RESUMO
Bisphenol compounds (BPs) have various industrial uses and can enter the environment through various sources. To evaluate the ecotoxicity of BPs and identify potential gene candidates involved in the plant toxicity, Arabidopsis thaliana was exposed to bisphenol A (BPA), BPB, BPE, BPF, and BPS at 1, 3, 10 mg/L for a duration of 14 days, and their growth status were monitored. At day 14, roots and leaves were collected for internal BPs exposure concentration detection, RNA-seq (only roots), and morphological observations. As shown in the results, exposure to BPs significantly disturbed root elongation, exhibiting a trend of stimulation at low concentration and inhibition at high concentration. Additionally, BPs exhibited pronounced generation of reactive oxygen species, while none of the pollutants caused significant changes in root morphology. Internal exposure concentration analysis indicated that BPs tended to accumulate in the roots, with BPS exhibiting the highest level of accumulation. The results of RNA-seq indicated that the shared 211 differently expressed genes (DEGs) of these 5 exposure groups were enriched in defense response, generation of precursor metabolites, response to organic substance, response to oxygen-containing, response to hormone, oxidation-reduction process and so on. Regarding unique DEGs in each group, BPS was mainly associated with the redox pathway, BPB primarily influenced seed germination, and BPA, BPE and BPF were primarily involved in metabolic signaling pathways. Our results provide new insights for BPs induced adverse effects on Arabidopsis thaliana and suggest that the ecological risks associated with BPA alternatives cannot be ignored.
Assuntos
Arabidopsis , Compostos Benzidrílicos , Oxirredução , Fenóis , Raízes de Plantas , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , RNA-Seq , Análise de Sequência de RNA , Poluentes do Solo/toxicidadeRESUMO
Acquiring lipid-producing strains of Saccharomyces cerevisiae is necessary for producing high-value palmitoleic acid. This study sought to generate oleaginous S. cerevisiae mutants through a combination of zeocin mutagenesis and fluorescence-activated cell sorting, and then to identify key mutations responsible for enhanced lipid accumulation by multi-omics sequencing. Following three consecutive rounds of mutagenesis and sorting, a mutant, MU310, with the lipid content of 44%, was successfully obtained. Transcriptome and targeted metabolome analyses revealed that a coordinated response involving fatty acid precursor biosynthesis, nitrogen metabolism, pentose phosphate pathway, ethanol conversion, amino acid metabolism and fatty acid ß-oxidation was crucial for promoting lipid accumulation. The carbon fluxes of acetyl-CoA and NADPH in lipid biosynthesis were boosted in these pathways. Certain transcriptional regulators may also play significant roles in modulating lipid biosynthesis. Results of this study provide high-quality resource for palmitoleic acid production and deepen the understanding of lipid synthesis in yeast.
Assuntos
Citometria de Fluxo , Mutagênese , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Metabolismo dos Lipídeos , Lipídeos/biossíntese , Transcriptoma/genética , Metaboloma , Mutação , Metabolômica , Ácidos Graxos/metabolismo , Multiômica , Ácidos Graxos MonoinsaturadosRESUMO
With the widespread use of bisphenol A (BPA) analogs, their health risks have attracted attention. The effects of maternal BPA analogs exposure on glucose homeostasis in adult offspring and the underlying fetal origins require further exploration. Herein, we exposed pregnant mice to two types of BPA analogsâBPB and BPAF; we evaluated glucose homeostasis in adult offspring and maternal-fetal glucose transport by testing intraperitoneal glucose tolerance, determining glucose and glycogen contents, conducting positron emission tomography (PET)/computed tomography (CT), detecting expression of placental nutrient transport factors, and assessing placental barrier status. We observed that adult female offspring maternally exposed to BPB and BPAF exhibited low fasting blood glucose in adulthood, with even abnormal glucose tolerance in the BPAF group. This phenomenon can be traced back to the elevated fetal glucose induced by the increased efficiency of placenta glucose transport in late pregnancy. On the other hand, the expression of genes associated with vascular development and glucose transport was significantly altered in the placenta in the BPAF group, potentially contributing to enhanced fetal glucose. These findings provide preliminary insights into potential mechanisms underlying the disturbance of glucose metabolism in adult female offspring mice induced by maternal exposure to BPA analogs.
Assuntos
Compostos Benzidrílicos , Exposição Materna , Fenóis , Feminino , Animais , Camundongos , Gravidez , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Glucose/metabolismo , Placenta/metabolismo , Placenta/efeitos dos fármacos , Feto/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-NatalRESUMO
The antioxidant N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidized quinone product 6PPD-quinone (6PPD-Q) in rubber have attracted attention due to the ecological risk that they pose. Both 6PPD and 6PPD-Q have been detected in various environments that humans cohabit. However, to date, a clear understanding of the biotransformation of 6PPD-Q and a potential biomarker for exposure in humans are lacking. To address this issue, this study presents a comprehensive analysis of the extensive biotransformation of 6PPD-Q across species, encompassing both in vitro and in vivo models. We have tentatively identified 17 biotransformation metabolites in vitro, 15 in mice in vivo, and confirmed the presence of two metabolites in human urine samples. Interestingly, different biotransformation patterns were observed across species. Through semiquantitative analysis based on peak areas, we found that almost all 6PPD-Q underwent biotransformation within 24 h of exposure in mice, primarily via hydroxylation and subsequent glucuronidation. This suggests a rapid metabolic processing of 6PPD-Q in mammals, underscoring the importance of identifying effective biomarkers for exposure. Notably, monohydroxy 6PPD-Q and 6PPD-Q-O-glucuronide were consistently the most predominant metabolites across our studies, highlighting monohydroxy 6PPD-Q as a potential key biomarker for epidemiological research. These findings represent the first comprehensive data set on 6PPD-Q biotransformation in mammalian systems, offering insights into the metabolic pathways involved and possible exposure biomarkers.
Assuntos
Benzoquinonas , Biomarcadores , Biotransformação , Exposição Ambiental , Poluentes Ambientais , Fenilenodiaminas , Animais , Camundongos , Exposição Ambiental/análise , Fenilenodiaminas/sangue , Fenilenodiaminas/metabolismo , Fenilenodiaminas/urina , Benzoquinonas/sangue , Benzoquinonas/metabolismo , Benzoquinonas/urina , Hidroxilação , Biomarcadores/metabolismo , Biomarcadores/urina , Borracha/química , Masculino , Adulto Jovem , Adulto , Ratos , Microssomos Hepáticos/metabolismo , Feminino , Poluentes Ambientais/sangue , Poluentes Ambientais/metabolismo , Poluentes Ambientais/urinaRESUMO
Reproductive disorders are considered a global health problem influenced by physiological, genetic, environmental, and lifestyle factors. The increased exposure to bisphenols, a chemical used in large quantities for the production of polycarbonate plastics, has raised concerns regarding health risks in humans, particularly their endocrine-disrupting effects on female reproductive health. To provide a basis for future research on environmental interference and reproductive health, we reviewed relevant studies on the exposure patterns and levels of bisphenols in environmental matrices and humans (including susceptible populations such as pregnant women and children). In addition, we focused on in vivo, in vitro, and epidemiological studies evaluating the effects of bisphenols on the female reproductive system (the uterus, ovaries, fallopian tubes, and vagina). The results indicate that bisphenols cause structural and functional damage to the female reproductive system by interfering with hormones; activating receptors; inducing oxidative stress, DNA damage, and carcinogenesis; and triggering epigenetic changes, with the damaging effects being intergenerational. Epidemiological studies support the association between bisphenols and diseases such as cancer of the female reproductive system, reproductive dysfunction, and miscarriage, which may negatively affect the establishment and maintenance of pregnancy. Altogether, this review provides a reference for assessing the adverse effects of bisphenols on female reproductive health.
RESUMO
Flower senescence is commonly enhanced by the endogenous hormone ethylene and suppressed by the gibberellins (GAs) in plants. However, the detailed mechanisms for the antagonism of these hormones during flower senescence remain elusive. In this study, we characterized one up-regulated gene PhOBF1, belonging to the basic leucine zipper transcription factor family, in senescing petals of petunia (Petunia hybrida). Exogenous treatments with ethylene and GA3 provoked a dramatic increase in PhOBF1 transcripts. Compared with wild-type plants, PhOBF1-RNAi transgenic petunia plants exhibited shortened flower longevity, while overexpression of PhOBF1 resulted in delayed flower senescence. Transcript abundances of two senescence-related genes PhSAG12 and PhSAG29 were higher in PhOBF1-silenced plants but lower in PhOBF1-overexpressing plants. Silencing and overexpression of PhOBF1 affected expression levels of a few genes involved in the GA biosynthesis and signaling pathways, as well as accumulation levels of bioactive GAs GA1 and GA3. Application of GA3 restored the accelerated petal senescence to normal levels in PhOBF1-RNAi transgenic petunia lines, and reduced ethylene release and transcription of three ethylene biosynthetic genes PhACO1, PhACS1, and PhACS2. Moreover, PhOBF1 was observed to specifically bind to the PhGA20ox3 promoter containing a G-box motif. Transient silencing of PhGA20ox3 in petunia plants through tobacco rattle virus-based virus-induced gene silencing method led to accelerated corolla senescence. Our results suggest that PhOBF1 functions as a negative regulator of ethylene-mediated flower senescence by modulating the GA production.
RESUMO
Gestation is a sensitive window to nitrogen dioxide (NO2) exposure, which may disturb fetal lung development and lung function later in life. Animal and epidemiological studies indicated that long noncoding RNAs (lncRNAs) participate in abnormal lung development induced by environmental pollutant exposure. In the present study, pregnant C57BL/6J mice were exposed to 2.5 ppm NO2 (mimicking indoor occupational exposure) or clean air, and lncRNAs expression profiles in the lungs of offspring mice were determined by lncRNA-seq on embryonic day 13.5 (E13.5), E18.5, postnatal day 1 (P1), and P14. The lung histopathology examination of offspring was performed, followed by weighted gene coexpression network analysis (WGCNA), prediction of lncRNAs-target genes, and the biological processes enrichment analysis of lncRNAs. Our results indicated that maternal NO2 exposure induced hypoalveolarization on P14 and differentially expressed lncRNAs showed a time-series pattern. Following WGCNA and enrichment analysis, 2 modules participated in development-related pathways. Importantly, the expressions of related genes were altered, some of which were confirmed to be related to abnormal vascular development and even lung diseases. The research points out that the maternal NO2 exposure leads to abnormal lung development in offspring that might be related to altered lncRNAs expression profiles with time-series-pattern.
Assuntos
Poluentes Ambientais , RNA Longo não Codificante , Animais , Feminino , Humanos , Camundongos , Gravidez , Perfilação da Expressão Gênica/métodos , Pulmão/metabolismo , Exposição Materna , Camundongos Endogâmicos C57BL , Dióxido de Nitrogênio/toxicidade , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Bisphenol AF (BPAF) is the most estrogenic compound among BPA analogs. Mammary glands (MDs) are special organs that undergo repeated cycles of structural development, metabolism, and functional differentiation. Gestation is a sensitive window for MDs. In the present study, plug-positive CD-1 mice were exposed to vehicle (Veh) or 300 µg/kg BPAF through oral gavage every second day during gestation, and maternal MDs were collected from different developmental windows at 9.5, 13.5, and 18.5 d of gestation (gestation day [GD]9.5, GD13.5 and GD18.5). The results showed that gestational BPAF exposure induced a significantly elevated MD density at GD18.5. Non-target metabolomics analysis was used to screen for tyrosine, valine, ornithine, proline, threonine, phenylalanine and asymmetrical dimethylarginine (ADMA) amino acids, which changed significantly at all time points. Furthermore, the mRNA expression levels of genes related to these amino acids also changed significantly. Additionally, amino acid levels in BPAF-treated MGs at GD18.5 were related to the serum ammonia concentration of the corresponding offspring. These results provide a comprehensive view of the adverse effects of BPAF exposure during gestation on the maternal MG structure and function, which may affect milk components during lactation. Moreover, higher amino acids content may lead to amino acid imbalance or hyperammonemia in newborns.
Assuntos
Amônia , Compostos Benzidrílicos , Aminoácidos , Animais , Compostos Benzidrílicos/toxicidade , Feminino , Fluorocarbonos , Camundongos , Ornitina , Fenilalanina , Gravidez , Prolina , RNA Mensageiro , Treonina , Tirosina , ValinaRESUMO
Lung growth is a critical window, when exposure to various pollutants can disturb the finely-tuned lung development and enhance risk of long-term structural and functional sequelae of lung. In this study, pregnant C57/6 mice were treated with NO2, and lungs of fetus/offspring were collected at different developmental windows and dynamic lung development was determined. The results showed that maternal NO2 exposure suppressed fetal weight, implying that fetal development can be disturbed. The time-series RNA-seq analysis of lungs showed that maternal NO2 exposure induced significant time-dependent changes in the expression profiles of genes associated with lung vein myocardium development in fetus/offspring. Most of these genes in NO2 exposure group were suppressed at middle gestation and at birth. Our results also indicated that the gene expressions of Nkx2.5 in NO2 exposure were suppressed to 0.27- and 0.44-fold of the corresponding Air group at E13.5 and PND1, and restored at later time points. This indicated that the transcription factor Nkx2.5 played an important role in abnormal lung development in fetus/offspring caused by maternal NO2 exposure. Importantly, gene expressions of lung vein myocardium development were related to transcription factors (TFs) and lung functions, and TFs showed similar trends with lung function. These results provide a comprehensive view of the adverse effects of maternal NO2 exposure on fetal lung development by uncovering molecular targets and related signaling pathways at the transcriptional level.
RESUMO
This study investigated the potential active components against cyclooxygenase-2(COX-2) from Trachelospermi Caulisetfolium and explored the pharmacodynamic material basis.A pharmacophore-based virtual screening method was adopted to establish a COX-2 ligands-based HipHop pharmacophore model on the basis of the information on compounds with COX-2 inhibitory activity reported in published research articles.The reported components in Trachelospermi Caulisetfolium were collected to establish the compound library and matched with the pharmacophores.Subsequently, the matched small molecule compounds underwent molecular docking with COX-2 targets(PDB ID: 3 LN1), and the interaction of potential active monomers and COX-2 was further explored by molecular dynamics.The antiepileptic effect of active monomer arctigenin(15) was determined based on the pentylenetetrazole(PTZ)-induced seizure model, and its modulatory effect on the COX-2 level was evaluated.A compound library containing 118 chemical constituents in Trachelospermi Caulisetfolium was established by literature retrieval.The preferred pharmacophore 04 was selected through test set verification for virtual screening of the compound library of Trachelospermi Caulisetfolium.After matching, six potential constituents with COX-2 inhibitory activity were obtained.The interaction of five compounds with COX-2 and COX-1 was analyzed by molecular docking, and 10 ns molecular dynamics was performed on two compounds.Compound 15 could prolong the latent time of PTZ-induced seizures at medium and high doses, improve the anxiety-and depression-like behaviors induced by PTZ, reduce the expression level of COX-2, and decrease the number of COX-2 immuno-posi-tive cells in the hippocampal CA1 region.The results showed that it was reasonable to investigate the components in Trachelospermi Caulisetfolium with COX-2 inhibitory activity based on virtual screening and activity evaluation.
Assuntos
Anticonvulsivantes , Inibidores de Ciclo-Oxigenase 2 , Anticonvulsivantes/farmacologia , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Humanos , Ligantes , Simulação de Acoplamento Molecular , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológicoRESUMO
Bisphenol A (BPA) and its analogs are frequently detected in human daily necessities and environmental media. Placental thyroid hormone plays an important role in fetal development. Herein, we followed the adverse outcome pathway (AOP) to explore the toxic mechanisms of BPA and its analogs toward placental thyroid hormone receptor (TR). First, the TOX21 database was used, and the interactions between BPA analogs and the ligand-binding domains (LBDs) of two subtypes of TR (TRα and TRß) were subjected to in silico screening using molecular docking (MD) and molecular dynamics simulation (MDS). Fluorescence spectra and circular dichroism (CD) showed that BPA and its analogs interfere with TRs as a molecular initiation event (MIE), including static fluorescence quenching and secondary structural content changes in TR-LBDs. Key events (KEs) of the AOP, including the toxicity induced in placental chorionic trophoblast cells (HTR-8/SVneo) by an inverted U-shaped dose effect and changes in ROS levels, were tested in vitro. BPA, BPB, and BPAF significantly changed the expression level of TRß, and only BPAF significantly downregulated the expression level of TRα. In conclusion, our study contributes to the health risk assessment of BPA and its analogs regarding placental adverse outcomes (AOs).
Assuntos
Receptores dos Hormônios Tireóideos , Trofoblastos , Compostos Benzidrílicos/toxicidade , Feminino , Humanos , Simulação de Acoplamento Molecular , Fenóis , Placenta/metabolismo , Gravidez , Receptores dos Hormônios Tireóideos/metabolismo , Receptores beta dos Hormônios Tireóideos , Trofoblastos/metabolismoRESUMO
High value unsaturated fatty acids can be produced by de novo synthesis in microalgal cells, especially via heterotrophic cultivation. Unfortunately, the lipid accumulation of heterotrophic microalgae cannot be improved efficiently in conventional ways. Here we reported heterotrophic Tribonema minus, a promising resource for the production of palmitoleic acid which has increasing demands in health service for patients with metabolic syndrome, as whole-cell biocatalyst to develop a novel way of shifting low value exogenous saturated fatty acids to high value ones. Results showed that myristic acid is the best precursor for whole-cell catalysis; it elevated the lipid content of T. minus to 42.2%, the highest among the tried precursors. The influences of cultivation condition on the utilization of extrinsic myristic acid and lipid accumulation were also determined. Under the optimized condition, the lipid content reached as high as 48.9%. In addition, our findings showed that ~13.0% of C16:1 in T. minus is derived from extrinsic myristic acid, and 30.1% of metabolized precursor is converted into heterologous fatty acids. Thus, a feasible approach for both increasing the value of low value saturated fatty acid by bioconversion and enhancing the lipid accumulation in microalgae is proposed by supplementing extrinsic myristic acid.
Assuntos
Microalgas , Estramenópilas , Biocombustíveis , Biomassa , Catálise , Ácidos Graxos/metabolismo , Humanos , Microalgas/metabolismo , Ácidos Mirísticos/metabolismoRESUMO
Herbaceous peony is an important cut-flower plant cultivated worldwide, but its short vase life substantially restricts its economic value. It is well established that endogenous hormones regulate the senescence process, but their molecular mechanism in flower senescence remains unclear. Here, we isolated a MYB transcription factor gene, PlMYB308, from herbaceous peony flowers, based on transcriptome data. Quantitative real-time PCR analysis showed that PlMYB308 is strongly up-regulated in senescing petals, and its expression was induced by abscisic acid or ethylene and reduced by gibberellin in petals. Treatment with abscisic acid or ethylene accelerated herbaceous peony petal senescence, and gibberellin delayed the process. PlMYB308 silencing delayed peony flower senescence and dramatically increased gibberellin, but reduced ethylene and abscisic acid levels in petals. PlMYB308 ectopic overexpression in tobacco accelerated flower senescence and reduced gibberellin, but increased ethylene and abscisic acid accumulation. Correspondingly, five endogenous hormone biosynthetic genes showed variable expression levels in petals after PlMYB308 silencing or overexpression. A dual-luciferase assay and yeast one-hybrid analysis showed that PlMYB308 specifically binds the PlACO1 promoter. Moreover, treatment with ethylene and 1-MCP can accelerate PlMYB308 silencing-reduced senescence and delay PlMYB308- overexpression-induced senescence. We also found that PlACO1 silencing delayed senescence in herbaceous peony petals. Taken together, our results suggest that the PlMYB308-PlACO1 regulatory checkpoints positively mediate the production of ethylene, and thus contribute to senescence in herbaceous peony flowers.
RESUMO
BACKGROUND: Patients with recurrent or locally advanced head and neck squamous cell carcinoma (HNSCC) typically have limited treatment options and poor prognosis. AIM: To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC. METHODS: This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days. Intensity-modulated radiation therapy with a conventional fraction was delivered 5 days per week. Objective response rate (ORR), disease control rate, and toxicity were observed as primary endpoints. Overall survival (OS) and progression free survival were recorded and analyzed as secondary endpoints. RESULTS: A total of 24 patients with HNSCC were enrolled. During the median 22.4-mo follow-up, both ORR and disease control rate were 100%. The one-year OS was 75%, and one-year progression-free survival (PFS) was 66.7% (median PFS was 15.1 mo). Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients, and patients who achieved complete response had better survival than those in the PR group (all P < 0.05). The most common grade 1-4 (100%) or grade 3-4 toxicities (75%) were hematological, and the most common grade 3-4 non-hematological toxicity was mucositis in 17 (71%) patients. CONCLUSION: Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability. Considering the high adverse event rate, the optimized dose and schedule must be further explored.
RESUMO
RNA silencing is a common antiviral mechanism in eukaryotic organisms. However, the transcriptional regulatory mechanism that controls the RNA silencing process remains elusive. Here, we performed high-depth transcriptome analysis on petunia (Petunia hybrida) leaves infected with tobacco rattle virus (TRV) strain PPK20. A total of 7,402 differentially expressed genes (DEGs) were identified. Of them, some RNA silencing-related transcripts, such as RNA-dependent RNA polymerases (RDRs), Dicer-like RNase III enzymes (DCLs), and Argonautes (AGOs), were induced by viral attack. Furthermore, we performed TRV-based virus-induced gene silencing (VIGS) assay on 39 DEGs encoding putative transcription factors (TFs), using green fluorescent protein (GFP) and phytoene desaturase (PhPDS) as reporters. Results showed that the down-regulation of PhbHLH41, PhbHLH93, PhZPT4-3, PhCOL4, PhHSF-B3A, PhNAC90, and PhWRKY75 led to enhanced TRV accumulation and inhibited PhPDS-silenced photobleaching phenotype. In contrast, silencing of PhERF22 repressed virus accumulation and promoted photobleaching development. Thus, these TFs were identified as potential positive and negative regulators of antiviral RNA silencing, respectively. One positive regulator PhCOL4, belonging to the B-box zinc finger family, was selected for further functional characterization. Silencing and transient overexpression of PhCOL4 resulted in decreased and increased expression of several RNA silencing-related genes. DNA affinity purification sequencing analysis revealed that PhCOL4 targeted PhRDR6 and PhAGO4. Dual luciferase and yeast one-hybrid assays determined the binding of PhCOL4 to the PhRDR6 and PhAGO4 promoters. Our findings suggest that TRV-GFP-PhPDS-based VIGS could be helpful to identify transcriptional regulators of antiviral RNA silencing.
RESUMO
Placental senescence is a normal physiological process of placenta, while premature placental senescence has been confirmed to be associated with some adverse pregnancy complications. Epidemiological studies indicate that NO2 exposure can aggravate placental senescence which is represented by fibrosis and abnormal telomere homeostasis, etc. In this study, pregnant C57BL/6 mice were exposed to NO2 (2.5 ppm, 5 h/day) daily in a dynamic exposure chamber throughout the gestation period, and were sacrificed at embryonic day 13.5 (E13.5), E15.5 and E18.5. Placenta were harvested and conducted for histopathological examination and telomere evaluation. Our results showed that gestational NO2 exposure significantly aggravated placental fibrosis and calcification, and up-regulated the related bio-markers (connective tissue growth factor (Ctgf) and transforming growth factor-ß1 (Tgf-ß1)) at E18.5. In addition, gestational exposure to NO2 also activated senescence related pathway (p53/p21) at E18.5. Furthermore, gestational NO2 exposure significantly shortened telomere length at E18.5, and the expression of telomere homeostasis regulation genes telomeric repeat binding factor 1 (Trf1), protection of telomeres 1a (Pot1a) and Pot1b were significantly increased while telomerase reverse transcriptase (Tert) was suppressed after NO2 exposure at E13.5 or E18.5, respectively. Importantly, DNA methylation status of the 22nd at E13.5 and 32nd at E18.5 site in sub-telomeric region of chromosome 1 was significantly altered. Based on the above results, our present study indicated that gestational NO2 exposure could lead to premature placental senescence during the late trimester of pregnancy via aggravation of fibrosis and telomere length shortening regulated by telomere regulatory enzyme and DNA methylation.
Assuntos
Dióxido de Nitrogênio , Placenta , Encurtamento do Telômero , Animais , Senescência Celular/genética , Proteínas de Ligação a DNA/genética , Feminino , Fibrose , Camundongos , Camundongos Endogâmicos C57BL , Dióxido de Nitrogênio/efeitos adversos , Placenta/metabolismo , Placenta/fisiopatologia , Gravidez , Telômero/metabolismoRESUMO
The high accuracy of short-term power load forecasting has a pivotal role in helping power companies to construct reasonable production scheduling plans and avoid resource waste. In this paper, a multi-model short-term power load prediction method based on Variational mode decomposition (VMD)-improved whale optimization algorithm (IWOA)-wavelet temporal convolutional network (WTCN)-bidirectional gated recurrent unit (BiGRU)-attention and CatBoost model fusion is proposed. First, VMD was employed to decompose the load data into different intrinsic mode functions. Second, a WTCN was utilized to extract the load data features, and multi-dimensional feature factors were integrated into the BiGRU network for model training. Moreover, an attention mechanism was added to enhance the influence degree of important information. The WTCN-BiGRU-attention model is improved by the WOA algorithm to optimize the hyperparameters of the network. Finally, the model was fused with the predicted data of the CatBoost network by the mean absolute percentage error-reciprocal weight (MAPE-RW) algorithm to construct the best fusion model. Compared with other forecasting models, the proposed multi-model fusion method has higher accuracy in short-term power load forecasting using the public data set for an Australian region.
Assuntos
Algoritmos , Redes Neurais de Computação , Austrália , PrevisõesRESUMO
Maternal smoking during pregnancy can induce permanent changes in neonatal inflammation, which will result in lifelong implications. An original study of data from GSE96978, composed of 2 subseries (GSE96976 and GSE96977), investigated genome-wide changes in ELT cells, the lungs of mouse dams and their juvenile offspring and focused on finding an in vitro alternative as a human tissue-based replacement for the use of animals. Therefore, the study only analyzed the similarities of GO terms between ELT cells and dams. However, the relationship between differentially expressed genes (DEGs) in dams and offspring was not investigated. The present study aimed to identify the key molecules involved in maternal smoking-induced dam and offspring lung injuries. Data from GSE96977 were downloaded from Gene Expression Omnibus (GEO) data sets. In our study, differentially expressed genes (DEGs) in dams and offspring were reanalyzed using the limma package. The results of Gene Set Enrichment Analysis (GSEA) showed that the DEGs in the lungs of dams were significantly enriched in immune-related functions and those in the lungs of offspring were enriched in cell growth. Furthermore, a total of 90 DEGs shared in the dam and offspring datasets were screened out. In addition, most of these DEGs were enriched in cytokine and cytokine receptor interaction KEGG pathways. Furthermore, protein-protein interaction (PPI) network analysis screened out 4 core genes in cluster 1. In addition, the miRNAs related to these core genes were predicted, and mmu-miR-1903 was screened out. Taken together, our data indicate that inflammatory responses may play an important role in maternal smoking induced lung injuries in dams and offspring. Furthermore, mmu-miR-1903 is a potential epigenetic biomarker of lung inflammation in the offspring of dams who smoked during pregnancy. In conclusion, by screening shared differential genes, we only need to detect maternal genes to predict maternal smoking-induced lung injuries in offspring.
Assuntos
Lesão Pulmonar , MicroRNAs , Animais , Citocinas/genética , Feminino , Lesão Pulmonar/induzido quimicamente , Camundongos , MicroRNAs/metabolismo , Gravidez , Mapas de Interação de Proteínas , Fumar/efeitos adversosRESUMO
Succinimides are well recognized heterocyclic compounds in drug discovery which produce diverse therapeutically related applications in pharmacological practices. Researches in medicinal chemistry field have isolated and synthesized succinimide derivatives with multiple medicinal properties including anticonvulsant, anti-inflammatory, antitumor and antimicrobial agents, 5-HT receptor ligands and enzyme inhibitors. Simultaneously, SAR (Structure-Activity Relationship) analysis has been gradually possessed, along with a great deal of derivatives have been derived for potential targets. In this article, we comprehensively summarize the biological activities and SAR for succinimide derivatives, along with the featuring bioactive molecules reported in patents, wishing to provide an overall retrospect and prospect on the succinimide analogues.
Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Anticonvulsivantes/farmacologia , Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Succinimidas/farmacologia , Anti-Infecciosos/química , Anti-Inflamatórios não Esteroides/química , Anticonvulsivantes/química , Antineoplásicos/química , Inibidores Enzimáticos/química , Humanos , Estrutura Molecular , Succinimidas/químicaRESUMO
BACKGROUND: As a class of endogenous non-coding RNAs with closed-loop structure, circular RNAs (circRNAs) are receiving more and more attention. CircRNAs have been reported to be widely expressed in various human cancers and are implicated in tumorigenesis and progression. The present study aimed to systematically evaluate the clinicopathological, diagnostic and prognostic values of circRNAs in lung cancer. METHODS: We searched literature from PubMed, Web of science, Cochrane Library, EMBASE and Ovid online databases up to May 29, 2020. Statistical analyses were undertaken based on Stata 11.0, Meta-DiSc 1.4, and RevMan 5.3 software. RESULTS: Finally, a total of 63 eligible articles were included in our meta-analysis, including 18 studies for diagnosis, 22 studies for prognosis and 57 studies for clinicopathological features. In terms of diagnostic values, circRNAs could discriminate between lung cancer patients and the normal individuals with a relatively high pooled area under the curve (AUC) of 0.83 (95%CI, 0.80-0.86). For the prognostic values, we found that elevated expression of oncogenic circRNAs could predict poor survival outcomes based on multivariate analysis (HR = 2.430, 95%CI = 2.003-2.948, P < 0.001 for OS; HR = 2.228, 95%CI = 1.289-3.853, P = 0.004 for DFS) while tumor-suppressor circRNAs was correlated with better OS in univariate analysis (HR = 0.627, 95%CI = 0.519-0.757, P < 0.001). The pooled results suggested that elevated expression of carcinogenic circRNAs was associated with tumor size (OR = 1.676, 95%CI = 1.209-2.323, P = 0.002), smoking statue (OR = 1.260, 95%CI = 1.062-1.494, P = 0.008), TNM stage (OR = 2.345, 95%CI = 1.617-3.399, P < 0.001), differentiation grade (OR = 1.843, 95%CI = 1.228-2.765, P = 0.003), and lymphatic metastasis (OR = 2.097, 95%CI = 1.482-2.967, P < 0.001). Moreover, the expression of tumor-suppressor circRNAs was related to the improved clinicopathological features (lymphatic metastasis: OR = 0.536, 95%CI = 0.311-0.926, P = 0.025). CONCLUSIONS: Our meta-analysis demonstrated that circRNAs could be used as feasible and important biomarkers for diagnosis, prognosis and clinicopathological features in lung cancer.