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PURPOSE: This study aims to understand the role of cirrhosis in promoting hepatocellular carcinoma (HCC) progression by analyzing the differential expression of long noncoding RNAs (lncRNAs) between cirrhotic hepatocellular carcinoma (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC). METHODS: A transcriptional profile array was used to identify differentially expressed lncRNAs. Subsequently, a specific lncRNA was selected to evaluate the clinical significance, potential functions, regulatory targets, and pathways through both in vitro and in vivo experiments. RESULTS: The study identified a lncRNA, which we termed DERCNC, an acronym for Differentially Expressed RNA between Cirrhotic and Non-Cirrhotic HCC. DERCNC was significantly more highly expressed in CHCC than in NCHCC. Clinically, elevated levels of DERCNC expression were positively correlated with both the cirrhotic state and tumor stage and inversely correlated with tumor differentiation. Furthermore, high expression of DERCNC was associated with a poor prognosis for patients. Conditioned medium from the hepatic stellate cell (LX2) was found to enhance DERCNC expression, SOX9 expression, and tumor proliferation. Overexpression of DERCNC similarly promoted tumor proliferation and increased SOX9 levels. Conversely, DERCNC silencing resulted in the opposite effects. Moreover, the pro-proliferative function of DERCNC was reversible through the modulation of SOX9 expression. Further mechanistic studies revealed that DERCNC upregulated SOX9 by increasing the enrichment of H3K27ac modifications near the SOX9 promoter. CONCLUSION: In conclusion, DERCNC expression in CHCC has significant clinical implications and can aggravate tumor proliferation by targeting SOX9. This represents a novel mechanism by which cirrhosis promotes tumor progression.
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The majority of the world's natural rubber comes from the rubber tree (Hevea brasiliensis). As a key enzyme for synthesizing phenylpropanoid compounds, phenylalanine ammonia-lyase (PAL) has a critical role in plant satisfactory growth and environmental adaptation. To clarify the characteristics of rubber tree PAL family genes, a genome-wide characterization of rubber tree PALs was conducted in this study. Eight PAL genes (HbPAL1-HbPAL8), which spread over chromosomes 3, 7, 8, 10, 12, 13, 14, 16, and 18, were found to be present in the genome of H. brasiliensis. Phylogenetic analysis classified HbPALs into groups I and II, and the group I HbPALs (HbPAL1-HbPAL6) displayed similar conserved motif compositions and gene architectures. Tissue expression patterns of HbPALs quantified by quantitative real-time PCR (qPCR) proved that distinct HbPALs exhibited varying tissue expression patterns. The HbPAL promoters contained a plethora of cis-acting elements that responded to hormones and stress, and the qPCR analysis demonstrated that abiotic stressors like cold, drought, salt, and H2O2-induced oxidative stress, as well as hormones like salicylic acid, abscisic acid, ethylene, and methyl jasmonate, controlled the expression of HbPALs. The majority of HbPALs were also regulated by powdery mildew, anthracnose, and Corynespora leaf fall disease infection. In addition, HbPAL1, HbPAL4, and HbPAL7 were significantly up-regulated in the bark of tapping panel dryness rubber trees relative to that of healthy trees. Our results provide a thorough comprehension of the characteristics of HbPAL genes and set the groundwork for further investigation of the biological functions of HbPALs in rubber trees.
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Regulación de la Expresión Génica de las Plantas , Hevea , Familia de Multigenes , Fenilanina Amoníaco-Liasa , Proteínas de Plantas , Perfilación de la Expresión Génica , Genoma de Planta , Hevea/genética , Hevea/enzimología , Hevea/metabolismo , Fenilanina Amoníaco-Liasa/genética , Fenilanina Amoníaco-Liasa/metabolismo , Filogenia , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiones Promotoras Genéticas/genética , Estrés Fisiológico/genéticaRESUMEN
Currently, one of the most serious threats to rubber tree is the tapping panel dryness (TPD) that greatly restricts natural rubber production. Over-tapping or excessive ethephon stimulation is regarded as the main cause of TPD occurrence. Although extensive studies have been carried out, the molecular mechanism underlying TPD remains puzzled. An attempt was made to compare the levels of endogenous hormones and the profiles of transcriptome and proteome between healthy and TPD trees. Results showed that most of endogenous hormones such as jasmonic acid (JA), 1-aminocyclopropanecarboxylic acid (ACC), indole-3-acetic acid (IAA), trans-zeatin (tZ) and salicylic acid (SA) in the barks were significantly altered in TPD-affected rubber trees. Accordingly, multiple hormone-mediated signaling pathways were changed. In total, 731 differentially expressed genes (DEGs) and 671 differentially expressed proteins (DEPs) were identified, of which 80 DEGs were identified as putative transcription factors (TFs). Further analysis revealed that 12 DEGs and five DEPs regulated plant hormone synthesis, and that 16 DEGs and six DEPs were involved in plant hormone signal transduction pathway. Nine DEGs and four DEPs participated in rubber biosynthesis and most DEGs and all the four DEPs were repressed in TPD trees. All these results highlight the potential roles of endogenous hormones, signaling pathways mediated by these hormones and rubber biosynthesis pathway in the defense response of rubber trees to TPD. The present study extends our understanding of the nature and mechanism underlying TPD and provides some candidate genes and proteins related to TPD for further research in the future.
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Hevea , Hevea/genética , Hevea/metabolismo , Goma/metabolismo , Transcriptoma , Látex/metabolismo , Proteoma/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transducción de Señal , Hormonas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
The first complete chloroplast genome of rice (Oryza sativa) was published in 1989, ushering in a new era of studies of chloroplast genomics in Poaceae. Progresses in Next-Generation Sequencing (NGS) and Third-Generation Sequencing (TGS) technologiesand in the development of genome assembly software, have significantly advanced chloroplast genomics research. Poaceae is one of the most targeted families in chloroplast genome research because of its agricultural, ecological, and economic importance. Over the last 30 years, 2,050 complete chloroplast genome sequences from 40 tribes and 282 genera have been generated, most (97%) of them in the recent ten years. The wealth of data provides the groundwork for studies on species evolution, phylogeny, genetic transformation, and other aspects of Poaceae chloroplast genomes. As a result, we have gained a deeper understanding of the properties of Poaceae chloroplast genomes. Here, we summarize the achievements of the studies of the Poaceae chloroplast genomes and envision the challenges for moving the area ahead.
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Tapping panel dryness (TPD) results in a severe reduction in latex yield in Hevea brasiliensis. However, the molecular regulatory mechanisms of TPD occurrence are still largely unclear. In this study, whole-transcriptome sequencing was carried out on latex from TPD and healthy trees. In total, 7078 long noncoding RNAs (lncRNAs), 3077 circular RNAs (circRNAs), 4956 miRNAs, and 25041 mRNAs were identified in latex, among which 435 lncRNAs, 68 circRNAs, 320 miRNAs, and 1574 mRNAs were differentially expressed in the latex of TPD trees. GO and KEGG analyses indicated that plant hormone signal transduction, MAPK signaling pathway, and ubiquitin-mediated proteolysis were the key pathways associated with TPD onset. Phytohormone profiling revealed significant changes in the contents of 28 hormonal compounds, among which ACC, ABA, IAA, GA, and JA contents were increased, while SA content was reduced in TPD latex, suggesting that hormone homeostasis is disrupted in TPD trees. Furthermore, we constructed a TPD-related competitive endogenous RNA (ceRNA) regulatory network of lncRNA/circRNA-miRNA-mRNA with 561 edges and 434 nodes (188 lncRNAs, 5 circRNAs, 191 miRNAs, and 50 mRNAs) and identified two hub lncRNAs (MSTRG.11908.1 and MSTRG.8791.1) and four hub miRNAs (hbr-miR156, miR156-x, miRf10477-y, and novel-m0452-3p). Notably, the lncRNA-miR156/157-SPL module containing three hubs probably plays a crucial role in TPD onset. The expression of network hubs and the lncRNA-miR156/157-SPL module were further validated by qRT-PCR. Our results reveal the TPD-associated ceRNA regulatory network of lncRNA/circRNA-miRNA-mRNA in latex and lay a foundation for further investigation of molecular regulatory mechanisms for TPD onset in H. brasiliensis.
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Hevea , MicroARNs , ARN Largo no Codificante , Látex , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Hevea/genética , Hevea/metabolismo , ARN Largo no Codificante/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Redes Reguladoras de GenesRESUMEN
To investigate the role of neuropilin1 (Nrp1) in glucose metabolism and proliferation of hepatocellular carcinoma (HCC) cells and to analyze its mechanism of action. The CRISPR gene knockout technique was used to knock out the Nrp1 gene in two HCC cell lines. The effect of Nrp1 on the proliferation of HCC cells was assessed in the CCK8 assay and plate cloning assay. The expression levels of glucose consumption, lactate production, and essential proteins of the glycolytic pathway were detected to explore the effect of Nrp1 on glucose metabolism in HCC cells. Using CoCl2 to revert the expression of hypoxia inducible factor-1α (HIF-1α), the role of HIF-1α in the pro-HCC cell metabolism of Nrp1 were demonstrated. The protein synthesis inhibitor CHX and proteasome inhibitor MG-132 was used to analyze the molecular mechanism of action of Nrp1 on HIF-1α. The Kaplan-Meier method was used to calculate survival rates and plot survival curves. Based on the CCK8 assay and plate cloning assay, we found that Nrp1 knockout significantly inhibited the proliferation of HCC cells. Nrp1 inhibitor suppressed lactate production and glucose consumption in HCC cells. Knockout of Nrp1 decreased the expression of glycolytic pathway-related proteins and HIF-1α protein. Furthermore, by joint use of CoCl2 and NRP1 knockout, we confirmed that reverting HIF-1α expression could reverse the effect of Nrp1 knockout on HCC cell metabolism in vitro. Mechanistically, Nrp1 showed a close correlation with the stability of HIF-1α protein in protein stability assay. Finally, we revealed that high expression of Nrp1 in HCC tissues was associated with poor overall survival and disease-free survival of the patients. Nrp1 accelerates glycolysis and promotes proliferation of HCC by regulating HIF-1α protein stability and through the VEGF/Nrp1/HIF-1α positive feedback loop.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Retroalimentación , Neuropilina-1/genética , Neuropilina-1/metabolismo , Proliferación Celular , Glucosa , Cobalto/farmacología , Cobalto/metabolismo , Lactatos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
As a noxious weed, weedy rice (Oryza sativa f. spontanea Roshev. 1931) has threatened global food security and sustainable crop production. On the other hand, weedy rice has a strong tolerance for abiotic stresses and the potential to provide rich resources for rice genetic improvement. Thus, for a more comprehensive understanding of its speciation, we sequenced and assembled the first complete chloroplast genome of Oryza sativa f. spontanea (japonica type). The complete chloroplast genome was 134,555 bp in length and encoded 133 genes, including 83 protein-coding genes, 42 tRNA genes and 8 rRNA genes. Phylogenetic analysis revealed that the indica-japonica differentiation of weedy rice was closely related to cultivated rice, and Oryza sativa f. spontanea (japonica type) was genetically more closely clustered with cultivated rice O. sativa (japonica type) than O. nivara or other wild rice.
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Momilactone A, an important plant labdane-related diterpenoid, functions as a phytoalexin against pathogens and an allelochemical against neighboring plants. The genes involved in the biosynthesis of momilactone A are found in clusters, i.e., momilactone A biosynthetic gene clusters (MABGCs), in the rice and barnyardgrass genomes. In addition, we know little about the origin and evolution of MABGCs. Here, we integrated results from comprehensive phylogeny and comparative genomic analyses of the core genes of MABGC-like clusters and MABGCs in 40 monocot plant genomes, providing convincing evidence for the birth and evolution of MABGCs in grass species. The MABGCs found in the PACMAD clade of the core grass lineage (including Panicoideae and Chloridoideae) originated from a MABGC-like cluster in Triticeae (BOP clade) via lateral gene transfer (LGT) and followed by recruitment of MAS1/2 and CYP76L1 genes. The MABGCs in Oryzoideae originated from PACMAD through another LGT event and lost CYP76L1 afterwards. The Oryza MABGC and another Oryza diterpenoid cluster c2BGC are two distinct clusters, with the latter originating from gene duplication and relocation within Oryzoideae. Further comparison of the expression patterns of the MABGC genes between rice and barnyardgrass in response to pathogen infection and allelopathy provides novel insights into the functional innovation of MABGCs in plants. Our results demonstrate LGT-mediated origination of MABGCs in grass and shed lights into the evolutionary innovation and optimization of plant biosynthetic pathways.
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Diterpenos , Echinochloa , Oryza , Diterpenos/metabolismo , Echinochloa/genética , Echinochloa/metabolismo , Familia de Multigenes , Oryza/metabolismo , Plantas/metabolismo , Poaceae/genética , Poaceae/metabolismoRESUMEN
Weedy rye (Secale cereale subsp. segetale Zhukov 1928) is a problematic weed species in wheat field. However, it can potentially provide valuable genetics resources to increase the genetic variations and introduce desirable genes for rye and wheat breeding. Here, we assembled the complete chloroplast genome of S. cereale subsp. segetale. The chloroplast genome is 137,051 bp in length, containing a large single copy region (81,090 bp), a small single copy region (12,795 bp) and two separated inverted repeat regions (21,583 bp). A total of 131 unique genes were annotated, consisting of 82 protein-coding genes, 41 tRNA genes, and 8 rRNA genes. The phylogenetic analysis showed that Secale cereale subsp. segetale (weedy rye) and S. cereale subsp. cereale (rye) clustered together as sisters to other Secale species.
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Ferritic/martensitic (F/M) steels whose matrix is Fe-Cr are important candidate materials for fuel cladding of fast reactors, and they have excellent irradiation-swelling resistance. However, the mechanism of irradiation-swelling of F/M steels is still unclear. We use a first-principles method to reveal the influence of irradiation defects, i.e., Frenkel pair including atomic vacancy and self-interstitial atom, on the change of lattice volume of Fe-13Cr lattice. It is found that vacancy causes lattice contraction, while a self-interstitial atom causes lattice expansion. The overall effect of a Frenkel pair on the change of lattice volume is lattice expansion, leading to swelling of the alloy. Furthermore, the diffusion properties of point defects in Fe-13Cr are investigated. Based on the diffusion barriers of the vacancies and interstitial atoms, we find that the defects in Fe-13Cr drain out to surfaces/grain boundaries more efficiently than those in pure α-Fe do. Therefore, the faster diffusion of defects in Fe-13Cr is one of important factors for good swelling resistance of Fe-13Cr compared to pure α-Fe.
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Secale strictum subsp. kuprijanovii is a perennial, hermaphrodite wild rye species and a progenitor of the modern cultivated rye, Secale cereale. With high adaptive capacity in stress conditions, it is valuable for enriching the germplasm resources of rye. Therefore, to elucidate its genetic and phylogenetic relationship is of great importance. We hereby sequenced, assembled and presented for the first time the complete chloroplast genome of this less studied species. The whole genome is 137,079 bp in size, including a large single copy region of 81,099 bp, a small single copy region of 12,820 bp and two separated inverted repeat regions of 43,160 bp. A total of 109 unique genes were annotated, including 67 protein-coding genes, 38 tRNA genes and 4 rRNA genes. Phylogenetic analysis showed that Secale strictum subsp. kuprijanovii clustered most closely with Secale cereal. A remarkably close evolutionary relationship of S.strictum subsp. kuprijanovii with various wheat varieties may indicate its usage as a genetic resource for the breeding of both the cultivated rye and wheat.
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Nicotiana plumbaginifolia Vivianiis 1802 is an annual herb, native to Mexico and South America. It is one of the most widely distributed tobacco species. As a wild tobacco, N. plumbaginifolia has provided several economically important disease-resistance genes to cultivated tobacco. We assembled the complete chloroplast genome of N. plumbaginifolia. The chloroplast genome is 155,945 bp in length, which includes a large single copy region (86,621 bp), a small single copy region (18,528 bp) and two separated inverted repeat regions (25,398 bp). A total of 117 unique genes were annotated, consisting of 84 protein-coding genes, 29 tRNA genes and 4 rRNA genes. Based on chloroplast genomes of 17 Nicotiana species, phylogenetic analyses indicated that N. plumbaginifolia was closely related to N. suaveolens and N. amplexicaulis.
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Rye (Secale cereale) is an important crop with multiple uses and a valuable genetic resource for wheat breeding. However, due to its complex genome and outcrossing nature, the origin of cultivated rye remains elusive. The geneticist N.I. Vavilov proposed that cultivated rye had been domesticated from weedy rye, rather than directly from wild species like other crops. Unraveling the domestication history of rye will extend our understanding of crop evolution and upend our inherent understanding of agricultural weeds. To this end, in this study we generated the 8.5 Tb of whole-genome resequencing data from 116 worldwide accessions of wild, weedy, and cultivated rye, and demonstrated that cultivated rye was domesticated directly from weedy relatives with a similar but enhanced genomic selection by humans. We found that a repertoire of genes that experienced artificial selection is associated with important agronomic traits, including shattering, grain yield, and disease resistance. Furthermore, we identified a composite introgression in cultivated rye from the wild perennial Secale strictum and detected a 2-Mb introgressed fragment containing a candidate ammonium transporter gene with potential effect on the grain yield and plant growth of rye. Taken together, our findings unravel the domestication history of cultivated rye, suggest that interspecific introgression serves as one of the likely causes of obscure species taxonomy of the genus Secale, and provide an important resource for future rye and wheat breeding.
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Domesticación , Secale , Evolución Molecular , Variación Genética , Genoma de Planta/genética , Metagenómica , Fitomejoramiento , Secale/genética , Triticum/genéticaRESUMEN
Noncoding RNAs (ncRNAs) play pivotal roles in various biological processes in plants. However, the role of ncRNAs in tapping panel dryness (TPD) of rubber tree (Hevea brasiliensis Muell. Arg.) is largely unknown. Here, the whole transcriptome analyses of bark tissues from healthy and TPD trees were performed to identify differentially expressed long ncRNAs (DELs), microRNAs/miRNAs (DEMs), genes (DEGs) and their regulatory networks involved in TPD. A total of 263 DELs, 174 DEMs and 1574 DEGs were identified in the bark of TPD tree compared with that of healthy tree. Kyoto Encyclopedia of Genes and Genomes analysis revealed that most of the DEGs and targets of DELs and DEMs were mainly enriched in metabolic pathways, biosynthesis of secondary metabolites and plant hormone signal transduction. Additionally, the majority of DEGs and DELs related to rubber biosynthesis were downregulated in TPD trees. Furthermore, 98 DEGs and 44 DELs were targeted by 54 DEMs, 190 DEGs were identified as putative targets of 56 DELs, and 2 and 44 DELs were predicted as precursors and endogenous target mimics of 2 and 6 DEMs, respectively. Based on these, the DEL-DEM-DEG regulatory network involved in TPD was constructed, and 13 hub DELs, 3 hub DEMs and 2 hub DEGs were identified. The results provide novel insights into the regulatory roles of ncRNAs underlying TPD and lay a foundation for future functional characterization of long ncRNAs, miRNAs and genes involved in TPD in rubber tree.
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Hevea , MicroARNs , ARN Largo no Codificante , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Hevea/fisiología , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismoRESUMEN
The emergence of weedy rice (Oryza sativa f. spontanea) has been considered as a serious global agricultural problem in recent decades. To better understand its speciation, here we assembled the complete chloroplast genome of O. sativa f. spontanea with the length of 134,502 bp. The assembly contains a large single-copy (LSC, 80,549 bp), a small single-copy (SSC, 12,347 bp) and a pair of inverted repeats (IRa and IRb, 20,803 bp each). A total of 132 unique genes were annotated, including 82 protein-coding genes, 42 tRNA genes and eight rRNA genes. Phylogenetic analysis showed that O. sativa f. spontanea (indica type) appears closely related to cultivated indica rice rather than wild rice, supporting the hypothesis that weedy rice originated from cultivated rice.
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Some categories of compounds, including quinones, coumarins, flavins, and xanthene dyes, were found to produce strong chemiluminescence (CL) signals with luminol in sample solution under the irradiation of light emitting diodes (LED) with proper wavelengths. Based on this phenomenon, a compact photochemical reactor was constructed to develop a novel LED induced CL detector for high performance liquid chromatography (HPLC). The effects of related parameters including LED wavelength, luminol concentration, flow rate, pH, and eluents of HPLC were investigated in detail. Under the optimized conditions, the limits of detections (LODs) were in the range of 0.2-80 ng mL(-1). The applications and accuracy of the proposed method were validated by analyzing food samples such as milk powder, beer, candy and beverage with satisfactory results.
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Cromatografía Líquida de Alta Presión/instrumentación , Electrónica/instrumentación , Luminiscencia , Acetonitrilos/química , Animales , Análisis de Inyección de Flujo , Análisis de los Alimentos , Colorantes de Alimentos/análisis , Concentración de Iones de Hidrógeno , Himecromona/análisis , Límite de Detección , Luminol/química , Metanol/química , Leche/química , Reproducibilidad de los Resultados , Reología , Riboflavina/análisis , Soluciones , Espectrometría de FluorescenciaRESUMEN
On the basis of the coarse grained model, we investigated the adsorption of nonuniformly charged fullerene-like nanoparticles on planar polyelectrolyte brushes (PEBs) in aqueous solution by using Brownian dynamics simulation. It is found that the electroneutral nanoparticles can be adsorbed by the PEB, which is attributed to the asymmetrical electrostatic interactions of the PEB with the positively charged sites and negatively charged sites of the fullerene-like nanoparticles. The simulation results indicated that the adsorption amount exhibits non-monotonic behavior with the dipole moment of nanoparticles. First, the adsorption amount increases with the dipole moment and then reaches the maximum at the dipole moment of micro = 10.45. Finally, the adsorption falls at the dipole moment of micro = 14.39. The reason may be that, at the extremely large dipole moment of micro = 14.39, the fullerene-like nanoparticles aggregate together to form a big cluster in the bulk phase, which can be confirmed by the extremely high peak in the radial distribution function between nanoparticles. Accordingly, it is difficult for nanoparticles to enter into the PEB at the dipole moment of micro = 14.39. In addition, it is also found that the brush grafting density is an important factor affecting the brush thickness.
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A Brownian dynamics (BD) simulation is performed to investigate the effect of the bridging conformation of a polyelectrolyte (PE) with two charged heads (two-heads PE) on the radial distribution function (RDF) and diffusion behavior of macroions on the basis of the coarse grained model. For comparison, the system containing macroions and the PE with only one charged head (one-head PE) is also investigated. The simulation results indicate that, at low concentrations, the bridging effect of the two-heads PE chain leads to correlation of macroions. The reason is that at low concentration the gyration radius of the PE chain is less than the average distance between two macroions. When the two-heads PE chains are adsorbed on different macroions, the bridging effect of the PE chain dominates the RDF and diffusion behavior of the macroions. With the increase of the concentration of the system, when the gyration radius of the PE chain is greater than the average distance between two macroions, the bridging effect of the PE chain becomes trivial. By investigating the mechanism of the two-heads PE chain affecting the static and dynamic properties of the macroions, we can provide useful information for the synthesis of stabilizers and destabilizers of colloidal particles.