Ultrasound manifestations and clinical analysis of 50 cases of heterotopic pregnancy.

OBJECTIVE: To investigate the value of ultrasonography in the diagnosis of heterotopic pregnancy and the follow-up. METHODS: A retrospective analysis of 50 cases of clinically diagnosed heterotopic pregnancy in our hospital was performed, the clinical characteristics and ultrasonographic manifestations of the patients were summarized, the reasons for initial ultrasound missed diagnosis and misdiagnosis were analyzed, and the pregnancy outcomes were followed up. RESULTS: Among the 50 cases, the initial ultrasound diagnoses of intrauterine pregnancy were all gestational sac type, 32 cases of ectopic pregnancy were located in the fallopian tube, and 10 cases were located in the uterine horn, 1 case at cervix, and 1 case at caesarean section scar. Forty-one cases were consistent with surgery and/or pathology, representing initial ultrasound diagnosis coincidence rate of about 82%. Six cases were missed in the initial ultrasound examination (12%), and three cases were misdiagnosed (6%). The maximum diameter of the intrauterine gestational sac was 9-48 mm, the average was about 24.90 ± 9.56 mm, the maximum diameter of the ectopic pregnancy gestational sac or mass was 11-63 mm, and the average was about 31.45 ± 13.82 mm (p < 0.05). Intrauterine pregnancy outcomes were followed up, 45 patients with complete data and 5 patients were lost to follow-up. The follow-up rate was about 90%. CONCLUSION: Combining the patient's medical history and clinical characteristics can reduce missed diagnosis and misdiagnosis of heterotopic pregnancy. Ultrasonography has important value in the assessment of intrauterine pregnancy growth and development, and the integrity of maternal uterus.

Comparison of cardiotoxicity induced by alectinib, apatinib, lenvatinib and anlotinib in zebrafish embryos.

Four tyrosine kinase inhibitors, alectinib, apatinib, lenvatinib and anlotinib, have been shown to be effective in the treatment of clinical tumors, but their cardiac risks have also raised concerns. In this study, zebrafish embryos at 6 h post fertilization (hpf) were exposed to the four drugs at concentrations of 0.05-0.2 mg/L until 72 hpf, and then the development of these embryos was quantified, including heart rate, body length, yolk sac area, pericardial area, distance between venous sinus and balloon arteriosus (SV-BA), separation of cardiac myocytes and endocardium, gene expression, vascular development and oxidative stress. At the same exposure concentrations, alectinib and apatinib had little effect on the cardiac development of zebrafish embryos, while lenvatinib and anlotinib could induce significant cardiotoxicity and developmental toxicity, including shortened of body length, delayed absorption of yolk sac, pericardial edema, prolonged SV-BA distance, separation of cardiomyocytes and endocardial cells, and downregulation of key genes for heart development. Heart rate decreased in all four drug treatment groups. In terms of vascular development, alectinib and apatinib did not inhibit the growth of embryonic intersegmental vessels (ISVs) and retinal vessels, while lenvatinib and anlotinib caused serious vascular toxicity, and the inhibition of anlotinib in vascular development was more obvious. Besides, the level of reactive oxygen species (ROS) in the lenvatinib and anlotinib treatment groups was significantly increased. Our results provide reference for comparing the cardiotoxicity of the four drugs.

Dimethyl fumarate induces cardiac developmental toxicity in zebrafish via down-regulation of oxidative stress.

Dimethyl fumarate (DMF) is an immunosuppressant commonly used to treat multiple sclerosis and other autoimmune diseases. Despite known side effects such as lymphopenia, the effect of DMF on cardiac development remains unclear. To assess this, we used zebrafish to evaluate the cardiac developmental toxicity of DMF. Our study showed that DMF reduced the survival rate of zebrafish embryos, with those exposed to 1, 1.3, and 1.6 mg/L exhibiting heart rate reduction, shortened body length, delayed yolk sac absorption, pericardial edema, increased distance from sinus venous to bulbus arteriosus, and separation of cardiomyocytes and endocardial cells at 72 hpf. Heart development-related genes showed disorder, apoptosis-related genes were up-regulated, and the oxidative stress response was down-regulated. Treatment with cysteamine ameliorated the heart development defects. Our study demonstrates that DMF induces cardiac developmental toxicity in zebrafish, possibly by down-regulating oxidative stress responses. This study provides a certain research basis for further study of DMF-induced cardiac developmental toxicity, and provides some experimental evidence for future clinical application and study of DMF.

Amino acids analysis reveals serum methionine contributes to diagnosis of the Kawasaki disease in mice and children.

BACKGROUND: Kawasaki disease (KD) patients often lack early and definitive diagnosis due to insufficient clinical criteria, whereas biomarkers might accelerate the diagnostic process and treatment. METHODS: The KD mouse models were established and thirteen amino acids were determined. A total of 551 serum samples were collected including KD patients (n = 134), HCs (n = 223) and KD patients after intravascular immunoglobulin therapy (IVIG, n = 194). A paired analysis of pre- and post-IVIG was employed in 10 KD patients. RESULTS: The pathological alterations of the aorta, myocardial interstitium and coronary artery vessel were observed in KD mice; the serum levels of methionine in KD mice (n = 40) were markedly altered and negatively correlated with the C-reactive protein levels. Consistent with the mouse model, serum methionine were significantly decreased in KD children, with the relative variation ratio of KD with HCs above 30% and AUROC value of 0.845. Serum methionine were correlated with Z-Score and significantly restored to the normal ranges after KD patient IVIG treatment. Another case-control study with 10 KD patients with IVIG sensitivity and 20 healthy controls validated serum methionine as a biomarker for KD patients with AUROC of 0.86. Elevation of serum DNMT1 activities, but no differences of DNMT3a and DNMT3b, were observed in KD patients when comparing with those in the HCs. CONCLUSIONS: Our study validated that serum methionine was a potential biomarker for KD, the alteration of which is associated with the activation of DNMT1 in KD patients.

Apatinib induces zebrafish hepatotoxicity by inhibiting Wnt signaling and accumulation of oxidative stress.

Apatinib, a small-molecule VEGFR2-tyrosine kinase inhibitor, has shown potent anticancer activity in various clinical cancer treatments, but also different adverse reactions. Therefore, it is necessary to study its potential toxicity and working mechanism. We used zebrafish to investigate the effects of apatinib on the development of embryos. Zebrafish exposed to 2.5, 5, and 10 µM apatinib showed adverse effects such as decreased liver area, pericardial oedema, slow yolk absorption, bladder atrophy, and body length shortening. At the same time, it leads to abnormal liver tissue structure, liver function and related gene expression. Furthermore, after exposure to apatinib, oxidative stress levels were significantly elevated but liver developmental toxicity was effectively ameliorated with oxidative stress inhibitor treatment. Apatinib induces down-regulation of key target genes of Wnt signaling pathway in zebrafish, and it is found that Wnt activator can significantly rescue liver developmental defects. These results suggest that apatinib may induce zebrafish hepatotoxicity by inhibiting the Wnt signaling pathway and up-regulating oxidative stress, helping to strengthen our understanding of rational clinical application of apatinib.

Roxadustat induces hepatotoxicity in zebrafish embryos via inhibiting Notch signaling.

Roxadustat is a novel and effective small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PHI). However, little research has been done on its toxicity to vertebrate embryonic development. In this study, we used zebrafish to assess the effects of roxadustat on early embryonic development. Exposure to 14, 28, and 56 µM roxadustat resulted in abnormal embryonic development in zebrafish embryos, such as shortened body length and early liver developmental deficiency. Roxadustat exposure resulted in liver metabolic imbalance and abnormal liver tissue structure in adult zebrafish. In addition, roxadustat could up-regulate oxidative stress, and astaxanthin (AS) could partially rescue liver developmental defects by down-regulation of oxidative stress. After exposure to roxadustat, the Notch signaling is down-regulated, and the use of an activator of Notch signaling can partially rescue hepatotoxicity. Therefore, our research indicates that roxadustat may induce zebrafish hepatotoxicity by down-regulating Notch signaling. This study provides a reference for the clinical use of roxadustat.

Cyclosporine A induces hepatotoxicity in zebrafish larvae via upregulating oxidative stress.

As a powerful immunosuppressant, cyclosporine A (CsA) is widely used clinically. However, it has been found to have many side effects including nephrotoxicity and neurotoxicity. Despite this, some patients cannot avoid using CsA during pregnancy and this can be detrimental to both the patient and the foetus. This study used zebrafish as a model animal to evaluate the hepatotoxic effects of CsA in zebrafish embryos. Zebrafish embryos cultured at 72 post-fertilization (hpf) were exposed to three concentrations of CsA at 2.5 mg/L, 5 mg/L, and 10 mg/L for 72 h. Liver developmental defects, smaller or missing swim bladder, slower heart rate, reduced body length, and delayed yolk sac absorption were observed. The level of oxidative stress (ROS) increased with the increase of CsA concentration. The indicators of related oxidative stress kinase activities including malondialdehyde (MDA), catalase (CAT) and SOD, all appeared to significantly increased. The use of astaxanthin (ATX) to inhibit oxidative stress was found to be useful for rescuing zebrafish hepatic development defects. Therefore, our results suggest that CsA induces zebrafish embryonic hepatic development defects by activating the oxidative stress. The study of CsA-induced hepatic development defects of zebrafish embryos is helpful for clinical evaluation of the safety of CsA and enables the search for new use without side effects.

Pamiparib Induces Neurodevelopmental Defects and Cerebral Haemorrhage in Zebrafish Embryos via Inhibiting Notch Signalling.

Pamiparib is a poly ADP-ribose polymerase (PARP) inhibitor used in clinical studies, which can penetrate the blood-brain barrier efficiently. At present, there are few studies on its effect on vertebrate neurodevelopment. In this study, we exposed zebrafish embryos to 1, 2 and 3 µM of Pamiparib from 6 to 72 h post-fertilisation (hpf). Results showed that pamiparib can specifically induce cerebral haemorrhage, brain atrophy and movement disorders in fish larvae. In addition, pamiparib exposure leads to downregulation of acetylcholinesterase (AChE) and adenosine triphosphate (ATPase) activities, and upregulation of oxidative stress which then leads to apoptosis and disrupts the gene expression involved in the neurodevelopment, neurotransmitter pathways and Parkinson's disease (PD) like symptoms. Meanwhile, astaxanthin can partially rescue neurodevelopmental defects by downregulating oxidative stress. After exposure to pamiparib, the Notch signalling is downregulated, and the use of an activator of Notch signalling can partially rescue neurodevelopmental toxicity. Therefore, our research indicates that pamiparib may induce zebrafish neurotoxicity by downregulating Notch signalling and provides a reference for the potential neurotoxicity of pamiparib during embryonic development.

Cyclosporine A Induces Cardiac Developmental Toxicity in Zebrafish by Up-Regulation of Wnt Signaling and Oxidative Stress.

Due to the widely application of Cyclosporine A (CsA) as an immunosuppressant in clinic, it is necessary to study its potential toxicity. Therefore, we used zebrafish as a model animal to evaluate the toxicity of CsA on embryonic development. Exposure of zebrafish embryos to CsA at concentrations of 5 mg/L, 10 mg/L, and 15 mg/L from 12 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered, and the apoptotic genes were up-regulated. Oxidative stress level was up-regulated and accumulated in pericardium in a dose-dependent manner. Astaxanthin (ATX) treatment could significantly alleviate zebrafish heart defects. CsA induced up-regulation of Wnt signaling in zebrafish, and IWR-1, an inhibitor of Wnt signaling pathway, could effectively rescue the heart defects induced by CsA. Together, our study indicated that CsA induced cardiac developmental toxicity in zebrafish larvae through up-regulating oxidative stress and Wnt signaling, contributing to a more comprehensive evaluation of the safety of the drug.

TLR4 Knockout Attenuates BDL-induced Liver Cholestatic Injury through Amino Acid and Choline Metabolic Pathways.

The exact mechanism by which knockout of Toll-like receptor 4 (TLR4) attenuates the liver injury remains unclear. The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation (BDL)-induced liver cholestatic injury and the underlying mechanism. Wild type (WT) mice and TLR4 knockout (TLR4-KO) mice were used for the establishment of the BDL model. Metabolomics were applied to analyze the changes of small molecular metabolites in the serum and liver of the two groups. The serum biochemical indexes and the HE staining results of liver tissue showed that liver damage was significantly reduced in TLR4-KO mice after BDL when compared with that in WT mice. The metabolite analysis results showed that TLR4 KO could maintain the metabolisms of amino acids- and choline-related metabolites. After BDL, the amino acids- and choline-related metabolites, especially choline and 3-hydroxybutyrate, were significantly increased in WT mice (both in serum and liver), but these metabolites in the liver of TLR4-KO mice after BLD were not significant different from those before BLD. In conclusion, TLR4 KO could attenuate BDL-induced liver cholestatic injury through regulating amino acid and choline metabolic pathways.

[Prenatal diagnosis of a fetus with 8q13.3 microdeletion through chromosomal microarray analysis].

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the prenatal diagnosis of a fetus with structural anomaly detected by ultrasonography. METHODS: The fetus and its parents were subjected to chromosomal karyotyping and CMA analysis. RESULTS: The fetus was found to carry a 46,XN,t(8;11)(q21.2;q13) translocation which was inherited from its mother. CMA has found no copy number variations (CNVs) in both parents but a de novo 2.00 Mb microdeletion in the fetus at 8q13.3. CONCLUSION: CMA is capable of detecting microdeletions and microduplications in fetuses with translocations detected by karyotyping analysis.

Ultrasonic manifestations and clinical analysis of 25 uterine rupture cases.

PURPOSE: To explore the risk factors, ultrasonic manifestations, clinical features, and maternal and neonatal outcomes associated with complete uterine rupture. BASIC PROCEDURES: All cases of complete uterine rupture diagnosed and treated in Jiangxi Maternal and Child Health Hospital from January 2012 to July 2018 were retrospectively analyzed. Risk factors, ultrasonic manifestations, clinical features, and maternal and infant outcomes were analyzed. RESULT: All patients had a history of uterine surgery or induced abortion. Ultrasound examination revealed 15 cases of complete rupture of the uterus, five cases of missed diagnosis, three cases of misdiagnosis, and two cases of direct emergency operation without ultrasonography because of typical clinical manifestations and critical conditions. The clinical manifestations of 25 cases of uterine rupture varied from asymptomatic to clinical signs of "resting" rupture of the uterus to severe pain, hypotension, shock, and coma. All patients underwent surgical treatment, of which one case underwent DIC and died after rescue. The maternal mortality rate was 4% (1/25), the mortality rate of newborns (two pregnant women was twins) was 44% (12/27). CONCLUSION: A history of uterine surgery is a major risk factor for uterine rupture. Attention should be paid not only to women who are pregnant again after cesarean section but also to those who have undergone other uterine operations (such as laparoscopic myomectomy, laparoscopic cornual pregnancy removal, etc.), delivery plans should be formulated accordingly. In cases of sudden abdominal pain during pregnancy or childbirth, the possibility of uterine rupture should be considered to achieve a timely and correct diagnosis and treatment.

Effects of cyhalofop-butyl on the developmental toxicity and immunotoxicity in zebrafish (Danio rerio).

Cyhalofop-butyl is a kind of aromatic phenoxypropionic acid herbicide widely used in agriculture. However, studies on its immunotoxicity to aquatic organisms have not been reported. In this study paper, morphological, immunological, cytological, biochemical and molecular biology methods were used to study the effects of cyhalofop-butyl on the developmental toxicity and immunotoxicity in zebrafish. After cyhalofop-butyl exposed, the results showed that the zebrafish embryos had shorter length, yolk sac edema, significantly reduced number of immune cells, inflammatory response and immunocytes apoptosis. In addition, we found that the expression of immune-related genes and pro-apoptotic genes were up-regulated, and the JAK-STAT signaling pathway mediated the immunotoxicity induced by cyhalofop-butyl. Therefore, our results indicate that cyhalofop-butyl has developmental toxicity and immunotoxicity to zebrafish, and this study offer new contents for the effects of cyhalofop-butyl exposure on aquatic organisms.

A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice.

High-intensity focused ultrasound (HIFU), a noninvasive ablation therapy that has been widely used clinically in ablation of solid tumors, induces immune sensitization. We therefore in this study investigated whether HIFU treatment could enhance the efficacy of a herpes simplex virus 2 (HSV-2) vaccine. First, we observed that in HSV-2-positive cervical intraepithelial neoplasia (CIN) II patients, HIFU treatment induced significantly higher anti-HSV-2 neutralization response than surgical removal. Next, we tested the efficacy of HIFU-treated, UV-inactivated HSV-2-infected cells as a proof-of-concept vaccine in mice. Our data showed that HIFU-treated formulation significantly enhanced HSV-2 antibody titers and neutralization titers, compared to UV-, microwave (MW)-, or freeze-thaw (FT)-treated formulations. HIFU treatment also promoted the Th1/2 cell-mediated response. A long-term full protection was observed in mice that received the HIFU-treated formulation, and no weight loss was detected. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.IMPORTANCE High-intensity focused ultrasound (HIFU) is mainly used in tumor ablation and tumor vaccinology study. It has been shown to induce immune sensitization and enhance tumor responsiveness to other therapies. Our study has shown enhanced anti-HSV-2 response in HIFU-treated CIN II patients. Furthermore, in a murine model, we have demonstrated that HIFU-treated HSV-2 vaccine induced long-term protective immunity against lethal challenge. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.

Single-cell transcriptome profiling reveals the mechanism of abnormal proliferation of epithelial cells in congenital cystic adenomatoid malformation.

OBJECTIVES: Congenital cystic adenomatoid malformation (CCAM) is the most common congenital pulmonary anomaly with unknown etiology. Here, single-cell RNA sequencing (scRNA-seq) was used to map its cellular landscape and identify the underlying cellular and molecular events related to CCAM. METHODS: This study involved a 4.25 year old patient with grade Ⅱ-Ⅲ CCAM at the Children's Hospital of Fudan University. Samples of lesioned and non-lesioned areas were collected during surgery for scRNA-seq. RESULTS: In total, 19,904 cells were obtained with median UMI counts of 7032 per cell and 1995 median genes per cell. In terms of lesioned and non-lesioned areas, epithelial cells accounted for 27.23% and 17.85%, respectively, while mesenchymal cells accounted for 2.67% and 16.06%, respectively (P < 0.0001). Further clustering of epithelial cells revealed that the fractions of alveolar type 1 cells (AT1, N: 23.65%; L: 49.81%), AT2(N: 2.02%; L: 5.26%), club-1(N: 9.02%; L: 17.57%), club-3(N: 1.18%; L: 4.15%), and basal cells (N: 0.34%; L: 2.93%) were increased in lesioned samples (P < 0.0001). Pseudotime trajectory analysis showed tracks of club-1/basal cells→AT2→club-3→AT1 and club-1,2/basal→AT2. Mast cells (N: 0.63%; L: 2.48%) were also increased in lesioned samples and interactions of CD44 with HBEGF and FGFR2 were detected between mast and epithelial cells. CONCLUSIONS: AT1, AT2, club, and basal cells were increased in CCAM patients, and newly defined club-1/3 and basal cells might be the origin of proliferating AT1 and AT2 cells. Increased mast cells might promote epithelial cell proliferation through interactions of CD44 with HBEGF and FGFR2.

Analysis of the predictors of surgical treatment and intestinal necrosis in children with intestinal obstruction.

PURPOSE: To explore the surgical treatment and predictors of intestinal necrosis in children with intestinal obstruction through analyzing blood biochemical indicators, and to establish a predictive model and evaluate its predictive accuracy, sensitivity and specificity. METHODS: The data of children with intestinal obstruction hospitalized in Jiangxi Provincial Children's Hospital from January 2014 to June 2019 were retrospectively analyzed. RESULTS: Thirty-six substances in the blood of children with successful conservative management and those requiring surgical treatment were significantly different. The model composed of 7 variables, including age, white blood cell count, creatine kinase, troponin I, myoglobin, C-reactive protein and fibrinogen, can be used to predict the unsuccessful conservative management in children with intestinal obstruction, whom need further operation. The average prediction accuracy was 83.50%, the false positive rate was 16.67% (32/192), AUROC is 0.9160 (95% CI, 0.8930-0.9390), and the sensitivity and specificity were 83.20% and 92.70% respectively. A prediction model based on the white blood cell count, creatine kinase, troponin I and myoglobin could predict the occurrence of intestinal necrosis. The average prediction accuracy was 73.70%, false positive rate was 4.49% (15/334), AUROC was 0.7390 (95% CI, 0.6820-0.7960), and the sensitivity and specificity were 71.70% and 64.70%, respectively. CONCLUSIONS: Combination of age, white blood cell count, creatine kinase, troponin I, myoglobin, C-reactive protein and fibrinogen can be used to predict whether the children with intestinal obstruction need surgical treatment or not. Leukocyte count, creatine kinase, troponin I and myoglobin are closely related to the condition of children with intestinal obstruction and can be used to predict whether intestinal necrosis occurs. TYPE OF STUDY: Retrospective Study LEVELS OF EVIDENCE: Level I.

Circular RNA DGKB Promotes the Progression of Neuroblastoma by Targeting miR-873/GLI1 Axis.

Accumulated evidences suggested that circular RNAs (circRNA) played critical roles in tumorigenesis and progression. To our knowledge, no study reported the function of circular RNA DGKB (circDGKB, circRNA ID: hsa_circ_0133622) on progression of neuroblastoma (NB). Here, we showed that circDGKB was upregulated in NB tissues compared to the normal dorsal root ganglia. Moreover, the expression level of circDGKB was negatively correlated with the survival rate of NB patients. Mechanically, overexpression of circDGKB promoted the proliferation, migration, invasion, and tumorigenesis of NB cells and reduced cell apoptosis, and vice versa. In addition, qRT-PCR and/or Western blot results showed that circDGKB overexpression inhibited the expression level of miR-873 and enhanced GLI1 expression. Moreover, miR-873 functioned an opposite role to circDGKB and significantly weakened circDGKB role in promoting NB progression. Furthermore, GLI1 upregulation also rescued the miR-873 role in inhibiting NB progression. In conclusion, our work proved that circDGKB promoted NB progression via targeting miR-873/GLI1 axis in vitro and in vivo. Our study provided a new target for NB treatment and indicated that circDGKB could act as a novel diagnostic marker for NB.

Effects of lincomycin hydrochloride on the neurotoxicity of zebrafish.

Lincomycin hydrochloride is one of the commonly used drugs in clinic. However, it has many side effects on patients, and its mechanism is still poorly understood. In this study, 6 h post-fertilization (6 hpf) zebrafish embryos were exposed to several concentrations of lincomycin hydrochloride (15, 30, 60 µg/mL) for up to 24 or 96 hpf to detect their developmental toxicity and neurotoxicity, and to 6 days post-fertilization (6 dpf) to detect their behavioral toxicity. Our results showed that lincomycin hydrochloride could lead to embryonic head deformities (unclear ventricles, smaller ventricles, fewer new neurons). The studies showed that the frequency of spontaneous tail flick of zebrafish embryo increased at 24 hpf, and the lincomycin hydrochloride exposed zebrafish embryos showed increased heart rate, shorter body length, and yolk sac edema with severe pericardial edema at 96 hpf. The studies also showed that lincomycin hydrochloride increased oxidative stress level, Acetylcholinesterase (AChE) activity, ATPase activity and apoptosis in zebrafish larvae. In addition, the swimming behavior of zebrafish larvae decreased with the increase of lincomycin hydrochloride concentration, but the angular velocity and meandering degree increased, which might be due to the decreased activity of AChE and ATPase, as well as the decreased expression of genes related to neurodevelopment and neurotransmitter system, leading to the change of their motor behaviors. In summary, we found that lincomycin hydrochloride induced developmental toxicity and neurotoxicity in zebrafish larvae, contributing to a more comprehensive evaluation of the safety of the drug.

Exposure to Oxadiazon-Butachlor causes cardiac toxicity in zebrafish embryos.

Oxadiazon-Butachlor (OB) is a widely used herbicide for controlling most annual weeds in rice fields. However, its potential toxicity in aquatic organisms has not been evaluated so far. We used the zebrafish embryo model to assess the toxicity of OB, and found that it affected early cardiac development and caused extensive cardiac damage. Mechanistically, OB significantly increased oxidative stress in the embryos by inhibiting antioxidant enzymes that resulted in excessive production of reactive oxygen species (ROS), eventually leading to cardiomyocyte apoptosis. In addition, OB also inhibited the WNT signaling pathway and downregulated its target genes includinglef1, axin2 and ß-catenin. Reactivation of this pathway by the Wnt activator BML-284 and the antioxidant astaxanthin rescued the embryos form the cardiotoxic effects of OB, indicating that oxidative stress, and inhibition of WNT target genes are the mechanistic basis of OB-induced damage in zebrafish. Our study shows that OB exposure causes cardiotoxicity in zebrafish embryos and may be potentially toxic to other aquatic life and even humans.