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BACKGROUND: Our previous study demonstrated that ß2-microglobulin (ß2M) promoted ER+/HER2- breast cancer survival via the SGK1/Bcl-2 signaling pathway. However, the role of ß2M has not been investigated in ER-/HER2+ breast cancer. Here, we aimed to determine the role of ß2M in ER-/HER2+ breast cancer. METHODS: The interaction between ß2M and HFE was confirmed by co-immunoprecipitation, mass spectrometry, yeast two-hybrid screening, and His pull-down. The knockdown and overexpression of ß2M or HFE were performed in MDA-MB-453 cells, and ERK signaling pathway was subsequently analyzed via western blotting. Apoptotic cells were detected using flow cytometer. ß2M, HFE, and p-ERK1/2 were examined in tumor and paired adjacent tissues via immunohistochemistry. RESULTS: HFE was found to be an interacting protein of ß2M in ER-/HER2+ breast cancer cells MDA-MB-453 by co-immunoprecipitation and mass spectrometry. A yeast two-hybrid system and His-pull down experiments verified that ß2M directly interacted with HFE. ß2M and HFE as a complex were mainly located in the cytoplasm, with some on the cytomembrane of MDA-MB-453 cells. In addition to breast cancer cells BT474, endogenous ß2M directly interacted with HFE in breast cancer cells MDA-MB-453, MDA-MB-231, and MCF-7. ß2M activated the ERK signaling pathway by interacting with HFE and induced apoptosis of MDA-MB-453 cells. The expression of HFE and p-ERK1/2 showed significantly high levels in HER2-overexpressing breast cancer tumor tissue compared with adjacent normal tissue, consistent with the results obtained from the cell experiments. CONCLUSIONS: ß2M induced apoptosis of tumor cells via activation of the ERK signal pathway by directly interacting with HFE in HER2-overexpressing breast cancer.
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Apoptosis , Neoplasias de la Mama , Proteína de la Hemocromatosis , Sistema de Señalización de MAP Quinasas , Receptor ErbB-2 , Microglobulina beta-2 , Humanos , Microglobulina beta-2/metabolismo , Microglobulina beta-2/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Femenino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Línea Celular Tumoral , Proteína de la Hemocromatosis/genética , Proteína de la Hemocromatosis/metabolismo , Unión Proteica , Regulación Neoplásica de la Expresión GénicaRESUMEN
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.
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Ferroptosis , Retardadores de Llama , Organofosfatos , Femenino , Animales , Factor 2 Relacionado con NF-E2/genética , Pez Cebra , Acetilcolinesterasa , Retardadores de Llama/toxicidad , Proteína 1 Asociada A ECH Tipo Kelch/genética , Especies Reactivas de Oxígeno , Compuestos Organofosforados/toxicidad , Estrés Oxidativo , XantófilasRESUMEN
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.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Éter , Humanos , Animales , Pez Cebra , Ecosistema , Éteres de Etila , Éteres Difenilos Halogenados/toxicidad , Estrés del Retículo Endoplásmico , BiomarcadoresRESUMEN
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.
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Translocador Nuclear del Receptor de Aril Hidrocarburo , Lepidópteros , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Quercetina/farmacología , Taninos/metabolismo , Transferasas/metabolismo , Glutatión/metabolismo , Receptores de Hidrocarburo de Aril/metabolismoRESUMEN
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.
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Flores , Proteínas de Plantas , Filogenia , Proteínas de Plantas/genética , Flores/genética , Familia de Multigenes , Meristema/metabolismo , Regulación de la Expresión Génica de las Plantas , Evolución Molecular , Estrés Fisiológico , Perfilación de la Expresión GénicaRESUMEN
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 (GCâMS)âbased 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.
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Animal studies have indicated that exposure to polybrominated diphenyl ethers (PBDEs) during development can permanently affect blood/liver lipid balance. However, no epidemiological study has assessed the relationship between PBDEs in adipose tissues and blood lipid metabolism. In this study, we explored the associations between PBDEs levels in female adipose tissues and lipid profiles. We recruited 150 female patients undergoing plastic surgery from hospital in Shantou, China, collected their characteristics, clinical information, and adipose tissue samples. Fourteen PBDE congeners in adipose tissues were analyzed by gas chromatography-mass spectrometry (GC-MS). Multiple linear and logistic regression models were used to explore the relationships between PBDEs and lipid profiles, while restricted cubic spline (RCS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the nonlinearity of mixtures. Median levels of ΣPBDEs and dominant congeners BDE-153, -209, and -183 in adipose tissues were 73.91, 26.12, 14.10 and 9.01 ng/g lipid, respectively. In the multiple linear model, BDE-153 and BDE-209 were negatively associated with triglycerides (TG), similarly for BDE-190 and total cholesterol (TC). While in the adjusted logistic models, BDE-138 was negatively associated with TC (OR = 0.76, 95%CI: 0.58, 0.99) and total lipids (TL) (OR = 0.76, 95%CI: 0.58, 0.99). Diastolic blood pressure was positively correlated with BDE-28 and BDE-71 (P < 0.05). Furthermore, a non-linear relationship was observed in BDE-138 and blood lipid levels using a RCS model (Pnonlinearity<0.05). BKMR analysis indicated that with the cumulative levels across PBDEs increased, the health risks of hypertriglyceridemia gradually rebounded, and the health risks of hypercholesterolemia and high total lipid gradually rebounded and then declined, but without statistical significance. PBDEs pollution was still prevalent in Shantou city, and several PBDE congeners were significant risk factors for dyslipidemia and blood pressure alteration. There exist deleterious effects of PBDEs and blood lipids.
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Monitoreo del Ambiente , Éteres Difenilos Halogenados , Tejido Adiposo/química , Teorema de Bayes , China , Monitoreo del Ambiente/métodos , Femenino , Éteres Difenilos Halogenados/análisis , Humanos , LípidosRESUMEN
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.
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Éter , Éteres Difenilos Halogenados , Adulto , Humanos , Animales , Femenino , Éteres Difenilos Halogenados/toxicidad , Pez Cebra , Éteres de Etila , Hormona Luteinizante , Hormona Folículo Estimulante , Superóxido DismutasaRESUMEN
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.
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Éter , Pez Cebra , Animales , Pez Cebra/genética , Transcriptoma , Éteres Difenilos Halogenados/toxicidad , Éteres de Etila , LarvaRESUMEN
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.
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Typically not assisted by proofreading, the RNA-dependent RNA polymerases (RdRPs) encoded by the RNA viruses may need to independently control its fidelity to fulfill virus viability and fitness. However, the precise mechanism by which the RdRP maintains its optimal fidelity level remains largely elusive. By solving 2.1-2.5 Å resolution crystal structures of the classical swine fever virus (CSFV) NS5B, an RdRP with a unique naturally fused N-terminal domain (NTD), we identified high-resolution intra-molecular interactions between the NTD and the RdRP palm domain. In order to dissect possible regulatory functions of NTD, we designed mutations at residues Y471 and E472 to perturb key interactions at the NTD-RdRP interface. When crystallized, some of these NS5B interface mutants maintained the interface, while the others adopted an 'open' conformation that no longer retained the intra-molecular interactions. Data from multiple in vitro RdRP assays indicated that the perturbation of the NTD-RdRP interactions clearly reduced the fidelity level of the RNA synthesis, while the processivity of the NS5B elongation complex was not affected. Collectively, our work demonstrates an explicit and unique mode of polymerase fidelity modulation and provides a vivid example of co-evolution in multi-domain enzymes.
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Virus de la Fiebre Porcina Clásica/genética , Inestabilidad Genómica/genética , Dominios y Motivos de Interacción de Proteínas , ARN Viral/biosíntesis , ARN Polimerasa Dependiente del ARN/química , Virus de la Fiebre Porcina Clásica/enzimología , Virus de la Fiebre Porcina Clásica/metabolismo , Cristalografía por Rayos X , Genoma Viral/genética , Modelos Moleculares , Conformación Molecular , Dominios y Motivos de Interacción de Proteínas/genética , ARN Viral/genética , ARN Viral/metabolismo , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismoRESUMEN
Isopropylate Triphenyl Phosphate (IPPP), a novel organophosphorus flame retardant, has become a widespread environmental pollutant. However, the toxic effects and mechanisms of IPPP remain unclear. In this study, we evaluated the neurodevelopmental toxicity effects of IPPP on zebrafish embryonic development, neurobehavior, and physiological and transcriptomic changes. The results showed that IPPP induced adverse developments such as low survival rates and hatching rates, decreased body length and eye distance, and also led to increased heart rates and embryonic malformation rates. The developmental defects mainly included typical pericardial edema, eye deformities, and a reduction in the number of newborn neurons. Mitochondrial energy metabolism disorders and apoptosis of cardiomyocytes may be responsible for heart malformation. Behavioral results showed that IPPP caused abnormal changes in swimming speed, total swimming distance and trajectory, and showed a low-dose effect. In addition, the decreased activity of neurotransmitters such as acetylcholinesterase (AchE) and dopamine (DA), and the changes in genes related to the central nervous system (CNS) and metabolism pathway may be the causes of neurodevelopmental toxicity of IPPP. Meanwhile, IPPP induced oxidative stress and apoptosis, and changed the ATPase activity of zebrafish larvae by altering nuclear factor erythroid2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing results indicated that Cytochrome P450 and drug metabolism, Energy metabolism-related pathways, Glutathione metabolism, Retinoid acid (RA) and REDOX signaling pathways were significantly enriched, and most of the genes in these pathways were up-regulated after IPPP treatment, which may be new targets for IPPP-induced neurodevelopment. In summary, the results of this study provide an important reference for a comprehensive assessment of the toxic effects and health risks of the new pollutant IPPP.
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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.
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Retardadores de Llama , Pez Cebra , Animales , Masculino , Pez Cebra/metabolismo , Compuestos Organofosforados/metabolismo , Larva/metabolismo , Retardadores de Llama/metabolismo , Organofosfatos/toxicidad , Neurotransmisores/metabolismoRESUMEN
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.
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Compuestos de Bencidrilo , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Fenoles , Pez Cebra , Animales , Pez Cebra/metabolismo , Osteoblastos/metabolismo , Estrés OxidativoRESUMEN
TPhP and IPPP, alternatives to PBDEs as flame retardants, have been studied for their developmental toxicity, but their visual toxicities are less understood. In this study, zebrafish larvae were exploited to evaluate the potential ocular impairments following exposure to BDE-47, TPhP, and IPPP. The results revealed a range of ocular abnormalities, including malformation, vascular issues within the eyes, and histopathological changes in the retina. Notably, the visually mediated behavioral changes were primarily observed in IPPP and TPhP, indicating that they caused more severe eye malformations and vision impairment than BDE-47. Molecular docking and MD simulations showed stronger binding affinity of TPhP and IPPP to RAR and RBP receptors. Elevated ROS and T3 levels induced by these compounds led to apoptosis in larvae eyes, and increased GABA levels induced by TPhP and IPPP hindered retinal repair. In summary, our results indicate TPhP and IPPP exhibit severer visual toxicity than BDE-47, affecting eye development and visually guided behaviors. The underlying mechanism involves disruptions in RA signaling, retinal neurotransmitters imbalance, thyroid hormones up-regulation, and apoptosis in larvae eyes. This work highlights novel insights into the need for cautious use of these flame retardants due to their potential biological hazards, thereby offering valuable guidance for their safer applications.
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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.
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Redes Neurales de la Computación , Sinapsis , Sinapsis/fisiología , Algoritmos , HumanosRESUMEN
A total of Eight hundred eighty-six children from 3 to 7 years old in 8 kindergartens were sampled in urban and rural area in Xianyang City from March to May 2012. The cellophane tape swab technique was used to examine pinworm eggs. Children's hygiene habits, clinical symptoms and hygienic condition were surveyed by questionnairing. The total infection rate of pinworm was 11.2% (99/886). The rate in males and females was 10.4% (52/500) and 12.2% (47/386), respectively. The infection rate in rural kindergartens (19.1%, 70/367) was higher than that of urban kindergartens (5.6%, 29/519) (chi2 = 39.39, P < 0.01). Among the investigated children aged 3-7 years, the infection rate in 4-5 years group (12.7%) was the highest, but no statistical difference was found among age groups (P> 0.05). Multivariate logistic regression analysis showed that the hygiene habits such as washing hands before eating (OR = 0.180), drinking unboiled water and eating non-cooked food (OR = 2.473), cleaning perianal region frequently (OR = 0.836), cutting nails frequently (OR = 0.450), drying the quilt regularly (OR = 0.224) and health education (OR = 0.639) were the influence factors on pinworm infection. The main symptoms of pinworm infection include pruritus and bruxism.
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Enterobiasis/epidemiología , Animales , Niño , Preescolar , China/epidemiología , Enterobiasis/parasitología , Enterobius , Femenino , Humanos , Masculino , Recuento de Huevos de Parásitos , Prevalencia , Población Rural , Población UrbanaRESUMEN
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.
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Propofol , Humanos , Propofol/efectos adversos , Alfentanilo , Endoscopía Gastrointestinal , Vómitos/inducido químicamente , Náusea/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
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Neoplasias Faríngeas , Procedimientos Quirúrgicos Robotizados , Herida Quirúrgica , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Espacio Parafaríngeo/cirugía , Neoplasias Faríngeas/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , DrenajeRESUMEN
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.