Preliminary investigation into the impact of BPA on osteoblast activity and bone development: In vitro and in vivo models.

Bisphenol A (BPA), an ingredient in consumer products, has been suggested that it can interfere with bone development and maintenance, whereas the molecule mechanism remains unclear. The objective of this study is to investigate the effect of BPA on early bone differentiation and metabolism, and its potential molecule mechanism by employing hFOB1.19 cell as an in vitro model, as well as larval zebrafish as an in vivo model. The in vitro experiments indicated that BPA decreased cell viability, inhibited osteogenic activity (such as ALP, RUNX2), increased ROS production, upregulated transcriptional or protein levels of apoptosis-related molecules (such as Caspase 3, Caspase 9), while suppressed transcriptional or protein levels of pyroptosis-specific markers (TNF-α, TNF-ß, IL-1ß, ASC, Caspase 1, and GSDMD). Moreover, the evidences from in vivo model demonstrated that exposure to BPA distinctly disrupted pharyngeal cartilage, craniofacial bone development, and retarded bone mineralization. The transcriptional level of bone development-related genes (bmp2, dlx2a, runx2, and sp7), apoptosis-related genes (bcl2), and pyroptosis-related genes (cas1, nlrp3) were significantly altered after treating with BPA in zebrafish larvae. In summary, our study, combining in vitro and in vivo models, confirmed that BPA has detrimental effects on osteoblast activity and bone development. These effects may be due to the promotion of apoptosis, the initiation of oxidative stress, and the inhibition of pyroptosis.

A Self-Oscillated Organic Synapse for In-Memory Two-Factor Authentication.

Entering the era of AI 2.0, bio-inspired target recognition facilitates life. However, target recognition may suffer from some risks when the target is hijacked. Therefore, it is significantly important to provide an encryption process prior to neuromorphic computing. In this work, enlightened from time-varied synaptic rule, an in-memory asymmetric encryption as pre-authentication is utilized with subsequent convolutional neural network (ConvNet) for target recognition, achieving in-memory two-factor authentication (IM-2FA). The unipolar self-oscillated synaptic behavior is adopted to function as in-memory asymmetric encryption, which can greatly decrease the complexity of the peripheral circuit compared to bipolar stimulation. Results show that without passing the encryption process with suitable weights at the correct time, the ConvNet for target recognition will not work properly with an extremely low accuracy lower than 0.86%, thus effectively blocking out the potential risks of involuntary access. When a set of correct weights is evolved at a suitable time, a recognition rate as high as 99.82% can be implemented for target recognition, which verifies the effectiveness of the IM-2FA strategy.

Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity.

Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe2+ content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe2+ metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.

Exposure of male adult zebrafish (Danio rerio) to triphenyl phosphate (TPhP) induces eye development disorders and disrupts neurotransmitter system-mediated abnormal locomotor behavior in larval offspring.

Triphenyl phosphate (TPhP) is a widely used organophosphorus flame retardant, which has become ubiquitous in the environment. However, little information is available regarding its transgenerational effects. This study aimed to investigate the developmental toxicity of TPhP on F1 larvae offspring of adult male zebrafish exposed to various concentrations of TPhP for 28 or 60 days. The findings revealed significant morphological changes, alterations in locomotor behavior, variations in neurotransmitter, histopathological changes, oxidative stress levels, and disruption of Retinoic Acid (RA) signaling in the F1 larvae. After 28 and 60 days of TPhP exposure, the F1 larvae exhibited a myopia-like phenotype with pathological alterations in the lens and retina. The genes involved in the RA signaling pathway were down-regulated following parental TPhP exposure. Swimming speed and total distance of F1 larvae were significantly reduced by TPhP exposure, and long-term exposure to environmental levels of TPhP had more pronounced effects on locomotor behavior and neurotransmitter levels. In conclusion, TPhP induced histological and morphological alterations in the eyes of F1 larvae, leading to visual dysfunction, disruption of RA signaling and neurotransmitter systems, and ultimately resulting in neurobehavioral abnormalities. These findings highlight the importance of considering the impact of TPhP on the survival and population reproduction of wild larvae.

Developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether induced endoplasmic reticulum stress on early life stages of zebrafish (Danio rerio).

Polybrominated diphenyl ether flame retardants are known to have adverse effects on the development of organisms. We investigated the molecular mechanisms associated with the developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in zebrafish, as well as the behavioral and morphological alterations involved, focusing on endoplasmic reticulum stress (ERS), oxidative stress, and apoptosis. Our study revealed behavioral alterations in zebrafish exposed to BDE-47, including impaired motor activity, reduced exploration, and abnormal swimming patterns. In addition, we observed malformations in craniofacial regions and other developmental abnormalities that may be associated with ERS-induced cellular dysfunction. BDE-47 exposure showed apparent changes in ERS, oxidative stress, and apoptosis biomarkers at different developmental stages in zebrafish through gene expression analysis and enzyme activity assays. The study indicated that exposure to BDE-47 results in ERS, as supported by the upregulation of ERS-related genes and increased activity of ERS markers. In addition, oxidative stress-related genes showed different expression patterns, suggesting that oxidative stress is involved in the BDE-47 toxic effects. Moreover, an assessment of apoptotic biomarkers revealed an imbalance in the expression levels of pro- and anti-apoptotic genes, suggesting that BDE-47 exposure activated the apoptotic pathway. These results highlight the complex interactions between ERS, oxidative stress, apoptosis, behavioral alterations, and morphological malformations following BDE-47 exposure in zebrafish. Understanding the mechanisms of toxicity of developmental hazards is essential to elucidate the toxicological effects of environmental contaminants. The knowledge can help develop strategies to mitigate their adverse effects on the health of ecosystems and humans.

Transgenerational effects of BDE-47 to zebrafish based on histomorphometry and toxicogenomic analyses.

Exposure to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) has been found to have an impact on reproductive output and endocrine function in female zebrafish (Danio rerio). However, the transgenerational effects of BDE-47 have not been fully explored in previous reports. In this study, female zebrafish were exposed to BDE-47 for three consecutive weeks. The oogenesis, sex hormones, reproductive histology, and transcriptional profiles of genes along the hypothalamus-pituitary-gonad (HPG) axis were assessed in the exposed-F0 generation. After mating with unexposed males, the transgenerational effects of BDE-47 were evaluated on the basis of histopathology, morphometry and toxicogenome of the unexposed F1 generations at the larval stage. Results indicated that exposure to BDE-47 impaired reproductive capacity, disrupted endocrine system in F0 zebrafish, and compromised craniofacial skeletons and vertebrae development in F1 generations. In addition, through the use of toxicogenomics approach, immune-responsive pathways were found to be significantly enriched, and the transcript expression profiling of immune-related DEGs (IRDs) were dramatically inhibited in F1 generations following maternal BDE-47 exposure, indicating its immunotoxicity to offspring larvae. These findings advance our understanding of the transgenerational toxicity of BDE-47 and advocate for a more comprehensive assessment of other PBDE congeners through histomorphometry and toxicogenomic approaches.

Efficacy and safety of alfentanil plus propofol versus propofol only in painless gastrointestinal endoscopy: A meta-analysis.

BACKGROUND: To systematically evaluate the efficacy and safety of alfentanil plus propofol versus propofol only for painless gastrointestinal endoscopy. METHODS: The Cochrane Library, PubMed, Embase, China Biology Medicine, CNKI, WanFang, and VIP databases were searched to identify randomized controlled trials on alfentanil combined with propofol versus propofol only for painless gastrointestinal endoscopy from the inception of the database to August 2022. The Rev Man 5.4 software was used for statistical analyses. RESULTS: Thirteen randomized controlled trials involving 1762 patients were identified as eligible for this study. The meta-analysis showed that compared with propofol, alfentanil combined with propofol had a more stable mean arterial pressure [mean difference (MD) = 5.38, 95% confidence interval (CI): 1.97-8.80; P = .002], heart rate (MD = 3.78, 95% CI: 1.30-6.26; P = .003) and pulse oxygen saturation (MD = 1.90, 95% CI: 0.93-2.78; P = .0001); a lower propofol dose (standard mean difference = -2.82, 95% CI: -3.70 to -1.94; P < .00001), lower awakening time (MD = -3.23, 95% CI: -4.01 to -2.45; P < .00001) and lower directional force recovery time (MD = -3.62, 95% CI: -4.22 to -3.03; P < .00001); a lower incidence of nausea and vomiting (relative risk [RR] = 0.32, 95% CI: 0.14-0.71; P = .005), body movement (RR = 0.27, 95% CI: 0.13-0.54; P = .0002), hypotension (RR = 0.23, 95% CI: 0.12-0.46; P < .0001), respiratory depression (RR = 0.37, 95% CI: 0.15-0.89; P = .03) and cough reflex (RR = 0.33, 95% CI: 0.12-0.89; P = .03). CONCLUSION: This meta-study found that current evidence indicates that alfentanil plus propofol is better than propofol alone for painless gastrointestinal endoscopy and is associated with a lower incidence of adverse reactions. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to validate these above conclusions.

A pilot study investigating early postmortem interval of rats based on ambient temperature and postmortem interval-related metabolites in blood.

Estimation of the postmortem interval (PMI), especially the early PMI, plays a key role in forensic practice. Although several studies based on metabolomics approaches have presented significant findings for PMI estimation, most did not examine the effects of ambient temperature. In this study, gas chromatography-mass spectrometry (GC‒MS)‒based metabolomics was adopted to explore the changes in metabolites in the cardiac blood of suffocated rats at various ambient temperatures (5 °C, 15 °C, 25 °C, and 35 °C) from 0 to 24 h after death. Isoleucine, alanine, proline, valine, glycerol, glycerol phosphate, xanthine, and hypoxanthine were found to contribute to PMI in all temperature groups. Hypoxanthine and isoleucine were chosen to establish estimation models (equations) with an interpolation function using PMI as the dependent variable (f(x, y)), relative intensity as the independent variable x, and temperature as the independent variable y. Thereafter, these two models were validated with predictive samples and shown to have potential predictive ability. The findings indicate that isoleucine, alanine, proline, valine, glycerol, glycerol phosphate, xanthine, and hypoxanthine may be significant for PMI estimation at various ambient temperatures. Furthermore, a method to determine PMI based on ambient temperature and PMI-related metabolites was explored, which may provide a basis for future studies and practical applications.

Fish to learn: insights into the effects of environmental chemicals on eye development and visual function in zebrafish.

Vision is the most essential sense system for the human being. Congenital visual impairment affects millions of people globally. It is increasingly realized that visual system development is an impressionable target of environmental chemicals. However, due to inaccessibility and ethical issues, the use of humans and other placental mammals is constrained, which limits our better understanding of environmental factors on ocular development and visual function in the embryonic stage. Therefore, as complementing laboratory rodents, zebrafish has been the most frequently employed to understand the effects of environmental chemicals on eye development and visual function. One of the major reasons for the increasing use of zebrafish is their polychromatic vision. Zebrafish retinas are morphologically and functionally analogous to those of mammalian, as well as evolutionary conservation among vertebrate eye. This review provides an update on harmful effects from exposure to environmental chemicals, involving metallic elements (ions), metal-derived nanoparticles, microplastics, nanoplastics, persistent organic pollutants, pesticides, and pharmaceutical pollutants on the eye development and visual function in zebrafish embryos. The collected data provide a comprehensive understanding of environmental factors on ocular development and visual function. This report highlights that zebrafish is promising as a model to identify hazardous toxicants toward eye development and is hopeful for developing preventative or postnatal therapies for human congenital visual impairment.

Cap 'n' Collar C and Aryl Hydrocarbon Receptor Nuclear Translocator Facilitate the Expression of Glutathione S-Transferases Conferring Adaptation to Tannic Acid and Quercetin in Micromelalopha troglodyta (Graeser) (Lepidoptera: Notodontidae).

Micromelalopha troglodyta (Graeser) (Lepidoptera: Notodontidae) is a notorious pest of poplar. Coevolution with poplars rich in plant secondary metabolites prompts M. troglodyta to expand effective detoxification mechanisms against toxic plant secondary metabolites. Although glutathione S-transferases (GSTs) play an important role in xenobiotic detoxification in M. troglodyta, it is unclear how GSTs act in response to toxic secondary metabolites in poplar. In this study, five GST gene core promoters were accurately identified by a 5' loss luciferase reporter assay, and the core promoters were significantly induced by two plant secondary metabolites in vitro. Two transcription factors, cap 'n' collar C (CncC) and aryl hydrocarbon receptor nuclear translocator (ARNT), were cloned in M. troglodyta. MtCncC and MtARNT clustered well with other insect CncCs and ARNTs, respectively. In addition, MtCncC and MtARNT could bind the MtGSTt1 promoter and strongly improve transcriptional activity, respectively. However, MtCncC and MtARNT had no regulatory function on the MtGSTz1 promoter. Our findings revealed the molecular mechanisms of the transcription factors MtCncC and MtARNT in regulating the GST genes of M. troglodyta. These results provide useful information for the control of M. troglodyta.

Identification, Molecular Characteristics, and Evolution of YABBY Gene Family in Melastoma dodecandrum.

The YABBY gene family plays an important role in plant growth and development, such as response to abiotic stress and lateral organ development. YABBY TFs are well studied in numerous plant species, but no study has performed a genome-wide investigation of the YABBY gene family in Melastoma dodecandrum. Therefore, a genome-wide comparative analysis of the YABBY gene family was performed to study their sequence structures, cis-acting elements, phylogenetics, expression, chromosome locations, collinearity analysis, protein interaction, and subcellular localization analysis. A total of nine YABBY genes were found, and they were further divided into four subgroups based on the phylogenetic tree. The genes in the same clade of phylogenetic tree had the same structure. The cis-element analysis showed that MdYABBY genes were involved in various biological processes, such as cell cycle regulation, meristem expression, responses to low temperature, and hormone signaling. MdYABBYs were unevenly distributed on chromosomes. The transcriptomic data and real-time reverse transcription quantitative PCR (RT-qPCR) expression pattern analyses showed that MdYABBY genes were involved in organ development and differentiation of M. dodecandrum, and some MdYABBYs in the subfamily may have function differentiation. The RT-qPCR analysis showed high expression of flower bud and medium flower. Moreover, all MdYABBYs were localized in the nucleus. Therefore, this study provides a theoretical basis for the functional analysis of YABBY genes in M. dodecandrum.

Transnasal drainage prevents surgical cavity related complications in transoral robotic surgery resected parapharyngeal space tumors.

BACKGROUND: There is no evidence about the relationship between surgical cavity drainage and related postoperative complications in transoral robotic surgery (TORS) resected parapharyngeal space (PPS) tumors. OBJECTIVES: To investigate the clinical efficacy and advantage of transnasal PPS drainage to prevent surgical cavity related complications (SCRC) in TORS resected PPS tumors. MATERIAL AND METHODS: Twenty-three patients undergoing TORS for PPS tumors were identified. In the experimental group (EG, 8 patients), the surgical incision was sutured directly and the transnasal drainage tube was placed. In the control group (CG, 15 patients), the surgical incision was partially sutured without drainage. The healing grade of surgical incision (HGSI), healing grade of surgical cavity (HGSC), SCRC, and other complications were compared. RESULTS: There were significant statistical differences in postoperative clinical rehabilitation indexes (HGSI/HGSC/SCRC) between the two groups. The comparison results of HGSI and HGSC in the two groups (EG vs CG) were (100% vs 66.7%) and (100% vs 46.7%) respectively. Compared with the EG, eight cases (53.3%) in the CG had postoperative SCRC such as hemorrhage, effusion, and swollen. CONCLUSIONS AND SIGNIFICANCE: For TORS resected PPS tumors, transnasal PPS drainage is an effective and comfortable method to improve postoperative HGSI and HGSC and prevent SCRC.

Comparative pharyngeal cartilage developmental toxicity of bisphenol A, bisphenol S and bisphenol AF to zebrafish (Danio rerio) larvae: A combination of morphometry and global transcriptome analyses.

Exposure to BPA is recently shown to affect cartilage development in teleost fishes; whether BPS and BPAF, its two most frequently used phenolic analogues have similar effect, however, remains unclear. Here, we utilize zebrafish (Danio rerio) as an in-vivo larval model for systematic comparison of the pharyngeal arch-derived cartilage developmental toxicity of BPA, BPS and BPAF. Zebrafish are continuously exposed to three bisphenol analogues (3-BPs) at a range of concentrations since the embryonic stage (0.5 hpf), and identified cartilage malformations of the mandibular and hyoid pharyngeal arches at larval stage (120 hpf). BPA and BPAF prolong length and broaden cartilage angles; however, BPS shortens length and narrows the angles of skull cartilages. The results of the comparative transcriptome show that FoxO and MAPK signaling pathways are closely associated with the toxicity of BPA and BPAF, while BPS exposure affects energy metabolism-related pathways. Moreover, exposure to 3-BPs have an impact on the oxidative stress status. Our data collectively indicate that BPS and BPAF may not be safer than BPA regarding the impact on pharyngeal cartilage development in fish model, the mechanisms still need explorations, and that these two analogues should be applied with caution.

Neurodevelopmental toxicity of organophosphate flame retardant triphenyl phosphate (TPhP) on zebrafish (Danio rerio) at different life stages.

As a substitute for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardant triphenyl phosphate (TPhP) is widely used in our daily products and diffusely exists in our living surroundings, but there is a paucity of information concerning its neurodevelopmental toxicity. Herein, we investigated the effects of TPhP exposure on developmental parameters, locomotor behavior, oxidative stress, apoptosis and transcriptional levels in zebrafish at different developmental stages, so as to explore the effects of TPhP exposure on zebrafish neural development and the underlying molecular mechanisms. TPhP concentration gradient exposure reduced the survival rate, hatchability, heart rate, body length and eye distance of zebrafish embryos/larvae, and caused malformations of zebrafish larvae. TPhP also leads to abnormal locomotor behaviors, such as reduced swimming distance and swimming speed, and impaired panic avoidance reflex to high light stimulation. TPhP caused ROS accumulation in 96 hpf larvae and induced Nrf2-antioxidant response in zebrafish. In addition, TPhP further activated mitochondrial signaling pathways, which affected apoptosis in the zebrafish eye region, resulting in visual impairment. Neurodevelopmental (mbpa, syn2a, foxo3a and pax6a), Retinoid acid metabolism (cyp26a1, raraa, rbp5, rdh1, crabp1a and rbp2a) and apoptosis-related genes (bcl2a, baxa and casp9) revealed the molecular mechanism of abnormal behavior and phenotypic symptoms, and also indicated that 96 hpf larvae are more sensitive than 7 dpf larvae. Thus, in the present study, we revealed the neurotoxic effects of TPhP at different early life stages in zebrafish, and zebrafish locomotor behavior impairments induced by TPhP exposure are attributed to co-regulation of visuomotor dysfunction and neuro-related genes. These results suggest that the safety of TPhP in organisms and even in humans needs to be further studied.

Trends in the surgical management of parapharyngeal space tumors: A single-center retrospective analysis.

PURPOSE: Surgery remains the mainstay treatment for parapharyngeal space (PPS) tumors. Given the rapid advance and increasing usage of endoscopic and robotic techniques, we aimed to investigate the surgical trends of PPS tumors in our institution and analyze their impact on patients' treatment outcomes. MATERIALS AND METHODS: All patients who underwent surgical resection of PPS tumors from 2014 to 2021 at the Eye, Ear, Nose, and Throat Hospital of Fudan University were retrospectively reviewed. Student's t-test, Chi-square test, and multinomial logistic regression analyses were used to compare the surgical outcomes between groups. RESULT: Of the included 389 patients, the recipients of endoscopic surgery have largely increased in our center, with 17 of 134 cases (12.7%) in the group 2014-2017 and 187 of 255 cases (73.3%) in the group 2018-2021. The use of transoral and trans-nasal approaches increased in recent years (5.2% in 2014-2017 vs. 26.0% in 2018-2021), while that of trans-mandibular and lateral skull base approaches decreased (5.9% in 2014-2017 vs. 0.8% in 2018-2021). Decreased blood loss of operation and decreased risks of postoperative neurovascular complications were observed in the group 2018-2021. Similar findings were observed among patients receiving endoscopic surgery when compared with those receiving conventional surgery. CONCLUSION: In our institution, the overall trends in the surgical management of PPS tumors moved towards minimally invasive approaches with the assistance of endoscopy or surgical robots. The two surgical techniques were feasible and safe, and to a great extent, contributed to the improved surgical outcomes we observed in recent years.

Effects of evodiamine on the proliferation, migration and invasion of neuroblastoma SK-N-SH cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨吴茱萸碱（Evo）是否通过调控lncRNA LINC00858表达调控神经母细胞瘤SK-N-SH细胞的增殖、迁移及侵袭。方法：在体外以3、6、12 μmol/L Evo处理人神经母细胞瘤SK-N-SH细胞，利用RNA干扰技术分别将si-NC、si-LINC00858转染至SK-N-SH细胞，将pcDNA、pcDNA-LINC00858转染至SK-N-SH细胞并经12 μmol/L Evo处理，实验分为对照组、Evo低剂量组、Evo中剂量组、Evo高剂量组、si-NC组、si-LINC00858组、Evo+pcDNA组、Evo+pcDNA-LINC00858组。采用qPCR法检测各组细胞LINC00858的表达量，MTT、Transwell实验分别检测细胞的增殖、迁移、侵袭能力，WB法检测细胞中cyclinD1、MMP-2、MMP-9和p21蛋白的表达。结果：与对照组相比，Evo低、中、高剂量组SK-N-SH细胞中LINC00858表达均显著降低（均P<0.05），细胞增殖抑制率显著升高、迁移及侵袭细胞数显著减少（均P<0.01），cyclinD1、MMP-2、MMP-9蛋白表达降低、p21蛋白表达升高（均P<0.01）。与si-NC组相比，si-LINC00858组细胞的增殖抑制率、迁移和侵袭细胞数及相关蛋白表达变化同Evo低、中、高剂量组。与Evo+pcDNA组相比，Evo+pcDNA-LINC00858组细胞的增殖抑制率显著降低、迁移及侵袭细胞数均显著增多（均P<0.01），cyclinD1、MMP-2、MMP-9蛋白表达升高、p21蛋白表达降低（均P<0.05）。结论：Evo通过下调LINC00858表达抑制神经母细胞瘤SK-N-SH细胞的增殖、迁移及侵袭。

Effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on reproductive and endocrine function in female zebrafish (Danio rerio).

BACKGROUND: Polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants (BFRs), were reported exist extensively in various ecological environmental. Studies have indicated that PBDEs induce reproductive toxic effects on human health, but the mechanisms remain poorly understood. In this study, the adult female zebrafish were used to investigate the effects of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) on the reproductive endocrine system and its mechanism. METHODS: Female zebrafish (AB strains) were continuously exposed to BDE-47 at the concentrations of 0, 10, 50, 100 and 500 µg/L till 21 days. The morphology of ovary were stained and evaluated with hematoxylin-eosin (H&E), and levels of sex hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and 17ß-estradiol (E2) and the biomarkers of oxidative stress such as superoxide dismutase (SOD) and malondialdehyde (MDA), were measured via ELISA. Subsequently, the expression of genes along the hypothalamic pituitary-gonad (HPG) and oxidative stress were determined using quantitative real-time PCR (qRT-PCR). RESULT: The results showed that exposure to high level of BDE-47 reduced the index of condition factor (CF) and gonadosomatic index (GSI). Treatment with BDE-47 impaired the normal development and structure of oocytes in zebrafish ovary. Moreover, the steroid hormone of FSH, LH, T and E2 were significantly decreased in BDE-47 exposure group. A dose-dependent elevation in SOD activity and MDA levels were recorded. Meanwhile, the transcription level of cyp19a, cyp19b, fshß, lhß were up-regulated while the transcription of fshr, lhr, cyp17a, 17ßhsd were down-regulated in the gonad of female adult zebrafish. CONCLUSION: Exposure to BDE-47 have detrimental impact on the development of ovary, decreasing sex hormone levels, inducing oxidative damage as well as altering HPG axis-related genes.

Uncommon variant of total anomalous pulmonary venous drainage in an infant with sudden death: a case report and review of the literature.

Total anomalous pulmonary venous drainage (TAPVD) is encountered less frequently in infancy than various other congenital cardiac anomalies. We present a 4-week-old boy with a hitherto unreported variant of TAPVD who died suddenly soon after presentation to our emergency department. At autopsy, we found both pulmonary veins draining abnormally into the pulmonary artery and an atrial septal defect. We wish to emphasize that examination of the major vessels and their connections should be done in situ in all autopsies of unexpected deaths in infants and children, even if there were no symptoms and signs in the ante-mortem period and despite the clinical picture not being suggestive of TAPVD.

Behavioral changes and transcriptomic effects at embryonic and post-embryonic stages reveal the toxic effects of 2,2',4,4'-tetrabromodiphenyl ether on neurodevelopment in zebrafish (Danio rerio).

Polybrominated biphenyl ethers (PBDEs) are new persistent pollutants that are widely exist in the environment and have many toxic effects. However, their toxicity mechanisms on neurodevelopment are still unclear. In this study, zebrafish embryos were exposed to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) (control, 10, 50 and 100 µg/L) at 2 h postfertilization (hpf) - 7 dpf. Locomotion analysis indicated that BDE-47 increased spontaneous coiling activity in zebrafish embryos under high-intensity light stimuli and decreased locomotor in zebrafish larvae. RNA-Seq analysis revealed that most of the up-regulated pathways were related to the metabolism of cells and tissues, while the down-regulated pathways were related to neurodevelopment. Consistent with the locomotion and KEGG results, BDE-47 affected the expression of genes for central nervous system (gfap, mbpa, bdnf & pomcb), early neurogenesis (neurog1 & elavl3), and axonal development (tuba1a, tuba1b, tuba1c, syn2a, gap43 & shha). Furthermore, BDE-47 interfered with gene expression of the Wnt signaling pathway, especially during embryonic stages, suggesting that the mechanisms of BDE-47 toxicity to zebrafish at various stages of neurodevelopment may be different. In summary, early neurodevelopment effects and metabolic disturbances may have contributed to the abnormal neurobehavioral changes induced by BDE-47 in zebrafish embryos/larvae, suggesting the neurodevelopmental toxicity of BDE-47.

[Serological Characteristics and Molecular Biological Mechanism of AEL.02 Subtype].

OBJECTIVE: To explore the serological characteristics and molecular biological mechanism of an ael subtype specimen. METHODS: The ABO blood typing was identified by routine blood group serological and absorption/elution methods; PCR-SBT method for ABO genotyping: 7 exons of ABO gene were amplified by PCR, the amplified products were purified, and then sequencing primers were designed and the amplified products were sequenced directly for analysis; 3D molecular model was constructed and the difference of free energy (ΔΔG) was used to predict the GTA mutant stability. RESULTS: A antigen was not detected on erythrocytes through absorption and elution tests, which was not consistent with the serological characteristics of ael, and the serological typing results were ambiguous. The ABO genotype was ABO*AEL.02/O.01.01, and there were two mutations in exon 7 of the gene, c.467C>T and c.646T>A, which could lead to the replacement of proline with leucine at position 156 (p.Pro156Leu) and phenylalanine with isoleucine at position 216 on the GTA, respectively. The 3D model predicts that the mutations do not introduce new hydrogen bonds to the GTA mutant and do not form a new secondary structure, but can lead to an increase in the ΔΔG value of the GTA mutant, suggesting a decrease in protein stability. CONCLUSION: The serological characteristics alone is not reliable to determine the ael subype; the ael phenotype may be due to the GTA mutant that reduces enzyme stability.