Triclosan facilitates the dissemination of antibiotic resistance genes during anaerobic digestion: Focusing on horizontal transfer and microbial response.

The present study aims to investigate the mechanism by which triclosan influences the dissemination of antibiotic resistance genes (ARGs) during the whole anaerobic digestion process. qPCR and metagenomic analyses revealed that triclosan facilitated ARGs dissemination in a dose- and time-dependent manner. Furthermore, integrons exhibited a significant correlation with the majority of quantified ARGs, and various ARGs were frequently linked on integron gene cassettes. Microbial community and redundancy analyses indicated that triclosan altered the components of dominant ARGs hosts Firmicutes, Synergistetes and Bacteroidetes. Path modeling analysis confirmed integrons was the main driving force for facilitating ARGs dissemination. The promoted ARGs dissemination may be associated with the increased reactive oxygen species generation, cell membrane permeability, close-connected the ARGs transfer related regulatory proteins induced by triclosan. This study broadens the understanding of triclosan facilitates ARGs dissemination through anaerobic treatment, the strategies for preventing potential risks should be proposed in practice.

Corynoline alleviates hepatic ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation through enhancing Nrf2/HO-1 signaling.

OBJECTIVE: Corynoline has displayed pharmacological effects in reducing oxidative stress and inflammatory responses in many disorders. However, its effects on hepatic ischemia-reperfusion (I/R) injury remain unclear. This study aimed to investigate the protective effects of corynoline against hepatic I/R injury and the underlying mechanisms. METHODS: Rat models with hepatic I/R injury and BRL-3A cell models with hypoxia/reoxygenation (H/R) insult were constructed. Models were pretreated with corynoline and/or other inhibitors for functional and mechanistic examination. RESULTS: Corynoline pretreatment effectively mitigated hepatic I/R injury verified by reduced serum transaminase levels, improved histological damage scores, and decreased apoptosis rates. Additionally, corynoline pretreatment significantly inhibited I/R-triggered oxidative stress and inflammatory responses, as indicated by enhanced mitochondrial function, reduced levels of ROS and MDA, reduced neutrophil infiltration and suppressed proinflammatory cytokine release. In vitro experiments further showed that corynoline pretreatment increased cellular viability, decreased LDH activity, reduced cellular apoptosis, and inhibited oxidative stress and inflammatory injury in H/R-induced BRL-3A cells. Mechanistically, corynoline significantly increased Nrf2 nuclear translocation and expression levels of its target gene, HO-1. It also blocked NLRP3 inflammasome activation both in vivo and in vitro. Furthermore, pretreatment with Nrf2 inhibitor ML-385 counteracted the protective effect of corynoline on hepatic I/R injury. Ultimately, in vitro studies revealed that the NLRP3 activator nigericin could also nullified the protective effects of corynoline in BRL-3A cells, but had minimal impact on Nrf2 nuclear translocation. CONCLUSIONS: Corynoline can exert protective effects against hepatic I/R injury by inhibiting oxidative stress, inflammatory responses, and apoptosis. These effects may be associated with inhibiting ROS-induced NLRP3 inflammasome activation by enhancing Nrf2/HO-1 signaling. These data provide new understanding about the mechanism of corynoline action, suggesting it is a potential drug applied for the treatment and prevention of hepatic I/R injury.

Plasticizers inhibit food waste anaerobic digestion performance by affecting microbial succession and metabolism.

The widely existed plastic additives plasticizers in organic wastes possibly pose negative influences on anaerobic digestion (AD) performance, the direct evidence about the effects of plasticizers on AD performance is still lacking. This study evaluated the influencing mechanism of two typical plasticizers bisphenol A (BPA) and dioctyl phthalate on the whole AD process. Results indicated that plasticizers addition inhibited methane production, and the inhibiting effects were reinforced with the increase of concentration. By contrast, 50 mg/L BPA exhibited the strongest inhibition on methane production. Physicochemical analysis showed plasticizers inhibited the metabolism efficiency of soluble polysaccharide and volatile fatty acids. Microbial communities analyses suggested that plasticizers inhibited the direct interspecies electron transfer participators of methanogenic archaea (especially Methanosarcina) and syntrophic bacteria. Furthermore, plasticizers inhibited the methane metabolisms, key coenzymes (CoB, CoM, CoF420 and methanofuran) biosynthesis and the metabolisms of major organic matters. This study shed light on the effects of plasticizers on AD performance and provided new insights for assessing the influences of plasticizers or plastic additives on the disposal of organic wastes.

Mitigated dissemination of antibiotic resistance genes by nanoscale zero-valent iron and iron oxides during anaerobic digestion: Roles of microbial succession and regulation.

Nanoscale zero-valent iron (ZVI) and the oxides have been documented as an effective approach for mitigating the dissemination of antibiotic resistance genes (ARGs) during anaerobic digestion (AD). However, the mechanism of ARGs dissemination mitigated by nanoscale ZVI and iron oxides remain unclear. Here, we investigated the influencing mechanisms of nanoscale ZVI and iron oxides on ARGs dissemination during AD. qPCR results indicated that nanoscale ZVI and iron oxides significantly declined the total ARGs abundances, and the strongest inhibiting effect was observed by 10 g/L nanoscale ZVI. Mantel test showed ARGs distribution was positively correlated with physiochemical properties, integrons and microbial community, among which microbial community primarily contributed to ARGs dissemination (39.74%). Furthermore, redundancy and null model analyses suggested the dominant and potential ARGs host was Fastidiosipila, and homogeneous selection in the determinism factors was the largest factor for driving Fastidiosipila variation, confirming the inhibition of Fastidiosipila was primary reason for mitigating ARGs dissemination by nanoscale ZVI and iron oxides. These results were related to the inhibition of ARGs transfer related functions. This work provides novel evidence for mitigating ARGs dissemination through regulating microbial succession and regulation induced by ZVI and iron oxides.

The metabolism-related lncRNA signature predicts the prognosis of breast cancer patients.

Long non-coding RNAs (lncRNAs) involved in metabolism are recognized as significant factors in breast cancer (BC) progression. We constructed a novel prognostic signature for BC using metabolism-related lncRNAs and investigated their underlying mechanisms. The training and validation cohorts were established from BC patients acquired from two public sources: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The prognostic signature of metabolism-related lncRNAs was constructed using the least absolute shrinkage and selection operator (LASSO) cox regression analysis. We developed and validated a new prognostic risk model for BC using the signature of metabolism-related lncRNAs (SIRLNT, SIAH2-AS1, MIR205HG, USP30-AS1, MIR200CHG, TFAP2A-AS1, AP005131.2, AL031316.1, C6orf99). The risk score obtained from this signature was proven to be an independent prognostic factor for BC patients, resulting in a poor overall survival (OS) for individuals in the high-risk group. The area under the curve (AUC) for OS at three and five years were 0.67 and 0.65 in the TCGA cohort, and 0.697 and 0.68 in the GEO validation cohort, respectively. The prognostic signature demonstrated a robust association with the immunological state of BC patients. Conventional chemotherapeutics, such as docetaxel and paclitaxel, showed greater efficacy in BC patients classified as high-risk. A nomogram with a c-index of 0.764 was developed to forecast the survival time of BC patients, considering their risk score and age. The silencing of C6orf99 markedly decreased the proliferation, migration, and invasion capacities in MCF-7 cells. Our study identified a signature of metabolism-related lncRNAs that predicts outcomes in BC patients and could assist in tailoring personalized prevention and treatment plans.

Intestinal microbiota dysbiosis and liver metabolomic changes during brain death.

Background: Whether a causative link exists between brain death (BD) and intestinal microbiota dysbiosis is unclear, and the distortion in liver metabolism associated with BD requires further exploration. Methods: A rat model of BD was constructed and sustained for 9 h (BD group, n=6). The sham group (n=6) underwent the same procedures, but the catheter was inserted into the epidural space without ballooning. Intestinal contents and portal vein plasma were collected for microbiota sequencing and microbial metabolite detection. Liver tissue was resected to investigate metabolic alterations, and the results were compared with those of a sham group. Results: α-diversity indexes showed that BD did not alter bacterial diversity. Microbiota dysbiosis occurred after 9 h of BD. At the family level, Peptostreptococcaceae and Bacteroidaceae were both decreased in the BD group. At the genus level, Romboutsia, Bacteroides, Erysipelotrichaceae_UCG_004, Faecalibacterium, and Barnesiella were enriched in the sham group, whereas Ruminococcaceae_UCG_007, Lachnospiraceae_ND3007_group, and Papillibacter were enriched in the BD group. Short-chain fatty acids, bile acids, and 132 other microbial metabolites remained unchanged in both the intestinal contents and portal vein plasma of the BD group. BD caused alterations in 65 metabolites in the liver, of which, carbohydrates, amino acids, and organic acids accounted for 64.6%. Additionally, 80.0% of the differential metabolites were decreased in the BD group livers. Galactose metabolism was the most significant metabolic pathway in the BD group. Conclusions: BD resulted in microbiota dysbiosis in rats; however, this dysbiosis did not alter microbial metabolites. Deterioration in liver metabolic function during extended periods of BD may reflect a continuous worsening in energy deficiency.

Environmental impacts of chlorpyrifos: Transgenerational toxic effects on aquatic organisms cannot be ignored.

Chlorpyrifos (CPF) has been extensively used in the world and frequently found in natural environments, might cause a range of environmental issues and pose a health risk to aquatic species. However, investigation of its toxic effects on offspring after parental exposure has been neglected, especially for aquatic organisms such as fish. In the current study, the effects of chronic CPF exposure (3 and 60 µg/L) on adult zebrafish (F0) was investigated to determine its influence on adult reproductive capacity and offspring (F1 and F2). The results showed the existence of CPF both in F0 ovaries and F1 embryos and larvae, indicating that CPF could be transferred directly from the F0 adult fish to F1 offspring. After 90 d exposure, we observed that F0 female fish showed increased proportion of perinucleolar oocyte in the ovaries, decreased proportion of mature oocyte, and decreased egg production, but not in F1 adult. The transcriptomic analysis revealed that the disruption of metabolism during oocyte maturation in the CPF treatment zebrafish might interfere with F0 oocytes development and quality and ultimately influence offspring survival. For the larvae, the parental CPF exposure distinctly inhibited heart rate at 72 and 120 hpf and increased the mortality of F1 but not F2 larvae. The changes of biochemical indicators confirmed a disturbance in the oxidative balance, induced inflammatory reaction and apoptosis in F1 larvae. Furthermore, the changing profiles of mRNA revealed by RNA-seq confirmed an increased susceptibility in F1 larvae and figured out potential disruptions of ROS metabolism, immune system, apoptosis, and metabolism pathways. Taken together, these results show that chronic CPF treatment can induce reproductive toxicity, and parental transfer of CPF occurs in fish, resulting in transgenerational alters in F1 generation survival and transcription that raising concerns on the ecological risk of CPF in the natural environment.

Conserved Covarying Gut Microbial Network in Preterm Infants and Childhood Growth During the First 5 Years of Life: A Prospective Cohort Study.

BACKGROUND: Longitudinally conserved microbe-microbe interactions may provide insights to understand the complex dynamic system of early-life gut microbiota among preterm infants. OBJECTIVES: We aimed to profile the covarying network of gut microbiota among preterm infants and investigate its potential influence on host growth (2-5 y). METHODS: We collected time-series stool samples (n = 717 from children and n = 116 from mothers) among 51 preterm and 51 full-term infants from birth up to 5 y of age and among 53 mothers. The included infants underwent time-series measurements of early-life gut microbiota (0-5 y) and growth (2-5 y) from June 2014 to April 2017. The covarying taxa that exhibited consistent covariation from day 1 to year 5 were defined as conserved features in the development of gut microbiota. Childrens' height-for-age z score (HAZ) and weight-for-age z score were calculated according to World Health Organization Child Growth Standards. RESULTS: We observed distinct dynamic patterns of both microbial alpha and beta diversity comparing preterm infants with full-term controls during the very early stage (<3 mo). Moreover, we identified a covarying network containing 10 taxa as a conserved gut microbial feature of these preterm infants from birth to 5 y old. This covarying network was distinctive between preterm and full-term infants before 3 mo of age (P < 0.001) and tended to be similar as the infants grew up. Several covarying taxa of the network during early life (<3 mo) were associated with childhood growth (2-5 y) (eg, Clostridium_sensu_stricto_1 with HAZ, ß = -0.32, q < 0.01), and the human milk feeding duration was a main modulating factor. CONCLUSIONS: Preterm born children possess conserved and distinct covarying microbiota during very early life, which may have a profound influence on their growth later in life. This trial was registered at clinicaltrials.gov as NCT03373721.

Comparative insight into the effects of different carbon source supplement on antibiotic resistance genes during whole-run and short-cut nitrification-denitrification processes.

Mature landfill leachate is known for nitrogen-removal challenging and meantime was considered as an important sink of antibiotic resistance genes (ARGs). The added external carbon sources, enabling the short-cut nitrification and denitrification, may facilitate the proliferation of bacteria that possibly carry ARGs. However, this speculation has yet to be studied. Here, we explored the effects of glucose, sodium acetate, and methanol supplements on ARGs during whole-run and short-cut treatment processes. The results showed that sodium acetate supplement during short-cut process efficiently reduced the abundances of total ARGs (0.84-1.99 copies/16S rRNA) and integrons (0.59-1.20 copies/16S rRNA), which were highly enhanced by methanol addition during whole-run treatment process (total ARGs: 3.60-11.01 copies/16S rRNA, integrons: 1.20-4.69 copies/16S rRNA). Indirect gradient analysis showed that the variation of ARGs was not correlated with the supplement of different external carbon source. Correlation analysis indicated that dominant intl1 (55.99 ± 17.61% of integrons) showed positively significant correlations with all detected ARGs expect for sul2 and ermB (p < 0.05), suggesting the significant role on ARGs dissemination. Redundancy analysis illustrated that the potential hosts of intl1, intl2, sul1, tetQ, tetM, mefA, and mexF were dominant Bacteroidetes and Actinobacteria. Interestingly, the numbers and significant extent of correlations under the supplement of sodium acetate during short-cut denitrification process were obviously declined, and it was in accordance with ARGs reduced by sodium acetate supplement, suggesting sodium acetate displayed the efficient ARGs reduction during short-cut process. In summary, this study provides a comparative understanding of the effects on ARGs by different carbon source supplements during nitrification-denitrification processes of leachate; sodium acetate is the optimal carbon source.

Enhanced anaerobic digestion performance of food waste by zero-valent iron and iron oxides nanoparticles: Comparative analyses of microbial community and metabolism.

The effects of zero-valent iron (ZVI) and iron oxides nanoparticles on anaerobic digestion (AD) performance of food waste (FW) were comparably clarified in this study. Results indicated that the nanoparticles supplement effectively enhanced the methane yields. As observed, these nanoparticles accelerated organics transformation and alleviated acidification process. Also, the enriched total methanogens and functional bacteria (e.g., Proteiniphilum) were consistent with the promotion of oxidative phosphorylation, citrate cycle, coenzymes biosynthesis and the metabolisms of amino acid, carbohydrate, methane. Additionally, these nanoparticles stimulated electron transfer potential via enriching syntrophic genera (e.g., Geobacter, Syntrophomonas), primary acetate-dependent methanogens (Methanosaeta, Methanosarcina) and related functions (pilus assembly protein, ferredoxins). By comparison, ZVI nanoparticle presented the excellent performance on methanogenesis. This study provides comprehensive understanding of the methanogenesis facilitated by ZVI and iron oxides nanoparticles through the enhancement of key microbes and microbial metabolisms, while ZVI is an excellent option for promoting the methane production.