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As abnormal acidic pH symbolizes dysfunctions of cells, it is highly desirable to develop pH-sensitive luminescent materials for diagnosing disease and imaging-guided therapy using high-energy radiation. Herein, we explored near-infrared-emitting Cr-doped zinc gallate ZnGa2O4 nanoparticles (NPs) in colloidal solutions with different pH levels under X-ray excitation. Ultrasmall NPs were synthesized via a facile hydrothermal method by controlling the addition of ammonium hydroxide precursor and reaction time, and structural characterization revealed Cr dopants on the surface of NPs. The synthesized NPs exhibited different photoluminescence and radioluminescence mechanisms, confirming the surface distribution of activators. It was observed that the colloidal NPs emit pH-dependent radioluminescence in a linear relationship, and the enhancement reached 4.6-fold when pH = 4 compared with the colloidal NPs in the neutral solution. This observation provides a strategy for developing new biomaterials by engineering activators on the nanoparticle surfaces for potential pH-sensitive imaging and imaging-guided therapy using high-energy radiation.
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Phosphofructokinase (PFK), the key enzyme of glycolysis, can catalyze the irreversible transphosphorylation of fructose-6-phosphate forming fructose-1, 6-biphosphate. In the present study, a PFK gene from the mud crab Scylla paramamosain, named SpPFK, was cloned and characterized. The full length of SpPFK contained a 5'untranslated region (UTR) of 249 bp, an open reading frame of 2,859 bp, and a 3'UTR of 1,248 bp. The mRNA of SpPFK was highly expressed in the gill, followed by the hemocytes and muscle. The expression of SpPFK was significantly up-regulated after mud crab dicistrovirus-1 (MCDV-1) infection. Knocking down SpPFK in vivo by RNA interference significantly reduced the expression of lactate dehydrogenase after MCDV-1 infection. Furthermore, silencing of SpPFK in vivo increased the survival rate of mud crabs and decreased the MCDV-1 copies in the gill and hepatopancreas after MCDV-1 infection. All these results suggested that SpPFK could play an important role in the process of MCDV-1 proliferation in mud crab.
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Braquiúros , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Braquiúros/genética , Braquiúros/metabolismo , Proliferação de Células , Fosfofrutoquinases/genética , Fosfofrutoquinases/metabolismo , FilogeniaRESUMO
Streptococcus iniae has become one the most serious aquatic pathogens causing invasive diseases in farmed marine and freshwater fish worldwide, and orally attenuated vaccine is still the best option in protecting these invasive diseases. In this study, the safety, stability, immunogenicity of the S. iniae attenuated strain YM011 were evaluated, and comprehensively analyzed its virulence weakening mechanism at whole genome level. The results shown that attenuated S. iniae strain YM011 completely lost its pathogenicity to tilapia and had good immunogenicity with relative percent survival being 93.25% at 15 days and 90.31% at 30 days via IP injection, respectively, and 76.81% at 15 days and 56.69% at 30 days via oral gavage, respectively. Back-passage safety assay indicated that YM011 did not cause diseases or death in tilapia after 100 generations of serial passaging. Comparative genome-wide sequencing shown that YM011 had a 0.4 M large inversion fragment compared with its parental strain virulent strain GX005, which encoded 372 genes including drug resistance genes pbp2A and tet, as well as known virulence factors including hemolysin transport system gene, recA, and mutator family transposase. The attenuated S. iniae strain YM011 is an ideal attenuated oral vaccine candidate with good immunogenicity, safety and stability. Abnormal expression of important drug resistance genes as well as known virulence factors due to inversion of a 0.4 M large fragment is the leading mechanism underlying its attenuated virulence.
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Vacinas Bacterianas/imunologia , Ciclídeos/imunologia , Doenças dos Peixes/imunologia , Estudo de Associação Genômica Ampla/veterinária , Infecções Estreptocócicas/veterinária , Animais , Doenças dos Peixes/microbiologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Streptococcus iniae , Vacinas Atenuadas/imunologia , Virulência , Fatores de Virulência/imunologiaRESUMO
An online monitoring technology of Pu-239 aerosol based on aerosol direct introduction device, membrane desolvation nebuliser and ICP-MS was established for workplaces of reprocessing plants. Briefly, 0.8 l min-1 Pu-239 aerosol from the workplace was introduced into the aerosol direct introduction device where the air was replaced by Argon, and then the aerosol was introduced into the ICP-MS for measurement. To determine the activity of Pu-239 aerosol, 1.10E-3 Bq ml-1 Pu-242 standard solution generated by a membrane desolvation nebuliser was used. The introduction efficiency of the nebuliser was determined by sampling the aerosol generated from the nebuliser with Lead Standard Solution by glass fiber filter, which was (26.82 ± 3.33) %. The mass bias between Pu-239 and Pu-242 for the ICP-MS measurement was determined by Pu-239 and Pu-242 standard solutions generated by the nebuliser, and mass discrimination correction factor for Pu-239/Pu-242 was 0.972 ± 0.010. The limit of detection (LOD) and limit of quantification (LOQ) of this system were calculated according to the ISO 20 899:2018, which were 2.24E-05 Bq m-3 and 7.45E-05 Bq m-3 with 1 min measurement. The main interference which was from U-238 was determined by U-238 standard solution generated by the nebuliser, and the interferences of U-238 to 239 was (8.50 ± 1.05) E-05. According to the counts of U-238 from several workplaces of reprocessing plant where this system was tested, 239 counts rate from the interferences of U-238 of those workplaces were at the same level of the system background counts, which meant that the LOD above was suitable for those places.
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Poluentes Radioativos do Ar/análise , Exposição Ocupacional/análise , Plutônio/análise , Monitoramento de Radiação/instrumentação , Urânio/análise , Aerossóis , Poluição do Ar em Ambientes Fechados/análise , Humanos , Limite de Detecção , Análise EspectralRESUMO
Anisotropic nanocrystal assembled supercrystals with open superlattices (SLs) manifest novel and unique properties, but poor understanding of the nucleation/growth mechanisms limits their design and fabrication for practical applications. Using highly anisotropic Pt3Ni octahedral nanocrystals, we have grown large single supercrystals with an open body-centered cubic (bcc) superlattice that has a low filling factor of 26.8%. Synchrotron-based X-ray structural reconstruction fully revealed the coherence of translational and orientational orderings and determined that the constituent octahedra arrange themselves with the vertex-to-vertex and face-to-face configurations along the SL[100] and SL[111] directions, respectively. The large face-to-face separation and flexible vertex-to-vertex elastic contact provided the rattle space and supporting axis for local rotations of Pt3Ni octahedra within the bcc superlattice. Development of orientational disordering along with robust preservation of translational ordering during the heating process of a supercrystal in the oleic acid wetting environment confirmed the dominance of rotational entropy of hard octahedra in the formation of the open bcc superlattice. Ultimate achievement of dynamic equilibrium between the vertex-oriented elastic repulsions and the face-oriented attractions of surface-coating ligands governs the structural and mechanical stability of the supercrystal. This discovery provides significant insights into the design and control of geometrical shapes for the fabrication of highly anisotropic nanocrystals into desired open superlattices with tailored optical and electronic properties.
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OBJECTIVE: To compare the clinical effect of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using a tubular retraction system with traditional transforaminal lumbar interbody fusion (TLIF) for the treatment of lumbar degenerative diseases. METHOD: From June 2009 to June 2013, a total of 96 patients in Department of Orthopaedics, Armed Police Jiangxi Corps Hospital, suffering from lumbar degenerative diseases were divided into 2 groups randomly. 42 patients underwent MIS-TLIF using a tubular retraction system. There were 23 males and 19 females with the age of 64.4 ± 4.9. The preoperative diagnosis included lumbar disc herniation with instability (17 cases), lumbar spinal stenosis (13 cases), lumbar degenerative spondylolisthesis (12 cases). 54 patients underwent traditional TLIF. There were 32 males and 22 females with the age of 66.5 ± 7.6. The preoperative diagnosis included lumbar disc herniation with instability (22 cases), lumbar spinal stenosis (17 cases), lumbar degenerative spondylolisthesis (15 cases). The general data, operating time, blood loss and volume of drainage after operation were compared between two groups. VAS, ODI evaluating standards were applied to evaluate the therapeutic effect. The intervertebral fusion were observed by X ray or CT scan. RESULTS: All patients underwent surgery safely without severe complication occurred. There was no significant difference in operation time between MIS-TLIF group (96±37) min and TLIF group (83 ± 25) min, P>0.05; the blood, volume of drainage after operation in MIS-TLIF group were significantly less than TLIF group (P<0.05). The follow-up time was( 26 ± 7) months in MIS-TLIF group and (27 ± 8) months in TLIF group. Compared with preoperative parameters, the scores of VAS and ODI were significantly decreased after surgery and at the final follow-up in both groups (P<0.05). Compared with TLIF group, VAS in MIS-TLIF group of post-operation and the final follow-up were improved, respectively (P<0.05), but there is no significant difference in ODI score. There occurred cage dislocation with no nerve symptom in MIS-TLIF group in 1 case and fat liquefaction in TLIF group in 1 case. At the follow-up after 6.5 months postoperatively, all the operated segments achieved fusion standard and no internal screw were loose or broken. CONCLUSION: MIS-TLIF technique could provide less operation trauma, blood lose and achieve the similar satisfied short-term effect as traditional TLIF.
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Degeneração do Disco Intervertebral , Procedimentos Cirúrgicos Minimamente Invasivos , Fusão Vertebral , Parafusos Ósseos , Drenagem , Feminino , Humanos , Deslocamento do Disco Intervertebral , Instabilidade Articular , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estenose Espinal , Espondilolistese , Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Self-organization of colloidal Pt nanocubes into two types of distinct ordered superlattices, simple-cubic and body-centered-tetragonal structures, has been achieved using a home-built setup. Detailed translational and orientational characteristics of these superstructures were determined using a transmission electron microscopy tomographic technique with 3D reconstruction analysis. The formation of these distinct superlattices is the result of a delicate choice of solvent (i.e., aliphatic hexane or aromatic toluene hydrocarbons), which serves as a dispersion medium to fine-tune the relative strengths of ligand-ligand and ligand-solvent interactions during the self-assembly process. This work provides important insights into the effects of ligand-solvent interactions on superlattice formation from nonspherical nanoparticles.
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Nanotubos/química , Platina/química , Coloides/química , Tamanho da Partícula , Solventes/química , Propriedades de SuperfícieRESUMO
Combining in situ high-pressure X-ray scattering with transmission electron microscopy, we investigated the pressure-induced structural switches between the rock salt and amorphous phases as well as the associated mechanisms of their crystallization and growth in 6 nm PbTe nanocrystal. It was observed that rock salt PbTe nanocrystal started to become amorphous above 10 GPa and then underwent a low-to-high density amorphous phase transformation at pressures over 15 GPa. The low-density amorphous phase exhibited a structural memory of the rock salt phase, as manifested by a backward transformation to the rock salt phase via single nucleation inside each nanoparticle upon the release of pressure. In contrast, the high-density amorphous phase remained stable and could be preserved at ambient conditions. In addition, electron beam-induced heating could drive a recrystallization of the rock salt phase on the recovered amorphous nanoparticles. These studies provide significant insights into structural mechanisms for pressure-induced switching between amorphous and crystalline phases as well as their associated growth processes.
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Replication of chloroplast in plant cells is an essential process that requires co-assembly of the tubulin-like plastid division proteins FtsZ1 and FtsZ2 at mid-chloroplast to form a ring structure called the Z-ring. The Z-ring is stabilized via its interaction with the transmembrane protein ARC6 on the inner envelope membrane of chloroplasts. Plants lacking ARC6 are defective in plastid division and contain only one or two enlarged chloroplasts per cell with abnormal localization of FtsZ: instead of a single Z-ring, many short FtsZ filaments are distributed throughout the chloroplast. ARC6 is thought to be the anchoring point for FtsZ assemblies. To investigate the role of ARC6 in FtsZ anchoring, the mobility of green fluorescent protein-tagged FtsZ assemblies was assessed by single particle tracking in mutant plants lacking the ARC6 protein. Mean square displacement analysis showed that the mobility of FtsZ assemblies is to a large extent characterized by anomalous diffusion behavior (indicative of intermittent binding) and restricted diffusion suggesting that besides ARC6-mediated anchoring, an additional FtsZ-anchoring mechanism is present in chloroplasts.
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Proteínas de Arabidopsis/metabolismo , Proteínas de Cloroplastos/metabolismo , Cloroplastos/fisiologia , Replicação do DNA , Arabidopsis , Genes Reporter , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/genética , Microscopia de Fluorescência , Ligação Proteica , Mapeamento de Interação de Proteínas , Coloração e Rotulagem/métodosRESUMO
Graphene nanosheets were effectively functionalized by in-situ deposition of hydroxyaptite through a facile chemical precipitation method. Prior to grafting of hydroxyapatite, chemically modified graphene nanosheets were obtained by the reduction of graphene oxide in presence of ethylenediamine. The resulting hydroxyapatite functionalized graphene nanosheets were characterized by attenuated total reflection IR spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, X-ray energy dispersive spectroscopy, Raman spectroscopy and thermogravimetric analysis. These characterization techniques revealed the successful grafting of hydroxyapatite over well exfoliated graphene nanosheets without destroying their structure.
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We demonstrate a direct fabrication of PbS nanocube supercrystals without size-selection pretreatment on the building blocks. Electron microscopic and synchrotron small angle X-ray scattering analyses confirm that nanocubes pack through a tilted face-centered-cubic (fcc) arrangement, that is, face-to-face along the <110>(super) direction, resulting in a real packing efficiency of as high as â¼83%. This new type of superstructure consisting of nanocubes as building blocks, reported here for the first time, is considered the most stable surfactant-capped nanocube superstructure determined by far.
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Fracture liaison service (FLS) is a management system for osteoporotic fractures, its difficulty lies in long-term management. Through this pilot single-center study, we found that FLS combined with an internet-based follow-up service (online home nursing care) can economically and conveniently monitor patients, reduce falls and refractures, and improve care and medication adherence. INTRODUCTION: Among potential e-health platforms, mobile internet encompasses the largest user group of mobile instant messaging software in Asia and offers strong interaction, low cost, and fast speed. The online home nursing care model prevents unnecessary hospital admissions and readmissions. This study aims to explore the effects of a fracture liaison service (FLS) model combined with online home nursing care on patients with fragility hip fracture. METHODS: Patients discharged after November 2020 received FLS care combined with online home nursing care. Patients discharged from May 2020 to November 2020 received only routine discharge guidance and were classified as the control group. The Parker Mobility Score (PMS), Medical Outcomes Study 36-item short-form health survey (MOS SF-36), general medication adherence scale (GMAS), complication rate, and fall/refracture rates were used to evaluate the efficacy of the FLS combined with online home nursing care during the 52-week follow-up period. RESULTS: Eighty-nine patients with complete follow-up information were included in the analysis at the 52-week follow-up. The FLS combined with online home nursing care was associated with improved osteoporosis patient care, including increased medication adherence (64.58% in the control group and 90.24% in the observation group), improved mental quality of life, reduced fall/refracture rate (12.5% and 4.88%, respectively), and reduced rates of bedsores and joint stiffness; however, there was no effect on functional recovery within 1 year. CONCLUSIONS: We recommend the combination of FLS with online home nursing care, considering the local environment, to economically and conveniently monitor patients, reduce falls and refractures, and improve care and medication adherence.
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Conservadores da Densidade Óssea , Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Humanos , Projetos Piloto , Qualidade de Vida , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Fraturas do Quadril/prevenção & controle , Assistência Domiciliar , Prevenção Secundária , Conservadores da Densidade Óssea/uso terapêuticoRESUMO
BACKGROUND: Anti-PD1/PD-L1 antibody plus human epidermal growth factor receptor 2 (HER2) antibody and chemotherapy have become the new first-line therapy for HER2 overexpression-positive advanced gastric cancers (GC), suggesting that HER2 and PD-L1 play a vital role in guiding systemic treatment for patients with GC. This study aimed to depict the genomic and immune landscapes of Chinese patients with GC and investigate their correlations with HER2 amplification and PD-L1 expression. PATIENTS AND METHODS: Next-generation targeted sequencing and PD-L1 immunohistochemistry were performed on tumor samples from 735 patients with pathologically diagnosed GC. The genomic and immune landscapes and their correlations with HER2 amplification and PD-L1 expression were analyzed. RESULTS: The most commonly mutated genes in Chinese GC were TP53 (64%), CDH1 (20%), ARID1A (18%), HMCN1 (15%), KMT2D (11%), and PIK3CA (11%). Seventy-six (10%) patients were HER2 amplification, and 291 (40%) had positive PD-L1 expression. Classifying the total population based on HER2 amplification and PD-L1 expression level, 735 patients were divided into four subgroups: HER2+/PD-L1+ (4.5%), HER2+/PD-L1- (5.9%), HER2-/PD-L1+ (35.1%), and HER2-/PD-L1- (54.5%). The HER2+/PD-L1- and HER2+/PD-L1+ subgroups exhibited dramatically higher rate of TP53 mutations, CCNE1 and VEGF amplifications. The HER2+/PD-L1- subgroup also had a markedly higher rate of MYC amplification and KRAS mutations. The HER2-/PD-L1+ subgroup had significantly higher rate of PIK3CA mutations. HER2+/PD-L1- subgroup had the highest TMB level and HER2-/PD-L1+ subgroup had the highest proportion of patients with microsatellite instability-high than other subgroups. Furthermore, we observed that different HER2 amplification levels had distinct impacts on the correlations between PD-L1 expression and therapeutic genomic alterations, but no impact on the prognosis. CONCLUSION: The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.
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Neoplasias Gástricas , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Genômica , Mutação , Prognóstico , Neoplasias Gástricas/patologiaRESUMO
Myostatin (mstn), also known as GDF8, is a growth and differentiation factor of the transforming growth factor-ß (TGF-ß) superfamily and plays a key inhibitory effect in the regulation of skeletal muscle development and growth in vertebrates. In the present study, to comprehend the role of the mstn2 gene of the yellowfin seabream Acanthopagrus latus (Almstn2b), the genomic sequence of Almstn2b is 2359 bp, which encodes 360 amino acids and is composed of three exons and two introns, was obtained. Two typical regions, a TGF-ß propeptide and TGF-ß domain, constitute Almstn2b. The topology indicated that Almstn2 was grouped together with other Perciformes, such as the gilthead seabream Sparus aurata. Moreover, Almstn2b was mainly expressed in the brain, fins, and spleen. Furthermore, five SNPs, one in the exons and four in the introns, were identified in the Almstn2b gene. The allele and genotype frequencies of SNP-Almstn2b +1885 A/G were significantly related to the total weight, interorbital distance, stem length, tail length, caudal length, caudal height, body length, and total length (p < 0.05). The allele and genotype frequencies of SNP-Almstn2b +1888 A/G were significantly related to the weight, interorbital distance, long head behind the eyes, body height, tail length, caudal length, and body length. Additionally, the relationship between the SNP-Almstn2b +1915 A/G locus and weight and long head behind the eyes was significant (p < 0.05). Furthermore, the other two SNPs were not significantly associated with any traits. Thus, the SNPs identified in this study could be utilized as candidate SNPs for breeding and marker-assisted selection in A. latus.
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Perciformes , Dourada , Animais , Dourada/genética , Sequência de Aminoácidos , Perciformes/genética , Perciformes/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Peptide-based hydrogels are attractive biological materials. Study of their self-assembly pathways from their monomer structures is important not only for undertaking the rational design of peptide-based materials, but also for understanding their biological functions and the mechanism of many human diseases relative to protein aggregation. In this work, we have monitored the conformation, morphological, and mechanical properties of a hydrogel-forming peptide during hydrogelation in different dimethylsulfoxide (DMSO)/H(2)O solutions. The peptide shows nanofiber morphologies in DMSO/H(2)O solution with a ratio lower than 4:1. Increased water percentage in the solution enhanced the hydrogelation rate and gel strength. One-dimensional and two-dimensional proton NMR and electron microscopy studies performed on the peptide in DMSO/H(2)O solution with different ratios indicate that the peptide monomer tends to adopt a more helical structure during the hydrogelation as the DMSO/H(2)O ratio is reduced. Interestingly, at the same DMSO/H(2)O ratio, adding Ca(2+) not only promotes peptide hydrogelation and gel strength, but also leads to special shear-thinning and recovery properties of the hydrogel. Without changing the peptide conformation, Ca(2+) binds to the charged Asp residues and induces the change of interfiber interactions that play an important role in hydrogel properties.
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Hidrogéis/química , Microscopia Eletrônica de Transmissão , Peptídeos/química , Fenômenos Físicos , Reologia , Sequência de Aminoácidos , Cálcio/química , Dimetil Sulfóxido/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Água/químicaRESUMO
Metal-organic polyhedra (MOPs) have been incorporated into silica nanopores for the first time. Three MOPs with identical geometries but different ligand functionality (namely tert-butyl, hydroxyl, and sulfonic groups) were employed. A typical mesoporous silica, SBA-15, with a two-dimensional hexagonal pore regularity was used as the host. In comparison with bulk MOPs, which prefer to aggregate, MOPs confined in silica nanopores can be well dispersed, making the active sites and pores in the MOPs accessible. These dispersed MOPs showed apparently superior H(2) adsorption capacity in comparison with aggregated bulk MOPs. Moreover, the thermal stability of the MOPs was enhanced upon their confinement in silica nanopores.
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We report a Kirkwood-Alder transition in a system of nonspherical Pt(3)Cu(2) nanoctahedra coated with oleic acid and oleylamine ligands. Using both transmission electron microscopy tomography with 3D reconstruction analysis and synchrotron-based in-situ grazing-incidence small-angle X-ray scattering (GISAXS) techniques, we specifically determined that these nanoctahedra can assemble into an open structure in which the nanoctahedra are arranged tip-to-tip to form a bcc superlattice with a low packing efficiency. Using in-situ and real-time GISAXS, we further observed a "nanoctahedron crystallization" as a soft Kirkwood-Alder transition, that is, the soft nanoactahedra crystallize at a critical concentration and possess continuous crystalline states during a period of solvent evaporation. Finally, we found a reversible change of the superlattice constant during the solvent annealing and evaporation/drying processes.
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Aminas/química , Cobre/química , Nanoestruturas/química , Ácido Oleico/química , Compostos de Platina/química , Cristalização , Nanoestruturas/ultraestrutura , Espalhamento a Baixo Ângulo , Solventes/química , Difração de Raios XRESUMO
Polyaniline (PANI) nanocomposites incorporating different loadings of graphene and various other carbon nanostructures including carbon nanotubes (CNTs) and carbon nanofibers (CNFs) have been synthesized using a surface-initiated polymerization (SIP) method. Transmission electron microscopy (TEM) results indicate that the graphene has been exfoliated into a few layers (typically one, two, and three layers) during polymerization and has been uniformly dispersed in the PANI matrix. The graphene layer dispersion degree is quantified by a free-path spacing measurement (FPSM) method based on the TEM microstructures. The SIP method also demonstrates its feasibility for coating PANI on one-dimensional (1D) CNFs and CNTs without introducing additional surface functional groups. The effects of graphene size, loading level, and surface functionality on the electrical conductivity and dielectric permittivity of their corresponding nanocomposites have been systematically studied. The temperature-dependent conductivity behavior revealed a quasi-3D variable range hopping (VRH) electron transport mechanism for all the nanocomposites. Giant magnetoresistance (GMR) at room temperature is observed in pure PANI, which can be enhanced by the incorporation of a high loading of graphene (5%) due to the π-π stacking-induced efficient electron transport at the PANI/graphene interface. More interestingly, negative permittivity is found in each composite which can be easily tuned by adjusting the filler loading, morphology, and surface functionality.