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Anthocyanins are water-soluble flavonoid pigments that play a crucial role in plant growth and metabolism. They serve as attractants for animals by providing plants with red, blue, and purple pigments, facilitating pollination and seed dispersal. The fruits of solanaceous plants, tomato (Solanum lycopersicum) and eggplant (Solanum melongena), primarily accumulate anthocyanins in the fruit peels, while the ripe fruits of Atropa belladonna (Ab) have a dark purple flesh due to anthocyanin accumulation. In this study, an R2R3-MYB transcription factor (TF), AbMYB1, was identified through association analysis of gene expression and anthocyanin accumulation in different tissues of A. belladonna. Its role in regulating anthocyanin biosynthesis was investigated through gene overexpression and RNA interference (RNAi). Overexpression of AbMYB1 significantly enhanced the expression of anthocyanin biosynthesis genes, such as AbF3H, AbF3'5'H, AbDFR, AbANS, and Ab3GT, leading to increased anthocyanin production. Conversely, RNAi-mediated suppression of AbMYB1 resulted in decreased expression of most anthocyanin biosynthesis genes, as well as reduced anthocyanin contents in A. belladonna. Overall, AbMYB1 was identified as a fruit-expressed R2R3-MYB TF that positively regulated anthocyanin biosynthesis in A. belladonna. This study provides valuable insights into the regulation of anthocyanin biosynthesis in Solanaceae plants, laying the foundation for understanding anthocyanin accumulation especially in the whole fruits of solanaceous plants.
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Antocianinas , Frutas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Antocianinas/biossíntese , Antocianinas/metabolismo , Frutas/metabolismo , Frutas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/genética , Interferência de RNARESUMO
Stomatal movements allow the uptake of CO2 for photosynthesis and water loss through transpiration, therefore play a crucial role in determining water use efficiency. Both red and blue lights induce stomatal opening, and the stomatal apertures under light are finetuned by both positive and negative regulators in guard cells. However, the molecular mechanisms for precisely adjusting stomatal apertures under light have not been completely understood. Here, we provided evidence supporting that Arabidopsis thaliana mitogen-activated protein kinase 11 (MPK11) plays a negative role in red light-induced stomatal opening. First, MPK11 was found to be highly expressed in guard cells, and MPK11-GFP signals were detected in both nuclear and cytoplasm of guard cells. The transcript levels of MPK11 in guard cells were upregulated by white light, and the stomata of mpk11 opened wider than that of wild type under white light. Consistent with the larger stomatal aperture, mpk11 mutant exhibited higher stomatal conductance and CO2 assimilation rate under white light. The transcript levels of the genes responsible for osmolytes increases were higher in guard cells of mpk11 than that of wild type, which may contribute to the larger stomatal aperture of mpk11 under white light. Furthermore, MPK11 transcript levels in guard cells were upregulated by red light, and mpk11 mutant showed a larger stomatal aperture under red light. Taken together, these results demonstrate that red light-upregulated MPK11 plays a negative role in stomatal opening, which finetuning the stomatal opening apertures and preventing excessive water loss by transpiration under light.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteína Quinase 11 Ativada por Mitógeno/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Dióxido de Carbono/metabolismo , Estômatos de Plantas/metabolismo , Luz , Água/metabolismoRESUMO
Recombination is one of the most important molecular mechanisms of prokaryotic genome evolution, but its exact roles are still in debate. Here we try to infer genome-wide recombination within a species, utilizing a dataset of 149 complete genomes of Escherichia coli from diverse animal hosts and geographic origins, including 45 in-house sequenced with the single-molecular real-time platform. Two major clades identified based on physiological, clinical and ecological characteristics form distinct genetic lineages based on scarcity of interclade gene exchanges. By defining gene-based syntenies for genomic segments within and between the two clades, we build a fine-scale recombination map for this representative global E. coli population. The map suggests extensive within-clade recombination that often breaks physical linkages among individual genes but seldom interrupts the structure of genome organizational frameworks as well as primary metabolic portfolios supported by the framework integrity, possibly due to strong natural selection for both physiological compatibility and ecological fitness. In contrast, the between-clade recombination declines drastically when phylogenetic distance increases to the extent where a 10-fold reduction can be observed, establishing a firm genetic barrier between clades. Our empirical data suggest a critical role for such recombination events in the early stage of speciation where recombination rate is associated with phylogenetic distance in addition to sequence and gene variations. The extensive intraclade recombination binds sister strains into a quasisexual group and optimizes genes or alleles to streamline physiological activities, whereas the sharply declined interclade recombination split the population into clades adaptive to divergent ecological niches.
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Escherichia coli/genética , Evolução Molecular , Variação Genética , Genoma Bacteriano , Recombinação Genética , Seleção Genética , Animais , Estudo de Associação Genômica Ampla , HumanosRESUMO
BACKGROUND: Germline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing. METHODS: We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of BRCA1/BRCA2/PALB2 (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomised comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway). RESULTS: Uptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety, with <5% of patients contacting the genetics specialist hotline. All progression criteria established for continuation of the study were met. CONCLUSION: Pilot data indicate preliminary demonstration of feasibility and acceptability of a fully digital pathway for BRCA-testing and support proceeding to a full powered study for evaluation of non-inferiority of the fully digital pathway, detailed quantitative assessment of outcomes and operational economic analyses. TRIAL REGISTRATION NUMBER: ISRCTN87845055.
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Neoplasias da Mama , Encaminhamento e Consulta , Humanos , Feminino , Medicina Estatal , Telefone , Testes Genéticos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Reino UnidoRESUMO
It is shown that the presence of hundreds of ppm of water in 1,3-dimethylurea (DMU) powder led to the large depression of the transition temperature between the two enantiotropically related polymorphic forms of DMU (Form II â Form I) from 58 °C to 25 °C, thus explaining the reported discrepancies on this temperature of transition. Importantly, this case study shows that thermodynamics (through the construction of the DMU-water temperature-composition phase diagram) rather than kinetics is responsible for this significant temperature drop. Furthermore, this work also highlights the existence of a monohydrate of DMU that has never been reported before with a non-congruent fusion at 8 °C. Interestingly, its crystal structure, determined from X-ray powder diffraction data at sub-ambient temperature, consists of a DMU-water hydrogen bonded network totally excluding homo-molecular hydrogen bonds (whereas present in forms I and II of DMU).
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BACKGROUND: Menstrual cycle length (MCL) and ovarian response varies widely among women of childbearing age. They are provided with anti-Mu¨llerian hormone (AMH) cutoffs for "normal" and "weakened" ovarian responses, which give an early warning of the onset of decreased ovarian response. METHODS: This was a retrospective study in women aged 21 to 35 years with MCLs of 21-35 days receiving in vitro fertilization (IVF) treatment at Center for Reproductive Medicine from October 2018 to October 2021. Intergroup variables were balanced using propensity score matching based on age and BMI, and each case patient (patients with MCLs of 21-25 days) was matched with three control patients (patients with MCLs of 26-35 days). A receiver operating characteristic curve was used to calculate the AMH cutoff values. RESULTS: We included 135 patients with MCLs of 21-25 days and 405 matched control patients with MCLs of 26-35 days who received IVF treatment. The case group had significantly fewer retrieved oocytes, lower AMH values and higher initial and total Gonadotropin (Gn) levels during controlled ovarian hyperstimulation than the control group. The ovarian response began to decrease when AMH was < 3.5 ng/ml in the case group and < 2.7 ng/ml in the control group. CONCLUSION: In young women with MCLs of 21-35 days, short MCL was negatively correlated with AMH values and the number of oocytes retrieved. In patients with MCLs of 21-25 days and 26-35 days, the AMH cutoff values corresponding to the onset of decreased ovarian response were 3.5 ng/ml and 2.7 ng/ml, respectively.
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Hormônio Antimülleriano , Indução da Ovulação , Feminino , Humanos , Adulto , Estudos Retrospectivos , Pontuação de Propensão , Ovário , Fertilização in vitroRESUMO
Bis(demethoxy)curcumin (BDMC) is one of the main active components found in turmeric. Major drawbacks for its usage are its low aqueous solubility, and the challenging separation from other curcuminoids present in turmeric. Co-crystallization can be applied to alter the physicochemical properties of BDMC in a desired manner. A co-crystal screening of BDMC with four hydroxybenzenes was carried out using four different methods of co-crystal production: crystallization from solution by slow solvent evaporation (SSE), and rapid solvent removal (RSR), liquid-assisted grinding (LAG), and crystallization from the melt phase. Two co-crystal phases of BDMC were obtained with pyrogallol (PYR), and hydroxyquinol (HYQ). PYR-BDMC co-crystals can be obtained only from the melt, while HYQ-BDMC co-crystals could also be produced by LAG. Both co-crystals possess an equimolar composition and reveal an incongruent melting behavior. Infrared spectroscopy demonstrated the presence of BDMC in the diketo form in the PYR co-crystals, while it is in a more stable keto-enol form in the HYQ co-crystals. Solubility measurements in ethanol and an ethanol-water mixture revealed an increase of solubility in the latter, but a slightly negative effect on ethanol solubility. These results are useful for a prospective development of crystallization-based separation processes of chemical similar substances through co-crystallization.
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Curcuma/química , Curcumina/química , Diarileptanoides/química , Pirogalol/química , Cristalização , Curcumina/síntese química , Diarileptanoides/síntese química , Etanol , Pirogalol/síntese química , Técnicas de Síntese em Fase Sólida , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , ÁguaRESUMO
Two polytypes of the new oxyvanadate matrix La7O6(VO4)3 were identified and deeply characterized. The crystal structure of the α-polytype was solved using a combination of precession electron diffraction and powder X-ray diffraction (XRD) techniques. It crystallizes in a monoclinic unit cell with space group P21, a = 13.0148(3) Å, b = 19.1566(5) Å, c = 7.0764(17) Å, and ß = 99.87(1)°. Its structure is built upon [La7O6]9+ polycationic units at the origin of a porous 3D network, evidencing rectangular channels filled by isolated VO4 tetrahedra. An in situ high-temperature XRD study highlights a number of complex phase transitions assorted with the existence of a ß-polytype also refined in a monoclinic unit cell, space group P21/n, a = 13.0713(4) Å, b = 18.1835(6) Å, c = 7.1382(2) Å, and ß = 97.31(1)°. Thus, during the transitions, while the polycationic networks are almost identical, the vanadate's geometry is largely modified. The use of Eu3+ and Sm3+ at different concentrations in the host lattice is possible using solid-state techniques. The photoluminescence (PL), PL excitation (PLE) spectra, and luminescence decay times were recorded and discussed. The phosphors present an emission light, being bright and reddish orange after excitation under UV. This is mainly due to the V-O band and f-f transitions. Whatever the studied polytype, the final luminescence properties are retained during the heating/cooling process.
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BACKGROUND: Next-generation sequencing (NGS) technologies have greatly promoted the genomic study of prokaryotes. However, highly fragmented assemblies due to short reads from NGS are still a limiting factor in gaining insights into the genome biology. Reference-assisted tools are promising in genome assembly, but tend to result in false assembly when the assigned reference has extensive rearrangements. RESULTS: Herein, we present GAAP, a genome assembly pipeline for scaffolding based on core-gene-defined Genome Organizational Framework (cGOF) described in our previous study. Instead of assigning references, we use the multiple-reference-derived cGOFs as indexes to assist in order and orientation of the scaffolds and build a skeleton structure, and then use read pairs to extend scaffolds, called local scaffolding, and distinguish between true and chimeric adjacencies in the scaffolds. In our performance tests using both empirical and simulated data of 15 genomes in six species with diverse genome size, complexity, and all three categories of cGOFs, GAAP outcompetes or achieves comparable results when compared to three other reference-assisted programs, AlignGraph, Ragout and MeDuSa. CONCLUSIONS: GAAP uses both cGOF and pair-end reads to create assemblies in genomic scale, and performs better than the currently available reference-assisted assembly tools as it recovers more assemblies and makes fewer false locations, especially for species with extensive rearranged genomes. Our method is a promising solution for reconstruction of genome sequence from short reads of NGS.
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Biologia Computacional/métodos , Genoma , Genômica/métodos , Células Procarióticas/metabolismo , Algoritmos , Reprodutibilidade dos TestesRESUMO
The chemical cleaning method is the simplest approach for degreasing oil-based drilling cuttings (ODCs), with the effectiveness of the treatment relying mainly on the selection of the surfactant and the cleaning conditions. However, achieving the standard treatment of ODCs directly using conventional surfactants proves challenging. In light of this, this study introduces a synthesized and purified Gemini surfactant named DCY-1. The structure of DCY-1 was confirmed through Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses. The characterization in this article encompasses the use of an interface tension meter, nanoparticle size analysis, scanning electron microscopy, and infrared oil measurement. The critical micelle concentration (CMC) of DCY-1 was determined to be 3.37 × 10-3 mol/L, with a corresponding γcmc value of 37.97 mN/m. In comparison to conventional surfactants, DCY-1 exhibited a larger micelle size of 4.52 nm, approximately 24.52% larger than that of SDS. Moreover, the residual oil rate of 3.96% achieved by DCY-1 was the lowest among the chemical cleaning experimental results. Through a single-factor experiment, the optimal cleaning ability of DCY-1 for ODCs was determined as follows: a surfactant concentration of 3 mmol/L, a temperature of 60 °C, an ODC/liquid mass ratio of 1:4, a cleaning duration of 40 min, and a stirring speed of 1000 rad/min. Under these optimal conditions and after merely two cleaning procedures, the residual oil content of ODCs was reduced to 1.64%, accompanied by a smooth and loose surface structure.
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Pancreatic cancer is one of the most aggressive cancers. PELI1 has been reported to promote cell survival and proliferation in multiple cancers. As of now, the role of PELI1 in pancreatic cancer is largely unknown. Here, we found that the PELI1 mRNA was higher expressed in pancreatic tumor tissues than in adjacent normal tissues, and the high PELI1 level in pancreatic cancer patients had a short survival time compared with the low level. Moreover, the results showed that PELI1 promoted cell proliferation, migration, and invasion, and inhibited apoptosis in vitro. Xenograft tumor experiments were used to determine the biological function of PELI1, and the results showed that PELI1 promoted tumor growth in vivo. Additionally, we found that Jagged1 activated PELI1 transcription in pancreatic cancer cells. To sum up, our results show that PELI1 affects the malignant phenotype of pancreatic cancer.
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Neoplasias Pancreáticas , Humanos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias PancreáticasRESUMO
The deposition of polycyclic aromatic hydrocarbon (PAHs) has far-reaching impacts on Earth's surface system and human health. However, a comprehensive understanding of PAHs' deposition in a high urbanized area is still lacking because of limited field measurements data and rough resolution of current models. In this research, a deposition map of PAHs with a resolution of 2 × 2 km in megacity Shanghai, China was established. Gridded annual total deposition of PAHs from July 2020 to June 2021 ranged from 385 to 10,631 ng/(m2·d), with a mean value of 2,611 ng/(m2·d). The highest PAHs deposition was found over the downtown Shanghai, which received 4.3 times the deposition flux of outlying areas. About 77 % of area in Shanghai was dominated by wet deposition which accounted for 62 % of total deposition in Shanghai. The total deposition showed a trend of summer>fall>spring>winter, which was similar to that of the amount of rain. Source apportionment and geographically weighted regression analysis showed that built-up land and human activities are key driving factors of PAHs' deposition in Shanghai. Our results suggest that intensive human activities could alter the PAHs deposition distribution in Shanghai, and improve the understanding of PAHs' environmental behavior in high urbanized area.
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Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental/métodos , China , Estações do Ano , Poluentes Atmosféricos/análiseRESUMO
Accurate quantification of arsenic migration and accumulation in brownfield site is critical for environmental management and soil remediation. However, the researches simulating arsenic in brownfield site in China are limited due to sparse data and complex migration behaviors. In this study, we simulated historic arsenic contamination using Hydrus-3D in an abandoned brownfield site in Hebei, China, from 1972 to 2019. Atmospheric discharge, wastewater leakage, solid waste discharge and tank leakage were calculated according to the factory processes for model simulation. Based on the results of Hydrus-3D, we assessed health risk of arsenic in this site. The results showed that total arsenic input to the soil surface from 4 pathways was 24.6 tons, the solid waste discharge was the highest contributor. The accumulation process mainly occurred in the unsaturated zone due to clay and silty clay absorbed arsenic and thus slow down the migration process. While in the saturation zone, abundant groundwater promoted migration of arsenic, resulting in widespread distribution of contaminated area. The model results represented good performance between simulated and measured values. Sensitivity analysis indicated that adsorption constant and water conductivity were the most influential parameters. Heath risk assessment showed that arsenic contamination continues to threaten resident health.
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OBJECTIVES: Pharyngocutaneous fistula (PCF) formation following open surgical treatment of hypopharyngeal cancer (HPC) is a common and troublesome complication. To date, the postoperative protocol of restarting oral intake is not clear, and vast discrepancies exist in the literature and among institutions. This study aimed to explore the impact of a postoperative protocol of restarting oral intake on PCF formation after open surgical treatment of primary HPC, and its impact on overall survival (OS) and swallowing function based on the functional outcome swallowing scale (FOSS). MATERIALS AND METHODS: This was a prospective observational study of 42 patients who received open surgical treatment for primary HPC at Beijing Friendship Hospital between April 2019 and August 2021. This cohort included two groups: patients who restarted oral intake on the 10th postoperative day (Group 1), and those who started on the 20th (Group 2). The Chi-square test and Fisher's exact chi-squared test were used for comparing qualitative data among the groups. RESULTS: Group 1 (n = 27) and Group 2 (n = 15) were comparable in clinical characteristics. PCF occurred in 7 (25.9%) patients in Group 1, while none occurred in Group 2 (P = 0.038). The 2-year OS of all 42 patients was 75.6%; 65.8% and 93.3% for Groups 1 and 2, respectively (P = 0.07). The swallowing function was satisfactory (FOSS Grades 0-III) for 19 (70.4%) patients in Group 1 and 15 (100%) patients in Group 2 (P = 0.035). Laryngeal preservation was achieved in 25 (59.5%) patients, while decannulation was successful in 22 (88.0%) patients. CONCLUSIONS: Delayed oral feeding significantly reduces PCF after open surgical treatment of primary HPC, and improves the swallowing function outcome without jeopardizing the OS.
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OBJECTIVE: Clinical diagnostic sequencing of circulating tumour DNA (ctDNA) is well advanced for adult patients, but application to paediatric cancer patients lags behind. METHODS: To address this, we have developed a clinically relevant (67 gene) NGS capture panel and accompanying workflow that enables sensitive and reliable detection of low-frequency genetic variants in cell-free DNA (cfDNA) from children with solid tumours. We combined gene panel sequencing with low pass whole-genome sequencing of the same library to inform on genome-wide copy number changes in the blood. RESULTS: Analytical validity was evaluated using control materials, and the method was found to be highly sensitive (0.96 for SNVs and 0.97 for INDEL), specific (0.82 for SNVs and 0.978 for INDEL), repeatable (>0.93 [95% CI: 0.89-0.95]) and reproducible (>0.87 [95% CI: 0.87-0.95]). Potential for clinical application was demonstrated in 39 childhood cancer patients with a spectrum of solid tumours in which the single nucleotide variants expected from tumour sequencing were detected in cfDNA in 94.4% (17/18) of cases with active extracranial disease. In 13 patients, where serial samples were available, we show a close correlation between events detected in cfDNA and treatment response, demonstrate that cfDNA analysis could be a useful tool to monitor disease progression, and show cfDNA sequencing has the potential to identify targetable variants that were not detected in tumour samples. CONCLUSIONS: This is the first pan-cancer DNA sequencing panel that we know to be optimised for cfDNA in children for blood-based molecular diagnostics in paediatric solid tumours.
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Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias , Adulto , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Criança , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , Sequenciamento Completo do Genoma/métodosRESUMO
Ostwald ripening (OR), one of the major processes of nanoparticle sintering, is critical for the rational design of functional nanomaterials. However, the atomistic mechanism of OR has not been fully understood, because the characterization of interparticle transport of atoms in real-time is challenging by either experiments or theoretical simulations. Thus, current understandings are based on ad hoc assumptions about the OR mechanism, which have never been confirmed yet at the atomic scale. Herein, we realized all-atom kinetic Monte Carlo simulation of sintering of TiO2 supported Au nanoparticles (NPs) through the OR mechanism at millisecond timescales. We demonstrated that the "semi-spherical" assumption should be removed. The OR process was a stagewise process determined by different rate-determining steps, which is in contrast to the single-stage presumption. Au dimers, rather than monomers as generally assumed, were exchanged among different NPs. Besides, we proposed a new kinetic model for describing the determining rate of OR without presumptions. This work brings deeper insights into the atomistic OR mechanism and also paves the way for real-time monitoring of catalyst sintering at the atomic scale.
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Magnetic resonance molecular imaging, as a safe imaging technology, provides a new idea for the early qualitative and hierarchical diagnosis of gliomas. The purpose of this study was to design and evaluate the value of neuropilin-1 (NRP-1) targeting molecular probes in the hierarchical diagnosis of gliomas. First, we created an NRP-1 targeted magnetic resonance molecular probe (USPIO-PEG-tLyP-1) by combining the polypeptide tLyP-1 with ultra-small superparamagnetic iron oxide nanoparticles (USPIONs), detecting the physical properties by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Second, in vivo experiments, we established two different degrees of malignant gliomas in-situ in nude mice by injecting U87 and CHG-5 cells. Then, to detect the binding ability of the probe with different grades of tumour tissues, we injected the probe into the tumour-bearing mice through the tail vein. Next, MRI was performed before injection, and 6 h, 12 h, 24 h after injection, and we found significantly more iron particles in the tumour tissues of U87 tumour-bearing mice than in tumour tissues of CHG-5 tumour-bearing mice. The signal intensities of the T2-weighted images of the tumour tissues of each group as well as microscopic observations by Prussian blue staining indicated that the binding ability of this molecular probe to U87 glioma (HGG) with high NRP-1 expression was significantly greater than that of CHG-5 glioma (LGG) with low NRP-1 expression (P < 0.01). Therefore, this study confirms that the novel molecular probe USPIO-PEG-tLyP-1 can be used for the grading diagnosis by MRI for gliomas of high and low grade with different NRP-1 expression levels.
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Meios de Contraste , Dextranos , Glioma/diagnóstico por imagem , Nanopartículas de Magnetita , Neuropilina-1/metabolismo , Peptídeos Cíclicos , Polietilenoglicóis , Animais , Linhagem Celular Tumoral , Peptídeos Penetradores de Células , Dextranos/ultraestrutura , Difusão Dinâmica da Luz , Glioma/metabolismo , Glioma/patologia , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão , Sondas Moleculares/ultraestrutura , Gradação de Tumores , Interferência de RNA , TransfecçãoRESUMO
Land use change has a significant impact on the structure and function of ecosystems, and the transformation of ecosystems affects the mode and efficiency of land use, which reflects a mutual interaction relationship. The prediction and simulation of future land use change can enhance the foresight of land use planning, which is of great significance to regional sustainable development. In this study, future land use changes are characterized under an ecological optimization scenario based on the grey prediction (1,1) model (GM) and a future land use simulation (FLUS) model. In addition, the ecosystem service value (ESV) of Anhui Province from 1995 to 2030 were estimated based on the revised estimation model. The results indicate the following details: (1) the FLUS model was used to simulate the land use layout of Anhui Province in 2018, where the overall accuracy of the simulation results is high, indicating that the FLUS model is applicable for simulating future land use change; (2) the spatial layout of land use types in Anhui Province is stable and the cultivated land has the highest proportion. The most significant characteristic of future land use change is that the area of cultivated land continues to decrease while the area of built-up land continues to expand; and (3) the ESV of Anhui Province is predicted to increase in the future. The regulating service is the largest ESV contributor, and water area is the land use type with the highest proportion of ESV. These findings provide reference for the formulation of sustainable development policies of the regional ecological environment.
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Conservação dos Recursos Naturais , Ecossistema , China , Previsões , Desenvolvimento SustentávelRESUMO
PURPOSE: Advanced breast cancer (ABC) has not been subjected to the same degree of molecular scrutiny as early primary cancer. Breast cancer evolves with time and under the selective pressure of treatment, with the potential to acquire mutations with resistance to treatment and disease progression. To identify potentially targetable mutations in advanced breast cancer, we performed prospective molecular characterization of a cohort of patients with ABC. EXPERIMENTAL DESIGN: Biopsies from patients with advanced breast cancer were sequenced with a 41 genes targeted panel in the ABC Biopsy (ABC-Bio) study. Blood samples were collected at disease progression for circulating tumor DNA (ctDNA) analysis, along with matched primary tumor to assess for acquisition in ABC in a subset of patients. RESULTS: We sequenced 210 ABC samples, demonstrating enrichment compared with primary disease for potentially targetable mutations in HER2 (in 6.19% of samples), AKT1 (7.14%), and NF1 (8.10%). Of these enriched mutations, we show that NF1 mutations were frequently acquired in ABC, not present in the original primary disease. In ER-positive cancer cell line models, loss of NF1 resulted in endocrine therapy resistance, through both ER-dependent and -independent mechanisms. NF1 loss promoted ER-independent cyclin D1 expression, which could be therapeutically targeted with CDK4/6 inhibitors in vitro. Patients with NF1 mutations detected in baseline circulating tumor DNA had a good outcome on the CDK4/6 inhibitor palbociclib and fulvestrant. CONCLUSIONS: Our research identifies multiple therapeutic opportunities for advanced breast cancer and identifies the previously underappreciated acquisition of NF1 mutations.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclina D1/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/genética , Mutação , Neurofibromina 1/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Feminino , Fulvestranto/administração & dosagem , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Estudos Prospectivos , Piridinas/administração & dosagem , Resultado do TratamentoRESUMO
Large amounts of aerosol particles suspended in the atmosphere pose a serious challenge to the climate and human health. In this study, we produced a dataset through merging the Moderate Resolution Imaging Spectrometers (MODIS) Collection 6.1 3-km resolution Dark Target aerosol optical depth (DT AOD) with the 10-km resolution Deep Blue aerosol optical depth (DB AOD) data by linear regression and made use of it to unravel the spatiotemporal characteristics of aerosols over the Pan Yangtze River Delta (PYRD) region from 2014 to 2017. Then, the geographical detector method and multiple linear regression analysis were employed to investigate the contributions of influencing factors. Results indicate that: (1) compared to the original Terra DT and Aqua DT AOD data, the average daily spatial coverage of the merged AOD data increased by 94% and 132%, respectively; (2) the values of four-year average AOD were high in the north-east and low in the south-west of the PYRD; (3) the annual average AOD showed a decreasing trend from 2014 to 2017 while the seasonal average AOD reached its maximum in spring; and that (4) Digital Elevation Model (DEM) and slope contributed most to the spatial distribution of AOD, followed by precipitation and population density. Our study highlights the spatiotemporal variability of aerosol optical depth and the contributions of different factors over this large geographical area in the four-year period, and can, therefore, provide useful insights into the air pollution control for decision makers.