recent studies revealed DNA methylation may be associated with fluorosis. This study was aimed to evaluate the dose-response effect of fluoride on DNA methylation in human and rat blood. A commercial ELISA kit was employed to evaluate 5-methylcytosine (5-mC) level of genome in human and rat blood. A total of 281 subjects were enrolled in this study and divided into four equal-size groups by the quartile of fluoride in drinking water. The difference of 5-mC among the four groups was significant. The U-shaped relationship was found between fluoride and 5-mC in the population. The U-shaped curve was also observed in the rats with three months of fluoride treatments. Taken together, these results clue the disruption of DNA methylation in mammals may has a certain association with fluoride in natural exposures.

Effects of Fluoride on Oxidative Stress Markers of Lipid, Gene, and Protein in Rats.

Endemic fluorosis is a systemic chronic disease caused by excessive intake of fluoride. It is widely accepted that oxidative stress is closely related to fluorosis; however, molecular mechanism of oxidative stress in fluorosis remains unclear. This study investigated the effects of fluoride (F) on oxidative stress markers of lipid, gene, and protein in rats for revealing molecular mechanism of oxidative stress in fluorosis. The results showed concentration and exposure time of fluoride both had a significant effect on MDA and 8-OHdG. Fluoride concentration significantly impacted AGEs level, but exposure time did not. AOPP was not statistically different among the groups. AGEs decreased with the increase of fluoride in the rats with 3 months of fluoride treatment. The correlation analysis showed the degree of dental fluorosis was significantly negatively correlated with 8-OHdG at 1 month and 3 months, and negatively correlated with AGEs at 3 months. In the rats with 100 mg/L of fluoride treatment, MDA was significant positively correlated with 8-OHdG, and negatively correlated with AGEs. 8-OHdG was significantly negatively correlated with AGEs in the control group and 100 mg/L fluoride group. Taken together, fluoride had different effects on oxidative stress markers of lipid, gene, and protein. Excessive fluoride could increase MDA content, and decrease 8-OHdG and AGEs. These findings suggest that oxidative stress involved in molecular pathogenesis of fluorosis is complicated, and needs to furtherly study in the future.

NDRG2 regulates adherens junction integrity to restrict colitis and tumourigenesis.

BACKGROUND: Paracellular barriers play an important role in the pathogenesis of Inflammatory bowel disease (IBD) and maintain gut homeostasis. N-myc downstream-regulated gene 2 (NDRG2) has been reported to be a tumour suppressor gene and to inhibit colorectal cancer metastasis. However, whether NDRG2 affects colitis initiation and colitis-associated colorectal cancer is unclear. METHODS: Intestine-specific Ndrg2 deficiency mice (Ndrg2ΔIEC) were subjected to DSS- or TNBS-induced colitis, and AOM-DSS-induced colitis-associated tumour. HT29 cells, Caco2 cells, primary intestinal epithelial cells (IECs) from Ndrg2ΔIEC mice, mouse embryo fibroblasts (MEFs) from systemic Ndrg2 knockout mice, HEK293 cells and human UC and DC specimens were used to investigate NDRG2 function in colitis and colitis-associated tumour. FINDINGS: Ndrg2 loss led to adherens junction (AJ) structure destruction via E-cadherin expression attenuation, resulting in diminished epithelial barrier function and increased intestinal epithelial permeability. Mechanistically, NDRG2 enhanced the interaction of E3 ligase FBXO11 with Snail, the repressor of E-cadherin, to promote Snail degradation by ubiquitination and maintained E-cadherin expression. In human ulcerative colitis patients, reduced NDRG2 expression is positively correlated with severe inflammation. INTERPRETATION: These findings demonstrate that NDRG2 is an essential colonic epithelial barrier regulator and plays an important role in gut homeostasis maintenance and colitis-associated tumour development. FUNDING: National Natural Science Foundation of China (No. 81770523, 31571437, 81672751), Creative Research Groups of China (No. 81421003), State Key Laboratory of Cancer Biology Project (CBSKL2019ZZ11, CBSKL201406, CBSKL2017Z08 and CBSKL2017Z11), Fund for Distinguished Young Scholars of ShaanXi province (2019JC-22).

The dose-time effects of fluoride on the expression and DNA methylation level of the promoter region of BMP-2 and BMP-7 in rats.

Skeletal fluorosis is a chronic metabolic bone disease caused by excessive exposed to fluoride. Recent studies have shown that fluoride causes abnormal bone metabolism through disrupting the expression of Bone Morphogenetic Proteins (BMPs). However, the relationship between fluoride and BMPs is not fully understood, and the mechanism of fluoride on BMPs expression is still unclear. This study investigated the dose-time effects of fluoride on BMP-2 and BMP-7 levels and DNA methylation status of the promoter regions of these two genes in peripheral blood of rats. Eighty Wistar male rats were randomly divided into four groups and treated for 1 month and 3 months with distilled water (control), 25 mg/L, 50 mg/L or 100 mg/L of sodium fluoride (NaF). Rats exposed to fluoride had higher protein expression of BMP-2 and BMP-7 in plasma at 1 month and 3 months. An increase in BMP-2 expression was also observed with an increase of fluoride exposure time. Significant hypomethylation was observed in 2 CpG sites (CpGs) of BMP-2 and 1 CpG site of BMP-7 promoter regions in the fluoride treatment groups. It concludes that fluoride has a dose-response effect on BMP-2 in fluorosis rats, and fluoride-induced hypomethylation of specific CpGs may play an essential role in the regulation of BMP-2 and BMP-7 expression in rats.

Colonization characteristics of bacterial communities on microplastics compared with ambient environments (water and sediment) in Haihe Estuary.

The bacterial communities on microplastics in marine and freshwater environments have been described by many studies. However, the migration and transportation processes of bacterial communities on microplastics in estuarine areas remain unclear. In this study, the bacterial communities on three substrates (microplastics, surface water and sediment) in estuarine areas (the Haihe Estuary (HHE) in Bohai Bay, China) were investigated based on 16S rRNA sequencing. The mean OTUs of the three substrates - water, microplastics and sediments - were 1091, 2213 and 3419, respectively. The partitioning of the OTUs among the three substrates indicated that the microplastics could be messengers facilitating the bacterial transportation between water and sediment. According to nMDS and relative abundance analyses, it was found that the microplastics enriched the particular bacteria (e.g., Halobacteriaceae and Pseudoalteromonadaceae) and weakened the influence of environmental variation. In addition, taxonomic and metabolic-pathway analyses indicated that the abundance of potentially pathogenic bacteria (e.g., Pseudomonas and Bacillus) on microplastics was significantly higher than that in the ambient environment. Meanwhile, the microplastic polymer types had little effect on the abundance and structure of the bacterial communities. Compared with surface water and sediments, microplastics could be a good habitat for bacterial communities and could lead to potential ecological risks because of the high stability, pathogenicity and stress tolerance of the bacterial communities on microplastics.