The incorporation of strontium and barium into the otoliths of the flounder Paralichthys olivaceus at early life stages demonstrates resilience to ocean acidification.

Ocean acidification could modify the bioavailability and chemical properties of trace elements in seawater, which could affect their incorporation into the calcareous structures of marine organisms. Fish otoliths, biomineralized ear stones made by aragonite, are suspended within the endolymph fluid of teleosts, indicating that the elemental incorporation of otoliths might also be susceptible to ocean acidification. In this study, we evaluated the combined effects of CO2-induced ocean acidification (pH 8.10, 7.70, and 7.30, corresponding to ocean acidification scenarios under the representative concentration pathway 8.5 model as projected by the Intergovernmental Panel on Climate Change) and water elemental concentrations of strontium (Sr) and barium (Ba; low, medium, and high) on elemental incorporation into otoliths of the flounder Paralichthys olivaceus at early life stages. Our results revealed that the elemental incorporation of Sr and Ba into otoliths was principally dependent on the corresponding water elemental concentrations rather than on ocean acidification. Moreover, the partition coefficients (DMe) of Sr and Ba may stabilize after dynamic equilibrium is reached as the water elemental concentration increases, but are not affected by ocean acidification. Therefore, the incorporation of Sr and Ba into otoliths of the flounder at early life stages may not serve as an effective indicator of ocean acidification. In other words, the findings suggest that ocean acidification does not impact the incorporation of Sr and Ba incorporation into otoliths when tracing the temperature or salinity experiences of the flounder. Our findings will provide new knowledge for understanding the potential ecological effects of ocean acidification on the recruitment dynamics of fish species.

In Situ Hydrogel Modulates cDC1-Based Antigen Presentation and Cancer Stemness to Enhance Cancer Vaccine Efficiency.

Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 is the key DC subtype for high-performance activation of CTLs. However, low cDC1 proportion, complex process, and high cost severely hindered cDC1 generation and application. Herein, the study proposes an in situ cDC1 recruitment and activation strategy with simultaneous inhibiting cancer stemness for inducing robust CTL responses and enhancing the anti-tumor effect. Fms-like tyrosine kinase 3 ligand (FLT3L), Poly I:C, and Nap-CUM (NCUM), playing the role of cDC1 recruitment, cDC1 activation, inducing antigen release and decreasing tumor cell stemness, respectively, are co-encapsulated in an in situ hydrogel vaccine (FP/NCUM-Gel). FP/NCUM-Gel is gelated in situ after intra-tumoral injection. With the near-infrared irradiation, tumor cell immunogenic cell death occurred, tumor antigens and immunogenic signals are released in situ. cDC1 is recruited to tumor tissue and activated for antigen cross-presentation, followed by migrating to lymph nodes and activating CTLs. Furthermore, tumor cell stemness are inhibited by napabucasin, which can help CTLs to achieve comprehensive tumor killing. Collectively, the proposed strategy of cDC1 in situ recruitment and activation combined with stemness inhibition provides great immune response and anti-tumor potential, providing new ideas for clinical tumor vaccine design.

Protective Mechanism of Eurotium amstelodami from Fuzhuan Brick Tea against Colitis and Gut-Derived Liver Injury Induced by Dextran Sulfate Sodium in C57BL/6 Mice.

The study explored the potential protective impact of the probiotic fungus Eurotium amstelodami in Fuzhuan brick tea on ulcerative colitis, along with the underlying mechanism. A spore suspension of E. amstelodami was administered to C57BL/6 mice to alleviate DSS-induced colitis. The findings indicated that administering E. amstelodami evidently enhanced the ultrastructure of colonic epithelium, showing characteristics such as enhanced TJ length, reduced microvilli damage, and enlarged intercellular space. After HLL supplementation, the activation of the liver inflammation pathway, including TLR4/NF-kB and NLRP3 inflammasome caused by DSS, was significantly suppressed, and bile acid metabolism, linking liver and gut, was enhanced, manifested by restoration of bile acid receptor (FXR, TGR5) level. The dysbiosis of the gut microbes in colitis mice was also restored by HLL intervention, characterized by the enrichment of beneficial bacteria (Lactobacillus, Bifidobacterium, Akkermansia, and Faecalibaculum) and fungi (Aspergillus, Trichoderma, Wallemia, Eurotium, and Cladosporium), which was closely associated with lipid metabolism and amino acid metabolism, and was negatively correlated with inflammatory gene expression. Hence, the recovery of gut microbial community structure, implicated deeply in the inflammatory index and metabolites profile, might play a crucial role in the therapeutic mechanism of HLL on colitis.

Interactive impacts of CO2-induced seawater acidification and cadmium exposure on antioxidant defenses of juvenile tongue sole Cynoglossus semilaevis.

Antioxidant responses of juvenile sole exposed to seawater acidification (SA) and Cd were investigated. SA increased lipid peroxidation (LPO) in the fish, independent of Cd concentrations. Cd at medium and high levels inflated LPO under no or moderate SA conditions. This effect was absent under high SA levels, due to SA effect exceeding and obscuring Cd effect. SA and Cd collaborated to provoke LPO, with SOD and CAT being stimulated to defend against oxidative stress, while those related to GSH redox cycle were inhibited under SA exposure. Responses of GSH-related antioxidants to Cd impact varied contingent on their interactions with SA. This defensive strategy was insufficient to protect fish from increased LPO. Antioxidants responded more sensitively to SA than Cd exposure. GSH, GR, SOD and CAT are sensitive biomarkers for SA conditions. The findings offer insights into assessing fish's antioxidant defense strategy under Cd and SA circumstances in natural habitats.

Nano-Regulator Inhibits Tumor Immune Escape via the "Two-Way Regulation" Epigenetic Therapy Strategy.

Tumor immune escape caused by low levels of tumor immunogenicity and immune checkpoint-dependent suppression limits the immunotherapeutic effect. Herein, a "two-way regulation" epigenetic therapeutic strategy is proposed using a novel nano-regulator that inhibits tumor immune escape by upregulating expression of tumor-associated antigens (TAAs) to improve immunogenicity and downregulating programmed cell death 1 ligand 1 (PD-L1) expression to block programmed death-1 (PD-1)/PD-L1. To engineer the nano-regulator, the DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) and the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 are co-loaded into the cationic liposomes with condensing the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine (CpG) via electrostatic interactions to obtain G-J/ZL. Then, asparagine-glycine-arginine (NGR) modified material carboxymethyl-chitosan (CMCS) is coated on the surface of G-J/ZL to construct CG-J/ZL. CG-J/ZL is shown to target tumor tissue and disassemble under the acidic tumor microenvironment (TME). Zeb upregulated TAAs expression to improve the immunogenicity; JQ1 inhibited PD-L1 expression to block immune checkpoint; CpG promote dendritic cell (DC) maturation and reactivated the ability of tumour-associated macrophages (TAM) to kill tumor cells. Taken together, these results demonstrate that the nano-regulator CG-J/ZL can upregulate TAAs expression to enhance T-cell infiltration and downregulate PD-L1 expression to improve the recognition of tumor cells by T-cells, representing a promising strategy to improve antitumor immune response.

An Effect of Layered Auxiliary Cathode on Thickness Uniformity in Micro Electroforming Process.

Thickness nonuniformity is a bottleneck in the micro electroforming process of micro-metal devices. In this paper, a new method of fabricating a layered auxiliary cathode is proposed to improve the thickness uniformity of a micro-electroforming layer. In order to analyze the general applicability of the proposed method, four basic microstructures, namely circular, square, regular triangular, and regular hexagonal were used to study the effect of a layered auxiliary cathode on thickness uniformity through simulation and experimentation. The simulation results showed that with the help of the proposed auxiliary cathode, the thickness nonuniformity of four microstructures should decrease due to the reduced edge effect of the current density. The experimental results showed that the thickness uniformity of four microstructures fabricated via the proposed method was improved by 190.63%, 116.74%, 80.43%, and 164.30% compared to that fabricated via the traditional method, respectively. Meanwhile, the micro-gear was fabricated and the nonuniformity was reduced by 101.15% using the proposed method.

Transforming Cancer-Associated Fibroblast Barrier into Drug Depots to Boost Chemo-Immunotherapy in "Shooting Fish in a Barrel" Pattern.

The cancer-associated fibroblast (CAF) barrier in pancreatic ductal adenocarcinoma (PDAC) greatly restricts clinical outcomes. Major obstacles to PDAC treatment include restricted immune cell infiltration and drug penetration and the immunosuppressive microenvironment. Here, we reported a "shooting fish in a barrel" strategy by preparing a lipid-polymer hybrid drug delivery system (PI/JGC/L-A) that could overcome the CAF barrier by turning it into a "barrel" with antitumor drug depot properties to alleviate the immunosuppressive microenvironment and increase immune cell infiltration. PI/JGC/L-A is composed of a pIL-12-loaded polymeric core (PI) and a JQ1 and gemcitabine elaidate coloaded liposomal shell (JGC/L-A) that has the ability to stimulate exosome secretion. By normalizing the CAF barrier to create a CAF "barrel" with JQ1, stimulating the secretion of gemcitabine-loaded exosomes from the CAF "barrel" to the deep tumor site, and leveraging the CAF "barrel" to secrete IL-12, PI/JGC/L-A realized effective drug delivery to the deep tumor site, activated antitumor immunity at the tumor site, and produced significant antitumor effects. In summary, our strategy of transforming the CAF barrier into antitumor drug depots represents a promising strategy against PDAC and might benefit the treatment of any tumors facing a drug delivery barrier.

Ocean acidification induces tissue-specific interactions with copper toxicity on antioxidant defences in viscera and gills of Asiatic hard clam Meretrix petechialis (Lamarck, 1818).

Toxicity of contaminants in organisms under ocean acidification (OA) has attracted increasing attention in ecotoxicological studies. This study investigated how pCO2-driven OA affected waterborne copper (Cu) toxicity in antioxidant defences in viscera and gills of Asiatic hard clam Meretrix petechialis (Lamarck, 1818). Clams were continuously exposed to Cu at ambient relevant (0/no metal exposure, 10 and 50 µg L-1) and polluted-high (100 µg L-1) concentrations in unacidified (pH 8.10) and acidified (pH 7.70/moderate OA and 7.30/extreme OA) seawater for 21 days. Following coexposure, metal bioaccumulation and responses of antioxidant defence-related biomarkers to OA and Cu coexposure were investigated. Results showed that metal bioaccumulation was positively correlated with waterborne metal concentrations but was not notably influenced by OA conditions. Both Cu and OA affected the antioxidant responses to environmental stress. Additionally, OA induced tissue-specific interactions with Cu on antioxidant defences, varying with exposure conditions. In unacidified seawater, antioxidant biomarkers were activated to defend against oxidative stress induced by Cu and prevented clams from lipid peroxidation (LPO or MDA), but failed to defend against DNA damage (8-OHdG). OA exacerbated Cu toxicity in antioxidant defences and increased LPO levels in tissues. Gills and viscera adopted adaptive antioxidant defence strategies to manage oxidative stress, with the former being more vulnerable to oxidative stress than the latter. MDA and 8-OHdG were sensitive to OA and Cu exposure, respectively, and were useful bioindicators for assessing oxidative stress. Integrated biomarker response (IBR) and PCA can reflect the integrative responses of antioxidant biomarkers to environmental stress and illuminate the contributions of specific biomarkers to antioxidant defence strategies. The findings provided insights for understanding antioxidant defences against metal toxicity in marine bivalves under OA scenarios, which is essential into managing wild populations.

CD13-Mediated Pegylated Carboxymethyl Chitosan-Capped Mesoporous Silica Nanoparticles for Enhancing the Therapeutic Efficacy of Hepatocellular Carcinoma.

Liver cancer, especially hepatocellular carcinoma, is an important cause of cancer-related death, and its incidence is increasing worldwide. Nano drug delivery systems have shown great promise in the treatment of cancers. In order to improve their therapeutic efficacy, it is very important to realize the high accumulation and effective release of drugs at the tumor site. In this manuscript, using doxorubicin (DOX) as a model drug, CD13-targeted mesoporous silica nanoparticles coated with NGR-peptide-modified pegylated carboxymethyl chitosan were constructed (DOX/MSN-CPN). DOX/MSN-CPN comprises a spherical shape with an obvious capping structure and a particle size of 125.01 ± 1.52 nm. With a decrease in pH, DOX/MSN-CPN showed responsive desorption from DOX/MSN-CPN and pH-responsive release of DOX was observed. Meanwhile, DOX/MSN-CPN could be efficiently absorbed through NGR-mediated internalization in vitro and could efficiently deliver DOX to tumor tissues with long accumulation times in vivo, suggesting good active targeting properties. Moreover, significant tumor inhibition has been observed in antitumor studies in vivo. This study provides a strategy of utilizing DOX/MSN-CPN as a nano-platform for drug delivery, which has superb therapeutic efficacy and safety for the treatment of hepatocellular carcinoma both in vivo and in vitro.

pCO2-driven seawater acidification affects aqueous-phase copper toxicity in juvenile flounder Paralichthys olivaceus: Metal accumulation, antioxidant defenses and detoxification in livers.

Ocean acidification potentially influences the biotoxicity of metals and the antioxidant defense systems of marine organisms. This study investigated how pCO2-driven seawater acidification (SA) affected aqueous-phase copper (Cu) toxicity in the juvenile flounder Paralichthys olivaceus from the perspective of hepatic oxidative stress and damage to better understand the mechanisms underlying the biological effects produced by the two stressors. Fish were exposed to aqueous-phase Cu at relevant ambient and polluted concentrations (0, 5, 10, 50, 100 and 200 µg L-1) at different pH levels (no SA: pH 8.10; moderate SA: pH 7.70, pCO2 ∼1353.89 µatm; extreme SA: pH 7.30, pCO2 ∼3471.27 µatm) for 28 days. A battery of biomarkers in the livers was examined to investigate their roles in antioxidant defense and detoxification in response to coexposure. Hepatic Cu accumulation (30.22-184.90 mg kg-1) was positively correlated with Cu concentrations. The biomarkers responded adaptively to different redox states following SA and Cu exposure. In unacidified seawater, increases in Cu concentrations significantly induced hepatic lipid peroxidation (LPO, by up to 27.03 %), although compensatory responses in antioxidant defenses and detoxification were activated. Moderate SA helped maintain hepatic redox homeostasis and alleviated LPO through different defense strategies, depending on Cu concentrations. Under extreme SA, antioxidant-based defenses were activated to cope with oxidative stress at ambient-low Cu concentrations but failed to defend against Cu toxicity at polluted Cu levels, and LPO (by up to 63.90 %) was significantly induced. Additionally, thiols (GSH and MT) responded actively to cope with Cu toxicity under SA. SOD, CAT, EROD, and GST were also sensitively involved in defending against hepatic oxidative stress during coexposure. These findings highlight the notable interactive effects of SA and Cu and provide a basis for understanding antioxidant-based defenses in marine fish confronting environmental challenges.

Risk Identification of Heavy Metals in Agricultural Soils from a Typically High Cd Geological Background Area in Upper Reaches of the Yangtze River.

This study adopted two risk assessment models to estimate the potential risk of heavy metals (HMs) in agricultural soils from a high Cd geological background area. Results were as follows: HMs posed an extremely high potential ecological risk (PER) (PER = 2051 > 1200) ascribed to Cd contribution. The overall non-carcinogenic risk (HI) of HMs for children (HI > 1) was unacceptable. Contributions of HMs to HI generally decreased in the order of Cr > As > Pb > Cd > Ni > Cu > Zn. The total carcinogenic risk (TCR) value for adults (2.1 × 10-4) and children (2.2 × 10-4) surpassed the reference value (1.0 × 10-4), indicating that the risks were unacceptable. Contributions of HMs to TCR generally decreased in the order of Cr ≈ Ni > Cd > As > Pb. These results suggested that risk control policies should not only consider the potential ecological risk of Cd but also take into consideration of the carcinogenic and non-carcinogenic risk of Cr and Ni in a typically high Cd geological background area.

Toxicological effects of cadmium on the immune response and biomineralization of larval flounder Paralichthys olivaceus under seawater acidification.

Seawater acidification can cause threats to both calcifying and uncalcifying marine organisms, affecting their acid-base regulatory functions, immune system and biomineralization. Marine pollutants, such as cadmium (Cd) that is globally distributed in coastal ecosystems, do not affect organisms alone but commonly as combined stressors. To investigate the toxicological effects of Cd on the immune and biomineralization of marine fishes under seawater acidification, flounder Paralichthys olivaceus was exposed to seawater acidification (control (pH 8.10), 7.70 and 7.30) and Cd exposure (control (0.36 µg L-1), 0.01 and 0.15 mg L-1 Cd) for 49 days from embryonic stage until they became settled. Immune and biomineralization-related biomarkers of flounder at the end of exposure were investigated. Results showed that single seawater acidification and Cd exposure or combined exposure significantly affected the immune system-related enzyme activities. Specifically, lysozyme (LZM) activity was significantly inhibited by single seawater acidification and Cd exposure, indicating innate immunosuppression under two stressors. Contents of IgM, HSP70 and MT were induced by seawater acidification or Cd exposure, indicating a detoxification mechanism that responded to the stressors. The expressions of immune-related genes were upregulated (hsp70 and mt) or downregulated (lzm) under Cd exposure. Of the biomineralization-related enzymes, activities of carbonic anhydrase (CA), Na+/K+-ATPase and Ca2+-ATPase increased under seawater acidification and Cd exposure, a potential mechanism in response to changes of acid-base balance induced by the stressors. Generally, immune and biomineralization of the flounder responded more sensitively to Cd exposure than seawater acidification. Seawater acidification aggravated the toxicological effects of Cd exposure on the two physiological functions, while high Cd exposure augmented their responses to seawater acidification.

Activation of CD200-CD200R1 Axis Attenuates Perioperative Neurocognitive Disorder Through Inhibition of Neuroinflammation in Mice.

Perioperative neurocognitive disorder (PND) is the mild cognitive impairment associated with surgery and anesthesia. It is a common surgical complication in the elderly. An important mechanism of PND is the surgically induced neuroinflammation. The interaction between the neuronal surface protein CD200 and its receptor in microglia, CD200R1, is an important regulatory pathway to control neuroinflammation. However, the potential role of the CD200-CD200R1 pathway in the acute period of PND has not been fully investigated. In this study, in a PND mouse model, we first measured the protein expression level of CD200, CD200R1, and the related pro- and anti-inflammatory cytokines in the hippocampus. Then, we investigated cognitive function, neuroinflammation and postsynaptic density protein 95 (PSD-95) expression after the injection of CD200-Fc (agonist), CD200R1-Fc (antagonist) or IgG1-Fc (vehicle) into lateral ventricle in PND models. Compared with the control group, the expression of CD200 was up-regulated at day 1 after surgery in PND models. The injection of the CD200-Fc into the lateral ventricle could mitigate primed neuroinflammation and cognitive decline, increase the expression of PSD-95 at day 1 after surgery in PND models. In conclusion, we have demonstrated that CD200-CD200R1 signaling was involved in the acute inflammatory process of PND, and activating CD200R1 can inhibit neuroinflammation and attenuate PND. Thus, the CD200-CD200R1 axis is a potential novel target for PND prevention and treatment.

Assessment of plastic pollution in the Bohai Sea: Abundance, distribution, morphological characteristics and chemical components.

Plastics are globally distributed in oceans and can pose a threat to the environment and organisms. In this study, plastic pollution in surface water and sediments of the Bohai Sea was assessed based on plastic abundance, distribution and characteristics (shape, polymer, size and color). Water and sediment samples were collected across the sea using a plankton net (330 µm) and a grab sampler, respectively. The following conclusions were reached. 1) In surface water, large plastics were less abundant (0.14 items/m3) and showed less diverse characteristics than microplastics (0.79 items/m3) but did not significantly differ in spatial distribution. 2) Microplastics in water were more abundant (1.95 items/m3) with more diverse characteristics in Liaodong Bay than in other regions of the sea (0.26-0.59 items/m3). Plastic waste from highly concentrated agricultural, industrial and fishery activities could make large contributions to microplastics in Liaodong Bay. Additionally, low hydrodynamics and long distance to Bohai Strait are unfavorable for diffusion of particles, facilitating the retention of microplastics and increasing the abundance in this bay. 3) Microplastics in sediments were smaller in terms of dominant sizes (<0.5 mm) with less diverse characteristics than particles in water (0.5-1.5 mm). Specifically, fragments, foams and lines dominated among the microplastics in water, whereas fibers and fragments were dominant particles in sediments; alkyd resin, polyethylene, polystyrene and polypropylene (PP) predominated among the particles in water, but rayon, cellulose and PP were dominant particles in sediments. 4) Neither abundance nor size of microplastics in the two media was proportionally correlated and showed low similarity indexes of polymer (0.16), shape (0.29) or color (0.38). This could be related to mismatch in spatiotemporal distributions and variations in the characteristics, fate and behavior of microplastics in the two media. The findings provide knowledge for tracing the sources of plastics in the Bohai Sea.

Tissue-Specific Accumulation and Antioxidant Defenses in Flounder (Paralichthys olivaceus) Juveniles Experimentally Exposed to Methylmercury.

Methylmercury (MeHg) is the most toxic form of mercury and can accumulate in the cells of marine organisms, such as fish, causing adverse effects on various physiological functions. This study examined MeHg accumulation and its toxicological role in antioxidant defenses in tissues, including the liver, gills, and muscle of flounder (Paralichthys olivaceus) juveniles. After 30 d of MeHg exposure (0, 0.1, 1.0, 10.0, and 20.0 µg L-1), the accumulation of MeHg in the three tissues correlated positively with the concentration of MeHg and exhibited tissue specificity in the order of liver > gills > muscle. Among the antioxidant markers, the activities of SOD (superoxide dismutase) and GST (glutathione S-transferase) as well as the content of glutathione (GSH) in the liver and gills were induced at 0.1-10.0 µg L-1 but repressed at 20.0 µg L-1. The activities of SOD and GST and the content of GSH in the muscle significantly increased with increasing MeHg concentration. Catalase (CAT) activity in the liver was induced at 0.1-1.0 µg L-1 but inhibited at 10.0-20.0 µg L-1, whereas exposure to MeHg did not remarkably affect CAT activity in the gills and muscle. The levels of lipid peroxidation (LPO) increased dose dependently, showing tissue specificity with the highest level in the liver, then the gills, followed by muscles. Overall, higher sensitivity to oxidative stress induced by MeHg was detected in the liver than the gills and muscle. These findings improve our understanding of the tissue-specific accumulation of heavy metals and their roles in antioxidant responses in marine fish subjected to MeHg exposure.

Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice.

OBJECTIVE: Postoperative neurocognitive disorder (PND) is a main complication that is commonly seen postoperatively in elderly patients. The underlying mechanism remains unclear, although neuroinflammation has been increasingly observed in PND. Atorvastatin is a pleiotropic agent with proven anti-inflammatory effects. In this study, we investigated the effects of atorvastatin on a PND mouse model after peripheral surgery. MATERIAL AND METHODS: The mice were randomized into five groups. The PND models were established, and an open field test and fear condition test were performed. Hippocampal inflammatory cytokine expression was determined using ELISA. Peroxisome proliferator-activated receptor-gamma (PPARγ) expression in the hippocampus was tested using qRT-PCR and western blot analysis. RESULTS: On day 1 after surgery, inflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß, and interleukin-6 showed a significant increase in the hippocampus, with prominent cognitive impairment. Atorvastatin treatment improved cognitive function in the mouse model, attenuated neuroinflammation, and increased PPARγ expression in the hippocampus. However, treatment with the PPARγ antagonist GW9662 partially reversed the protective effects of atorvastatin. CONCLUSIONS: These results indicated that atorvastatin improves several hippocampal functions and alleviates inflammation in PND mice after surgery, probably through a PPARγ-involved signaling pathway.

Effects of seawater acidification and cadmium on the antioxidant defense of flounder Paralichthys olivaceus larvae.

Increasing atmospheric carbon dioxide has led to a decrease in the pH of the ocean, which influences the speciation of heavy metals and consequently affects metal toxicity in marine organisms. To investigate the effects of seawater acidification and metals on the antioxidant defenses of marine fishes, the flounder Paralichthys olivaceus, was continuously exposed to cadmium (Cd; control, 0.01 and 0.15 mg L-1) and acidified seawater (control (pH 8.10), 7.70 and 7.30) for 49 days from embryogenesis to settlement. The results demonstrated that both Cd and acidified seawater could induce oxidative stress and consequently cause lipid peroxidation (LPO) in the larvae. Antioxidants (i.e., superoxide dismutase, SOD; catalase, CAT; reduced glutathione, GSH; glutathione S-transferase, GST; glutathione peroxidase, GPx; and glutathione reductase, GR) functioned to defend the larvae against oxidative damage. Overall, Cd induced (SOD, GST and GSH) or inhibited (CAT and GPx) the enzymatic activities or contents of all the selected antioxidants except for GR. The antioxidants responded differently to seawater acidification, depending on their interaction with the metal. Similarly, the mRNA expressions of the antioxidant-related genes were upregulated (sod, gr and gst) or downregulated (cat and gpx) in response to increasing Cd exposure. Seawater acidification did not necessarily affect all of the biomarkers; in some cases (e.g., SOD and sod, GR and gr), Cd stress may have exceeded and masked the stress from seawater acidification in regulating the antioxidant defense of the larvae. The integrated biomarker response (IBR) was enhanced with increasing levels of the stressors. These findings support the hypothesis that seawater acidification not only directly affects the antioxidant defense in flounder larvae but also interacts with Cd to further regulate this defense. This study has ecological significance for assessing the long-term impacts of ocean acidification and metal pollution on the recruitment of fish populations in the wild.

Biomagnification of methylmercury in a marine food web in Laizhou Bay (North China) and associated potential risks to public health.

The concentrations of total mercury (THg) and methylmercury (MeHg) were assessed in water, sediment and biota (54 species) samples from the coast of Laizhou Bay, to evaluate MeHg biomagnification in Laizhou Bay food web. The trophic web structure was determined with stable isotope ratios. The MeHg concentrations were highly variable among species ranged from 4.8 ng g-1 in primary producers to 411.2 ng g-1 in spotted sea bass. Weight and ecotype were the principal parameters related to the mercury concentrations for most species. The trophic magnification factors (TMFs) for MeHg and THg were 2.09 and 1.69, respectively, indicating that mercury biomagnification is occurring in this marine food web. The estimated weekly intake (EWI) and target hazard quotient (THQ) values demonstrated that consuming predatory fishes from the bay could cause potential health risks to humans.

Antioxidant defenses and immune responses of flounder Paralichthys olivaceus larvae under methylmercury exposure.

Methylmercury (MeHg) is a highly toxic contaminant in coastal environments and poses threats to marine fish in early life stages (ELSs). However, MeHg toxicity to fish embryos and larvae is not well investigated. This study investigated the antioxidant defenses and immune responses of flounder Paralichthys olivaceus larvae exposed to waterborne MeHg (0, 0.1, 1.0 and 10.0 µg L-1) for 35 days, from embryogenesis to settlement. The results revealed that metal accumulation in the larvae was positively correlated with MeHg concentration, reduced larval growth and survival. The activities of catalase and glutathione reductase were significantly increased at 10.0 µg L-1, while glutathione peroxidase activity and lipid peroxidation level were significantly increased at concentrations over 1.0 µg L-1. The corresponding antioxidant-related genes were upregulated under MeHg exposure (cat and gpx at 10.0 µg L-1; gr over 1.0 µg L-1). Lysozyme content was significantly increased, but immunoglobulin M content was significantly decreased at 10.0 µg L-1. The immune-related genes were significantly upregulated (hsp70 at 0.1 and 10.0 µg L-1; lzm and il-1ß over 1.0 µg L-1; tnf-α and il-6 at 10.0 µg L-1) or downregulated (igm, over 0.1 µg L-1). Overall, MeHg exposure induced oxidative stress and caused immunotoxicity at concentrations over 1.0 µg L-1 and 10.0 µg L-1, respectively. The transcription of selected genes correlated with the corresponding biochemical markers in response to MeHg toxicity. These findings improve our knowledge to better understand the mechanisms by which marine fish at ELSs cope with oxidative stress and immunotoxicity induced by MeHg.

Interactive effects of strontium and barium water concentration on otolith incorporation in juvenile flounder Paralichthys olivaceus.

Although the relationship between the incorporation of an element into otoliths and the concentration of the element in water has been extensively investigated in many fish species, the interactive effects of multiple elements in water on the otolith incorporation of an element are not adequately explored or well understood. In this study, 16 treatments in triplicate using strontium (Sr; 1, 2, 3 and 4 times the ambient baseline, 6.5 mg l-1) and barium (Ba; 1, 2, 4 and 6 times the ambient baseline, 40 µg l-1) as categorical variables in an orthogonal design were established to evaluate the relative or interactive effects of water elements on otolith elemental incorporation in juvenile flounder Paralichthys olivaceus (from 15 to 116 days post hatching). The results revealed that otolith incorporation (Me:CaOtolith) of Sr and Ba were positively dependent on the concentrations of the elements in water (Me:CaWater). Overall, Sr was incorporated into otoliths more efficiently than was Ba, and the partition efficiency (DMe) of both elements decreased with increasing water elemental concentrations. Increasing Sr concentrations in water appeared to negatively affect the uptake of Ba into otoliths rather than facilitate it, as previously reported in fish reared in freshwater and brackish water, or showed no effect on fish in seawater. Conversely, the Ba concentration in water did not influence the otolith uptake of Sr, which agrees with the findings for other fish species. When applying otolith microchemistry to fish ecology studies, it is essential to cautiously address the interactive effects of multiple elements in the environment on otolith elemental incorporation.