Immunotoxic response of bio-based plastic on early life stage zebrafish (Danio rerio): A safe alternative to petroleum-based plastics?

Bio-based plastics are marketed as environmentally friendly alternatives to petroleum-based plastics, although they require specific composting conditions for degradation, which leads to their accumulation in the environment and potential risks to aquatic organisms. We hypothesized that the accumulation of bio-based plastics may induce immunotoxic responses in fish. Our research focused on the accumulation and immunotoxicity of 80 nm polylactic acid (PLA) and polystyrene (PS) (0.1-10 mg/L) on early life stage zebrafish (Danio rerio) exposed for 7 days. Compared to PS, there was a higher accumulation of PLA in larvae. Exposure to PLA resulted in a significant increase in neutrophils and macrophages, while immune protein levels such as Complement 3 (C3), Immunoglobulin M (IgM), and C-reactive protein (CRP) were significantly reduced. Furthermore, the mRNA expression of pro-inflammatory cytokines, including tnf-α and il-6, were significantly elevated in PLA treatments. Additionally, PLA-exposed zebrafish were more susceptible to infection by Vibrio parahaemolyticus. Interestingly, at the same concentration, exposures to PS did not induce significant changes in macrophages or immune protein levels, C3 and IgM. This suggests that PLA has a greater immunotoxic response relative to PS. Our research findings contradict the popular belief that bio-based plastics are non-toxic and harmless, which may have potential risk to aquatic organisms.

Experimental and modeling insights into mixing-limited reactive transport in heterogeneous porous media: Role of stagnant zones.

The understanding of mixing-controlled reactive dynamics in heterogeneous porous media remains limited, presenting significant challenges for modeling subsurface contaminant transport processes and for designing cost-effective environmental remedial efforts. The complexity of accurately observing, measuring, and modeling mixing-limited reactive transport has led to inadequate exploration of these critical processes. This study investigates the mixing and reaction kinetics affected by stagnant zones, which are commonly found in alluvial aquifers-aquitards and fracture-matrix systems. By conducting experiments involving conservative and bimolecular reactive transport through porous media within translucent chambers filled with two sizes of glass beads and under varying flow rates, we explored the effects of grain size and hydrodynamic conditions. Using a high-resolution camera, we monitored the concentration changes of conservative and reactive tracers, with subsequent interpretation through three-dimensional numerical simulations. The outcomes revealed the emergence of distinct mixing interfaces within both mobile and stagnant zones, culminating in a bi-peaked plume formation. Notably, the mixing and reaction times in media containing stagnant zones were found to be approximately 10 times longer than in homogeneous media. These findings, through experimental and modeling efforts, advance our understanding of mixing-limited reactive transport phenomena within heterogeneous media, underscoring the significant role of stagnant zones-a topic previously underexplored.

Perfluorohexanesulfonic Acid (PFHxS) Impairs Lipid Homeostasis in Zebrafish Larvae through Activation of PPARα.

Perfluorohexanesulfonic acid (PFHxS), an emerging short-chain per- and polyfluoroalkyl substance, has been frequently detected in aquatic environments. Adverse outcome pathway studies have shown that perfluorinated compounds impair lipid homeostasis through peroxisome proliferator activated receptors (PPARs). However, many of these studies were performed at high concentrations and may thus be a result of overt toxicity. To better characterize the molecular and key events of PFHxS to biota, early life-stage zebrafish (Danio rerio) were exposed to concentrations detected in the environment (0.01, 0.1, 1, and 10 µg/L). Lipidomic and transcriptomic evaluations were integrated to predict potential molecular targets. PFHxS significantly impaired lipid homeostasis by the dysregulation of glycerophospholipids, fatty acyls, glycerolipids, sphingolipids, prenol lipids, and sterol lipids. Informatic analyses of the lipidome and transcriptome indicated alterations of the PPAR signaling pathway, with downstream changes to retinol, linoleic acid, and glycerophospholipid metabolism. To assess the role of PPARs, potential binding of PFHxS to PPARs was predicted and animals were coexposed to a PPAR antagonist (GW6471). Molecular simulation indicated PFHxS had a 27.1% better binding affinity than oleic acid, an endogenous agonist of PPARα. Antagonist coexposures rescued impaired glycerophosphocholine concentrations altered by PFHxS. These data indicate PPARα activation may be an important molecular initiating event for PFHxS.

Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.

Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2 (HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

Perfluorooctane Sulfonamide Induced Autotoxic Effects on the Zebrafish Immune System.

Perfluorooctane sulfonamide (PFOSA) is an immediate perfluorooctanesulfonate (PFOS) precursor (PreFOS). Previous studies have shown PFOSA to induce stronger toxic responses compared to other perfluorinated compounds (PFCs). However, the specific nature of PFOSA-induced toxicity, whether autonomous or mediated by its metabolite PFOS, has not been fully elucidated. This study systematically investigates the immunomodulatory effects of PFOSA and PFOS in zebrafish (Danio rerio). Exposure to PFOSA compromised the zebrafish's ability to defend against pathogenic infections, as evidenced by increased bacterial adhesion to their skin and reduced levels of the biocidal protein lysozyme (LYSO). Moreover, PFOSA exposure was associated with disruptions in inflammatory markers and immune indicators, along with a decrease in immune cell counts. The findings from this study suggest that the immunotoxicity effects of PFOSA are primarily due to its own toxicity rather than its metabolite PFOS. This conclusion was supported by dose-dependent responses, the severity of observed effects, and multivariate analysis. In addition, our experiments using NF-κB-morpholino knock-down techniques further confirmed the role of the Nuclear factor-κappa B pathway in mediating PFOSA-induced immunotoxicity. In conclusion, this study reveals that PFOSA impairs the immune system in zebrafish through an autotoxic mechanism, providing valuable insights for assessing the ecological risks of PFOSA.

Spatial distribution, trophic magnification, and risk assessment of per- and polyfluoroalkyl substances in Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis): Risks of emerging alternatives.

The Yangtze finless porpoise (YFP, Neophocaena asiaeorientalis asiaeorientalis) is the only freshwater cetacean found in China. However, per- and polyfluoroalkyl substances (PFASs) risks in YFPs remain unclear. In this study, legacy PFASs, their precursors and alternatives, were determined in YFP muscles (n = 32), liver (n = 29), kidney (n = 24), skin (n = 5), and blubbers (n = 25) collected from Poyang Lake (PL) and Yangtze River (YR) between 2017 and 2023. Perfluorooctane sulfonic acid (PFOS) was the predominant PFAS in all YFP tissues, with a median hepatic concentration of 1700 ng/g wet weight, which is higher than that in other finless porpoises worldwide. PFOS, chlorinated polyfluorinated ether sulfonates (Cl-PFESAs), and perfluoroalkane sulfonamides concentrations in YFP livers from PL were significantly higher than those from YR (p < 0.05); however, the opposite was observed for hexafluoropropylene oxide acids. Biomagnification and trophic magnification factors (BMF and TMF, respectively) of most PFASs in the YFP food web were > 1. Perfluoroheptane sulfonic acid had the highest BMF value (99), followed by 6:2 Cl-PFESA (94) and PFOS (81). The TMFmuscle and TMFliver values of the total PFASs were 3.4 and 6.6, respectively, and were significantly positively correlated with the fluorinated carbon chain length (p < 0.01). In addition, up to 62 % of the hazard quotients for 6:2 Cl-PFESA were > 1, which was higher than that of PFOS (48 %), suggesting a high hepatotoxicity of 6:2 Cl-PFESA to YFPs. Bioaccumulation and biotoxicity of legacy and emerging alternatives in aquatic organisms continue to be a concern, especially for underscoring the vulnerability of the long-lived and endangered species.

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Microeukaryotic plankton community dynamics under ecological water replenishment: Insights from eDNA metabarcoding.

Ecological water replenishment (EWR) is an important strategy for river restoration globally, but timely evaluation of its ecological effects at a large spatiotemporal scale to further adjust the EWR schemes is of great challenge. Here, we examine the impact of EWR on microeukaryotic plankton communities in three distinct river ecosystems through environmental DNA (eDNA) metabarcoding. The three ecosystems include a long-term cut-off river, a short-term connected river after EWR, and long-term connected rivers. We analyzed community stability by investigating species composition, stochastic and deterministic dynamics interplay, and ecological network robustness. We found that EWR markedly reduced the diversity and complexity of microeukaryotic plankton, altered their community dynamics, and lessened the variation within the community. Moreover, EWR disrupted the deterministic patterns of community organization, favoring dispersal constraints, and aligning with trends observed in naturally connected rivers. The shift from an isolated to a temporarily connected river appeared to transition community structuring mechanisms from deterministic to stochastic dominance, whereas, in permanently connected rivers, both forces concurrently influenced community assembly. The ecological network in temporarily connected rivers post-EWR demonstrated significantly greater stability and intricacy compared to other river systems. This shift markedly bolstered the resilience of the ecological network. The eDNA metabarcoding insights offer a novel understanding of ecosystem resilience under EWR interventions, which could be critical in assessing the effects of river restoration projects throughout their life cycle.

Microplastic-mediated new mechanism of liver damage: From the perspective of the gut-liver axis.

Microplastics (MPs) are environmental contaminants that are present in all environments and can enter the human body, accumulate in various organs, and cause harm through the ingestion of food, inhalation, and dermal contact. The connection between bowel and liver disease and the interplay between gut, liver, and flora has been conceptualized as the "gut-liver axis". Microplastics can alter the structure of microbial communities in the gut and the liver can also be a target for microplastic invasion. Numerous studies have found that when MPs impair human health, they not only promote dysbiosis of the gut microbiota and disruption of the gut barrier but also cause liver damage. For this reason, the gut-liver axis provides a new perspective in understanding this toxic response. The cross-talk between MPs and the gut-liver axis has attracted the attention of the scientific community, but knowledge about whether MPs cause gut-liver interactions through the gut-liver axis is still very limited, and the effect of MPs on liver injury is not well understood. MPs can directly induce microbiota disorders and gut barrier dysfunction. As a result, harmful bacteria and metabolites in the gut enter the blood through the weak intestinal barrier (portal vein channel along the gut-liver axis) and reach the liver, causing liver damage (inflammatory damage, metabolic disorders, oxidative stress, etc.). This review provides an integrated perspective of the gut-liver axis to help conceptualize the mechanisms by which MP exposure induces gut microbiota dysbiosis and hepatic injury and highlights the connection between MPs and the gut-liver axis. Therefore, from the perspective of the gut-liver axis, targeting intestinal flora is an important way to eliminate microplastic liver damage.

Maternal or Paternal Antibiotics? Intergenerational Transmission and Reproductive Toxicity in Zebrafish.

Despite the known direct toxicity of various antibiotics to aquatic organisms, the potential chronic impact through intergenerational transmission on reproduction remains elusive. Here, we exposed zebrafish to a mixture of 15 commonly consumed antibiotics at environmentally relevant concentrations (1 and 100 µg L-1) with a cross-mating design. A high accumulation of antibiotics was detected in the ovary (up to 904.58 ng g-1) and testis (up to 1704.49 ng g-1) of F0 fish. The transmission of antibiotics from the F0 generation to the subsequent generation (F1 offspring) was confirmed with a transmission rate (ki) ranging from 0.11 to 2.32. The maternal transfer of antibiotics was significantly higher, relative to paternal transfer, due to a greater role of transmission through ovarian enrichment and oviposition compared to testis enrichment. There were similar impairments in reproductive and developmental indexes on F1 eggs found following both female and male parental exposure. Almost all antibiotics were eliminated in F2 eggs in comparison to F1 eggs. However, there were still reproductive and developmental toxic responses observed in F2 fish, suggesting that antibiotic concentration levels were not the only criterion for evaluating the toxic effects for each generation. These findings unveil the intergenerational transmission mechanism of antibiotics in fish models and underscore their potential and lasting impact in aquatic environments.

Impact of antioxidants on PM2.5 oxidative potential, radical level, and cytotoxicity.

Antioxidants are typically seen as agents that mitigate environmental health risks due to their ability to scavenge free radicals. However, our research presents a paradox where these molecules, particularly those within lung fluid, act as prooxidants in the presence of airborne particulate matter (PM2.5), thus enhancing PM2.5 oxidative potential (OP). In our study, we examined a range of antioxidants found in the respiratory system (e.g., vitamin C, glutathione (GSH), and N-acetylcysteine (NAC)), in plasma (vitamin A, vitamin E, and ß-carotene), and in food (tert-butylhydroquinone (TBHQ)). We aimed to explore antioxidants' prooxidant and antioxidant interactions with PM2.5 and the resulting OP and cytotoxicity. We employed OH generation assays and electron paramagnetic resonance assays to assess the pro-oxidative and anti-oxidative effects of antioxidants. Additionally, we assessed cytotoxicity interaction using a Chinese hamster ovary cell cytotoxicity assay. Our findings revealed that, in the presence of PM2.5, all antioxidants except vitamin E significantly increased the PM2.5 OP by generating more OH radicals (OH generation rate: 0.16-24.67 pmol·min-1·m-3). However, it's noteworthy that these generated OH radicals were at least partially neutralized by the antioxidants themselves. Among the pro-oxidative antioxidants, vitamin A, ß-carotene, and TBHQ showed the least ability to quench these radicals, consistent with their observed impact in enhancing PM2.5 cytotoxicity (PM2.5 LC50 reduced to 91.2 %, 88.8 %, and 75.1 % of PM2.5's original level, respectively). Notably, vitamin A and TBHQ-enhanced PM2.5 OP were strongly associated with the presence of metals and organic compounds, particularly with copper (Cu) contributing significantly (35 %) to TBHQ's pro-oxidative effect. Our study underscores the potential health risks associated with the interaction between antioxidants and ambient pollutants.

Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length.

Previous studies have reported the immunotoxicity of per- and polyfluoroalkyl substances (PFASs), but it remains a significant challenge to assess over 10,000 distinct PFASs registered in the distributed structure-searchable toxicity (DSSTox) database. We aim to reveal the mechanisms of immunotoxicity of different PFASs and hypothesize that PFAS immunotoxicity is dependent on the carbon chain length. Perfluorobutanesulfonic acid (PFBA), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) representing different carbon chain lengths (4-9) at environmentally relevant levels strongly reduced the host's antibacterial ability during the zebrafish's early-life stage. Innate and adaptive immunities were both suppressed after PFAS exposures, exhibiting a significant induction of macrophages and neutrophils and expression of immune-related genes and indicators. Interestingly, the PFAS-induced immunotoxic responses were positively correlated to the carbon chain length. Moreover, PFASs activated downstream genes of the toll-like receptor (TLR), uncovering a seminal role of TLR in PFAS immunomodulatory effects. Myeloid differentiation factor 88 (MyD88) morpholino knock-down experiments and MyD88 inhibitors alleviated the immunotoxicity of PFASs. Overall, the comparative results demonstrate differences in the immunotoxic responses of PFASs due to carbon chain length in zebrafish, providing new insights into the prediction and classification of PFASs mode of toxic action based on carbon chain length.

Perfluorononanoic Acid Induces Neurotoxicity via Synaptogenesis Signaling in Zebrafish.

Perfluorononanoic acid (PFNA), commonly used as an alternative polyfluorinated compound (PFC) of perfluorooctanoic acid (PFOA), has been widely detected in the aquatic environment. Previous ecotoxicological and epidemiological results suggested that some neurobehavioral effects were associated with PFC exposure; however, the ecological impacts and underlying neurotoxicity mechanisms remain unclear, particularly in aquatic organisms during sensitive, early developmental stages. In this study, zebrafish embryos were exposed to environmentally relevant concentrations of PFNA for 120 h, and the neurological effects of PFNA were comprehensively assessed using transcriptional, biochemical, morphological, and behavioral assays. RNA sequencing and advanced bioinformatics analyses predicted and characterized the key biological processes and pathways affected by PFNA exposure, which included the synaptogenesis signaling pathway, neurotransmitter synapse, and CREB signaling in neurons. Neurotransmitter levels (acetylcholine, glutamate, 5-hydroxytryptamine, γ-aminobutyric acid, dopamine, and noradrenaline) were significantly decreased in zebrafish larvae, and the Tg(gad67:GFP) transgenic line revealed a decreased number of GABAergic neurons in PFNA-treated larvae. Moreover, the swimming distance, rotation frequency, and activity degree were also significantly affected by PFNA, linking molecular-level changes to behavioral consequences.

Sunlight-mediated CaO2 inactivation of pathogen indicator organisms in surface water system: Roles of reactive species, characterization of pathogen inactivation.

In the era of the current epidemic, it is urgent to control pathogens in sewage, eliminate the source of infection, and optimize the technology for killing pathogens. Combining calcium peroxide (CaO2) with sunlight is considered a potentially efficient, economical, and eco-friendly method for pathogen-contaminated water remediation. This paper evaluated the solar activating properties of CaO2 for inactivating pathogenic indicators and explored the roles of reactive species contributing to pathogen inactivation. Moreover, these reactive species' average steady-state concentrations and second-order reaction rate were tentatively explored, and mechanistic model for photoinactivation were establishment. Pathogen's inactivation was mainly attributed to direct photoinactivation (13∼50%) and exogenous indirect mechanisms with corresponding contributions of reactive species, i.e., OH- (14∼23%), 1O2 (12∼28%), •OH (20∼32%), O2•- (12∼16%), and H2O2 (6∼11%). Furthermore, cell membrane rupture and DNA damage were observed by transmission electron microscopy (TEM) and agarose gel electrophoresis (AGE) experiments. Among experiments on common aqueous constituents influencing photoinactivation, copper and iron ions were found to promote a pathogen-inactivating ability of the system, while fulvic acids (FA) and humic acid (HA) had the opposite effect. This study revealed the potential of CaO2/sunlight to inactivate pathogens and laid a foundation for its application in inactivating pathogens in surface water.

Performance and mechanisms for tetrabromobisphenol A efficient degradation in a novel homogeneous advanced treatment based on S2O42- activated by Fe3.

Tetrabromobisphenol A (TBBPA), a representative brominated flame retardant (BFR), generally could be debrominated and degraded effectively in photolysis systems with the high energy consumption. In this study, the novel sulfate radical (SO4•-) generation resource of dithionite (S2O42-), activated by the common transition metal of Fe3+, has been applied for establishing an innovative homogeneous advance treatment system for BFR treatment in water. When coupling Fe3+ with S2O42-, TBBPA degradation efficiency could be remarkably improved from 38.7% to 93.8% with the debromination and mineralization efficiency of 83.9% and 18.5% in 60 min, respectively. The primary reactive species also have been identified as SO3•-, SO4•- and •OH responsible for TBBPA treatment and the contributions of SO4•- and •OH have been calculated as 43.8% and 28.4% for TBBPA degradation, respectively. In Fe3+/S2O42- system, TBBPA was effectively degraded in a wide initial pH range (3.0-9.0), whose activation energy was calculated as 32.01 kJ mol-1. Due to the only operation of reagents dosing, the energy consumption and cost could be decreasing significantly without any light energy input and reaction conditions (e.g., pH and dissolved oxygen) adjustment compared with the general photolysis process. Moreover, some possible degradation approaches of TBBPA also have been proposed via GC-MS including debromination, hydroxylation, methylation, and mineralization in Fe3+/S2O42- system. And these probable degradation pathways also have been confirmed with the decreased Gibbs free energy (ΔG) based on density functional theory (DFT). This study has revealed that it was promising of Fe3+/S2O42- system for BFRs degradation and detoxification efficiently through the simple operation and mild condtions.

Dysregulation of Angiopoietin-like-4 Associated with Hyperlipidemia-induced Renal Injury by AMPK/ACC Pathway.

BACKGROUND: Angiopoietin-like protein 4 (Angptl4) is a glycoprotein that is involved in regulating lipid metabolism, which has been indicated as a link between hypertriglyceridemia and albuminuria in glomerulonephropathy. Deregulated lipid metabolism is increasingly recognized as an important risk factor of glomerulonephropathy. This study aimed to investigate the Angptl4 expression in renal tissue and podocyte under hyperlipidemia conditions and explore the potential molecular mechanisms. OBJECTIVE: The role of Angptl4 in hyperlipidemia-induced glomerular disease and the detailed underlying mechanisms are unclear. This study sought new insights into this issue. METHODS: We measured Angptl4 levels in the plasma and urine from patients with hyperlipidemia and healthy people. Rats were fed a high fat diet (HFD) to induce dyslipidemia model and the human podocytes were stimulated by palmitic acid as in vivo and in vitro experiments. The podocytes injury and the Angptl4 level in renal tissues were evaluated. Furthermore, the mechanism of Angptl4 on podocytes injury was investigated. RESULTS: The urinary Angptl4 level was gradually upregulated in both patients with hyperlipidaemia and high fat-diet-induced rats. HFD rats showed increased 24 h urinary protein and glomerular tuft area at week 12. The levels of nephrin and WT-1 were down-regulated, but the Angptl4 levels were markedly upregulated on the glomerular of rats on HFD. In the human podocytes, lipid accumulation accompanied by increases of Angptl4, but the expression of nephrin, WT-1, p-AMPKα and p-ACC was decreased after palmitic acid treatment. However, this injury effect was mediated by the aminoimidazole-4-carboxamide-1ß-D-ribofuranoside (AICAR), activator of the low energy sensor AMPK/ACC signaling. CONCLUSION: This study was the first of its kind to show that podocyte damage induced by dyslipidemia could be associated with upregulated Angptl4 and that patients with hyperlipidemia might have relatively high urinary Angptl4 expression. The dysregulation of Angptl4 in the podocytes under hyperlipidemia is possibly carried out through AMPK/ACC signaling pathway.

Parental transfer of an antibiotic mixture induces cardiotoxicity in early life-stage zebrafish: A cross-generational study.

Antibiotic residues in the aquatic environment have been shown to induce significant adverse effects on the early-life stage development of aquatic organisms, though the underlying molecular mechanisms of these effects have not been well characterized. In this study, we performed global mRNA-miRNA sequencing, canonical pathway analyses, morphological, physiological, immunohistochemical, and behavioral analyses to comprehensively assess the cross-generational cardiotoxicity and mechanisms of antibiotic mixtures in zebrafish. Following parental treatment to 1 and 100 µg/L antibiotic mixtures (15 of the most commonly detected antibiotics) for 150 days, all 15 assessed antibiotics were detected in the F1 eggs, indicating the cross-generational transfer of antibiotics. Global mRNA-miRNA sequencing functional analysis predicted cardiotoxicity in the F1 generation by using the F1 whole fish. Consistent with canonical pathway analyses, significant cardiotoxicity was observed in F1 larvae, as well as the apoptosis of cardiac cells. Furthermore, let-7a-5p regulated the cardiac hypertrophy signaling pathway, suggesting mechanisms of miRNA of let-7 family mediating cross-generational cardiotoxicity of antibiotics in zebrafish. This study lays some groundwork for developing interventions to prevent parental exposure to environmental pollutants such as antibiotics from adversely affecting offspring development.

Microbial community assembly and co-occurrence relationship in sediments of the river-dominated estuary and the adjacent shelf in the wet season.

In the estuarine ecosystem, microbial community plays a vital role in controlling biogeochemical processes. However, there is currently limited comprehensive study on the deterministic and stochastic processes that drive the microbial community assembly in the estuaries and adjacent shelves. In this study, we systematically investigated the co-occurrence relationship and microbial community assembly in the sediments along a large river-dominated estuary to shelf in the northern South China Sea during the wet season. The sampling sites were divided into estuary, transection, and shelf sections based on their salinity values. The microbial co-occurrence networks, hierarchical partitioning-based canonical analysis, null model, neutral community model, and the Mantel test were used to investigate the community assembly. Results suggested that microbial community in the estuary section exhibited more interactions and a higher positive interaction ratio than those in the transition and shelf sections. Stochastic processes dominated community assembly in the study, with homogenizing dispersal contributing the most. The estuary exhibited a higher degree of heterogeneous selection than the transition and shelf sections, whereas homogeneous selection showed an opposite trend. Only the estuary section showed dispersal limitation and undominated processes. The river inflow and the resulting environmental heterogeneity were believed to be the key regulators of the community assembly in the studied area. Our study improved the understanding of how microbial community assembly in estuaries and adjacent shelves.

Perfluorooctane Sulfonamide (PFOSA) Induces Cardiotoxicity via Aryl Hydrocarbon Receptor Activation in Zebrafish.

Perfluorooctane sulfonamide (PFOSA), a precursor of perfluorooctanesulfonate (PFOS), is widely used during industrial processes, though little is known about its toxicity, particularly to early life stage organisms that are generally sensitive to xenobiotic exposure. Here, following exposure to concentrations of 0.01, 0.1, 1, 10, and 100 µg/L PFOSA, transcriptional, morphological, physiological, and biochemical assays were used to evaluate the potential effects on aquatic organisms. The top Tox functions in exposed zebrafish were related to cardiac diseases predicted by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Ingenuity Pathway Analysis (IPA) analysis. Consistent with impacts predicted by transcriptional changes, abnormal cardiac morphology, disordered heartbeat signals, as well as reduced heart rate and cardiac output were observed following the exposure of 0.1, 1, 10, or 100 µg/L PFOSA. Furthermore, these PFOSA-induced cardiac effects were either prevented or alleviated by supplementation with an aryl hydrocarbon receptor (AHR) antagonist or ahr2-morpholino knock-down, uncovering a seminal role of AHR in PFOSA-induced cardiotoxicity. Our results provide the first evidence in fish that PFOSA can impair proper heart development and function and raises concern for PFOSA analogues in the natural environment.