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N 6-methyladenosine (m6A), which is the mostly prevalent modification in eukaryotic mRNAs, is involved in gene expression regulation and many RNA metabolism processes. Accurate prediction of m6A modification is important for understanding its molecular mechanisms in different biological contexts. However, most existing models have limited range of application and are species-centric. Here we present PEA-m6A, a unified, modularized and parameterized framework that can streamline m6A-Seq data analysis for predicting m6A-modified regions in plant genomes. The PEA-m6A framework builds ensemble learning-based m6A prediction models with statistic-based and deep learning-driven features, achieving superior performance with an improvement of 6.7% to 23.3% in the area under precision-recall curve compared with state-of-the-art regional-scale m6A predictor WeakRM in 12 plant species. Especially, PEA-m6A is capable of leveraging knowledge from pretrained models via transfer learning, representing an innovation in that it can improve prediction accuracy of m6A modifications under small-sample training tasks. PEA-m6A also has a strong capability for generalization, making it suitable for application in within- and cross-species m6A prediction. Overall, this study presents a promising m6A prediction tool, PEA-m6A, with outstanding performance in terms of its accuracy, flexibility, transferability, and generalization ability. PEA-m6A has been packaged using Galaxy and Docker technologies for ease of use and is publicly available at https://github.com/cma2015/PEA-m6A.
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Adenosina , Adenosina/análogos & derivados , Adenosina/metabolismo , ARN de Planta/genética , Aprendizaje Automático , Pisum sativum/genética , Pisum sativum/metabolismo , Plantas/genética , Plantas/metabolismoRESUMEN
BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.
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INTRODUCTION: Nurses are identified as having higher work stress and poor mental health risk among health care workforce globally. It remains unclear which modifiable stress factors pose the greatest risk for poor psychological health among nursing workforce and needed to inform targeted practice and policy change. To determine which occupation-related or personal stress factors precipitate higher risk for burnout, depression, anxiety, job satisfaction or intention to leave one's position among nurses globally. DESIGN: A cross-sectional anonymous survey was administered via email using a snowball recruitment strategy. METHODS: Academic researchers and clinical industry leaders across 3 global regions collaborated to generate an email listserv of professional nursing contacts for survey distribution. The survey included valid and reliable measures to scale stress factors (Work Stress Questionnaire), and screen for burnout (single item), depression (Patient Health Questionnaire-2), anxiety (Generalized Anxiety Disorder-2), resilience (Brief Resilience Scale) and intention to leave one's job (single item). We used logistic regression, first unadjusted and then adjusted for personal and professional characteristics, to determine associations between stress factors and psychological health risk. RESULTS: The final sample consisted of responses from 2864 nurses working across 13 countries. Most respondents reported working as a clinical nurse in the Philippines (n = 2275), United States (n = 424) and Saudi Arabia (n = 104). One third of nursing respondents endorsed high burnout and intention to leave their job. Those reporting work conflict had significantly higher odds of burnout (odds ratio 3.18; 95% CI 2.22-4.54) and three times more likely to screen positive for depression (odds ratio 3.02; 95% CI 1.36-6.72) and anxiety (odds ratio 2.92; 95% CI 1.57-5.43). Those endorsing difficulty sleeping were 15 times more likely to screen positive for depression (odds ratio 15.63; 95% CI 2.09-117.06). Lack of social support was significantly associated to higher risk for burnout, job dissatisfaction, depression, anxiety, and intention to leave one's position. CONCLUSIONS: Nurses remain at risk for burnout and poor psychological health stemming from work stress. Factors such as clear workplace goals and assignments, increased engagement, good sleep health and social support may serve as protective factors against suboptimal psychological health, and in-turn poor workforce retention. CLINICAL RELEVANCE: Nurses reporting conflict in the workplace are three times more likely to screen positive for burnout, depression, and anxiety. Nurses reporting difficulty sleeping are 15 times more likely to screen positive for depression. Several modifiable factors can be targeted to reduce poor psychological health and high workforce turnover among nurses across countries.
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BACKGROUND: N6-methyladenosine (m6A) modification is the most abundant type of RNA modification in eukaryotic cells, playing pivotal roles in multiple plant growth and development processes. Yet the potential role of m6A in conferring the trait of male sterility in plants remains unknown. RESULTS: In this study, we performed RNA-sequencing (RNA-Seq) and m6A-sequencing (m6A-Seq) of RNAs obtained from the anther tissue of two wolfberry lines: 'Ningqi No.1' (LB1) and its natural male sterile mutant 'Ningqi No.5' (LB5). Based on the newly assembled transcriptome, we established transcriptome-wide m6A maps for LB1 and LB5 at the single nucleus pollen stage. We found that the gene XLOC_021201, a homolog of m6A eraser-related gene ALKBH10 in Arabidopsis thaliana, was significantly differentially expressed between LB1 and LB5. We also identified 1642 and 563 m6A-modified genes with hypermethylated and hypomethylated patterns, respectively, in LB1 compared with LB5. We found the hypermethylated genes significantly enriched in biological processes related to energy metabolism and lipid metabolism, while hypomethylation genes were mainly linked to cell cycle process, gametophyte development, and reproductive process. Among these 2205 differentially m6A methylated genes, 13.74% (303 of 2205) were differentially expressed in LB1 vis-à-vis LB5. CONCLUSIONS: This study constructs the first m6A transcriptome map of wolfberry and establishes an association between m6A and the trait of male sterility in wolfberry.
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Infertilidad Masculina , Lycium , Masculino , Humanos , Perfilación de la Expresión Génica , Lycium/genética , Transcriptoma , ARN , Metilación de ADN/genética , Infertilidad Masculina/genéticaRESUMEN
BACKGROUND: Seed size is an important factor contributing to maize yield, but its molecular mechanism remains unclear. The seed coat, which serves as one of the three components of the maize grain, determines seed size to a certain extent. The seed coat also shares the maternal genotype and is an ideal material for studying heterosis. RESULTS: In this study, the self-pollinated seeds of the maize hybrid Yudan888 and its parental lines were continuously collected from 0 day after pollination (DAP) to 15 DAP for phenotyping, cytological observation and RNA-seq. The phenotypic data showed that 3 DAP and 8 DAP are the best time points to study maize seed coat heterosis. Cytological observations indicated that maize seed coat heterosis might be the result of the coordination between cell number and cell size. Furthermore, the RNA-seq results showed that the nonadditive genes changed significantly between 3 and 8 DAP. However, the number of genes expressed additively was not significantly different. Our findings suggest that seed coat heterosis in hybrid is the result of nonadditive expression caused by dynamic changes in genes at different time points during seed expansion and seed coat development. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that genes related to DNA replication, cell cycle regulation, circadian rhythms and metabolite accumulation contributed significantly to hybrid seed coat heterosis. CONCLUSION: Maize seed coat phenotyping allowed us to infer that 3 DAP and 8 DAP are important time points in the study of seed coat heterosis. Our findings provide evidence for genes involved in DNA replication, cell cycle regulation, circadian rhythms and metabolite accumulation in hybrid with high or low parental expression as major contributors to hybrid seed coat heterosis.
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Vigor Híbrido , Zea mays , Zea mays/genética , Semillas/genética , Genotipo , Expresión Génica , Regulación de la Expresión Génica de las Plantas , Hibridación GenéticaRESUMEN
BACKGROUND: A growing number of studies have shown that prenatal exposure to chemical and non-chemical stressors has effects on fetal growth. The co-exposure of both better reflects real-life exposure patterns. However, no studies have included air pollutants and pregnancy-related anxiety (PrA) as mixtures in the analysis. METHOD: Using the birth cohort study method, 576 mother-child pairs were included in the Ma'anshan Maternal and Child Health Hospital. Evaluate the exposure levels of six air pollutants during pregnancy using inverse distance weighting (IDW) based on the pregnant woman's residential address and air pollution data from monitoring stations. Prenatal anxiety levels were assessed using the PrA Questionnaire. Generalized linear regression (GLR), quantile g-computation (QgC) and bayesian kernel machine regression (BKMR) were used to assess the independent or combined effects of air pollutants and PrA on birth weight for gestational age z-score (BWz). RESULT: The results of GLR indicate that the correlation between the six air pollutants and PrA with BWz varies depending on the different stages of pregnancy and pollutants. The QgC shows that during trimester 1, when air pollutants and PrA are considered as a whole exposure, an increase of one quartile is significantly negatively correlated with BWz. The BKMR similarly indicates that during trimester 1, the combined exposure of air pollutants and PrA is moderately correlated with a decrease in BWz. CONCLUSION: Using the method of analyzing mixed exposures, we found that during pregnancy, the combined exposure of air pollutants and PrA, particularly during trimester 1, is associated with BWz decrease. This supports the view that prenatal exposure to chemical and non-chemical stressors has an impact on fetal growth.
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Contaminantes Atmosféricos , Contaminación del Aire , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Humanos , Peso al Nacer , Estudios de Cohortes , Estudios Prospectivos , Teorema de Bayes , Exposición Materna , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , China , Ansiedad , Material Particulado/análisisRESUMEN
BACKGROUND: The placenta serves as the sole maternal organ responsible for transmitting nutrients to the fetus, playing a crucial role in supporting standard fetal growth and development. To date, only a small number of studies have investigated the impact of maternal gestational weight gain and lipid concentrations on placental development. This study aimed to explore the influence of weight gain during pregnancy and lipid levels in the second trimester on placental weight, volume, and the placental weight ratio. METHODS: This birth cohort study encompassed 1,358 mother-child pairs. Placental data for each participant was gathered immediately post-delivery, and the study incorporated data on gestational weight gain throughout pregnancy and lipid profiles from the mid-trimester. A linear regression model was employed to assess the correlations between gestational weight gain, mid-trimester lipid levels, and metrics such as placental weight, placental volume, and the placental-to-birth weight ratio (PFR). RESULTS: In the study groups of pre-pregnancy underweight, normal weight, and overweight, the placental weight increased by 4.93 g (95% CI: 1.04-8.81), 2.52 g (95% CI: 1.04-3.99), and 3.30 g (95% CI: 0.38-6.22) per 1 kg of gestational weight gain, respectively. Within the pre-pregnancy underweight and normal weight groups, the placental volume increased by 6.79 cm^3 (95% CI: 3.43-10.15) and 2.85 cm^3 (95% CI: 1.31-4.39) per 1 kg of gestational weight gain, respectively. Additionally, placental weight exhibited a positive correlation with triglyceride (TG) levels (ß = 9.81, 95% CI: 3.28-16.34) and a negative correlation with high-density lipoprotein (HDL-C) levels (ß = - 46.30, 95% CI: - 69.49 to - 23.11). Placental volume also showed a positive association with TG levels (ß = 14.54, 95% CI: 7.69-21.39). Conversely, PFR demonstrated a negative correlation with increasing HDL-C levels (ß = - 0.89, 95% CI: - 1.50 to - 0.27). CONCLUSIONS: Gestational weight gain was significantly correlated with both placental weight and volume. This association was especially pronounced in women who, prior to pregnancy, were underweight or of normal weight. Additionally, TG and HDL-C levels during the mid-trimester were linked to placental development.
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Ganancia de Peso Gestacional , Placenta , Femenino , Humanos , Embarazo , Peso al Nacer , Estudios de Cohortes , Pueblos del Este de Asia , Lípidos , Placenta/embriología , Delgadez , Tamaño de los ÓrganosRESUMEN
It is important to determine the ideal combination of housing materials, groups of refractive materials, and their optical powers for athermalizing achromatic and apochromatic optical systems. This study proposes a combined design approach that utilizes three or more glass types to resolve thermal aberrations and defocus achromatic and apochromatic optical systems. It selects a suitable glass type using a 3D glass chart and calculates the optical power analytically. Furthermore, a temperature-insensitive optical system with a 450-750 nm band based on refractive materials (CDGM Glass Co., Ltd.) is designed, with the modular transfer function value of the center field of view decreasing by less than 0.024 in the temperature range of -40∘ C to +80∘ C and the secondary spectrum aberration decreasing by over three times and being maintained within 0.08 mm.
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BACKGROUND: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. METHODS: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24-28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. RESULTS: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium-high-risk pregnant women at 17-24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium-high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. CONCLUSION: In medium-high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium-high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted.
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We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.
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Contaminantes Atmosféricos , Contaminación del Aire , Gingivitis , Enfermedades Periodontales , Periodontitis , Humanos , Anciano , Dióxido de Nitrógeno/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Conceptos Meteorológicos , Enfermedades Periodontales/etiología , Enfermedades Periodontales/inducido químicamente , Periodontitis/inducido químicamente , Gingivitis/inducido químicamente , Gingivitis/epidemiología , China , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisisRESUMEN
BACKGROUND: Rice is a salt-sensitive crop. Complex gene regulatory cascades are likely involved in salinity stress in rice roots. microRNA168 (miR168) is a conserved miRNA among different plant species. It in-directly regulates the expression of all miRNAs by targeting gene ARGONAUTE1(AGO1). Short Tandem Target Mimic (STTM) technology is an ideal approach to study miRNA functions by in-activating mature miRNA in plants. RESULTS: In this study, rice miR168 was inactivated by STTM. The T3 generation seedlings of STTM168 exhibited significantly enhanced salt resistance. Direct target genes of rice miR168 were obtained by in silico prediction and further confirmed by degradome-sequencing. PINHEAD (OsAGO1), which was previously suggested to be a plant abiotic stress response regulator. RNA-Seq was performed in root samples of 150mM salt-treated STTM168 and control seedlings. Among these screened 481 differentially expressed genes within STTM168 and the control, 44 abiotic stress response related genes showed significant difference, including four known salt-responsive genes. CONCLUSION: Based on sequencing and qRT-PCR, a "miR168-AGO1-downstream" gene regulation model was proposed to be responsible for rice salt stress response. The present study proved miR168-AGO1 cascade to play important role in rice salinity stress responding, as well as to be applied in agronomic improvement in further.
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MicroARNs , Oryza , Tolerancia a la Sal/genética , Oryza/genética , Estrés Salino/genética , Plantones/genética , MicroARNs/genéticaRESUMEN
BACKGROUND: Heterosis has been extensively utilized in plant breeding, however, the underlying molecular mechanism remains largely elusive. Maize (Zea mays), which exhibits strong heterosis, is an ideal material for studying heterosis. RESULTS: In this study, there is faster imbibition and development in reciprocal crossing Zhengdan958 hybrids than in their parent lines during seed germination. To investigate the mechanism of heterosis of maize germination, comparative transcriptomic analyses were conducted. The gene expression patterns showed that 1324 (47.27%) and 1592 (66.44%) of the differential expression genes between hybrids and either parental line display parental dominance up or higher levels in the reciprocal cross of Zhengdan958, respectively. Notably, these genes were mainly enriched in metabolic pathways, including carbon metabolism, glycolysis/gluconeogenesis, protein processing in endoplasmic reticulum, etc. CONCLUSION: Our results provide evidence for the higher expression level genes in hybrid involved in metabolic pathways acting as main contributors to maize seed germinating heterosis. These findings provide new insights into the gene expression variation of maize embryos and improve the understanding of maize seed germination heterosis.
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Vigor Híbrido , Zea mays , Regulación de la Expresión Génica de las Plantas , Germinación/genética , Vigor Híbrido/genética , Hibridación Genética , Fitomejoramiento , Semillas/genética , Semillas/metabolismo , Transcriptoma , Zea mays/metabolismoRESUMEN
Marine biodiversity provides a range of diverse biological resources, including seafoods that are rich in protein and a well-balanced amino acid composition. Previous studies have shown that peptides can improve bone formation and/or inhibit bone resorption, suggesting the potential for seafood bioactive peptides (SBPs) in development of food and pharmaceuticals for management of osteoporosis. In this review, we provided an up-to-date overview of the anti-osteoporosis activity of SBPs and describe their underlying molecular mechanisms. We focus on SBPs' development, broadening the scope and depth of research, as well as strengthening in vivo and clinical research. In vitro cell cultures and in vivo animal osteoporosis models have demonstrated the potential for seafood-derived SBPs, including fish, mollusks, crustaceans, seaweed and microalgae, in preventing osteoporosis. These peptides may act by activating the signaling pathways, such as BMP/Smads, MAPK, OPG/RANKL/RANK, and NF-κB, which are associated with modulation bone health.
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Resorción Ósea , Osteoporosis , Alimentos Marinos , Animales , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/prevención & control , Humanos , FN-kappa B , Osteogénesis , Osteoporosis/tratamiento farmacológico , Osteoporosis/prevención & control , PéptidosRESUMEN
This study evaluated the relationship between the neuroprotective effects of procyanidins and their structural characteristics. In vitro, a rat pheochromocytoma cell line (PC12) was exposed to the grape seed-derived procyanidin monomers: catechin (C), epicatechin (EC), and epicatechin gallate (ECG); the procyanidin dimers: procyanidin B1 (B1), procyanidin B2 (B2), procyanidin B3 (B3), procyanidin B4 (B4), procyanidin B1-3-O-gallate (B1-G), and procyanidin B2-3-O-gallate (B2-G); and the procyanidin trimers: procyanidin C1 (C1) and N-acetyl-l-cysteine (NAC) for 24 h. Cells were then incubated with 200 µM H2O2 for 24 h. In vivo, zebrafish larvae (AB strain) 3 days post-fertilization were incubated with NAC or procyanidins (C, EC, ECG, B1, B2, B3, B4, B1-G, B2-G, C1) in 300 µM H2O2 for 4 days. Different grape seed procyanidins increased the survival of PC12 cells challenged with H2O2, improved the movement behavior disorder of zebrafish caused by H2O2, inhibited the increase of ROS and MDA and the decrease of GSH-Px, CAT, and SOD activities, and up-regulated the Nrf2/ARE pathway. The neuroprotective effects of the procyanidin trimer C1 treatment group were greater than the other treatment groups. These results suggest that the neuroprotective effect of procyanidins is positively correlated with their degree of polymerization.
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Biflavonoides , Catequina , Fármacos Neuroprotectores , Proantocianidinas , Animales , Biflavonoides/química , Biflavonoides/farmacología , Catequina/química , Catequina/farmacología , Peróxido de Hidrógeno/farmacología , Fármacos Neuroprotectores/farmacología , Proantocianidinas/química , Proantocianidinas/farmacología , Ratas , Pez CebraRESUMEN
This study evaluated the effect of grape seed-derived monomer, dimeric, and trimeric procyanidins on rat pheochromocytoma cell line (PC12) cells and in a zebrafish Parkinson's disease (PD) model. PC12 cells were cultured with grape seed-derived procyanidins or deprenyl for 24 h and then exposed to 1.5 mm 1-methyl-4-phenylpyridinium (MPP+) for 24 h. Zebrafish larvae (AB strain) 3 days post-fertilization were incubated with deprenyl or grape seed-derived procyanidins in 400 µM 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 4 days. The results showed that the procyanidin dimers procyanidin B1 (B1), procyanidin B2 (B2), procyanidin B3 (B3), procyanidin B4 (B4), procyanidin B1-3-O-gallate (B1-G), procyanidin B2-3-O-gallate (B2-G), and the procyanidin trimer procyanidin C1 (C1) had a protective effect on PC12 cells, decreasing the damaged dopaminergic neurons and motor impairment in zebrafish. In PC12 cells and the zebrafish PD model, procyanidin (B1, B2, B3, B4, B1-G, B2-G, C1) treatment decreased the content of reactive oxygen species (ROS) and malondialdehyde (MDA), increased the activity of antioxidant enzymes glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD), and upregulated the expression of nuclear factor-erythroid 2-related factor (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1). These results suggest that in PC12 cells and the zebrafish PD model, the neuroprotective effects of the procyanidins were positively correlated with their degree of polymerization.
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Enfermedad de Parkinson , Proantocianidinas , 1-Metil-4-fenilpiridinio , Animales , Biflavonoides , Catequina , Estrés Oxidativo , Enfermedad de Parkinson/tratamiento farmacológico , Proantocianidinas/química , Proantocianidinas/farmacología , Ratas , Selegilina/farmacología , Pez CebraRESUMEN
Antibiotics are widely found in nitrogen-containing wastewater, which may affect the operation stability of anaerobic ammonium oxidation (anammox)-based biological treatment systems. Extracellular polymeric substances (EPSs) of anammox sludge play a pivotal role in combining with antibiotics; however, the exact role and how the structure of the leading component of EPSs (i.e., extracellular proteins) changes under antibiotic stress remain to be elucidated. Here, the interaction between sulfamethoxazole and the extracellular proteins of anammox sludge was investigated via multiple spectra and molecular simulation. Results showed that sulfamethoxazole statically quenched the fluorescent components of EPSs, and the quenching constant of the aromatic proteins was the largest, with a value of 1.73 × 104 M-1. The overall binding was an enthalpy-driven process, with ΔH = -75.15 kJ mol-1, ΔS = -0.175 kJ mol-1 K-1, and ΔG = -21.10 kJ mol-1 at 35 °C. The O-P-O and CâO groups responded first under the disturbance of sulfamethoxazole. Excessive sulfamethoxazole (20 mg L-1) would decrease the ratio of α-helix/(ß-sheet + random coil) of extracellular proteins, resulting in a loose structure. Molecular docking and dynamic simulation revealed that extracellular proteins would provide abundant sites to bind with sulfamethoxazole, through hydrogen bond and Pi-Akyl hydrophobic interaction forces. Once sulfamethoxazole penetrates into the cell surface and combines with the transmembrane ammonium transport domain, it may inhibit the NH4+ transport. Our findings enhance the understanding on the interaction of extracellular proteins and sulfamethoxazole, which may be valuable for deciphering the response property of anammox sludge under the antibiotic stress.
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Compuestos de Amonio , Aguas del Alcantarillado , Oxidación Anaeróbica del Amoníaco , Anaerobiosis , Reactores Biológicos , Simulación del Acoplamiento Molecular , Nitrógeno , Oxidación-Reducción , SulfametoxazolRESUMEN
BACKGROUND: Sonodynamic therapy (SDT) is an emerging non-invasive therapeutic technique. SDT-based cancer therapy strategies are presently underway, and it may be perceived as a promising approach to improve the efficiency of anti-cancer treatment. In this work, multifunctional theranostic nanoparticles (NPs) were synthesized for synergistic starvation therapy and SDT by loading glucose oxidase (GOx, termed G) and 5,10,15,20-tetrakis (4-chlorophenyl) porphyrin) Cl (T (p-Cl) PPMnCl, termed PMnC) in Poly (lactic-co-glycolic) acid (PLGA) NPs (designated as MG@P NPs). RESULTS: On account of the peroxidase-like activity of PMnC, MG@P NPs can catalyze hydrogen peroxide (H2O2) in tumor regions to produce oxygen (O2), thus enhancing synergistic therapeutic effects by accelerating the decomposition of glucose and promoting the production of cytotoxic singlet oxygen (1O2) induced by ultrasound (US) irradiation. Furthermore, the NPs can also serve as excellent photoacoustic (PA)/magnetic resonance (MR) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSION: Multifunctional MG@P NPs can effectuate the synergistic amplification effect of cancer starvation therapy and SDT by hypoxia modulation, and act as contrast agents to enhance MR/PA dual-modal imaging. Consequently, MG@P NPs might be a promising nano-platform for highly efficient cancer theranostics.
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Hipoxia/tratamiento farmacológico , Nanomedicina/métodos , Nanopartículas/uso terapéutico , Inanición , Animales , Antineoplásicos/uso terapéutico , Glucemia , Línea Celular Tumoral , Contención de Riesgos Biológicos , Femenino , Humanos , Peróxido de Hidrógeno , Imagen por Resonancia Magnética , Ratones Endogámicos BALB C , Nanopartículas/química , Oxígeno , Preparaciones FarmacéuticasRESUMEN
The tracking and positioning of transmission lines is a key element for UAVs (Unmanned Aerial Vehicles) to achieve autonomous inspection of transmission lines. Current methods are vulnerable to weather and environmental factors, have high costs, and have difficulties in data processing. Therefore, this paper proposes a transmission line tracking and localization method based on the electric field sensor array, which calculates the current UAV's heading angle deflection angle, the distance between the transmission line and the UAV, and the elevation angle, providing a new idea to solve the problem of UAV inspection of transmission lines. At the same time, the electric field distribution of different arrangements of three-phase transmission lines was analyzed using COMSOL to determine the flight area of the UAV. By comparing the electric field distribution of the UAV flight area and single-phase transmission lines, it was verified that the current method is also applicable in the three-phase transmission line scenario, and it was further verified that the sensor array used can sense the change of the UAV position in the flight area, indicating that the electric field sensor array can realize the transmission line tracking and localization of transmission lines. The experimental results showed that, in the three-phase transmission line scenario, when the sensor array moves along the transmission straight wire, the maximum absolute error of the heading angle deflection angle calculated according to this method was 8.2°, the maximum absolute error of the distance between the array and the transmission line was 19.3 cm, and the maximum absolute error of the elevation angle was 11.37°; the error was within a reasonable range and can be used for the UAV to realize autonomous inspection.
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This research assessed the molecular mechanism of procyanidins (PCs) against neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridinium (MPP+) induced Parkinson's disease (PD) models. In vitro, PC12 cells were incubated with PCs or deprenyl for 24 h, and then exposed to 1.5 mM MPP+ for 24 h. In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were incubated with deprenyl or PCs in 400 µM MPTP for 4 days. Compared with MPP+/MPTP alone, PCs significantly improved antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), and decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, PCs significantly increased nuclear Nrf2 accumulation in PC12 cells and raised the expression of NQO1, HO-1, GCLM, and GCLC in both PC12 cells and zebrafish compared to MPP+/MPTP alone. The current study shows that PCs have neuroprotective effects, activate the nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and alleviate oxidative damage in MPP+/MPTP-induced PD models.
Asunto(s)
Enfermedad de Parkinson , Proantocianidinas , Animales , Antioxidantes , Estrés Oxidativo , Células PC12 , RatasRESUMEN
This study evaluated the neuroprotective effects and mechanisms of procyanidins (PCs). In vitro, rat pheochromocytoma cells (PC12 cells) were exposed to PCs (1, 2 or 4 µg/mL) or N-Acetyl-L-cysteine (NAC) (20 µM) for 24 h, and then incubated with 200 µM of H2O2 for 24 h. Compared with H2O2 alone, PCs significantly increased antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation and increased the expression of quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC). In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were exposed to NAC (30 µM) or PCs (4, 8 or 16 µg/mL) in the absence or presence of 300 µM of H2O2 for 4 days. Compared with H2O2 alone, PCs enhanced antioxidant activities (e.g., GSH-Px, CAT, and SOD), decreased levels of ROS and MDA, and enhanced Nrf2/ antioxidant response element (ARE) activation and raised expression levels of NQO1, HO-1, GCLM, and GCLC. In conclusion, these results indicated that PCs exerted neuroprotective effects via activating the Nrf2/ARE pathway and alleviating oxidative damage.