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During cell division, transcription factors (TFs) are removed from chromatin twice, during DNA synthesis and during condensation of chromosomes. How TFs can efficiently find their sites following these stages has been unclear. Here, we have analyzed the binding pattern of expressed TFs in human colorectal cancer cells. We find that binding of TFs is highly clustered and that the clusters are enriched in binding motifs for several major TF classes. Strikingly, almost all clusters are formed around cohesin, and loss of cohesin decreases both DNA accessibility and binding of TFs to clusters. We show that cohesin remains bound in S phase, holding the nascent sister chromatids together at the TF cluster sites. Furthermore, cohesin remains bound to the cluster sites when TFs are evicted in early M phase. These results suggest that cohesin-binding functions as a cellular memory that promotes re-establishment of TF clusters after DNA replication and chromatin condensation.
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Proteínas de Ciclo Celular/metabolismo , Ciclo Celular , Proteínas Cromossômicas não Histona/metabolismo , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Motivos de Nucleotídeos , CoesinasRESUMO
Although the proteins that read the gene regulatory code, transcription factors (TFs), have been largely identified, it is not well known which sequences TFs can recognize. We have analyzed the sequence-specific binding of human TFs using high-throughput SELEX and ChIP sequencing. A total of 830 binding profiles were obtained, describing 239 distinctly different binding specificities. The models represent the majority of human TFs, approximately doubling the coverage compared to existing systematic studies. Our results reveal additional specificity determinants for a large number of factors for which a partial specificity was known, including a commonly observed A- or T-rich stretch that flanks the core motifs. Global analysis of the data revealed that homodimer orientation and spacing preferences, and base-stacking interactions, have a larger role in TF-DNA binding than previously appreciated. We further describe a binding model incorporating these features that is required to understand binding of TFs to DNA.
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Imunoprecipitação da Cromatina , Modelos Biológicos , Técnica de Seleção de Aptâmeros , Fatores de Transcrição/metabolismo , Animais , DNA/química , Humanos , Cadeias de Markov , Camundongos , Filogenia , Fatores de Transcrição/genéticaRESUMO
Many sequence variants have been linked to complex human traits and diseases1, but deciphering their biological functions remains challenging, as most of them reside in noncoding DNA. Here we have systematically assessed the binding of 270 human transcription factors to 95,886 noncoding variants in the human genome using an ultra-high-throughput multiplex protein-DNA binding assay, termed single-nucleotide polymorphism evaluation by systematic evolution of ligands by exponential enrichment (SNP-SELEX). The resulting 828 million measurements of transcription factor-DNA interactions enable estimation of the relative affinity of these transcription factors to each variant in vitro and evaluation of the current methods to predict the effects of noncoding variants on transcription factor binding. We show that the position weight matrices of most transcription factors lack sufficient predictive power, whereas the support vector machine combined with the gapped k-mer representation show much improved performance, when assessed on results from independent SNP-SELEX experiments involving a new set of 61,020 sequence variants. We report highly predictive models for 94 human transcription factors and demonstrate their utility in genome-wide association studies and understanding of the molecular pathways involved in diverse human traits and diseases.
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Polimorfismo de Nucleotídeo Único/genética , Técnica de Seleção de Aptâmeros , Máquina de Vetores de Suporte , Fatores de Transcrição/metabolismo , Sítios de Ligação/genética , Doença/genética , Genoma Humano/genética , Humanos , Ligantes , Ligação ProteicaRESUMO
Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2â¢-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2â¢-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.
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Aterosclerose , Cicloexilaminas , Ferroptose , Fenilenodiaminas , Animais , Camundongos , Humanos , Fosfolipídeos , Fosforilcolina , Éteres Fosfolipídicos/metabolismo , Éteres Fosfolipídicos/farmacologia , Camundongos Endogâmicos C57BL , Células Endoteliais da Veia Umbilical Humana/metabolismo , Endotélio/metabolismo , Glutationa/metabolismo , Ferro/metabolismo , Proteína 3 Ligante de Ácido GraxoRESUMO
Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.
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Fibrose Oral Submucosa , Humanos , Ratos , Animais , Fibrose Oral Submucosa/metabolismo , Fibrose Oral Submucosa/patologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Transição Epitelial-Mesenquimal , Miofibroblastos/metabolismo , Células Epiteliais/metabolismoRESUMO
Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.
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Escherichia coli , Polietilenoglicóis , Animais , Camundongos , Escherichia coli/efeitos dos fármacos , Polietilenoglicóis/química , Géis/química , Modelos Animais de Doenças , Colite/tratamento farmacológico , Colite/induzido quimicamente , Metacrilatos/químicaRESUMO
OBJECTIVE: This study aimed to study the correlation between preeclampsia (PE) and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and to examine the molecular mechanisms behind the development of PE. METHODS: 30 PE and 30 normal pregnant women placental samples were assessed the levels of NEAT1 and miR-217 by quantitative real-time PCR (qRT-PCR). The trophoblast cell line HTR8/SVneo was used for silencing NEAT1 or miR-217 inhibitor in the absence or presence of an inhibitor and H2O2. Cell counting Kit 8 (CCK-8), flow cytometry, and Transwell were used to detect cell proliferation, apoptosis, migration, and invasion. Luciferase reporter gene assay was utilized to verify the binding between miR-217 and Wnt family member 3 (Wnt3), and between the miR-217 and NEAT1. Proteins related to the Wnt/ß-catenin signaling pathway were detected using western blotting. RESULTS: The PE group exhibited a significantly downregulated expression of miR-217 and a significantly upregulated expression of NEAT1. NEAT1 targeted miR-217, and Wnt is a miR-217 target gene. siRNA-NEAT1 inhibited the apoptosis of trophoblast cells, but promoted their invasion, migration, and proliferation. MiR-217 inhibitor could partially reverse the effects of siRNA-NEAT1. The expression of the Wnt/ß-catenin signaling pathway-related proteins, WNT signaling pathway inhibitor 1 (DKK1), cyclin-D1 and ß-catenin, was significantly increased after siRNA-NEAT1. CONCLUSIONS: NEAT1 could reduce trophoblast cell invasion and migration by suppressing miR-217/Wnt signaling pathway, leading to PE.
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Amomum tsao-ko Crevost et Lemarie (Zingiberaceae), an aromatic plant, has been considered to have diverse medicinal values and economic significance. It has been reported to possess antibacterial, antioxidant, and antidiabetic effects. With the increasing risk of diseases in aquaculture, there is a need for alternative solutions to chemical antibiotics. Plant extracts have shown promise as natural feed additives for aquatic animals. In this study, the antibacterial effect of Amomum tsao-ko crude extracts was evaluated using the Oxford cup method. The extracts exhibited significant antimicrobial activity against Salmonella typhimurium and Salmonella enteritidis. Furthermore, the addition of Amomum tsao-ko to fish feed resulted in notable changes in the gut structure of zebrafish and tilapia. The length and morphology of intestinal villi were enhanced, promoting improved digestion. Analysis of the gut microbial community revealed that Amomum tsao-ko supplementation induced key changes in the gut microbial community composition of both zebrafish and tilapia. Notably, a 1% inclusion of Amomum tsao-ko resulted in a marked rise in Proteobacteria levels in zebrafish, which diminished at 10% dosage. The supplement elicited mixed reactions among other bacterial phyla like Actinobacteria and Verrucomicrobiota. Fluctuations were also observed at the genus level, pointing to the concentration of Amomum tsao-ko playing a pivotal role in influencing the structure of intestinal bacteria. The findings of this study suggest that Amomum tsao-ko has antibacterial properties and can positively influence the gut health of fish. The potential use of Amomum tsao-ko as a natural feed additive holds promise for improving aquaculture practices and reducing reliance on chemical antibiotics. Further research is needed to explore the full potential and applications of Amomum tsao-ko in fish feed development.
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Atmospheric water harvesting (AWH) is considered a promising strategy for sustainable freshwater production in landlocked and arid regions. Hygroscopic salt-based composite sorbents have attracted widespread attention for their water harvesting performance, but suffer from aggregation and leakage issues due to the salting-out effect. In this study, we synthesized a PML hydrogel composite by incorporating zwitterionic hydrogel (PDMAPS) and MIL-101(Cr) as a host for LiCl. The PML hydrogel was characterized using various techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and thermogravimetric analysis (TGA). The swelling properties and water vapor adsorption-desorption properties of the PML hydrogel were also assessed. The results demonstrate that the MIL-101(Cr) was uniformly embedded into PDMAP hydrogel, and the PML hydrogel exhibits a swelling ratio of 2.29 due to the salting-in behavior. The PML hydrogel exhibited exceptional water vapor sorption capacity of 0.614 g/g at 298 K, RH = 40% and 1.827 g/g at 298 K, RH = 90%. It reached 80% of its saturated adsorption capacity within 117 and 149 min at 298 K, RH = 30% and 90%, respectively. Additionally, the PML hydrogel showed excellent reversibility in terms of water vapor adsorption after ten consecutive cycles of adsorption-desorption. The remarkable adsorption capacity, favorable adsorption-desorption rate, and regeneration stability make the PML hydrogel a potential candidate for AWH. This polymer-MOF synergistic strategy for immobilization of LiCl in this work offers new insights into designing advanced materials for AWH.
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Defect engineering for vacancies, holes, nano precipitates, dislocations, and strain are efficient means of suppressing lattice thermal conductivity. Multiple microstructural defects are successfully designed in Cu1- x Agx GaTe2 (0 ≤ x ≤ 0.5) solid solutions through high-ratio alloying and vibratory ball milling, to achieve ultra-low thermal conductivity and record-breaking thermoelectric performance. Extremely low total thermal conductivities of 1.28 W m-1 K-1 at 300 K and 0.40 W m-1 K-1 at 873 K for the Cu0.5 Ag0.5 GaTe2 are observed, which are ≈79% and ≈58% lower than that of the CuGaTe2 matrix. Multiple phonon scattering mechanisms are collectively responsible for the reduction of thermal conductivity in this work. On one hand, large amounts of nano precipitates and dislocations are formed via vibrating ball milling followed by the low-temperature hot press, which can enhance phonon scattering. On the other hand, the difference in atomic sizes, distorted chemical bonds, elements fluctuation, and strained domains are caused by the high substitution ratio of Ag and also function as a center for the strong phonon scattering. As a result, the Cu0.7 Ag0.3 GaTe2 exhibits a record high ZTmax of ≈1.73 at 873 K and ZTave of ≈0.69 between 300-873 K, which are the highest values of CuGaTe2 -based thermoelectric materials.
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We have developed CRISPR-assisted RNA-protein interaction detection method (CARPID), which leverages CRISPR-CasRx-based RNA targeting and proximity labeling to identify binding proteins of specific long non-coding RNAs (lncRNAs) in the native cellular context. We applied CARPID to the nuclear lncRNA XIST, and it captured a list of known interacting proteins and multiple previously uncharacterized binding proteins. We generalized CARPID to explore binders of the lncRNAs DANCR and MALAT1, revealing the method's wide applicability in identifying RNA-binding proteins.
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Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Proteínas de Ligação a DNA/metabolismo , Células HEK293 , Humanos , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Underwater images have the advantage of carrying high information density and are widely used for marine information acquisition. Due to the complex underwater environment, the captured images are often unsatisfactory and often suffer from color distortion, low contrast, and blurred details. Physical model-based methods are often used in relevant studies to obtain clear underwater images; however, water selectively absorbs light, making the use of a priori knowledge-based methods no longer applicable and thus rendering the restoration of underwater images ineffective. Therefore, this paper proposes an underwater image restoration method based on adaptive parameter optimization of the physical model. Firstly, an adaptive color constancy algorithm is designed to estimate the background light value of underwater image, which effectively guarantees the color and brightness of underwater image. Secondly, aiming at the problem of halo and edge blur in underwater images, a smoothness and uniformity transmittance estimation algorithm is proposed to make the estimated transmittance smooth and uniform, and eliminate the halo and blur of the image. Then, in order to further smooth the edge and texture details of the underwater image, a transmittance optimization algorithm for smoothing edge and texture details is proposed to make the obtained scene transmittance more natural. Finally, combined with the underwater image imaging model and histogram equalization algorithm, the image blurring is eliminated and more image details are retained. The qualitative and quantitative evaluation on the underwater image dataset (UIEBD) shows that the proposed method has obvious advantages in color restoration, contrast and comprehensive effect, and has achieved remarkable results in application testing. It shows that the proposed method can effectively restore underwater degraded images and provide a theoretical basis for the construction of underwater imaging models.
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The Brewster effect has been previously reported as an essential mechanism for terahertz (THz) wave sensing application. However, generally in a sensing application, a complex rotation apparatus is required for detecting the slight change in Brewster angle. Here, we propose a graphene-based Brewster angle device operating at a specific terahertz frequency capable of sensing the refractive index at a fixed incident angle. In other words, our sensing device could avoid the impact of Brewster angle shift and eliminate the need for high-precision rotating equipment, which is usually required in traditional sensing applications. The conversion from the refractive index to a Volt-level detectable voltage roots from the tunability of graphene's Fermi level in the external electrical field. A linear correlation between the output voltage and the background refractive index is observed and theocratically analyzed. Furthermore, we present the improvement of our device in terms of sensing range and sensitivity by adjusting the permittivity of the dielectric substrate. As a demonstration of our proposed device, a detection range of 1.1-2.4 and a sensitivity of 20.06â V/RIU for refractive index is achieved on a high-resistance silicon substrate operating at 0.3 THz.
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BACKGROUND: More and more studies have demonstrated that potassium channel tetramerization domain-containing 5 (KCTD5) plays an important role in the development of cancer, but there is a lack of comprehensive research on the biological function of this protein in pan-cancer. This study systematically analyzed the expression landscape of KCTD5 in terms of its correlations with tumor prognosis, the immune microenvironment, programmed cell death, and drug sensitivity. METHODS: We investigated a number of databases, including TCGA, GEPIA2, HPA, TISIDB, PrognoScan, GSCA, CellMiner, and TIMER2.0. The study evaluated the expression of KCTD5 in human tumors, as well as its prognostic value and its association with genomic alterations, the immune microenvironment, tumor-associated fibroblasts, functional enrichment analysis, and anticancer drug sensitivity. Real-time quantitative PCR and flow cytometry analysis were performed to determine the biological functions of KCTD5 in lung adenocarcinoma cells. RESULTS: The results indicated that KCTD5 is highly expressed in most cancers and that its expression is significantly correlated with tumor prognosis. Moreover, KCTD5 expression was related to the immune microenvironment, infiltration by cancer-associated fibroblasts, and the expression of immune-related genes. Functional enrichment analysis revealed that KCTD5 is associated with apoptosis, necroptosis, and other types of programmed cell death. In vitro experiments showed that knockdown of KCTD5 promoted apoptosis of A549 cells. Correlation analysis confirmed that KCTD5 was positively correlated with the expression of the anti-apoptotic genes Bcl-xL and Mcl-1. Additionally, KCTD5 was significantly associated with sensitivity to multiple antitumor drugs. CONCLUSION: Our results suggest that KCTD5 is a potential molecular biomarker that can be used to predict patient prognosis, immunoreactions and drug sensitivity in pan-cancer. KCTD5 plays an important role in regulating programmed cell death, especially apoptosis.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Biomarcadores Tumorais/genética , Apoptose/genética , Células A549 , Prognóstico , Microambiente Tumoral/genética , Canais de PotássioRESUMO
It is highly desirable to avoid using rare or toxic metals for oxidative reactions in the synthesis of pharmaceuticals and fine chemicals. Hypervalent iodine compounds are environmentally benign alternatives, but their catalytic use has been quite limited. Herein, the protocol for in situ hypoiodite-catalyzed oxidative rearrangement of chalcones is first realized under mild and metal-free conditions, which provided a nontoxic, environmental-benign, and catalytic alternative to the thallium-based protocol. Also, the applicability and effectiveness of this catalytic protocol got well demonstrated via gram-scale synthesis and product derivatization. What is more, control and NMR tracking experiments were performed to figure out the possible catalytic species and intermediates.
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BACKGROUND: The present study aims to explore the clinical application of enhanced recovery after surgery (ERAS) in pediatric patients with congenital upper gastrointestinal obstruction (CUGIO). METHODS: A total of 82 pediatric patients with CUGIO admitted to the neonatal intensive care unit in Kunming Children's Hospital between June 2017 and June 2021 were enrolled in the present study and divided into two groups: the ERAS group (n = 46) and the control group (n = 36). The ERAS management mode was adopted in the ERAS group, and the conventional perioperative management mode was adopted in the control group. RESULTS: In the ERAS group and the control group, the time to the first postoperative bowel movement was 49.2 ± 16.6 h and 58.4 ± 18.8 h, respectively, and the time to the first postoperative feeding was 79 ± 7.1 h and 125.2 ± 8.3 h, respectively. The differences in the above two indicators between the two groups were statistically significant (P < 0.05). In the ERAS group, the days of parenteral nutrition and the length of hospital stay were 14.5 ± 2.3 d and 18.8 ± 6.4 d, respectively. In the control group, 17.6 ± 2.2 d and 23.1 ± 8.1 d, respectively. The differences in these two indicators between the two groups were statistically significant (P < 0.05). CONCLUSION: The ERAS management model had a positive effect on early postoperative recovery in pediatric patients with CUGIO.
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Obstrução Duodenal , Recuperação Pós-Cirúrgica Melhorada , Recém-Nascido , Humanos , Criança , Obstrução Duodenal/etiologia , Obstrução Duodenal/cirurgia , Intestinos , Período Pós-Operatório , Tempo de Internação , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
Rhizosphere microbiota are an important factor impacting plant uptake of pollutants. However, little is known about how microbial nitrogen (N) transformation in the rhizosphere affects the uptake and accumulation of antibiotics in plants. Here, we determined recruitment of N transformation functional bacteria upon ciprofloxacin (CIP) exposure, by comparing differences in assembly processes of both rhizospheric bacterial communities and N transformation between two choysum (Brassica parachinensis) varieties differing in CIP accumulation. The low accumulation variety (LAV) of CIP recruited more host bacteria (e.g., Nitrospiria and Nitrolancea) carrying nitrification genes (mainly nxrA) but fewer host bacteria carrying denitrification genes, especially narG, relative to the high accumulation variety (HAV) of CIP. The nxrA and narG abundance in the LAV rhizosphere were, respectively, 1.6-7.8 fold higher and 1.4-3.4 fold lower than those in the HAV rhizosphere. Considering that nitrate can decrease CIP uptake into choysum through competing for the proton motive force and energy, such specific bacteria recruitment in LAV favored the production and utilization of nitrate in its rhizosphere, thus limiting its CIP accumulation with 1.6-2.4 fold lower than the HAV. The findings give insight into the mechanism underlying low pollutant accumulation, filling the knowledge gap regarding the profound effects of rhizosphere microflora and N transformation processes on antibiotic accumulation in crops.
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Brassica , Ciprofloxacina , Rizosfera , Nitratos , Nitrogênio/análise , Antibacterianos , Bactérias/genética , Plantas , Solo , Microbiologia do SoloRESUMO
BACKGROUNDS: Two technologies, cardiac contractility modulation (CCM) and subcutaneous implantable cardioverter-defibrillator (S-ICD), can be successfully combined and applied to patients with advanced heart failure (HF) with reduced left ventricular ejection fraction (LVEF). CASE REPORT: We reported a case of a 51-year-old man with reduced ejection fraction (LVEF = 33%) and a narrow QRS complex who first underwent simultaneous implantation of CCM and S-ICD. CONCLUSION: Our case report aimed to reveal that the simultaneous implantation of CCM and S-ICD could be successfully used in patients with advanced HF, which could significantly improve the clinical symptoms of such patients during one surgery.
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Desfibriladores Implantáveis , Insuficiência Cardíaca , Marca-Passo Artificial , Disfunção Ventricular Esquerda , Masculino , Humanos , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda , Resultado do Tratamento , DesfibriladoresRESUMO
In contrast to somatic mutations, mutations in germ cells affect every cell of any organism derived from the germ cell and therefore are related to numerous genetic diseases. However, there is no suitable assay to evaluate the mutagenic sensitivities of both male and female germ cells. The main type of Caenorhabditis elegans (C. elegans) is hermaphroditic, where spermatogenesis and oogenesis occur chronologically at specific stages, allowing induction of mutations in either sperm or eggs exclusively. In this study, we used the alkylating agent ethyl methanesulfonate and N-ethyl-N-nitrosourea to induce germline mutations in C. elegans at different developmental stages and analyzed mutation frequency and mutational spectrum from data gathered using next-generation sequencing (NGS) technology. Our results revealed low spontaneous mutation rates of C. elegans, along with distinct mutagenic effects elicited by the two mutagens. Our data show that the parental worms treated during germ cell mitosis, spermatogenesis, and oogenesis resulted in different mutation frequencies in their offspring, and female germ cells could be very susceptible to mutagen exposure during oogenesis. In summary, our study indicates that the use of C. elegans and its specific chronological hermaphroditism would be a promising way to explore the sensitivities of both male and female germ cells to mutagens.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Masculino , Feminino , Caenorhabditis elegans/genética , Mutagênicos/toxicidade , Sêmen , Células Germinativas/metabolismo , Espermatogênese/genética , Sequenciamento Completo do Genoma , Proteínas de Caenorhabditis elegans/genéticaRESUMO
A quantitative analysis method for corrosion products based on terahertz spectroscopy is proposed in this paper. Mixture samples consisting of three major corrosion products (magnetite, hematite, and goethite) were prepared in 51 different concentrations. The refractive index spectra measured by terahertz time-domain spectroscopy were projected to the 2D score diagram by performing principal component analysis. The Euclidean distances between the mixtures and pure analyte on the diagram were used to build a concentration prediction model. The results indicate that the established model can precisely predict the concentration of magnetite, which is essential for a stability evaluation of the corrosion system.