RESUMO
AIMS: This study aims to analyze the association between combustible/electronic cigarettes and the risk of stroke. METHODS: We obtained data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). The stroke history and combustible/electronic cigarette use were acquired by questionnaires. Considering the sole or dual use of combustible cigarettes and electronic cigarettes (e-cigarettes), we divided all the individuals into four subgroups, including nonsmokers (reference group), sole combustible cigarette, sole e-cigarette, and dual use of both combustible cigarettes and e-cigarettes. We performed multivariable logistic regression to determine the association between cigarette use with the prevalence of stroke. We used odds ratios (ORs) with 95% confidence intervals (CIs) to show the effect size. Finally, we developed a prediction model to evaluate the risk of stroke for individuals with combustible or electronic cigarette use based on a random forest model. RESULTS: We included a total of 4022 participants in the study. The median age was 55, and 48.3% of the participants were males. When we adjusted for age, gender, education attainment, race, total-to-HDL cholesterol (< 5.9 or ≥ 5.9), diabetes, hypertension, and alcohol consumption, the groups of sole e-cigarette use, sole combustible cigarette use, and dual use of combustible and electronic cigarettes were significantly associated with the prevalence of stroke with ORs (with 95%CI) of 2.07 (1.04-3.81), 2.36 (1.52-3.59), 2.34 (1.44-3.68), respectively. In the testing set, the AUC was 0.74 (95%CI = 0.65-0.84), sensitivity was 0.68, and specificity was 0.75. CONCLUSION: Sole e-cigarettes and dual use of e-cigarettes with combustible cigarettes might increase the risk of stroke.
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Sistemas Eletrônicos de Liberação de Nicotina , Acidente Vascular Cerebral , Produtos do Tabaco , Vaping , Masculino , Humanos , Feminino , Vaping/efeitos adversos , Vaping/epidemiologia , Inquéritos Nutricionais , Acidente Vascular Cerebral/epidemiologiaRESUMO
It is generally acknowledged that the stability evaluation of surrounding rock denotes nonlinear complex system engineering. In order to accurately and quantitatively assess the safety states of surrounding rock and provide a scientific basis for the prevention and control of surrounding rock stability, the analysis method of the synergetic theory of information entropy using the failure approach index has been proposed. By means of deriving the general relationship between the total two-dimensional plastic shear strain and the total three-dimensional plastic shear strain and obtaining the numerical limit analysis step of the plastic shear strain, the threshold value of the ultimate plastic shear strain can be determined, which has provided the key criterion for the calculation of the information entropy based on the failure approach index. In addition, combining with the synergetic theory of the principle of maximum information entropy, the evolution equation of the excavation step and information entropy based on the failure approach index of the surrounding rock system in underground mining space are established, and the equations of the general solution and particular solution as well as the expression of the destabilizing excavation step are given. To account for this, the method is applied to analyze the failure states of the floor surrounding rock after the mining of the 71 coal seam in Xutuan Coal Mine and involve the disturbance effect and stability control method of the underlying 72 coal seam roof from the macroscopic and microscopic aspects. Consequently, the validity of the analysis method of synergetic theory of information entropy based on the failure approach index has been verified, which presents an updated approach for the stability evaluation of surrounding rock systems that is of satisfactory capability and value in engineering applications.
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Estrogen signaling plays important roles in diverse physiological and pathophysiological processes. However, the relationship between estrogen signaling and epigenetic regulation is not fully understood. Here, we explored the effect of estrogen signaling on the expression of Ten-Eleven Translocation (TET) family genes and DNA hydroxylmethylation in estrogen receptor alpha positive (ERα+) breast cancer cells. By analyzing the RNA-seq data, we identified TET2 as an estradiol (E2)-responsive gene in ERα+ MCF7 cells. RT-qPCR and Western blot analyses confirmed that both the mRNA and protein levels of TET2 gene were upregulated in MCF7 cells by E2 treatment. ChIP-seq and qPCR analyses showed that the enrichment of ERα and H3K27ac on the upstream regulatory regions of TET2 gene was increased in MCF7 cells upon E2 treatment. Moreover, E2 treatment also led to a significant increase in the global 5-hydroxymethylcytosine (5hmC) level, while knockout of TET2 abolished such E2-induced 5hmC increase. Conversely, treatment with ICI 182780, a potent and selective estrogen receptor degrader (SERD), inhibited TET2 gene expression and down-regulated the 5hmC level in MCF7 cells. Taken together, our study identified an ERα/TET2/5hmC epigenetic pathway, which may participate in the estrogen-associated physiological and pathophysiological processes.
Assuntos
5-Metilcitosina/metabolismo , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Dioxigenases/genética , Estrogênios/metabolismo , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Dioxigenases/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Elementos Facilitadores Genéticos/genética , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Feminino , Fulvestranto/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Oxirredução , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacosRESUMO
Boosting the replacement of traditional NH3 production (Haber-Bosch process) with photocatalytic technology is of great importance for energy and environment remediation. Herein, to develop a photocatalyst with efficient charge separation and abundant reactive sites for photocatalytic N2 fixation, a biomass-induced diphase-carbon doping strategy is proposed by adding lotus root starch which can be environmentally produced into the preparation of carbon nitride (CN). The adjustment to the CN framework by planar-fused carbon optimizes the band alignment of the catalyst, improving its response to sunlight. In particular, the in-plane-fused carbon in collaboration with the physically piled carbon initiates unique dual electron transfer pathways from different dimensions. The diphasic carbons can both function as qualified reactive sites according to the experimental explorations and further theoretical calculations, which effectively regulate the electron transfer and energy barrier associated with the N2 reduction on catalyst. The bio-carbon-doped catalyst exhibits drastically enhanced photocatalytic N2 fixation performance, and the NH3 yield on the optimized DC-CN0.1 reaches 167.35 µmol g-1 h-1 , which is fivefold of g-C3 N4 and stands far out from the single-phase doped systems. These explorations expand the metal-free skeleton engineering toolbox and provide new guidance for the solar energy utilizations.
Assuntos
Carbono , Nitrilas , Biomassa , Eletrônica , Nitrilas/químicaRESUMO
5-aminolevulinic acid (ALA), a plant growth regulator with great application potential in agriculture and horticulture, induces stomatal opening and inhibits stomatal closure by decreasing guard cell H2 O2 . However, the mechanisms behind ALA-decreased H2 O2 in guard cells are not fully understood. Here, using type 2A protein phosphatase (PP2A) inhibitors, microtubule-stabilizing/disrupting drugs and green fluorescent protein-tagged α-tubulin 6 transgenic Arabidopsis (GFP-TUA6), we find that PP2A and cortical microtubules (MTs) are involved in ALA-regulated stomatal movement. Then, we analyze stomatal responses of Arabidopsis overexpressing C2 catalytic subunit of PP2A (PP2A-C2) and pp2a-c2 mutant to ALA and abscisic acid (ABA) under both light and dark conditions, and show that PP2A-C2 participates in ALA-induced stomatal movement. Furthermore, using pharmacological methods and confocal studies, we reveal that PP2A and MTs function upstream and downstream, respectively, of H2 O2 in guard cell signaling. Finally, we demonstrate the role of H2 O2 -mediated microtubule arrangement in ALA inhibiting ABA-induced stomatal closure. Our findings indicate that MTs regulated by PP2A-mediated H2 O2 decreasing play an important role in ALA guard cell signaling, revealing new insights into stomatal movement regulation.
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Ácido Aminolevulínico/farmacologia , Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Peróxido de Hidrogênio/metabolismo , Microtúbulos/fisiologia , Fosfoproteínas Fosfatases/fisiologia , Estômatos de Plantas/fisiologia , Ácido Abscísico , Estômatos de Plantas/citologia , Transdução de SinaisRESUMO
The histone H3 Lys 27 (H3K27) demethylase JMJD3 has been shown to play important roles in transcriptional regulation and cell differentiation. However, the mechanism underlying JMJD3-mediated transcriptional regulation remains incompletely understood. Here we show that JMJD3 is associated with KIAA1718, whose substrates include dimethylated H3K27 (H3K27me2), and proteins involved in transcriptional elongation. JMJD3 and KIAA1718 directly bind to and regulate the expression of a plethora of common target genes in both a demethylase activity-dependent and -independent manner in the human promyelocytic leukemia cell line HL-60. We found that JMJD3 and KIAA1718 collaborate to demethylate trimethylated H3K27 (H3K27me3) on a subset of their target genes, some of which are bivalently marked by H3K4me3 and H3K27me3 and associated with promoter-proximal, paused RNA polymerase II (Pol II) before activation. Reduction of either JMJD3 or KIAA1718 diminishes Pol II traveling along the gene bodies of the affected genes while having no effect on the promoter-proximal Pol II. Furthermore, JMJD3 and KIAA1718 also play a role in localizing elongation factors SPT6 and SPT16 to the target genes. Our results support the model whereby JMJD3 activates bivalent gene transcription by demethylating H3K27me3 and promoting transcriptional elongation. Taken together, these findings provide new insight into the mechanisms by which JMJD3 regulates gene expression.
Assuntos
Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Lisina/metabolismo , Transcrição Gênica , Sítios de Ligação , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Macrófagos/citologia , Metilação/efeitos dos fármacos , Modelos Biológicos , Fenótipo , RNA Polimerase II/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
Demethylation by the AlkB dioxygenases represents an important mechanism for repair of N-alkylated nucleotides. However, little is known about their functions in mammalian cells. We report the purification of the ALKBH3 complex and demonstrate its association with the activating signal cointegrator complex (ASCC). ALKBH3 is overexpressed in various cancers, and both ALKBH3 and ASCC are important for alkylation damage resistance in these tumor cell lines. ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. In cell lines that are dependent on ALKBH3 and ASCC3 for alkylation damage resistance, loss of ALKBH3 or ASCC3 leads to increased 3-methylcytosine and reduced cell proliferation, which correlates with pH2A.X and 53BP1 foci formation. Our data provide a molecular mechanism by which ALKBH3 collaborates with ASCC to maintain genomic integrity in a cell-type specific manner.
Assuntos
Proliferação de Células , DNA Helicases/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Reparo do DNA , Dioxigenases/metabolismo , Neoplasias da Próstata/enzimologia , Homólogo AlkB 3 da Dioxigenase Dependente de alfa-Cetoglutarato , Alquilação , Animais , Antineoplásicos Alquilantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA Helicases/genética , Enzimas Reparadoras do DNA/genética , Dioxigenases/genética , Relação Dose-Resposta a Droga , Células HEK293 , Histonas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Metanossulfonato de Metila , Camundongos , Camundongos Endogâmicos NOD , Mutação , Transplante de Neoplasias , Fosforilação , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Interferência de RNA , Fatores de Tempo , Transfecção , Carga Tumoral , Proteína 1 de Ligação à Proteína Supressora de Tumor p53RESUMO
DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds to unmodified C or 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.
Assuntos
5-Metilcitosina/metabolismo , Citosina/análogos & derivados , Proteínas de Ligação a DNA/metabolismo , Células-Tronco Embrionárias/enzimologia , Regulação da Expressão Gênica no Desenvolvimento , Oxigenases de Função Mista/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Citosina/metabolismo , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Estudo de Associação Genômica Ampla , Camundongos , Ligação Proteica , Estrutura Terciária de ProteínaRESUMO
Untreated combined sewer overflows (CSOs) cause serious water pollution problems. In this study, the effects of CSO-induced heavy metals and the remediation practice of installation of a long-term water diversion (LTWD) on the microbial environment in river sediments were analyzed in an inland river. The Zn, Cd, Cr, and Cu contents in sediments and water were analyzed. DNA extraction and polymerase chain reaction analysis were conducted based on the Illumina MiSeq platform. The results showed that CSOs have a significant adverse impact on the diversity of microbial populations in river sediments. The LTWD is helpful in improving the richness of microorganisms and the proportion of Gram -ves, but it is challenging to reduce the accumulation of heavy metals in the sediment. The correlation analysis shows a strong relationship between some metabolic pathways and Zn and Cd accumulation in river sediments. Some detoxification compound metabolisms are also promoted at these sites. Thus, chronic exposure to environmental heavy metals from CSOs decreases the river microbial community, and further affects the ecological environment of the river. Therefore, without eliminating CSOs or reducing overflow frequency, it is difficult to alleviate the accumulation of heavy metals in river sediments and improve river ecology via water diversion alone.
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Sedimentos Geológicos/microbiologia , Metais Pesados , Microbiota , Poluentes Químicos da Água , China , Monitoramento Ambiental , Recuperação e Remediação Ambiental , Medição de Risco , Rios , Água , Microbiologia da ÁguaRESUMO
The characteristics of surface runoff and the infiltration properties of urban green land are important to determine the effects of runoff reduction by low-impact development (LID) facilities. In this paper, two typical types of urban green land (lawn and shrub) in Shanghai were selected to study the runoff characteristics under eight rainfall events. The sensitivity of the runoff parameters was analyzed, and then, the optimal parameters were determined using the Stormwater Management Model (SWMM). The results showed that the interception and infiltration capacities of shrub were greater than those of lawn. The rainfall intensity and rainfall pattern were the major factors that influenced the interception and infiltration of rainwater. The threshold value that generates runoff varied across the eight rainfall events ranged from 1.6 to 28.5 mm for lawn and 4.5 to 32.0 mm for shrub. The maximum reduction ratios of runoff and peak flow for shrub were 52 and 57% higher than them for lawn, respectively. The parameters for shrub were more sensitive to runoff and peak flow compared with those for lawn. Under light rainfalls with a short duration, the maximum infiltration rate and depression storage were more sensitive than those under heavy rainfalls with a long duration. Antecedent dry weather period was not found to be a sensitive parameter except for the shrub under light rainfalls. The relative errors of runoff and dynamic mean runoff (60 min) for lawn and shrub were within ± 9.5%. The errors of peak flow ranged between - 21 and 16.6%. The dynamic runoff characteristics and the parameters for lawn and shrub determined in this study can provide references for simulating urban runoff and planning LID areas.
Assuntos
Simulação por Computador , Drenagem Sanitária/métodos , Monitoramento Ambiental/métodos , Chuva , Movimentos da Água , Calibragem , China , Cidades , Poaceae/crescimento & desenvolvimentoRESUMO
Ten Eleven Translocation (TET) protein-catalyzed 5mC oxidation not only creates novel DNA modifications, such as 5hmC, but also initiates active or passive DNA demethylation. TETs' role in the crosstalk with specific histone modifications, however, is largely elusive. Here, we show that TET2-mediated DNA demethylation plays a primary role in the de novo establishment and maintenance of H3K4me3/H3K27me3 bivalent domains underlying methylated DNA CpG islands (CGIs). Overexpression of wild type (WT), but not catalytic inactive mutant (Mut), TET2 in low-TET-expressing cells results in an increase in the level of 5hmC with accompanying DNA demethylation at a subset of CGIs. Most importantly, this alteration is sufficient in making de novo bivalent domains at these loci. Genome-wide analysis reveals that these de novo synthesized bivalent domains are largely associated with a subset of essential developmental gene promoters, which are located within CGIs and are previously silenced due to DNA methylation. On the other hand, deletion of Tet1 and Tet2 in mouse embryonic stem (ES) cells results in an apparent loss of H3K27me3 at bivalent domains, which are associated with a particular set of key developmental gene promoters. Collectively, this study demonstrates the critical role of TET proteins in regulating the crosstalk between two key epigenetic mechanisms, DNA methylation and histone methylation (H3K4me3 and H3K27me3), particularly at CGIs associated with developmental genes.
Assuntos
Ilhas de CpG/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Metilação de DNA/genética , Dioxigenases , Células-Tronco Embrionárias/metabolismo , Genoma , Células HEK293 , Histonas/metabolismo , Humanos , Lisina/metabolismo , Camundongos , Modelos Biológicos , Transcrição GênicaRESUMO
To investigate the different erosion patterns of sediments in combined and storm sewers, sediments from three separate sewer systems and two combined sewer systems in urban Shanghai were collected for the flushing experiments. These experiments were conducted with different consolidation periods and shear velocities. As the consolidation period increases, dissolved oxygen exhibits a positive effect on the microbial transformations of organic substrates. Potential structural changes and separations of the surface and bottom layers of sediments are observed. The results also reveal that the organic matter, particle size and moisture have different effects on the erosion resistance of sediments. Furthermore, illicit connections behaved as an important factor affecting the viscosity and static friction force of particles, which directly alter the erosion resistance of sewer sediments.
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Sedimentos Geológicos/química , Chuva/química , Esgotos/química , China , Oxigênio/química , Tamanho da PartículaRESUMO
For storm drainages inappropriately connected with sewage, wet weather discharge is a major factor that adversely affects receiving waters. A study of the wet weather influences of rainfall-discharge variables on storm drainages connected with sewage was conducted in the downtown Shanghai area (374 ha). Two indicators, event mean concentration (EMC) and event pollutant load per unit area (EPL), were used to describe the pollution discharge during 20 rain events. The study showed that the total rainfall and discharge volume were important factors that affect the EMCs and EPLs of the chemical oxygen demand, total phosphorus, and especially those of NH4+-N. The pollutant concentrations at the beginning of the discharge and the discharge period were also major factors that influence the EMCs of these three pollutants. Regression relationships between the rainfall-discharge variables and discharge volume/ EPLs (R2 = 0.824-0.981) were stronger than the relationships between the rainfall-discharge variables and EMCs. These regression equations can be considered reliable in the system, with a relative validation error of less than ±10% for the discharge volume, and less than ±20% for the EPLs. The results presented in this paper provide guidance for effectively controlling pollution in similar storm drainages.
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Chuva/química , Esgotos/análise , Análise da Demanda Biológica de Oxigênio , China , Monitoramento Ambiental , Fósforo/análise , Águas Residuárias , Movimentos da Água , Poluentes Químicos da Água/química , Tempo (Meteorologia)RESUMO
The objective of this study was to explore the efficacy of glial fibrillary acidic protein (GFAP) in differentiating intracerebral hemorrhage (ICH) from ischemic stroke (IS). Suspicious patients of acute stroke were screened and finally diagnosed by computed tomography and magnetic resonance imaging. Blood samples were collected within 2-6 h after onset of symptoms, and serum GFAP level was determined by ELISA assay. The functional outcome for the patients was determined by modified Rankin Scale (mRS) 90 days after onset of symptoms. 43 ICH patients and 65 IS patients were enrolled. GFAP concentration in ICH group was significantly higher than in IS group (p < 0.001). Significant correlation was found when comparing GFAP with National Institutes of Health Stroke Scale (NIHSS) (r = 0.418, p = 0.005) and hemorrhage volume (r = 0.840, p < 0.001) in ICH group, while such correlation was not observed in IS group. ROC analysis indicated that GFAP level at the cut-point of 0.7 ng/ml yielded an AUC of 0.901 (95 % CI 0.828-0.950) with high sensitivity (86.0 %) and specificity (76.9 %) to differentiate ICH from IS. Patients with higher serum GFAP concentration in ICH group experienced poorer functional disability (r = 0.755, p < 0.001), while this phenomenon was not observed in IS group (r = -0.114, p = 0.368). ROC curve analysis found that GFAP level at the cut-point of 1.04 ng/ml yielded an AUC of 0.936 (95 % CI 0.817-0.988) in identifying patients with poor functional outcome, at the sensitivity and specificity of 95.7 and 80.0 %, respectively. GFAP test is a promising technique for diagnosis of ICH from IS and prediction of short-term functional outcomes.
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Hemorragia Cerebral/sangue , Proteína Glial Fibrilar Ácida/sangue , Idoso , Área Sob a Curva , Povo Asiático , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/terapia , China , Diagnóstico Diferencial , Avaliação da Deficiência , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Prognóstico , Curva ROC , Recuperação de Função Fisiológica/fisiologia , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Fatores de TempoRESUMO
The genome-wide distribution patterns of the '6th base' 5-hydroxymethylcytosine (5hmC) in many tissues and cells have recently been revealed by hydroxymethylated DNA immunoprecipitation (hMeDIP) followed by high throughput sequencing or tiling arrays. However, it has been challenging to directly compare different data sets and samples using data generated by this method. Here, we report a new comparative hMeDIP-seq method, which involves barcoding different input DNA samples at the start and then performing hMeDIP-seq for multiple samples in one hMeDIP reaction. This approach extends the barcode technology from simply multiplexing the DNA deep sequencing outcome and provides significant advantages for quantitative control of all experimental steps, from unbiased hMeDIP to deep sequencing data analysis. Using this improved method, we profiled and compared the DNA hydroxymethylomes of mouse ES cells (ESCs) and mouse ESC-derived neural progenitor cells (NPCs). We identified differentially hydroxymethylated regions (DHMRs) between ESCs and NPCs and uncovered an intricate relationship between the alteration of DNA hydroxymethylation and changes in gene expression during neural lineage commitment of ESCs. Presumably, the DHMRs between ESCs and NPCs uncovered by this approach may provide new insight into the function of 5hmC in gene regulation and neural differentiation. Thus, this newly developed comparative hMeDIP-seq method provides a cost-effective and user-friendly strategy for direct genome-wide comparison of DNA hydroxymethylation across multiple samples, lending significant biological, physiological and clinical implications.
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Citosina/análogos & derivados , Células-Tronco Embrionárias/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Imunoprecipitação , Células-Tronco Neurais/metabolismo , Análise de Sequência de DNA/métodos , 5-Metilcitosina/análogos & derivados , Animais , Linhagem da Célula , Células Cultivadas , Citosina/análise , Citosina/metabolismo , Metilação de DNA , Células-Tronco Embrionárias/citologia , Expressão Gênica , Genoma , CamundongosRESUMO
BACKGROUND: The aim of this study was to analyze the CYP2C19 genetic polymorphism among Han and Uyghur patients with cardiovascular and cerebrovascular diseases in the Kashi area of Xinjiang. MATERIAL/METHODS: We enrolled 1020 patients with cardiovascular and cerebrovascular diseases, including 220 Han subjects and 800 Uyghur subjects. We used the gene chip method to detect polymorphisms in CYP2C19. The allele frequencies of CYP2C19 and the metabolic phenotype frequencies were then compared between the 2 ethnic groups. RESULTS: The frequency of CYP2C19 *1 was 0.6454 in Han subjects and 0.7869 in Uyghur subjects, and the difference was statistically significant (P<0.05). The frequency of CYP2C19 *2 was 0.3273 in Han subjects and 0.1837 in Uyghur subjects (P<0.05). The frequency of the homozygous extensive metabolizer phenotype was 42.72% and 62.13% in Han and Uyghur subjects, respectively (P<0.01). The frequency of the heterozygous extensive metabolizer phenotype was 43.64% and 33.13% in Han and Uyghur subjects, respectively (P<0.01). The frequency of poor metabolizers in Han and Uyghur subjects was 13.64% and 4.76%, respectively (P<0.01). CONCLUSIONS: Among patients with cardiovascular and cerebrovascular diseases located in the Kashgar Prefecture of Xinjiang, there is a differential distribution of CYP2C19 genotypes between the Han and Uyghur populations. Uyghur patients showed higher frequencies of extensive metabolizer genotypes than Han patients, while Han patients showed higher frequencies of poor metabolizer genotypes than Uyghur patients.
Assuntos
Povo Asiático/genética , Transtornos Cerebrovasculares/genética , Citocromo P-450 CYP2C19/genética , Etnicidade/genética , Predisposição Genética para Doença , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/genética , China , Citocromo P-450 CYP2C19/metabolismo , Frequência do Gene , Humanos , Pessoa de Meia-Idade , Mutação/genética , Fenótipo , Adulto JovemRESUMO
Relationships between land use and water quality of rivers and lakes vary spatially and temporally. These variations were analyzed using spatial analysis and mathematical statistical methods for the Suzhou Creek in Shanghai. Based on the data of water quality and land use in 2001ï¼ 2005ï¼ 2010ï¼ 2015ï¼ and 2020ï¼ five spatial scales ï¼200ï¼ 500ï¼ 1 000ï¼ 2 000ï¼ and 5 000 m reach bufferï¼ of the landscape pattern were extracted using correlation and redundancy analysis to explore the impact of land use composition and spatial pattern on water quality at different spatial and temporal scales. The results showed thatï¼ â the water quality of Suzhou Creek has gradually improved in the past 20 yearsï¼ other indicators were between Class II to Class IV in 2020 except TNï¼ and TN was the main pollutant. â¡ The main land use type of the buffer zone was construction landï¼ and the proportion of greenland and woodland showed a small growth trend. ⢠The water quality was closely related to landscape patternï¼ showing temporal and spatial scale effects. On the time scaleï¼ indicators such as construction landï¼ agricultural landï¼ landscape dominanceï¼ aggregationï¼ and diversity had significant correlations with various water quality parametersï¼ and there was an inverse correlation in 2010 compared with that in other years for NH4+-Nï¼ TPï¼ and TN. The landscape pattern in 2001 had the greatest explanation for water qualityï¼ with an explanation rate of 93.65%. The impact of greenland and woodland on water quality has begun to emerge in the past 10 years. ⣠On the spatial scaleï¼ there were significant correlations between greenland and woodlandï¼ patch numberï¼ landscape shape indexï¼ diversity indexï¼ and water quality. There was a strong positive regulatory effect of greenland and woodland on NH4+-Nï¼ TPï¼ and TN at the scale of 2 000 m. The patch number and landscape shape index had relatively strong regulatory effects on water quality on a larger spatial scaleï¼ whereas the Shannon diversity index had a better positive regulatory effect on water quality on a small scale. The landscape pattern within a buffer of 2 000 m had the highest interpretation degree for all factorsï¼ with an explanation rate of 68.47%. The study showed that rationally planning the proportion of greenland and woodland within the 2 000 m buffer zone and optimizing its landscape configuration is an important measure to purify the surface water quality of Suzhou Creek.
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Objective: Existing studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases. Methods: We utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action. Results: The MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease. Conclusions: From predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.
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Frequent waterlogging occurs in old high-density urban areas where the sewage is inappropriately connected to storm drainages, resulting in serious wet weather discharge pollution (WWDP). To address urban waterlogging and runoff, the optimization of green infrastructures (GIs) and grey infrastructures (GRs) has been proposed to improve rainwater management efficiency. However, most strategies neglect WWDP and fail to achieve integrated control of runoff, waterlogging, and discharge pollution. In the present study, a new optimization method was introduced to identify optimal solutions for renovating outdated storm drainage systems, considering the management of discharge pollution in wet weather. A case study in Shanghai, China was conducted to demonstrate the application of the method. The cost-benefit index (CBI) of optimized GIs (0.06) was lower than that of optimized GRs (2.78) under 22.2 mm rainfall (no runoff and WWDP), but the costs of the former were only half those of the latter. In a 5-year return period storm (no waterlogging), optimized GIs had a significantly higher CBI (2.85 times) compared to optimized GRs, costing only 44 % of the latter. When WWDP reached the control objective (COD≤70 mg/L), the optimized GIs needed to be further optimized with GRs. The CBI of optimized GI-GRs was higher than GRs by 2.50, and the cost was 58% of the latter. In areas with frequent low-intensity rainfall, optimized GIs and GRs should be selected based on local cost or benefit requirements for drainage reconstruction. In high-intensity storm-prone areas, the optimized GI-GR combination should be selected for drainage reconstruction. The proposed method can compensate for the shortcomings of existing optimization methods in controlling WWDP for the reconstruction of old storm drainages.
RESUMO
In order to investigate the composition and diversity of groundwater bacterial communities in typical industrial areas in Shanghai, the Illumina MiSeq high-throughput technology was adopted to explore the correlation and response mechanism of groundwater bacterial communities and environmental factors in typical industries, combined with the analysis of groundwater tri-nitrogen, heavy metals, organic matter, and other indicators. The results showed that the ammonia nitrogen in the groundwater of the petrochemical industry was 64.49%, 32.46%, and 113.91% higher than that of the textile industry, metal products industry, and other industries (P<0.05), respectively. The main detectable indicators of organic matter were total petroleum hydrocarbons (TPH) and volatile phenol. The mass concentration of volatile phenol in groundwater of the petrochemical industry was significantly higher than that of the textile industry, metal products industry, and other industries (P<0.05). The mass concentration of arsenic in the metal products industry was 49.26% and 50.59% higher than that in the petrochemical industry and other industries (P<0.05), respectively. Chloride, manganese, sulfate, etc., were significantly different in different industries (P<0.05). The Shannon index of groundwater in the textile industry was the highest at 3.14, whereas the Shannon index and Ace index of the groundwater in the metal products industry were as low as at 2.42 and 960.46, respectively. The dominant bacterial phylum in groundwater in the industrial area was Proteobacteria, accounting for 80.05%-86.18%. Arsenic, mercury, TPH, etc. were the main influencing factors in groundwater in industrial areas, whereas the nitrifying bacteria, denitrifying bacteria, and organic matter-degrading bacteria were mostly related to groundwater environmental factors. The results of this study can provide theoretical support for groundwater pollution risk management and microbial remediation in petrochemical and metal product industrial areas.