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It is important to achieve the 3D reconstruction of UAV remote sensing images in deep learning-based multi-view stereo (MVS) vision. The lack of obvious texture features and detailed edges in UAV remote sensing images leads to inaccurate feature point matching or depth estimation. To address this problem, this study improves the TransMVSNet algorithm in the field of 3D reconstruction by optimizing its feature extraction network and costumed body depth prediction network. The improvement is mainly achieved by extracting features with the Asymptotic Pyramidal Network (AFPN) and assigning weights to different levels of features through the ASFF module to increase the importance of key levels and also using the UNet structured network combined with an attention mechanism to predict the depth information, which also extracts the key area information. It aims to improve the performance and accuracy of the TransMVSNet algorithm's 3D reconstruction of UAV remote sensing images. In this work, we have performed comparative experiments and quantitative evaluation with other algorithms on the DTU dataset as well as on a large UAV remote sensing image dataset. After a large number of experimental studies, it is shown that our improved TransMVSNet algorithm has better performance and robustness, providing a valuable reference for research and application in the field of 3D reconstruction of UAV remote sensing images.
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Premium wheat with a high end-use quality is generally lacking in China, especially high-quality hard and soft wheat. Pina-D1 and Pinb-D1 (puroindoline genes) influence wheat grain hardness (i.e., important wheat quality-related parameter) and are among the main targets in wheat breeding programs. However, the mechanism by which puroindoline genes control grain hardness remains unclear. In this study, three hard wheat puroindoline variants (MY26, GX3, and ZM1) were compared with a soft wheat variety (CM605) containing the wild-type puroindoline genotype. Specifically, proteomic methods were used to screen for differentially abundant proteins (DAPs). In total, 6253 proteins were identified and quantified via a high-throughput tandem mass tag quantitative proteomic analysis. Of the 208 DAPs, 115, 116, and 99 proteins were differentially expressed between MY26, GX3, and ZM1 (hard wheat varieties) and CM605, respectively. The cluster analysis of protein relative abundances divided the proteins into six clusters. Of these proteins, 67 and 41 proteins were, respectively, more and less abundant in CM605 than in MY26, GX3, and ZM1. Enrichment analyses detected six GO terms, five KEGG pathways, and five IPR terms that were shared by all three comparisons. Furthermore, 12 proteins associated with these terms or pathways were found to be differentially expressed in each comparison. These proteins, which included cysteine proteinase inhibitors, invertases, low-molecular-weight glutenin subunits, and alpha amylase inhibitors, may be involved in the regulation of grain hardness. The candidate genes identified in this study may be relevant for future analyses of the regulatory mechanism underlying grain hardness.
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It is difficult to find correct correspondences for infrared and visible image registration because of different imaging principles. Traditional registration methods based on the point feature require designing the complicated feature descriptor and eliminate mismatched points, which results in unsatisfactory precision and much calculation time. To tackle these problems, this paper presents an artful method based on constrained point features to align infrared and visible images. The proposed method principally contains three steps. First, constrained point features are extracted by employing an object detection algorithm, which avoids constructing the complex feature descriptor and introduces the senior semantic information to improve the registration accuracy. Then, the left value rule (LV-rule) is designed to match constrained points strictly without the deletion of mismatched and redundant points. Finally, the affine transformation matrix is calculated according to matched point pairs. Moreover, this paper presents an evaluation method to automatically estimate registration accuracy. The proposed method is tested on a public dataset. Among all tested infrared-visible image pairs, registration results demonstrate that the proposed framework outperforms five state-of-the-art registration algorithms in terms of accuracy, speed, and robustness.
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The effectiveness of depth information in saliency detection has been fully proved. However, it is still worth exploring how to utilize the depth information more efficiently. Erroneous depth information may cause detection failure, while non-salient objects may be closer to the camera which also leads to erroneously emphasis on non-salient regions. Moreover, most of the existing RGB-D saliency detection models have poor robustness when the salient object touches the image boundaries. To mitigate these problems, we propose a multi-stage saliency detection model with the bilateral absorbing Markov chain guided by depth information. The proposed model progressively extracts the saliency cues with three level (low-, mid-, and high-level) stages. First, we generate low-level saliency cues by explicitly combining color and depth information. Then, we design a bilateral absorbing Markov chain to calculate mid-level saliency maps. In mid-level, to suppress boundary touch problem, we present the background seed screening mechanism (BSSM) for improving the construction of the two-layer sparse graph and better selecting background-based absorbing nodes. Furthermore, the cross-modal multi-graph learning model (CMLM) is designed to fully explore the intrinsic complementary relationship between color and depth information. Finally, to obtain a more highlighted and homogeneous saliency map in high-level, we structure a depth-guided optimization module which combines cellular automata and suppression-enhancement function pair. This optimization module refines the saliency map in color space and depth space, respectively. Comprehensive experiments on three challenging benchmark datasets demonstrate the effectiveness of our proposed method both qualitatively and quantitatively.
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Heterosis utilization is the most effective way to improve rice yields. The cytoplasmic male-sterility (CMS) and photoperiod/thermosensitive genic male-sterility (PTGMS) systems have been widely used in rice production. However, the rate of resource utilization for the CMS system hybrid rice is low, and the hybrid seed production for the PTGMS system is affected by the environment. The technical limitations of these two breeding methods restrict the rapid development of hybrid rice. The advantages of the genic male-sterility (GMS) rice, such as stable sterility and free combination, can fill the gaps of the first two generations of hybrid rice technology. At present, the third-generation hybrid rice breeding technology is being used to realize the application of GMS materials in hybrid rice. This study aimed to use an artificial CMS gene as a pollen killer to create a smart sterile line for hybrid rice production. The clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) technology was used to successfully obtain a CYP703A3-deficient male-sterile mutant containing no genetically modified component in the genetic background of indica 9311. Through young ear callus transformation, this mutant was transformed with three sets of element-linked expression vectors, including pollen fertility restoration gene CYP703A3, pollen-lethality gene orfH79 and selection marker gene DsRed2. The maintainer 9311-3B with stable inheritance was obtained, which could realize the batch breeding of GMS materials. Further, the sterile line 9311-3A and restorer lines were used for hybridization, and a batch of superior combinations of hybrid rice was obtained.
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Oryza , Infertilidade das Plantas/genética , Oryza/genética , Melhoramento Vegetal , TecnologiaRESUMO
Satellite thermal infrared remote sensing has received worldwide attention in the exploration for earthquake precursors; however, this method faces great controversy. Obtaining repeatable phenomena related to earthquakes is helpful to reduce this controversy. In this paper, a total of 15 or 17 years of Moderate-resolution Imaging Spectroradiometer (MODIS)/Aqua and MODIS/Terra satellite remote sensing land surface temperature (LST) products is selected to analyze the temperature changes before and after the Mw 7.9 earthquake in Nepal on 25 April 2015 and to explore possible thermal information associated with this earthquake. Major findings are given as follows: (1) from the time course, the temperature slowly cooled before the earthquake, reached a minimum at the time of the earthquake, and returned to normal after the earthquake. Since these changes were initiated before the earthquake, they may even have been precursors to the Nepal earthquake. (2) From the space distribution, the cooling areas correspond to the seismogenic structure during the earthquake. These cooling areas are distributed along the Himalayas and are approximately 1300 km long. The widths of the East and West sides are slightly different, with an average temperature decrease of 5.6 °C. For these cooling areas, the Western section is approximately 90 km wide and 500 km long; the East side is approximately 190 km wide and 800 km long. The Western side of the cooling strips appeared before the earthquake. In short, these kinds of spatial and temporal changes are tectonically related to the earthquake and may have been caused by the tectonic activity associated with the Nepal earthquake. This process began before the earthquake and therefore might even be potentially premonitory information associated with the Nepal earthquake.
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OBJECTIVE: To evaluate the protective effect of S-isopentenyl-L-cysteine,a new cysteine derivative,on DNA damage induced by radiation by using acute radiation injury animal models. METHODS: Forty ICR mice were randomly divided into five groups:the control group,1.0Gy gamma irradiation group,1.0Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,7.2Gy gamma irradiation group,and 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,with 8 mice in each group.The comet assay and bone marrow polychromatic micronucleus experiments were performed to evaluate the double-strand DNA breaks in ICR mice exposed to 1.0 and 7.2Gy gamma-ray, respectively. RESULTS: The tail DNA percentage,tail length,tail moment,and olive tail moment of peripheral blood lymphocytes in 7.2Gy gamma irradiation group were significantly higher than that of the control group (P<0.01).And it was also observed that above experimental indexes of 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group was significantly less than that of 7.2Gy gamma irradiation group (P<0.05). In addition,the micronucleus rate of 1.0Gy gamma irradiation group and 7.2Gy gamma irradiation group were both significantly higher than in the control group (P<0.01). In addition,in mice given S-isopentenyl-L-cysteine before irradiation,the micronucleus rate of ICR mice exposed to 1.0 and 7.2Gy gamma-ray decreased from (39.5000 ± 3.3141) to (28.1667±4.1345) (P=0.033) and from (76.5000 ± 4.6242) to (22.8333 ± 3.6553)(P=0.000),respectively. The bone marrow polychromatic micronucleus experiment indicated that the value of polychromatic erythrocyte (PCE)/normochromatic erythrocyte(NCE) of ICR mice exposed to 1.0 and 7.2Gy gamma-ray was less than the control group(P<0.05). Meanwhile,after irradiating by certain dose,the value of PCE/NCE in mice given S-isopentenyl-L-cysteine before irradiation was significantly higher than the corresponding groups (P<0.05). CONCLUSION: S-isopentenyl-L-cysteine has a good protective effect against DNA damage induced by radiation.
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Dano ao DNA , Lesões por Radiação , Animais , Medula Óssea , Cisteína , Modelos Animais de Doenças , Raios gama , Camundongos , Camundongos Endogâmicos ICR , Protetores contra RadiaçãoRESUMO
Spleen tyrosine kinase (Syk) plays an indispensable role through preliminary extracellular antigen-induced crosslinking of Fc receptor (FcR) in the pathogenesis of autoimmune disorders, such as rheumatoid arthritis. In this study, we identify Vam3, a dimeric derivative of resveratrol isolated from grapes, as an ATP-competitive inhibitor of Syk with an IC50 of 62.95 nM in an in vitro kinase assay. Moreover, docking and molecular dynamics simulation approaches were performed to get more detailed information about the binding mode of Vam3 and Syk. The results show that 11b-OH on ring-C and 4b-OH on ring-D could form two hydrogen bonds with Glu449 and Phe382 of Syk, respectively. In addition, arene-cation interaction between ring-D of Vam3 and Lys402 of Syk was also observed. These results indicate that ring-C and D play an essential role in Vam3-Syk interaction. Our studies may be helpful in the structural optimization of Vam3, and also aid the design of novel Syk inhibitors in the future.
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Benzofuranos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Estilbenos/química , Estilbenos/farmacologia , Trifosfato de Adenosina/metabolismo , Benzofuranos/química , Cristalografia por Raios X , Dimerização , Humanos , Ligação de Hidrogênio , Concentração Inibidora 50 , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Ligação Proteica , Conformação Proteica , Inibidores de Proteínas Quinases/química , Resveratrol , Relação Estrutura-Atividade , Quinase Syk , Vitis/químicaRESUMO
The use of nanoparticles holds promise for medical applications, such as X-ray imaging, photothermal therapy and radiotherapy. However, the in vivo toxicity of inorganic nanoparticles raises some concern regarding undesirable side effects which prevent their further medical application. Ultrasmall sub-5.5 nm particles can pass through the barrier for renal clearance, minimizing their toxicity. In this letter we address some recent interesting work regarding in vivo toxicity and renal clearance, and discuss the possible strategy of utilizing ultrasmall nanomaterials. We propose that small hydrodynamic sized nanoclusters can achieve both nontoxic and therapeutic clinical features.
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Desenho de Fármacos , Barreira de Filtração Glomerular/química , Rim/química , Nanoconjugados/química , Nanoconjugados/ultraestrutura , Reabsorção Renal , Animais , Estabilidade de Medicamentos , Humanos , Tamanho da Partícula , Distribuição TecidualRESUMO
A new type of metabolizable and efficient radiosensitizers for cancer radiotherapy is presented by combining ultrasmall Au nanoclusters (NCs, <2 nm) with biocompatible coating ligands (glutathione, GSH). The new nanoconstruct (GSH-coated Au25 NCs) inherits attractive features of both the Au core (strong radiosensitizing effect) and GSH shell (good biocompatibility). It can preferentially accumulate in tumor via the improved EPR effect, which leads to strong enhancement for cancer radiotherapy. After the treatment, the small-sized GSH-Au25 NCs can be efficiently cleared by the kidney, minimizing any potential side effects due to the accumulation of Au25 NCs in the body.
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Ouro/química , Nanopartículas Metálicas/química , Neoplasias/radioterapia , Radiossensibilizantes/uso terapêutico , Animais , Materiais Biocompatíveis/química , Carbocianinas/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Raios gama , Glutationa/química , Glutationa/metabolismo , Meia-Vida , Células HeLa , Humanos , Masculino , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Nus , Tamanho da Partícula , Radiossensibilizantes/química , Radiossensibilizantes/farmacocinética , Transplante HeterólogoRESUMO
A traditional Chinese medicine (TCM) formula network including 362 TCM formulas was built by using complex network methodologies. The properties of this network were analyzed including network diameter, average distance, clustering coefficient, and average degree. Meanwhile, we built a TCM chemical space and a TCM metabolism room under the theory of chemical space. The properties of chemical space and metabolism room were calculated and analyzed. The properties of the medicine pairs in "eighteen antagonisms and nineteen mutual inhibitors," an ancient rule for TCM incompatibility, were studied based on the TCM formula network, chemical space, and metabolism room. The results showed that the properties of these incompatible medicine pairs are different from those of the other TCM based on the analysis of the TCM formula network, chemical space, and metabolism room. The lines of evidence derived from our work demonstrated that the ancient rule of TCM incompatibility, "eighteen antagonisms and nineteen mutual inhibitors," is probably scientifically based.
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Gold nanoparticles have received wide interest in disease diagnosis and therapy, but one of the important issues is their toxicological effects in vivo. Sex differences in the toxicity of gold nanoparticles are not clear. In this work, body weight, organ weight, hematology, and biochemistry were used to evaluate sex differences in immune response and liver and kidney damage. Pathology was used to observe the general toxicity of reproductive organs. The immune response was influenced significantly in female mice, with obvious changes in spleen and thymus index. Hematology results showed that male mice treated with 22.5 nm gold nanoparticles received more significant infection and inflammation than female mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold nanoparticles caused more significant liver damage in male mice than female mice, while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney damage in female mice than male mice. No significant toxicological response was found in the reproductive system for female or male mice. It was found that gold nanoparticles caused more serious liver toxicity and infection in male mice than female mice. These findings indicated that sex differences may be one of the important elements for in vivo toxicity of gold nanoparticles.
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Peso Corporal/efeitos dos fármacos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Tamanho do Órgão/efeitos dos fármacos , Polietilenoglicóis/toxicidade , Animais , Contagem de Células Sanguíneas , Feminino , Ouro/química , Histocitoquímica , Masculino , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Polietilenoglicóis/química , Fatores Sexuais , Espectrofotometria , Baço/imunologia , Baço/fisiologia , Testículo/patologia , Timo/imunologia , Timo/fisiologia , Útero/patologiaRESUMO
OBJECTIVE: This study aims to explain the mechanisms at the molecular level of a traditional Chinese medicine (TCM) for the treatment of sepsis. METHODS: We first identified 16 targets involved in the sepsis disease network; then we constructed a molecular ligand database and investigated the effects between the ligand database and the sepsis targets using computational biology methods. The results of the calculation were validated with in vitro biological testing against bovine thrombin. RESULTS AND CONCLUSION: We found that multiple active compounds contained in the TCM interact with multiple sepsis-related targets. We predicted several promising compounds for sepsis treatment, and the first 10 compounds were characterised. Among those tested, rosmarinic acid displayed the strongest biological activity in the in vitro activity test with a half-maximal inhibitory concentration (IC(50)) of 85µM. This study demonstrates a novel way of identifying naturally occurring chemical entities as new leads for sepsis treatment.
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Bases de Dados Factuais , Descoberta de Drogas/métodos , Medicamentos de Ervas Chinesas/farmacologia , Sepse/tratamento farmacológico , Animais , Bovinos , Biologia Computacional/métodos , Simulação por Computador , Medicamentos de Ervas Chinesas/química , Ligantes , Modelos Biológicos , Trombina/antagonistas & inibidoresRESUMO
Inducible Nitric Oxide Synthase (iNOS) has been involved in a variety of diseases, and thus it is interesting to discover and optimize new iNOS inhibitors. In previous studies, a series of benzimidazole-quinolinone derivatives with high inhibitory activity against human iNOS were discovered. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking and molecular dynamics (MD) simulation approaches were applied to investigate the functionalities of active molecular interaction between these active ligands and iNOS. A QSAR model with R(2) of 0.9356, Q(2) of 0.8373 and Pearson-R value of 0.9406 was constructed, which presents a good predictive ability in both internal and external validation. Furthermore, a combined analysis incorporating the obtained model and the MD results indicates: (1) compounds with the proper-size hydrophobic substituents at position 3 in ring-C (R(3) substituent), hydrophilic substituents near the X(6) of ring-D and hydrophilic or H-bond acceptor groups at position 2 in ring-B show enhanced biological activities; (2) Met368, Trp366, Gly365, Tyr367, Phe363, Pro344, Gln257, Val346, Asn364, Met349, Thr370, Glu371 and Tyr485 are key amino acids in the active pocket, and activities of iNOS inhibitors are consistent with their capability to alter the position of these important residues, especially Glu371 and Thr370. The results provide a set of useful guidelines for the rational design of novel iNOS inhibitors.
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Benzimidazóis/química , Desenho de Fármacos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Quinolonas/química , Benzimidazóis/metabolismo , Sítios de Ligação , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Óxido Nítrico Sintase Tipo II/química , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , Quinolonas/metabolismoRESUMO
PREMISE OF THE STUDY: The aim of this study was to assess the feasibility of developing chromosome-arm-specific microsatellite markers in wheat on a large scale based on chromosome survey sequences obtained with next-generation sequencing (NGS) technology. METHODS AND RESULTS: The Illumina Hi Seq2000 sequencing platform was used to sequence DNA of isolated wheat chromosome-arm 7DL. The data were assembled and microsatellite loci were identified computationally. In total, 16315 microsatellites were identified from 161061 assembled contigs. Thirty-three markers were randomly selected for validation across 20 diverse wheat cultivars. Two nulli-tetrasomic stocks were also screened to validate the specificity of the newly developed markers. CONCLUSIONS: This is the first study on identification of chromosome-arm-specific microsatellite markers using NGS technology. These new chromosome-arm-specific markers will facilitate saturation of the 7DL genetic map, and their availability will support genetic mapping and positional cloning in wheat.
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Cromossomos de Plantas/genética , Repetições de Microssatélites/genética , Análise de Sequência de DNA/métodos , Triticum/genética , Primers do DNA/metabolismo , Marcadores Genéticos , Dados de Sequência MolecularRESUMO
Gold nanoparticles have been conceived as a radiosensitizer in cancer radiation therapy, but one of the important questions for primary drug screening is what size of gold nanoparticles can optimally enhance radiation effects. Herein, we perform in vitro and in vivo radiosensitization studies of 4.8, 12.1, 27.3, and 46.6 nm PEG-coated gold nanoparticles. In vitro results show that all sizes of the PEG-coated gold nanoparticles can cause a significant decrease in cancer cell survival after gamma radiation. 12.1 and 27.3 nm PEG-coated gold nanoparticles have dispersive distributions in the cells and stronger sensitization effects than 4.8 and 46.6 nm particles by both cell apoptosis and necrosis. Further, in vivo results also show all sizes of the PEG-coated gold nanoparticles can significantly decrease tumor volume and weight after 5 Gy radiations, and 12.1 and 27.3 nm PEG-coated gold nanoparticles have greater sensitization effects than 4.8 and 46.6 nm particles, which can lead to almost complete disappearance of the tumor. In vivo biodistribution confirms that 12.1 and 27.3 nm PEG-coated gold nanoparticles are accumulated in the tumor with high concentrations. The pathology, immune response, and blood biochemistry indicate that the PEG-coated gold nanoparticles have not caused spleen and kidney damages, but give rise to liver damage and gold accumulation. It can be concluded that 12.1 and 27.3 nm PEG-coated gold nanoparticles show high radiosensitivity, and these results have an important indication for possible radiotherapy and drug delivery.
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Ouro/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias/radioterapia , Tamanho da Partícula , Polietilenoglicóis/química , Tolerância a Radiação , Animais , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/patologia , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Tamanho do Órgão/efeitos dos fármacos , Plasma , Tolerância a Radiação/efeitos dos fármacos , Distribuição Tecidual/efeitos dos fármacosRESUMO
OBJECTIVE: To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms. METHODS: C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously, then divided into 5 groups (14 per group), and treated with oxysophoridine (50, 100, or 150 mg/kg) or cisplatin (4 mg/kg) for 10 days. Inhibitory rate of tumor, body weight gain, and influence indices on internal organs (liver, spleen and thymus) were evaluated. The differentially expressed genes between the oxysophoridine-treated group, and the control group were analyzed using cDNA microarray and quantitative real-time PCR (qRT-PCR) experiments. RESULTS: Compared with the tumor weight of the control group (2.75±0.66 g), oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice (P <0.01), with 0.82±0.36 g, 0.57±0.22 g, and 1.22±0.67 g for the tumor weight in the low, moderate, and high dose treatment group, respectively. The moderate dose led to the highest inhibitory rate, 79.3%. Observation of body weight gain and influence on three organs showed that compared with cisplatin, oxysophoridine produced fewer side effects in vivo. cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis, with the Tnfrsf11b (osteoprotegerin) gene being the most significantly affected. CONCLUSION: Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma, and its anti-hepatoma effect was probably related to osteoprotegerin activation.
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Alcaloides/farmacologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Carga Tumoral/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacosRESUMO
Gold nanoparticles have shown great prospective in cancer diagnosis and therapy, but they can not be metabolized and prefer to accumulate in liver and spleen due to their large size. The gold nanoclusters with small size can penetrate kidney tissue and have promise to decrease in vivo toxicity by renal clearance. In this work, we explore the in vivo renal clearance, biodistribution, and toxicity responses of the BSA- and GSH-protected gold nanoclusters for 24 h and 28 days. The BSA-protected gold nanoclusters have low-efficient renal clearance and only 1% of gold can be cleared, but the GSH-protected gold nanoclusters have high-efficient renal clearance and 36% of gold can be cleared after 24 h. The biodistribution further reveals that 94% of gold can be metabolized for the GSH-protected nanoclusters, but only less than 5% of gold can be metabolized for the BSA-protected nanoclusters after 28 days. Both of the GSH- and BSA-protected gold nanoclusters cause acute infection, inflammation, and kidney function damage after 24 h, but these toxicity responses for the GSH-protected gold nanoclusters can be eliminated after 28 days. Immune system can also be affected by the two kinds of gold nanoclusters, but the immune response for the GSH-protected gold nanoclusters can also be recovered after 28 days. These findings show that the GSH-protected gold nanoclusters have small size and can be metabolized by renal clearance and thus the toxicity can be significantly decreased. The BSA-protected gold nanoclusters, however, can form large compounds and further accumulate in liver and spleen which can cause irreparable toxicity response. Therefore, the GSH-protected gold nanoclusters have great potential for in vivo imaging and therapy, and the BSA-protected gold nanoclusters can be used as the agent of liver cancer therapy.
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Ouro/química , Ouro/metabolismo , Rim/metabolismo , Nanopartículas Metálicas/química , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Hematologia , Nanopartículas Metálicas/efeitos adversos , Nanopartículas Metálicas/ultraestrutura , Camundongos , Microscopia Eletrônica de Transmissão , Distribuição AleatóriaRESUMO
BACKGROUND: Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice. METHODS: Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 µg/kg over 28 days. RESULTS: The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver. CONCLUSION: The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future.
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Ouro , Nanopartículas Metálicas , Tamanho da Partícula , Animais , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Peso Corporal/efeitos dos fármacos , Ouro/administração & dosagem , Ouro/toxicidade , Hematócrito , Injeções Intravenosas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Nanomedicina , Tamanho do Órgão/efeitos dos fármacos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/toxicidade , Baço/efeitos dos fármacos , Baço/metabolismo , Distribuição TecidualRESUMO
Gold nanoclusters have the tunable optical absorption property, and are promising for cancer cell imaging, photothermal therapy and radiotherapy. First-principle is a very powerful tool for design of novel materials. In the present work, structural properties, band gap engineering and tunable optical properties of Ag-doped gold clusters have been calculated using density functional theory. The electronic structure of a stable Au(20) cluster can be modulated by incorporating Ag, and the HOMO-LUMO gap of Au(20-) (n)Ag(n) clusters is modulated due to the incorporation of Ag electronic states in the HOMO and LUMO. Furthermore, the results of the imaginary part of the dielectric function indicate that the optical transition of gold clusters is concentration-dependent and the optical transition between HOMO and LUMO shifts to the low energy range as the Ag atom increases. These calculated results are helpful for the design of gold cluster-based biomaterials, and will be of interest in the fields of radiation medicine, biophysics and nanoscience.