Single and mixture toxicity of cadmium and copper to swim bladder in early life stages of Japanese medaka (Oryzias latipes).

Toxicity observed in aquatic ecosystems often cannot be explained by the action of a single pollutant. Likewise, evaluation standards formulated by a single effect cannot truly reflect the environmental quality requirements. The study of mixtures is needed to provide environmental relevance and knowledge of combined toxicity. In this study, the embryos of Japanese medaka (Oryzias latipes) were treated with individual and binary mixture of copper (Cu) and cadmium (Cd) until 12 days post-fertilization (dpf). Hatching, mortality, development, histology and gene expression were assessed. Our results showed that the highest concentration mixture of Cd (10 mg/L) and Cu (1 mg/L) affected survival, hatching time and hatching success. Occurrence of uninflated swim bladder was the highest (value) with exposure to 10 mg/L Cd. Swim bladder was commonly over-inflated in a mixture (0.1 mg/L Cd + 1.0 mg/L Cu) exposure. Individuals exposed to the mixture (0.1 Cd + 1.0 Cu mg/L) showed up to a 7.69% increase in swim bladder area compared to the control group. The mixtures containing 0.1 or 10 mg/L Cd, each with 1.0 mg/L Cu resulted in significantly increased of Pbx1b expression, higher than any Cd or Cu alone (p < 0.01). In the co-exposure group (0.1/10 Cd + 1.0 Cu mg/L), Pbx1b expression was found at 12 dpf but not 7 dpf in controls. Higher concentrations of Cd may progressively reduce Pbx1b expression, potentially explaining why 75% of individuals in the 10 mg/L Cd group failed to inflate their swim bladders. Additionally, the swim bladder proved to be a valuable bio-indicator for biological evaluation.

Inhibitory Effect of Acetaminophen on Ocular Pigmentation and its Relationship with Thyroxine in Zebrafish Embryos.

Acetaminophen (N-acetyl-p-aminophenol; APAP) is one of the most widely used analgesics. To examine the toxicity of APAP, we used zebrafish embryos as model animals to detect the effect of APAP on the thyroid system of zebrafish embryos. The zebrafish embryos were exposed to APAP from 4 h post fertilization (4 hpf) until observation. The experimental results showed that APAP caused pericardial edema and decreased pigmentation in the zebrafish embryos or larvae. The APAP treatment caused a decrease in the expression of tpo and thrß in the zebrafish at 36 and 72 hpf. The transcriptomic analysis found that APAP affected retinol metabolism, the metabolism of xenobiotics by cytochrome P450, and the tyrosine metabolism pathway. The harmful effect of APAP on zebrafish embryos might be due to its disrupting effect on the functional regulation of the thyroid hormone system.

Incidental gall bladder cancer in the laparoscopic treatment and magnetic resonance imaging era: A single institution experience.

BACKGROUND: Incidental gall bladder cancer (IGBC) is often discovered unexpectedly in patients after cholecystectomy. Currently, magnetic resonance imaging (MRI) has been widely applied in the pre-operative diagnosis of gall bladder diseases as laparoscopic cholecystectomy developed into the preferred method. AIMS AND OBJECTIVES: This study aimed to evaluate the pre-operative MRI application and laparoscopic management in the IGBCs. MATERIALS AND METHODS: Between January 2011 and January 2020, a total of 7917 patients with gall bladder diseases treated by laparoscopy were enrolled in this study. RESULTS: Amongst 49 patients diagnosed with IGBCs, the incidence of IGBCs in polypoid lesions, biliary pancreatitis, cholecystitis, cholecystocholedocholithiasis and gall bladder stones was 0.42%, 1.19%, 0.62%, 1.20% and 0.49%, respectively. MRI evaluation showed more remarkable pre-operative imaging as compared to ultrasonographic evaluation (40.8 vs. 26.5, P < 0.05). Furthermore, 14 patients were diagnosed with gall bladder cancer through intraoperative histological examination and 11 received laparoscopic extensive resection after cholecystectomy. MRI findings with diffuse thickening of the gall bladder detected IGBCs with 6.1% sensitivity, 96.02 specificity, 0.95% positive predictive values and 99.4% negative predictive values; diffuse thickening of the gall bladder with suspicion of malignancy detected IGBCs with 12.2% sensitivity, 99.1% specificity, 7.6% positive predictive values and 99.5% negative predictive values; focal thickening of the gall bladder detected IGBCs with 16% sensitivity, 99.8% specificity, 32% positive predictive values and 99.5% negative predictive values; moreover, suspicious lesion detected IGBCs with 6.1% sensitivity, 99.6% specificity, 8.8% positive predictive values and 99.4% negative predictive values. CONCLUSIONS: Patients with biliary pancreatitis and cholecystocholedocholithiasis have a higher incidence of IGBC. MRI evaluation could provide more accurate information for the IGBCs, which should be recommended for patients accepting cholecystectomy. MRI findings exhibited an unsatisfactory sensitivity when detecting IGBCs, but they represented high specificity. Pre-operative MRI evaluation and intraoperative histological examination may help some IGBCs to achieve one-stage laparoscopic extensive resection.

The effectiveness of endoscopic ultrasonography findings to distinguish benign and malignant intraductal papillary mucinous neoplasm.

BACKGROUND AND AIMS: Accurate evaluation of intraductal papillary mucinous neoplasm (IPMN) is necessary to inform clinical decision-making. But it is still difficult to distinguish benign and malignant IPMN preoperatively. This study aims to evaluate the utility of EUS to predict the pathology of IPMN. METHODS: Patients with IPMN who underwent endoscopic ultrasound within 3 months before surgery were collected from six centers. Logistic regression model and random forest model were used to determine risk factors associated with malignant IPMN. In both models, 70% and 30% of patients were randomly assigned to the exploratory group and validation group, respectively. Sensitivity, specificity, and ROC were used in model assessment. RESULTS: Of the 115 patients, 56 (48.7%) had low-grade dysplasia (LGD), 25 (21.7%) had high-grade dysplasia (HGD), and 34 (29.6%) had invasive cancer (IC). Smoking history (OR = 6.95, 95%CI: 1.98-24.44, p = 0.002), lymphadenopathy (OR = 7.91, 95%CI: 1.60-39.07, p = 0.011), MPD > 7 mm (OR = 4.75, 95%CI: 1.56-14.47, p = 0.006) and mural nodules > 5 mm (OR = 8.79, 95%CI: 2.40-32.24, p = 0.001) were independent risk factors predicting malignant IPMN according to the logistic regression model. The sensitivity, specificity, and AUC were 0.895, 0.571, and 0.795 in the validation group. In the random forest model, the sensitivity, specificity, and AUC were 0.722, 0.823, and 0.773, respectively. In patients with mural nodules, random forest model could reach a sensitivity of 0.905 and a specificity of 0.900. CONCLUSIONS: Using random forest model based on EUS data is effective to differentiate benign and malignant IPMN in this cohort, especially in patients with mural nodules.

Cardiotoxicity of (-)-borneol, (+)-borneol, and isoborneol in zebrafish embryos is associated with Na+ /K+ -ATPase and Ca2+ -ATPase inhibition.

Borneol is an example of traditional Chinese medicine widely used in Asia. There are different isomers of chiral borneol in the market, but its toxicity and effects need further study. In this study, we used zebrafish embryos to examine the effects of exposure to three isomers of borneol [(-)-borneol, (+)-borneol, and isoborneol] on heart development and the association with Na+ /K+ -ATPase from 4 h post-fertilization (4 hpf). The results showed that the three isomers of borneol increased mortality and decreased hatching rate when the zebrafish embryo developed to 72 hpf. All three isomers of borneol (0.01-1.0 mM) significantly reduced heart rate from 48 to 120 hpf and reduced the expression of genes related to Ca2+ -ATPase (cacna1ab and cacna1da) and Na+ /K+ -ATPase (atp1b2b, atp1a3b, and atp1a2). At the same time, the three isomers of borneol significantly reduced the activities of Ca2+ -ATPase and Na+ /K+ -ATPase at 0.1 to 1.0 mM. (+)-Borneol caused the most significant reduction (p < 0.05), followed by isoborneol and (-)-borneol. Na+ /K+ -ATPase was mainly expressed in otic vesicles and protonephridium. All three isomers of borneol reduced Na+ /K+ -ATPase mRNA expression, but isoborneol was the most significant (p < 0.01). Our results indicated that (+)-borneol was the least toxic of the three isomers while the isoborneol showed the most substantial toxic effect, closely related to effects on Na+ /K+ -ATPase.

Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease.

A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1ß and NO. In addition, compound 3f presented significant neuroprotective effect on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl3-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.

Pseudoephedrine hydrochloride causes hyperactivity in zebrafish via modulation of the serotonin pathway.

This study aimed to explore behavioral changes of embryonic and larval zebrafish caused by pseudoephedrine hydrochloride (PSE) and its underlying mechanism. Zebrafish embryos were exposed to 0.5 µM, 2 µM, and 8 µM PSE at 4 h post-fertilization (4 hpf) or 22-23 hpf. Mortality, hatching rate, coiling frequency, heart rate, behavior changes, and related gene expression were observed at different developmental stages. PSE below 8 µM did not affect zebrafish mortality, hatching rate, and heart rate compared with the control group. For embryos, PSE caused an increase at 16-32 hpf in zebrafish coiling frequency which could be rescued by serotonin antagonist WAY100635. Similarly, PSE caused an increase in the swimming distance of zebrafish larvae at 120 hpf. PSE also elevated the expression of serotonin (5-HT)-related genes 5-htr1ab and tph2 and dopamine-related gene dbh. Behavioral changes in zebrafish embryos and larvae caused by PSE may be closely associated with increased expression of 5-HT and dopamine-related genes. This may be reflected that the behavioral changes in zebrafish are a possible PSE monitoring indicator.

Effect of artificial skin membrane on the expression of miR-155 and miR-506-3p in patients with second-degree burns.

OBJECTIVE: To investigate the effect of artificial skin on the expression of miR-155 and miR-506-3p in patients with second-degree burns. METHODS: The study subjects included 50 patients with second-degree burns treated from July 2019 to July 2021. The control group received routine nursing, while the research group received both routine and artificial skin intervention simultaneously. The changes in wound tissue fibrosis and prognosis were observed. The expression levels of miR-155 and miR-506-3p and their downstream regulatory factors were detected and correlated with the rehabilitation of patients after artificial skin treatment. RESULTS: After treating second-degree burns with artificial skin membranes, the patient's wound tissue fibrosis and inflammation level improved. At the same time, the expression levels of miR-155 and miR-506-3p in related tests were higher than those in patients with available treatment. CONCLUSION: The effect of artificial skin membrane on the wound healing of second-degree burn patients may be realized by influencing the expression levels of miR-155 and miR-506-3p and their related signaling pathways.

Altered life history traits and transcripts of molting- and reproduction-related genes by cadmium in Daphnia magna.

Cadmium (Cd) is a non-essential element and can be toxic to aquatic organisms at low concentrations. Despite its well-known toxicity to Daphnia magna, the effects of Cd on physiological parameters (heart rate and thoracic limb activity) and molting- and reproduction-related genes are relatively understudied. In this study, D. magna were exposed to 0 (control), 25, 50 and 75 µg L-1 of Cd for 7 d and 21 d to determine the toxicity of Cd. The results showed that the Cd body burden in D. magna was significantly increased with elevated Cd concentrations, up to 13.4 µg Cd/g dry weight (dw) after exposure to 75 µg L-1 for 21 d. After 21 d of exposure, the body length and body weight of D. magna were significantly decreased in all Cd treatments compared to the control. The heart rate and thoracic limb activity were reduced by 4.3-11.7 and 5.0-10.3%, respectively. The levels of malondialdehyde (MDA) were increased by ~24-37% and the activity of catalase (CAT) was inhibited by ~50% compared to the control. The reproductive parameters (i.e., size of the first brood, the total number of offspring per female and the number of offspring per brood) were remarkably reduced, causing adverse effects on the population dynamics. In addition, the transcripts of genes (cyp314, cyp18a1, ecra, usp, hr3, cut, cht and cht3) related to the molting of D. magna were altered, whereas the transcripts of genes (vtg1, vtg2 and vmo1) related to reproduction were down-regulated. This study helps better understand the effects of Cd at different biological levels.

Effects of ferulic acid on muscle development and intestinal microbiota of zebrafish.

Ferulic acid (FA) is one of a common ingredients in Chinese herbal medicine. FA has the interesting property of promoting growth and improving meat quality in livestock, but the mechanism is not understood. This study evaluated both safety and mechanism of efficacy in zebrafish model. At 15 µg/mL or above, FA led to pericardial oedema and delayed growth in zebrafish embryos. Dietary FA promoted growth and feed assimilation in male adult zebrafish. Genes related to myogenic development (myod1, myog and myf5) were significantly upregulated by FA and muscle fibre width in skeletal muscle was increased. At 20 µg/g, FA significantly increased number of goblet cells in zebrafish intestinal tissue, and gut microbiota composition also changed. Based on 16s rRNA gene sequences, 20 µg/g FA decreased Firmicutes and increased Bacteroides. 20 µg/g FA also stimulated the expression of PPAR-α, a gene associated with fat metabolism, and decreased the expression of PPAR-ß and PPAR-γ. These gene expression changes were beneficial to fatty acid synthesis and metabolism and decreased fat deposition. Our overall results indicated that FA can be a safe growth promotor in fish particularly in skeletal muscles.

Real-time capture of single particles in controlled flow by a rapidly generated foci array with adjustable intensity and pattern.

We propose a new, to the best of our knowledge, technique to capture single particles in real-time in a microfluidic system with controlled flow using micro-pillar traps fabricated by one-step. The micro pillars are fabricated in parallel by femtosecond multi-foci laser beams, which are generated by multiplexing gratings. As the generation process does not need integration loops, the pattern and the intensity distribution of the foci array can be controlled in real-time by changing the parameters of gratings. The real-time control of the foci array enables rapidly fabricating microtraps in the microchannel with adjustment of the pillar spaces and patterns according to the sizes and shapes of target particles. This technology provides an important step towards using platforms based on single-particle analysis, and it paves the way for the development of innovative microfluidic devices for single-cell analysis.

Aconitine disrupts serotonin neurotransmission via 5-hydroxytryptamine receptor in zebrafish embryo.

Medicinal plants of the genus Aconitum are one of the most commonly used herbs in traditional medicine in East Asia to treat conditions related to the heart, pain, or inflammation. However, these herbs are also dangerous as accidental poisoning due to misuse is a recurring issue. These plants contain a number of diester-diterpenoid alkaloid compounds and aconitine is the most abundant and active one. This study investigated neurotoxicity of aconitine to zebrafish embryos in early development in relation to serotonin regulation. Experimental results showed that aconitine exposure (1, 10, and 100 µM) increased frequency of coiling behavior in zebrafish embryos in a dose-dependent manner and this effect can be triggered by either exposure to 5-hydroxytryptamine 1A (5-HT1A) receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) or overexpression of serotonin receptor 5-htr1ab. At the same time, coiling behavior caused by aconitine exposure could be rescued by co-exposure to 5-HT1A receptor antagonist WAY-100635 Maleate (WAY100635) and knockdown of 5-htr1ab using morpholino. Exposure to aconitine also significantly increased serotonin receptor 5-htr1ab and 5-htr1bd gene expression at 24 h post fertilization (hpf), but decreased their expression and protein expression of the serotonin receptor at 96 hpf with the high dose. These results suggest that neurotoxicity caused by aconitine is mediated through the 5-HT receptor.

Career choice and influential factors among medical students majoring in psychiatry in China.

BACKGROUND: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. METHOD: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career. RESULTS: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career. CONCLUSION: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

In silico analysis of the immune microenvironment in bladder cancer.

BACKGROUND: Infiltrating immune and stromal cells are vital components of the bladder cancer (BC) microenvironment, which can significantly affect BC progression and outcome. However, the contribution of each subset of tumour-infiltrating immune cells is unclear. The objective of this study was to perform cell phenotyping and transcriptional profiling of the tumour immune microenvironment and analyse the association of distinct cell subsets and genes with BC prognosis. METHODS: Clinical data of 412 patients with BC and 433 transcription files for normal and cancer tissues were downloaded from The Cancer Genome Atlas. The CIBERSORT algorithm was used to determine the relative abundance of 22 immune cell types in each sample and the ESTIMATE algorithm was used to identify differentially expressed genes within the tumour microenvironment of BC, which were subjected to functional enrichment and protein-protein interaction (PPI) analyses. The association of cell subsets and differentially expressed genes with patient survival and clinical parameters was examined by Cox regression analysis and the Kaplan-Meier method. RESULTS: Resting natural killer cells and activated memory CD4+ and CD8+ T cells were associated with favourable patient outcome, whereas resting memory CD4+ T cells were associated with poor outcome. Differential expression analysis revealed 1334 genes influencing both immune and stromal cell scores; of them, 97 were predictive of overall survival in patients with BC. Among the top 10 statistically significant hub genes in the PPI network, CXCL12, FN1, LCK, and CXCR4 were found to be associated with BC prognosis. CONCLUSION: Tumour-infiltrating immune cells and cancer microenvironment-related genes can affect the outcomes of patients and are likely to be important determinants of both prognosis and response to immunotherapy in BC.

Subchronic effects of dietary selenium yeast and selenite on growth performance and the immune and antioxidant systems in Nile tilapia Oreochromis niloticus.

Selenium is an essential element but toxic at high levels in animals. The effects of Se on growth performance and the immune system in Nile tilapia remain inconclusive. In this study, Nile tilapia Oreochromis niloticus was fed on selenium yeast (Se(Y))- and selenite (Se(IV))-enriched feed at 0, 3, 6, and 12 µg/g (dry wt) for 45 and 90 d. The growth, bioaccumulation, biochemical markers related to antioxidant, immunological, nervous and digestive systems were evaluated in various fish tissues (liver, intestine, kidney, muscle, brain, spleen, gills). The results showed that the accumulation of Se(Y) was 1.3-2 folds of Se(IV) in most tissues. The growth of tilapia was enhanced by both Se(Y) and Se(IV) at 3 µg/g after 90 d, with Se(Y) better than Se(IV) in tilapia feed. After 45 d, the levels of lipid peroxidation, the activity of the antioxidant enzymes, and the transcriptional levels of the immune related genes (IL-1ß, IFN-γ and TNF-α) and stress proteins (HSP70 and MT) were enhanced in all treatments, except that of MT in the 12 µg/g Se(Y) group. In addition, both Se species inhibited the activity of acetylcholinesterase (AChE) in the brain and one digestive enzyme α-glucosidase (α-Glu) in the intestine at 12 µg/g. However, after 90 d, the effects on most biochemical markers were less pronounced, implying a possible acclimation after prolonged duration. The results demonstrate Se is beneficial to O. niloticus at low levels and toxic at elevated levels. The immunostimulation by Se might be greatly weakened after long term feeding Se-enriched feed. This study helps to better understand the effects of Se on the antioxidant and immune systems and to establish the optimal Se levels in the feed and duration for O. niloticus.

Metallic elements in human hair from residents in smelting districts in northeast China: Environmental factors and differences in ingestion media.

The health of residents in Huludao City is affected by the emissions of heavy metals from smelting, diet and atmospheric precipitation. This study investigated the concentrations of Hg, Cd, Pb, Cu and Zn in scalp hair samples from 259 residents of different ages and genders from five districts in Huludao City and examined the main factors for heavy metal exposure. Cd and Pb concentrations in hair samples exceeded the normal concentration ranges for human hair (Cd < 0.3 mg/kg; Pb < 9.3 mg/kg), and the highest Pb concentrations were found in subjects in the age range 0-15 years. Samples from men were higher in Cd and Pb compared to those for women. Workers from the Huludao zinc plant (HZP) had higher concentrations of all metals in their hair relative to other occupations except for Cu. Geographically, the highest Cd and Pb concentrations in hair were found for residents living in Daochi district (DCD) and the Zn plant district (ZPD), respectively. In smelting regions, the effects of dust ingestion on heavy metal exposure were more important than in non-smelting regions.

UCP2 protect the heart from myocardial ischemia/reperfusion injury via induction of mitochondrial autophagy.

Uncoupling protein 2 (UCP2), located in the mitochondrial inner membrane, is a predominant isoform of UCP that expressed in the heart and other tissues of human and rodent tissues. Nevertheless, its functional role during myocardial ischemia/reperfusion (I/R) is not entirely understood. Ischemic preconditioning (IPC) remarkably improved postischemic functional recovery followed by reduced lactate dehydrogenase (LDH) release with simultaneous upregulation of UCP2 in perfused myocardium. We then investigated the role of UCP2 in IPC-afforded cardioprotective effects on myocardial I/R injury with adenovirus-mediated in vivo UCP2 overexpression (AdUCP2) and knockdown (AdshUCP2). IPC-induced protective effects were mimicked by UCP2 overexpression, while which were abolished with silencing UCP2. Mechanistically, UCP2 overexpression significantly reinforced I/R-induced mitochondrial autophagy (mitophagy), as measured by biochemical hallmarks of mitochondrial autophagy. Moreover, primary cardiomyocytes infected with AdUCP2 increased simulated ischemia/reperfusion (sI/R)-induced mitophagy and therefore reversed impaired mitochondrial function. Finally, suppression of mitophagy with mdivi-1 in cultured cardiomyocytes abolished UCP2-afforded protective effect on sI/R-induced mitochondrial dysfunction and cell death. Our data identify a critical role for UCP2 against myocardial I/R injury through preventing the mitochondrial dysfunction through reinforcing mitophagy. Our findings reveal novel mechanisms of UCP2 in the cardioprotective effects during myocardial I/R.

The case for thyroid disruption in early life stage exposures to thiram in zebrafish (Danio rerio).

Thiram, a pesticide in the dithiocarbamate chemical family, is widely used to prevent fungal disease in seeds and crops. Its off-site movement to surface waters occurs and may place aquatic organisms at potential harm. Zebrafish embryos were used for investigation of acute (1 h) thiram exposure (0.001-10 µM) at various developmental stages. Survival decreased at 1 µM and 10 µM and hatching was delayed at 0.1 µM and 1 µM. Notochord curvatures were seen at 0.1 and 1 µM thiram when exposure was initiated at 2 and at 10 hpf. Similar notochord curvatures followed exposure to the known TPO inhibitor, methimazole (MMI). Changes were absent in embryos exposed at later stages, i.e., 12 hpf. In embryos exposed to 0.1 or 1 µM at 10 hpf, levels of the thyroid enzyme, Deiodinase 3, increased by 12 hpf. Thyroid peroxide (TPO), important in T4 synthesis, decreased by 48 hpf in embryos exposed to 1 µM at 10 hpf. Thiram toxicity was stage-dependent and early life stage exposure may be responsible for adverse effects seen later. These effects may be due to impacts on the thyroid via regulation of specific thyroid genes including TPO and Deiodinase 3.

Use of biological detection methods to assess dioxin-like compounds in sediments of Bohai Bay, China.

Bohai Bay, in the western region of northeastern China's Bohai Sea, receives water from large rivers containing various pollutants including dioxin-like compounds (DLCs). This study used the established zebrafish (Danio rerio) model, its known developmental toxicity endpoints and sensitive molecular analyses to evaluate sediments near and around an industrial effluent site in Bohai Bay. The primary objective was to assess the efficacy of rapid biological detection methods as an addition to chemical analyses. Embryos were exposed to various concentrations of sediment extracts as well as a 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) positive control. Exposure to sediment extract nearest the discharge site (P1) resulted in the most severe- and highest rates of change in embryos and larvae, suggesting that DLC contaminated sediment probably did not occur much beyond it. P1 extract resulted in concentration dependent increases in mortality and pericardial edema. Its highest concentration caused up-regulation of P-450 (CYP)-1A1(CYP1A) mRNA expression at 72 h post fertilization (hpf), an increase in its expression in gill arches as observed by whole mount in situ hybridization, and an increased signal in the Tg(cyp1a: mCherry) transgenic line. The pattern and magnitude of response was very similar to that of TCDD and supported the presence of DLCs in these sediment samples. Follow-up chemical analysis confirmed this presence and identified H7CDF, O8CDF and O8CDD as the main components in P1 extract. This study validates the use of biological assays as a rapid, sensitive, and cost-effective method to evaluate DLCs and their effects in sediment samples. Additionally, it provides support for the conclusion that DLCs have limited remobilization capacity in marine sediments.

The Toxicological Effects of Mercury Exposure in Marine Fish.

Since the Minamata incident in Japan, the public have become increasingly aware of the negative health effects caused by mercury pollution in the ocean. Consequently, there has been significant interest in the health of humans eating fish exposed to mercury (Hg). However, the toxicity of mercury to the marine fish themselves has received far less attention. In this review, we summarize mercury accumulation in marine fish and the toxicological effects of mercury exposure. Results showed that the bioaccumulation of mercury in marine fish was highly variable, and its concentration was affected by the specific physiological and ecological characteristics of different fish species. Mercury exposure can produce teratogenic, neurotoxic effects, and reproductive toxicity. These effects can then cause harm to cells, tissues, proteins and genes, and ultimately, the survival, growth, and behavior of marine fish. Future studies should afford more attention to the toxicological effect of mercury exposure upon marine fish.