RESUMO
Determining cancer subtypes and estimating patient prognosis are crucial for cancer research. The massive amount of multi-omics data generated by high-throughput sequencing technology is an important resource for cancer prognosis. Deep learning methods can integrate such data to accurately identify more cancer subtypes. We propose a prognostic model based on a convolutional autoencoder (ProgCAE) that can predict cancer subtypes associated with survival using multi-omics data. We demonstrated that ProgCAE predicted subtypes of 12 cancer types with significant survival differences and outperformed traditional statistical methods for predicting the survival of most patients with cancer. Supervised classifiers can be constructed based on subtypes predicted by robust ProgCAE.
Assuntos
Aprendizado Profundo , Neoplasias , Humanos , Multiômica , Algoritmos , Neoplasias/genéticaRESUMO
BACKGROUND: Cattle (Bos taurus) are a major large livestock, however, compared with other species, the transcriptional specificity of bovine oocyte development has not been emphasised. RESULTS: To reveal the unique transcriptional signatures of bovine oocyte development, we used integrated multispecies comparative analysis and weighted gene co-expression network analysis (WGCNA) to perform bioinformatic analysis of the germinal follicle (GV) and second meiosis (MII) gene expression profile from cattle, sheep, pigs and mice. We found that the expression levels of most genes were down-regulated from GV to MII in all species. Next, the multispecies comparative analysis showed more genes involved in the regulation of cAMP signalling during bovine oocyte development. Moreover, the green module identified by WGCNA was closely related to bovine oocyte development. Finally, integrated multispecies comparative analysis and WGCNA picked up 61 bovine-specific signature genes that participate in metabolic regulation and steroid hormone biosynthesis. CONCLUSION: In a short, this study provides new insights into the regulation of cattle oocyte development from a cross-species comparison.
Assuntos
Oócitos , Transcriptoma , Bovinos , Animais , Camundongos , Ovinos/genética , Suínos , Oócitos/metabolismo , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oogênese/genética , Perfilação da Expressão GênicaRESUMO
Halo blight, caused by Pseudomonas syringae pv. phaseolicola, is one of the major bacterial diseases on snap bean in Florida, and the outbreaks of this disease have occurred more often in recent years. Current management of this disease primarily depends on application of fixed copper-based bactericides but climate change and resistance development in the pathogen populations still cause hardship for management of this disease, especially in south Florida. In this study, nicotinamide adenine dinucleotide (NAD+) was evaluated in the greenhouse for its potential to reduce halo blight on snap bean. When NAD+ at 5 mM was applied by soil drench, foliar spray, or leaf infiltration, NAD+ significantly (P < 0.05) reduced disease severity of halo blight on snap bean compared with the untreated control. When NAD+ was applied by leaf infiltration, among the tested concentrations, NAD+ at 0.5 to 1.0 mM was most effective in decreasing halo blight disease. NAD+ at 2.5 mM applied as a foliar spray in rotation with Kocide 3000 (copper hydroxide) at 0.5 mg/ml further reduced disease severity compared with Kocide 3000 alone. In the in vitro study, no inhibitory effects of NAD+ were detected on the bacterial pathogen P. syringae pv. phaseolicola. Results of real-time PCR showed that the defense-related genes PR1, AZI1, EDS1, SARD1, PDF1.2, and PAL1 were upregulated in the NAD+ treatment. Taken together, these data indicated that NAD+ significantly suppressed halo blight on snap bean, and application of NAD+ has the potential in management of this important disease.
Assuntos
Fabaceae , NAD , Fabaceae/microbiologia , Pseudomonas syringae/genética , FloridaRESUMO
CircRNAs are newly identified special endogenous RNA molecules that covalently close a loop by back-splicing with pre-mRNA. In the cytoplasm, circRNAs would act as molecular sponges to bind with specific miRNA to promote the expression of target genes. However, knowledge of circRNA functional alternation in skeletal myogenesis is still in its infancy. In this study, we identified a circRNA-miRNA-mRNA interaction network in which the axis may be implicated in the progression of chicken primary myoblasts' (CPMs) myogenesis by multi-omics (i.e., circRNA-seq and ribo-seq). In total, 314 circRNA-miRNA-mRNA regulatory axes containing 66 circRNAs, 70 miRNAs, and 24 mRNAs that may be relevant to myogenesis were collected. With these, the circPLXNA2-gga-miR-12207-5P-MDM4 axis aroused our research interest. The circPLXNA2 is highly differentially expressed during differentiation versus proliferation. It was demonstrated that circPLXNA2 inhibited the process of apoptosis while at the same time stimulating cell proliferation. Furthermore, we demonstrated that circPLXNA2 could inhibit the repression of gga-miR-12207-5p to MDM4 by directing binding to gga-miR-12207-5p, thereby restoring MDM4 expression. In conclusion, circPLXNA2 could function as a competing endogenous RNA (ceRNA) to recover the function of MDM4 by directing binding to gga-miR-12207-5p, thereby regulating the myogenesis.
Assuntos
MicroRNAs , RNA Circular , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , Mioblastos/metabolismo , Apoptose/genética , Proliferação de Células/genéticaRESUMO
One negative consequence of international trade of agricultural commodities is the inadvertent global spread of crop diseases. Yam (Dioscorea spp.) is a staple food crop in many countries and is traded globally. Most of the commercially traded yams in the United States are imported. In late 2020, samples of yam tubers from a commercial facility were submitted to the plant diagnostic clinic at the UF/IFAS Tropical Research and Education Center in Homestead, Florida. Samples showed rotten symptoms and were drawn from lots that were marked to be destroyed because the source of the rotting symptoms was unknown. Preliminary isolation showed that a fungus was consistently associated with the symptoms and was confirmed in the subsequent pathogenicity test as the causal agent. The fungus grew profusely on potato dextrose agar (PDA) with highly melanized hyphae. Matured conidia showed longitudinal striations. Based on its growth pattern and morphology, it was suspected that this fungus may be in the genus Lasiodiplodia. DNA-based identification using partial sequences of the internal transcribed spacer (ITS), ß-tubulin (TUB2), 28S rDNA (LSU), and elongation factor alpha (EF1-α) genes confirmed the identity of the isolates as Lasiodiplodia iraniensis Abdollahz., Zare & A.J.L. Phillips (synonym: L. iranensis). This is the first report of L. iraniensis affecting yam and has implications for international trade. This finding will provide an important foundation for making quarantine decisions to prevent spread of this disease.
Assuntos
Ascomicetos , Dioscorea , Quarentena , Comércio , Internacionalidade , Ascomicetos/genética , FloridaRESUMO
Bacterial spot of tomato continues to pose a significant problem to tomato production worldwide. In Florida, bacterial spot of tomato caused by Xanthomonas perforans is one of the most important diseases responsible for tomato yield loss. This disease is difficult to control, and new strategies are continually being investigated to combat the devastating effect of this disease. Recent efforts focusing on essential oils based on small molecules have spurred interests in the utilization of this class of chemicals for disease management. In this study, we evaluated the efficacy of eugenol for the management of bacterial spot of tomato caused by X. perforans. In the greenhouse experiments, eugenol applied as a foliar spray significantly (p < 0.5) reduced bacterial spot disease compared to the untreated control. In the field experiments, the area under the disease progress curve (AUDPC) was significantly (p < 0.5) lower in the plots treated with eugenol or eugenol combined with the surfactant Cohere than in the untreated control plots, and it was comparable to the copper-based treatments. To provide additional insights into the possible pathways of eugenol activities, we applied a liquid chromatography mass spectrometry (LC-MS)-based metabolomic study using a thermo Q-Exactive orbitrap mass spectrometer with Dionex ultra high-performance liquid chromatography (UHPLC) on X. perforans strain 91−118 treated with eugenol. Our results showed that eugenol affected metabolite production in multiple pathways critical to bacterial survival. For example, treatment of cells with eugenol resulted in the downregulation of the glutathione metabolism pathway and associated metabolites, except for 5-oxoproline, which accumulation is known to be toxic to living cells. While the peaks corresponding to the putatively identified sarmentosin showed the most significant impact and reduced in response to eugenol treatment, branched-chain amino acids, such as L-isoleucine, increased in production, suggesting that eugenol may not negatively affect the protein biosynthesis pathways. The results from our study demonstrated the efficacy of eugenol in the management of bacterial spot of tomato under greenhouse and field conditions and identified multiple pathways that are targeted.
Assuntos
Solanum lycopersicum , Xanthomonas , Eugenol/farmacologia , Doenças das Plantas/microbiologia , Redes e Vias MetabólicasRESUMO
Disuse muscle atrophy is identified as the physiological, biochemical, morphological, and functional changes during restricted movement, immobilization, or weightlessness. Although its internal mechanism has been extensively studied in mammals and was thought to be mainly related to oxidative stress, it was unclear whether it behaved consistently in non-mammals such as chickens. In this study, we tried to construct a disuse atrophy model of the gastrocnemius muscle in chickens by limb immobilization, and collected the gastrocnemius muscles of the fixed group and the control group for RNA sequencing. Through analysis of muscle loss, HE staining, immunohistochemistry, and oxidative stress level, we found that limb immobilization could lead to loss of muscle mass, decrease in muscle fiber diameter, decrease in the proportion of slow muscle fibers, and increase in the proportion of fast muscle fibers, and also cause elevated levels of oxidative stress. In addition, a total of 565 different expression genes (DEGs) were obtained by RNA sequencing, which was significantly enriched in the biological processes such as cell proliferation and apoptosis, reactive oxygen species metabolism, and fast and slow muscle fiber transformation, and it showed that the FOXO signaling pathway, closely related to muscle atrophy, was activated. In brief, we initially confirmed that limb immobilization could induce disuse atrophy of skeletal muscle, and oxidative stress was involved in the process of disuse muscle atrophy.
Assuntos
Galinhas , Transtornos Musculares Atróficos , Animais , Mamíferos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Transtornos Musculares Atróficos/genética , Transtornos Musculares Atróficos/metabolismoRESUMO
Bacterial spot caused by Xanthomonas spp. is one of the major diseases in tomato. Xanthomonas perforans is the main pathogen of bacterial spot on tomato in Florida. Currently, application of copper fungicides is the primary measure used to manage this disease. However, the development of copper resistance in X. perforans and accumulation of copper in the environment are major concerns for excessive use of copper-based products in agriculture. Due to its antibacterial properties and low environmental impact, N-acetylcysteine (NAC), a small molecule commonly used in medicine for human bacterial diseases, has been studied in agriculture for the control of plant bacterial pathogens, including X. citri and Xylella fastidiosa. This study evaluated the effect of NAC alone and in combination with copper on a copper-resistant X. perforans strain in vitro and its ability to control bacterial spot of tomato under greenhouse and field conditions. In vitro, the minimum inhibitory concentration of NAC against the X. perforans strain was 2,048 mg liter-1. NAC increased sensitivity of the copper-resistant X. perforans to copper in vitro when application of NAC was followed by copper application after 6 h. In greenhouse assays, NAC applied alone or in combination with copper significantly (P < 0.05) reduced the disease severity of bacterial spot on tomato compared with the untreated control. NAC at 100 mg liter-1 + copper at 300 mg liter-1 consistently exhibited synergistic effects against bacterial spot. In the field trials, NAC at 1,000 mg liter-1 + copper at 150 mg liter-1 significantly reduced disease severity compared with the untreated control. Results from this study demonstrated that NAC significantly reduced the disease severity of bacterial spot of tomato and enhanced the efficacy of copper against copper-resistant X. perforans, indicating that NAC could be applied for the effective management of bacterial spot of tomato.
Assuntos
Solanum lycopersicum , Xanthomonas , Acetilcisteína/farmacologia , Cobre/farmacologia , Florida , Doenças das Plantas , XylellaRESUMO
Carvacrol, a plant-derived volatile small molecule, is effective against various agents that can cause damage to humans, the food processing industry, and plants, and is considered a safe substance for human consumption. In this short communication, previous studies on the effectiveness of carvacrol against various agents, particularly plant pathogens and their associated mechanisms are described. In our study, carvacrol was found to be effective on media against several soilborne pathogens and in planta against three foliar pathogens (Xanthomonas perforans, Alternaria tomatophila, and Podosphaeraxanthii) of important vegetable crops in south Florida of the United States. Current research findings indicated that the effectiveness of carvacrol against various plant pathogens tested was associated with its direct bactericidal/fungicidal effect, which was affected greatly by its volatility. Development of new formulations to overcome the volatility and to prolong the effectiveness of carvacrol was also presented. Our studies on carvacrol suggested that, with advanced development of new formulations, carvacrol could be used as a promising tool in the integrated pest management for bacterial, fungal, and viral pathogens of important vegetable crops in Florida, the USA, and the world.
Assuntos
Cimenos/farmacologia , Doenças das Plantas/prevenção & controle , Verduras/microbiologia , Anti-Infecciosos/farmacologiaRESUMO
Glutathione S-transferases (GST) play a prominent role in protecting cells against oxidative stress. Our previous study showed that the reactive oxygen species (ROS) generated from pentachlorophenol (PCP) could cause an acute impact on freshwater bivalve Anodonta Woodiana, but its chronic toxicity remain unclear. In order to investigate the chronic effect of PCP, clams A. Woodiana were randomly grouped into PCP treated group in which animals were administrated with 13.9 µg/L concentrations of PCP, and control group those with similar volume dimethyl sulfoxide. In addition, two complete GST sequences were isolated from A. Woodianaa and respectively named AwGST1 and AwGST2. The full-length cDNA of AwGST1 was consisted of a 5' untranslated region (UTR) of 132 bp, a 3' UTR of 80 bp and an open reading frame (ORF) of 609 bp encoding a polypeptide of 203 amino acids. The full-length cDNA of AwGST2 contained a 5' UTR of 57 bp, a 3' UTR of 291 bp and an ORF of 678 bp encoding a polypeptide of 226 amino acids. The constitutive expression levels of AwGST1 and AwGST2 were examined in different tissues including foot, mantle, adductor muscle, heart, hepatopancreas, hemocytes and gill. Administration of PCP could result in a significant increase of AwGST1 and AwGST2 expression in the hepatopancreas, gill and hemocytes. In the hepatopancreas, AwGST1 mRNA levels of PCP treated group increased more than 28.73% at day 1, then 70.37% (P < 0.05) at day 3, reach to 6.64 times (P < 0.01) at day 15 in contrasted with that of control group. AwGST2 increased more 18.18%, 82.88% (P < 0.05) and 2.43 times (P < 0.01) at day 1, 3 and 15, respectively. In the gill, AwGST1 expression showed a significant up-regulation in the PCP treated group during experiment observed compared with that of control group, mRNA level of AwGST2 increased more than 1.44 times (P < 0.05). In addition, expressions of AwGST1 and AwGST2 were significantly induced after PCP treatment in the hemocytes. These results indicated that up-regulations of AwGST1 and AwGST2 expression in bivalve A. woodiana are contribute to against oxidative stress derived from PCP treatment during experiment observed.
Assuntos
Anodonta/efeitos dos fármacos , Anodonta/genética , Glutationa Transferase/genética , Pentaclorofenol/toxicidade , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Glutationa Transferase/química , Glutationa Transferase/metabolismo , Filogenia , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Alinhamento de SequênciaRESUMO
Presently, the exposure of plasticizers to humans and animals occurs daily, which pose a potential threat to reproductive health. In the present study, a pregnant mouse model exposed to di(2-ethylhexyl) phthalate (DEHP, one of the most common plasticizers) and melatonin was established, and the single-cell transcriptome technology was applied to investigate the effects of melatonin in ovarian cells against DEHP. Results showed that DEHP markedly altered the gene expression pattern of ovarian cells, and severely weakened the histone methylation modification of oocytes. The administration of melatonin recovered the expression of LHX8 and SOHLH1 proteins that essential for primordial follicle formation, and increased the expression of CEBPB, as well as key genes of histone methylation modification (such as Smyd3 and Kdm5a). In addition, the ovarian damage caused by DEHP was also relieved after the overexpression of CEBPB, which suggested melatonin could improve primordial follicle formation progress via enhancing CEBPB expression in mice. Besides, the apoptosis of ovarian cells induced by DEHP also was diminished by melatonin. The study provides evidence of melatonin preventing the damage mediated by plasticizers on the reproductive system in females and CEBPB may serve as a downstream target factor of melatonin in the process.
Assuntos
Dietilexilftalato , Melatonina , Ácidos Ftálicos , Gravidez , Feminino , Humanos , Animais , Camundongos , Melatonina/farmacologia , Plastificantes/toxicidade , Dietilexilftalato/toxicidade , Histonas , Oócitos , Proteína beta Intensificadora de Ligação a CCAAT/farmacologiaRESUMO
Rationale: Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the effects of SD on the growth and development of oocytes in females. The present work aimed to investigate whether SD influences ovarian folliculogenesis in adolescent female mice. Methods: Using a dedicated device, SD conditions were established in 3-week old female mice (a critical stage of follicular development) for 6 weeks and gut microbiota and systemic metabolomics were analyzed. Analyses were related to parameters of folliculogenesis and reproductive performance of SD females. Results: We found that the gut microbiota and systemic metabolomics were severely altered in SD females and that these were associated with parameters of premature ovarian insufficiency (POI). These included increased granulosa cell apoptosis, reduced numbers of primordial follicles (PmFs), correlation with decreased AMH, E2, and increased LH in blood serum, and a parallel increased number of growing follicles and changes in protein expression compatible with PmF activation. SD also reduced oocyte maturation and reproductive performance. Notably, fecal microbial transplantation from SD females into normal females induced POI parameters in the latter while niacinamide (NAM) supplementation alleviated such symptoms in SD females. Conclusion: Gut microbiota and alterations in systemic metabolomics caused by SD induced POI features in juvenile females that could be counteracted with NAM supplementation.
Assuntos
Disbiose , Microbioma Gastrointestinal , Metabolômica , Insuficiência Ovariana Primária , Privação do Sono , Animais , Feminino , Insuficiência Ovariana Primária/metabolismo , Camundongos , Disbiose/microbiologia , Disbiose/metabolismo , Metabolômica/métodos , Privação do Sono/complicações , Privação do Sono/metabolismo , Folículo Ovariano/metabolismo , Oócitos/metabolismo , Transplante de Microbiota Fecal , Modelos Animais de Doenças , ApoptoseRESUMO
CONTEXT: Qi-Wei-Xiao-Yan-Tang (XYT), composed of Radix et Rhizoma Rhei, Radix Astragali, Radix Wikstroemiae Indicae, Fructus Ligustri Lucidi, Poria and Radix Glycyrrhizae, has been widely used as an anti-inflammatory drug. OBJECTIVE: The present study investigated the anti-inflammatory, antibacterial effects and serum pharmacochemistry of XYT. METHODS: The dimethylbenzene-induced inflammation test, the acetic acid-induced vascular permeability test and the carrageenan-induced paw edema test were used to evaluate the anti-inflammatory activity of XYT (200, 100 and 50 mg/kg); minimal inhibitory concentration (MIC). Minimal bactericidal concentration (MBC) tests were used to evaluate the antibacterial activity of XYT. Additionally, serum pharmacochemistry was performed to study the biologically active substances. RESULTS: All the tests for anti-inflammatory effects were shown active with these test systems; the anti-inflammatory effects at doses of 100 and 200 mg/kg were significant (p < 0.05); MIC and MBC tests indicated that XYT showed a broader antimicrobial spectrum and stronger toxicity to the tested microbes. Additionally, calycosin-7-glucoside, sennoside A, aloeemodin and rhein were detected as the predominant components in rat serum which may play the key role in the anti-inflammatory activities of XYT. CONCLUSIONS: This is the first report of the pharmacological activities and serum pharmacochemistry of XYT, and the first evidence of anti-inflammatory and antimicrobial properties of the extracts of XYT. The results of our work demonstrated that XYT has significant anti-inflammatory and antibacterial properties, and calycosin-7-glucoside, sennoside A aloeemodin and rhein may be the biologically active substances of XYT. XYT can be utilized as an effective and safe disease preventive or therapeutic agent.
Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Carragenina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Edema/tratamento farmacológico , Edema/patologia , Inflamação/patologia , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the antioxidant and hepatoprotective properties of the different extracts Guizhencao (Herba Bidentis Bipinnatae) against liver injury in hyperlipidemia rats. METHODS: The rats were divided into 7 groups, with 10 rats in each. Rats were treated with high-fat diet for 18 weeks besides the normal control group, then rats in both normal control and model groups were received 5 mL/kg(-1) x day(-1) of saline and those in the positive control group with 2 mg/kg(-1) x day(-1) of lovastatin. Rats in the positive control group and different Guizhencao (Herba Bidentis Bipinnatae) extracts treatment groups (ethyl acetate extract group, n-hexane extract group, ethanol extract group, and aqueous extract group) were treated with corresponding extract at a concentration of 5 mL/kg(-1) x day(-1). After 8 weeks treatment, all rats were sacrificed and total blood samples were collected. Histological analysis of liver was underdone by hematoxylin and eosin. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glouse (GLU), cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol were measured according to standard procedure using auto-analyzer. The superoxide dismutase (SOD) and malondialdehyde (MDA) levels in liver were ananlyzed by procedure instruction. RESULTS: The histopathological analysis implied that the administration of Guizhencao (Herba Bidentis Bipinnatae) extracts resulted in hepatoprotective role compared with that of the model group. In addition, the high-fat diet caused a remarkable increase of ALT, AST, GLU, TC, TG, LDL-C and MDA levels. A decline in HDL-C and SOD concentrations and a reversal of effects were observed in different Guizhencao (Herba Bidentis Bipinnatae) extracts groups, especially in the aqueous extract and ethanol extract groups. CONCLUSION: The different extracts of Guizhencao (Herba Bidentis Bipinnatae) can play a protecting role against liver injury in hyperlipidemia rats maybe through decreasing ALT, AST, GLU, TC, TG, LDL-C and MDA levels and enhancing the liver anti-oxidative ability.
Assuntos
Antioxidantes/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Fígado/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Alanina Transaminase/metabolismo , Animais , Colesterol/metabolismo , Glucose/metabolismo , Humanos , Hiperlipidemias/enzimologia , Hiperlipidemias/metabolismo , Fígado/lesões , Fígado/metabolismo , Masculino , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Triglicerídeos/metabolismoRESUMO
Zearalenone (ZEN) is a widespread and transgenerational toxicant that can cause serious reproductive health risks, which poses a potential threat to global agricultural production and human health; its estrogenic activity can lead to reproductive toxicity through the induction of granulosa cell apoptosis. Herein, comparative transcriptome analysis, single-cell transcriptome analysis, and weighted gene co-expression network analysis (WGCNA) combined with gene knockout in vivo and RNA interference in vitro were used to comprehensively describe the damage caused by ZEN exposure on ovarian granulosa cells. Comparative transcriptome analysis and WGCNA suggested that the tumor necrosis factor (TNF)-α-mediated mitogen-activated protein kinase 7 (MAP2K7)/ AKT serine/threonine kinase 2 (AKT2) axis was disordered after ZEN exposure in porcine granulosa cells (pGCs) and mouse granulosa cells (mGCs). In vivo gene knockout and in vitro RNA interference verified that TNF-α-mediated MAP2K7/AKT2 was the guiding signal in ZEN-induced apoptosis in pGCs and mGCs. Moreover, single-cell transcriptome analysis showed that ZEN exposure could induce changes in the TNF signaling pathway in offspring. Overall, we concluded that the TNF-α-mediated MAP2K7/AKT2 axis was the main signaling pathway of ZEN-induced apoptosis in pGCs and mGCs. This work provides new insights into the mechanism of ZEN toxicity and provides new potential therapeutic targets for the loss of livestock and human reproductive health caused by ZEN.
Assuntos
Zearalenona , Animais , Feminino , Camundongos , Apoptose , MAP Quinase Quinase 7 , Proteína Quinase 7 Ativada por Mitógeno , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Suínos , Transcriptoma , Fator de Necrose Tumoral alfa/genética , Zearalenona/toxicidadeRESUMO
Understanding the relationship between CO2 emissions from commuting (CEC) and the built environment is crucial for sustainable transportation and land-use policymaking during the process of constructing a low carbon city. Previous studies usually assume that the relationship is linear, which may lead to inaccurate CEC prediction and ineffective policy. Using daily travel survey data of residents in the central city of Jinan, this study adopted a gradient boosting decision tree model to explore the threshold effect and the non-linear relationship between built environments and CEC. Our findings suggest that 40% of CEC is related to the workplace environment, which is higher than the residential environment and other socioeconomic variables. The five most important variables are road density within 1 km radius of the workplace (13.493%), distance to the center at workplace and residence (10.908%, 10.530%), population density at workplace (9.097%) and distance to bus stop from the residence (8.399%). Distance to city center plays the most important role and its non-linear relationship reflects the influence of the urban spatial structure of Jinan on CEC. Furthermore, the thresholds and non-linear relationships provide planning guidelines to support urban planning development policies for low carbon city.
Assuntos
Dióxido de Carbono , Características de Residência , Meios de Transporte , Ambiente Construído , Local de TrabalhoRESUMO
We examine the influence of cationic poly(amidoamine) (PAMAM) dendrimers on capillary electroseparation-UV analysis of proteins. PAMAMs adsorbing to the capillary surface suppressed the wall-adsorption of proteins; meanwhile, PAMAMs added to the buffer exhibited selectivity toward proteins. Presence of 3 x 10â»4 g/mL PAMAM generation one (G 1.0) in 30 mM phosphate, at pH 2.6, rendered significant enhancement in separation efficiency; the merged peaks of myoglobin and trypsin inhibitor were separated. Moreover, the protein-dendrimer interactions changed the inherent UV absorbance profiles of proteins. UV-Vis study showed that the absorbance of cytochrome C and transferrin increased at the detection wavelength of 214 nm; their detection sensitivity enhanced by 2.44 and 2.01-folds, respectively, with addition of 5 x 10â»4 g/mL PAMAM G 1.0.
Assuntos
Dendrímeros/química , Eletroforese Capilar/métodos , Proteínas/isolamento & purificação , Animais , Cátions/química , Bovinos , Eletrólitos , Concentração de Íons de Hidrogênio , Fosfatos/química , Ácidos Fosfóricos/químicaRESUMO
OBJECTIVE: To investigate the chemical constituents from the aerial part of Atractylodes macrocephala. METHOD: The constituents were isolated and purified by repeated column chromatography on silica gel, Sephadex LH-20 and ODS. Their structures were identified by physicochemical properties and spectrum analysis. RESULT: Fourteen compounds were isolated and identified as atractylenolide I-III (1-3), 2-[(2E) -3, 7-dimethyl-2, 6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione(4), 2, 6-dimethoxyphenol (5), scopoletin (6), 4-methoxycinnamic acid (7), caffeic acid (8), ferulic acid (9) protocatechuic acid (10), 3-hydroxy-1-(4-hydroxy-3- methoxyphenyl) propan-1-one (11), dictamnoside A (12), syringin (13), D-mannitol (14). CONCLUSION: All the compounds were isolated from the aerial part of A. macrocephala for the first time and compounds 4, 5, 7-12, 14 were isolated from this species for the first time.
Assuntos
Atractylodes/química , Componentes Aéreos da Planta/química , Cromatografia em Gel , Análise EspectralRESUMO
OBJECTIVE: To study the transportation of Xiaochaihu Tang in Caco-2 cell model. METHOD: The safety concentration of Xiaochaihu Tang in Caco-2 cells was determined by MTT assay. Then the Caco-2 cell model was used to investigate the bi-directional transportation of Xiaochaihu Tang. The multicomponents of Xiaochaihu Tang and the influence of time were measured by high performance liquid chromatography (HPLC). RESULT: The P(app) values of wogonoside and wogonin were (1.23 +/- 0.09) x 10(-6), (1.07 +/- 0.89) x 10(-5) cm x s(-1) from the AP side to BL side, and (2.12 +/- 0.19) x 10(-6) and (7.12 +/- 1.02) x 10(-6) cm x s(-1) from the BL side to AP side, respectively. The P(appAP --> BL)/P(app BL --> AP) ratio of wogonoside and wogonin were 0.58 and 1.49, respectively. Baicalin, baicalein and glycyrrhizic acid could not permeate the Caco-2 cell model. CONCLUSION: The transportation of wogonoside and wogonin in Caco-2 cell model may be a passive transportation.
Assuntos
Células CACO-2/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Flavanonas/metabolismo , Glucosídeos/metabolismo , Transporte Biológico Ativo , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Flavanonas/análise , Flavonoides/análise , Flavonoides/metabolismo , Glucosídeos/análise , Ácido Glicirrízico/análise , Ácido Glicirrízico/metabolismo , HumanosRESUMO
The study was conducted to compare the pharmacokinetics and safety profiles of 2 brands of tenofovir alafenamide (TAF) fumarate tablets. This research was a 2-preparation, 2-sequence, 4-period crossover, completely replicated study in 68 healthy Chinese subjects under fasting and fed conditions. The mean values of the area under the concentration-time curve from time 0 to the last time point with blood sample collection (AUC0-t ), area under the concentration-time curve from time 0 to infinity (AUC0-∞ ), and maximum concentration (Cmax ) for the test and reference products of TAF were 248.5 and 275.7 ng/mL, 148.1 and 157.8 ng ⢠h/mL, and 148.4 and 158.1 ng ⢠h/mL, respectively, under the fasting condition. On the other hand, the mean value of Cmax , AUC0-t , and AUC0-∞ for the test and reference formulations of TAF were 244.6 and 246.7 ng/mL, 230.4 and 244.9 ng ⢠h/mL, and 233.2 and 246.2 ng ⢠h/mL, respectively, under the fed condition. The 90% confidence intervals for geometric mean ratios of AUC0-t and AUC0-∞ of TAF in fasting and fed states were within the bioequivalence acceptance limits when tested using the average-bioequivalence method. The point estimate value for geometric mean ratio of Cmax in fasting and fed states (88.4% and 95.5%, respectively) were within the bioequivalence acceptance limits as per the reference-scaled average-bioequivalence method. The safety profiles of the 2 formulations were comparable. Pharmacokinetic analysis demonstrated that the test formulations of TAF exhibited bioequivalence to the reference and were well tolerated by healthy Chinese subjects (Study Registry Identification Number: CTR20190086; CTR20190087).