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1.
J Am Chem Soc ; 145(17): 9540-9547, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-36988585

RESUMO

Downsizing metal nanoparticles to single atoms (monoatomization of nanoparticles) has been actively pursued to maximize the metal utilization of noble-metal-based catalysts and regenerate the activity of agglomerated metal catalysts. However, precise control of monoatomization to optimize the catalytic performance remains a great challenge. Herein, we developed a laser ablation strategy to achieve the accurate regulation of Pt nanoparticles (PtNP) to Pt single atoms (Pt1) conversion on CeO2. Owing to the excellent tunability of input laser energy, the proportion of Pt1 versus total Pt on CeO2 can be precisely controlled from 0 to 100% by setting different laser powers and irradiation times. The obtained Pt1PtNP/CeO2 catalyst with approximately 19% Pt1 and 81% PtNP exhibited much-enhanced CO oxidation activity than Pt1/CeO2, PtNP/CeO2, and other Pt1PtNP/CeO2 catalysts. Density functional theory (DFT) calculations showed that PtNP was the major active center for CO oxidation, while Pt1 changed the chemical potential of lattice oxygen on CeO2, which decreased the energy barrier required for CO oxidation by lattice oxygen and resulted in an overall performance improvement. This work provides a reliable strategy to redisperse metal nanoparticles for designing catalysts with various single-atom/nanoparticle ratios from a top-down path and valuable insights into understanding the synergistic effect of nano-single-atom catalysts.

2.
J Am Chem Soc ; 144(40): 18155-18174, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36175359

RESUMO

Single-atom-site catalysts (SASCs) featuring maximized atom utilization and isolated active sites have progressed tremendously in recent years as a highly prosperous branch of catalysis research. Varieties of SASCs have been developed that show excellent performance in many catalytic applications. The major goal of SASC research is to establish feasible synthetic strategies for the preparation of high-performance catalysts, to achieve an in-depth understanding of the active-site structures and catalytic mechanisms, and to develop practical catalysts with industrial value. This Perspective describes the up-to-date development of SASCs and related catalysts, such as dual-atom-site catalysts (DASCs) and nano-single-atom-site catalysts (NSASCs), analyzes the current challenges encountered by these catalysts for industrial applications, and proposes their possible future development path.


Assuntos
Metais , Catálise , Domínio Catalítico , Metais/química
3.
J Am Chem Soc ; 144(50): 23223-23229, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36490370

RESUMO

Exploring the transformation/interconversion pathways of catalytic active metal species (single atoms, clusters, nanoparticles) on a support is crucial for the fabrication of high-efficiency catalysts, the investigation of how catalysts are deactivated, and the regeneration of spent catalysts. Sintering and redispersion represent the two main transformation modes for metal active components in heterogeneous catalysts. Herein, we established a novel solid-state atomic replacement transformation for metal catalysts, through which metal atoms exchanged between single atoms and nanoalloys to form a new set of nanoalloys and single atoms. Specifically, we found that the Ni of the PtNi nanoalloy and the Zn of the ZIF-8-derived Zn1 on nitrogen-doped carbon (Zn1-CN) experienced metal interchange to produce PtZn nanocrystals and Ni single atoms (Ni1-CN) at high temperature. The elemental migration and chemical bond evolution during the atomic replacement displayed a Ni and Zn mutual migration feature. Density functional theory calculations revealed that the atomic replacement was realized by endothermically stretching Zn from the CN support into the nanoalloy and exothermically trapping Ni with defects on the CN support. Owing to the synergistic effect of the PtZn nanocrystal and Ni1-CN, the obtained (PtZn)n/Ni1-CN multisite catalyst showed a lower energy barrier of CO2 protonation and CO desorption than that of the reference catalysts in the CO2 reduction reaction (CO2RR), resulting in a much enhanced CO2RR catalytic performance. This unique atomic replacement transformation was also applicable to other metal alloys such as PtPd.

4.
Phys Chem Chem Phys ; 24(29): 17417-17438, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35837883

RESUMO

Single-atom site catalysts (SASCs) are characterized with atomically dispersed isolated metal active sites and theoretically 100% metal dispersion. Supports with high specific surface area are crucial for the fabrication of highly efficient SASCs with maximized metal dispersion. The high specific surface area supports provide anchoring sites that stabilize the monodispersed active metal atoms. The metal atoms and their coordination environment jointly constitute the metal single-atom sites, which represent the active sites of SASCs. The selection of suitable supports is one of the key factors that determine the structures and properties of SASCs. In this perspective, we introduce various types of SASCs based on high specific surface area supports from 0-dimension to 3-dimension with different sorts of active sites and coordination environments. In particular, we select the most representative high specific surface supports in each dimension and introduce the corresponding SASCs and how different supports cooperate with single metal atoms to achieve efficient catalysis. We summarize the current developments, and also present future opportunities and challenges of SASCs, aiming to provide an instructive perspective of the SASCs based on high specific surface area supports.

5.
Bioorg Chem ; 128: 106041, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35907378

RESUMO

Metal-organic frameworks (MOFs), as advanced enzyme immobilization platforms for improving biocatalysis and protein biophysics, are rarely investigated as solid supports in the enzymatic synthesis of carbohydrate and derivatives, which can be attributed to the complex biochemical reaction mechanisms and the adverse interactions between the high polarity of substrate sugars, glycoenzymes and traditional MOFs. Here, we introduced divalent metal ion Mn2+ into MOF to prepare bimetallic MOF microreactor that encapsulated N-acetylhexosamine 1-Kinase (NahK), a critical anomeric kinase involved in the enzymatic synthesis of sugar nucleotide. The introduced Mn ions not only adjusted the microstructure of MOFs, but also participated in the enzymatic catalysis as cofactor, thus facilitated the N-acetylglucosamine/ N-acetylgalactosamine (GlcNAc/GalNAc) phosphorylation. The Mn-doped NahK@Zn-metal organic material (MOM), integrated with high catalytic activity, high stability, and high recoverability, solved the issues of immobilization related to glucokinase activity. These features significantly improved the operability and reduced the processing cost, assuring industrial application prospects for sugar nucleotides synthesis.


Assuntos
Acetilgalactosamina , Acetilglucosamina , Acetilgalactosamina/metabolismo , Acetilglucosamina/metabolismo , Catálise , Fosforilação , Fosfotransferases/metabolismo , Açúcares
6.
BMC Cancer ; 14: 798, 2014 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-25366878

RESUMO

BACKGROUND: Automated breast volume scanner (ABVS) and US elastography (UE) have been useful for the differentiation of benign and malignant lesions. However, combining these two methods applied in diagnosis of breast lesions has not yet been reported. The aim of this study is to analyze the inter-examiner reliability of ABVS and UE, and compare diagnostic performance among ABVS, UE, and the combination of these two methods. METHODS: Forty-one patients (forty-six lesions) underwent both ABVS and UE examinations. ABVS images were acquired by medial and lateral scans for each breast and classified a BI-RADS category based on the distribution, size, shape, echogenicity and microcalcification of the lesions. UE images were assigned an elasticity score according to the distribution of strain induced by light compression. Kappa statistics was used to examine the reproducibility between examiners with ABVS and UE, and the concordance between pathology and ABVS, UE, and the combination of these two methods. χ2 test was used to compare diagnostic performance among these three methods.Two examiners blinded to the patients' history evaluated the results of breast imaging independently. RESULTS: Inter-examiner reliability with ABVS (κ = 0.62, 95% confidence interval (CI): 0.44-0.80) and UE (κ = 0.65, 95% CI: 0.48-0.82) was substantial. With respect to the pathology results, the inter-rater coefficient of concordance was κ = 0.81 (95% CI: 0.64-0.98) for ABVS, κ = 0.77 (95% CI: 0.58-0.96) for UE, and κ = 0.90 (95% CI: 0.77-1.00) for combination of ABVS and UE. Examiner variability was reduced from UE to ABVS, and to the combination of ABVS with UE.The diagnostic accuracy, sensitivity, and specificity for the combination of ABVS and UE were 95.7% (95%CI: 84.0-99.2), 100% (95% CI: 85.9-100), and 87.5% (95% CI: 60.4-97.8), respectively. When comparing, the diagnostic performance of ABVS combined with UE was better than, or at least equal to, that of ABVS (accuracy 91.3% (95% CI: 78.3-97.2), sensitivity 100% (95% CI: 85.0-1.00), specificity 77.8% (95% CI: 51.9-92.6)) or UE (accuracy 89.1% (95% CI: 75.6-95.9), sensitivity 96.4% (95% CI: 79.8-99.8), specificity 77.8% (95% CI: 51.9-92.6)) alone, though the improvement was no statistically significance. CONCLUSIONS: Both ABVS and UE demonstrated substantial inter-examiner reliability. With high diagnostic performance for differentiation of benign and malignant lesions in the breast, the combination of ABVS and UE are useful to improve the diagnostic accuracy and specificity.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Mama/patologia , Técnicas de Imagem por Elasticidade , Ultrassonografia Mamária , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Tamanho do Órgão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
7.
J Ultrasound Med ; 32(3): 429-37, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23443183

RESUMO

OBJECTIVES: The purpose of this study was to show potential applications of 2-dimensional (2D) and 3-dimensional (3D) contrast-enhanced sonography for assessment of the vascularity of benign and malignant renal tumors. METHODS: Sixty-eight patients with renal tumors were examined with both 2D and reconstructed 3D contrast-enhanced sonography. The contrast enhancement characteristics of benign and malignant renal tumors were compared on both 2D and 3D contrast-enhanced sonograms. The diagnoses of the lesions were made by surgical pathologic examination in 50 patients and by contrast-enhanced computed tomography in 18 patients. RESULTS: Both 2D and 3D contrast-enhanced sonography showed hypoenhancement with a few small peritumoral feeding blood vessels and regular intratumoral branches in 18 benign tumors, whereas hyperenhancement with multiple irregular peritumoral feeding vessels and tortuous intratumoral branches was shown in 50 malignant tumors. Compared to 2D contrast-enhanced sonography, 3D contrast-enhanced sonography displayed more intratumoral microvessels and spatial distributions, especially for the vessel network, and tortuous branches in the malignant tumors. Compared to 2D contrast-enhanced sonography, 3D contrast-enhanced sonography was better for detecting and displaying renal tumor vascularity, with a statistically significant difference (P < .05). CONCLUSIONS: Reconstructed 3D contrast-enhanced sonography is a useful complementary tool in addition to 2D contrast-enhanced sonography for assessing the characteristics and distribution of blood vascularity in renal tumors.


Assuntos
Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Neoplasias Renais/diagnóstico por imagem , Neovascularização Patológica/diagnóstico por imagem , Fosfolipídeos , Hexafluoreto de Enxofre , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Aumento da Imagem/métodos , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/complicações , Pessoa de Meia-Idade , Neovascularização Patológica/complicações , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
8.
Cancer Biol Ther ; 24(1): 2249173, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37700507

RESUMO

Aberrant expression of adipogenic regulatory factors (ADIRF) in tumor cells is critical for tumor growth and metastasis. N6-methyladenosine (m6A) modifications have an important role in a variety of biological activities. Our study aimed to investigate the role of ADIRF in adenocarcinoma and to elucidate the regulatory role of m6A signaling on ADIRF. Differential expression of genes in tumor and normal tissues was analyzed using the LUAD dataset (GSE1987). The Kaplan-Meier method and receiver operating characteristic (ROC) curve analysis were performed to evaluate the prognostic and diagnostic value of ADIRF in LUAD. Loss-of-function or gain-of-function experiments were performed to study the effect of ADIRF on LUAD growth in vitro. The molecular mechanism of action of ADIRF in LUAD was confirmed using a dual-luciferase reporter system and MeRIP-qPCR. We identified a loss of ADIRF expression in LUAD tissues and cells. Furthermore, the restoration of ADIRF levels attenuated LUAD cell growth and metastasis in vitro. Mechanistically, an m6A "eraser," α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), eliminated the ADIRF m6A modification motif and further blocked the binding of the YTH domain-containing 2 (YTHDC2)-binding protein to ADIRF. At the molecular level, ALKBH5 enrichment increased ADIRF mRNA levels and prevented the attenuation of ADIRF mRNA by YTHDC2. The effects of ALKBH5 overexpression could also extend to the inhibition of LUAD cell proliferation and metastasis. This study linked ADIRF with the m6A modifying regulators ALKBH5 and YTHDC2, providing a promising molecular intervention for LUAD and deepening the understanding of LUAD mechanisms.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Prognóstico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Adenosina , Biomarcadores
9.
Talanta ; 254: 124120, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36463799

RESUMO

CRISPR is reshaping biosensing technology due to its programmability, sensitivity, and specificity. Most current CRISPR-based biosensors are developed based on Cas12 and Cas13, while the biosensing potentials of the newly discovered Cas14 have not been fully elucidated yet. Herein, a fluorometric biosensor named HARRY (highly sensitive aptamer-regulated Cas14 R-loop for bioanalysis) was developed. The diblock ssDNA is designed to contain the activator sequence of Cas14 and the aptamer sequence of specific targets. In the absence of targets, the ssDNA activates Cas14a, then the Cas14a trans-cleavages the fluorescent reporter, causing fluorescence enhancement. In the presence of the targets, ssDNA-target assembly is formed via aptamer interaction, resulting in the inhibition of Cas14a activation. HARRY can detect ATP, Cd2+, histamine, aflatoxin B1, and thrombin with detection limits at the low-nanomolar level, which shows improvement compared with Cas12a-based aptasensors in sensitivity and versatility. We reasoned that the improvement is derived from the ssDNA specificity of Cas14a and found that the detection limit of HARRY is correlated to the binding affinities of aptamers. This study unlocks the potential of Cas14a in versatile aptasensing, which may inspire the development of CRISPR-based biosensors from the Cas14a branch.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , Oligonucleotídeos , DNA de Cadeia Simples/genética , Técnicas Biossensoriais/métodos , Aflatoxina B1/análise
10.
Biotechnol Lett ; 34(12): 2275-82, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22941369

RESUMO

Sampling of intracellular metabolites in Mortierella alpina was investigated as part of a metabolomics study. After comparison of four sampling protocols, rapid filtration of the culture using a laboratory-made nylon filter and absorbent gauze under normal pressure followed by quenching in liquid N(2) and grinding (the improved protocol) was the most effective. Rapid filtration under normal pressure decreased intracellular metabolites leakage and subsequent grinding of cells contributed to intracellular metabolites extraction. The above quenching method together with 75 % (v/v) ethanol, buffered with 60 mM HEPES, at 80 °C for 3 min is therefore suitable for sampling intracellular metabolites in M. alpina.


Assuntos
Metaboloma , Metabolômica/métodos , Mortierella/química , Mortierella/metabolismo , Micologia/métodos
11.
Front Oncol ; 12: 1039737, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387252

RESUMO

Background: Hitherto, no study has evaluated postoperative pain in patients with non-small cell lung cancer (NSCLC) treated with video-assisted mini-thoracotomy (VAMT). In this study, we aimed to assess postoperative pain related to the width of the metal rib spreader in patients who underwent lobectomy using VAMT. Methods: We retrospectively analysed the data of 94 consecutive patients with NSCLC who underwent lobectomy using VAMT at our institution between March 2019 and May 2022. We divided the patients into groups according to the width ratio of the rib spreader to that of a single intercostal space. Patients with width ratios ≤ 2.5 times were assigned to group A, and those with width ratios > 2.5 times were assigned to group B. Pre-, intra-, and postoperative data were collected and reviewed. Results: We successfully performed VAMT in 94 patients with NSCLC. Forty-five patients were in group A, and 49 were in group B. There were no intraoperative mortalities, although one patient, due to respiratory failure, experienced 30-day mortality. There were no significant differences between the two groups in terms of the blood loss volume, operative time, drainage time, postoperative complications, length of hospital stay, or number of lymph node stations explored and retrieved. The drainage volumes (Day 1-Day 3) were higher in group B than in group A (P < 0.05). The postoperative visual analogue scale (VAS) pain scores were significantly lower in Group A than in Group B at 12, 24, and 48 h (P < 0.05), although there was no significant difference in the VAS scores between the two groups at 72 h and 1 week postoperatively (P > 0.05). Conclusion: The smaller the width of the metal rib spreader used in surgery, the less pain experienced by the patient and the faster the recovery. Multicentre, randomised, controlled trials should be conducted in the future.

12.
Colloids Surf B Biointerfaces ; 216: 112555, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35598509

RESUMO

Heparin, the most widely used anticoagulant drug in the world today, suffers from the risk of overdose and a short serum half-life, limiting its clinical applications. Concerning the controlled, sustained, and targeted release of heparin, a delivery system was fabricated in this research using the layered composites of Fe3O4 magnetic particles and pH-sensitive metal-organic framework, Fe3O4@ZIF-8. The composite demonstrated a high loading capacity for the heparin, 66.8 mg/g. The composite had a saturation magnetization of 1.5 emu/g and thus owned a magnetic targeting function, i.e. drug can be centered at a certain point using an external magnetic field. The anticoagulant activity was assessed by monitoring their activated partial thromboplastin time. The results showed that the pH-responsive and sustained release of the heparin reduced the systemic adverse effects associated with high concentrations. Moreover, control over the dose exhibited excellent anticoagulant features with fewer side effects.


Assuntos
Estruturas Metalorgânicas , Anticoagulantes/farmacologia , Preparações de Ação Retardada/farmacologia , Heparina , Concentração de Íons de Hidrogênio , Fenômenos Magnéticos
13.
Nat Chem ; 12(8): 764-772, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32541950

RESUMO

Single-atom catalysts not only maximize metal atom efficiency, they also display properties that are considerably different to their more conventional nanoparticle equivalents, making them a promising family of materials to investigate. Herein we developed a general host-guest strategy to fabricate various metal single-atom catalysts on nitrogen-doped carbon (M1/CN, M = Pt, Ir, Pd, Ru, Mo, Ga, Cu, Ni, Mn). The iridium variant Ir1/CN electrocatalyses the formic acid oxidation reaction with a mass activity of 12.9 [Formula: see text] whereas an Ir/C nanoparticle catalyst is almost inert (~4.8 × 10-3 [Formula: see text]). The activity of Ir1/CN is also 16 and 19 times greater than those of Pd/C and Pt/C, respectively. Furthermore, Ir1/CN displays high tolerance to CO poisoning. First-principle density functional theory reveals that the properties of Ir1/CN stem from the spatial isolation of iridium sites and from the modified electronic structure of iridium with respect to a conventional nanoparticle catalyst.

14.
Adv Mater ; 30(25): e1800588, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29726038

RESUMO

Heteroatom-doped Fe-NC catalyst has emerged as one of the most promising candidates to replace noble metal-based catalysts for highly efficient oxygen reduction reaction (ORR). However, delicate controls over their structure parameters to optimize the catalytic efficiency and molecular-level understandings of the catalytic mechanism are still challenging. Herein, a novel pyrrole-thiophene copolymer pyrolysis strategy to synthesize Fe-isolated single atoms on sulfur and nitrogen-codoped carbon (Fe-ISA/SNC) with controllable S, N doping is rationally designed. The catalytic efficiency of Fe-ISA/SNC shows a volcano-type curve with the increase of sulfur doping. The optimized Fe-ISA/SNC exhibits a half-wave potential of 0.896 V (vs reversible hydrogen electrode (RHE)), which is more positive than those of Fe-isolated single atoms on nitrogen codoped carbon (Fe-ISA/NC, 0.839 V), commercial Pt/C (0.841 V), and most reported nonprecious metal catalysts. Fe-ISA/SNC is methanol tolerable and shows negligible activity decay in alkaline condition during 15 000 voltage cycles. X-ray absorption fine structure analysis and density functional theory calculations reveal that the incorporated sulfur engineers the charges on N atoms surrounding the Fe reactive center. The enriched charge facilitates the rate-limiting reductive release of OH* and therefore improved the overall ORR efficiency.

15.
Ultrasound Med Biol ; 42(12): 2926-2937, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27597128

RESUMO

The purpose of this study was to evaluate whether ultrasound-targeted microbubble destruction transfer of interfering RNA against connective tissue growth factor (CTGF) in the kidney would ameliorate renal fibrosis in vivo. A short hairpin RNA (shRNA) targeting CTGF was cloned into a tool plasmid and loaded onto the surface of a cationic microbubble product. A unilateral ureteral obstruction (UUO) model in mice was used to evaluate the effect of CTGF knockdown. Mice were administered the plasmid-carrying microbubble intravenously, and ultrasound was applied locally to the obstructed kidney. Mice undergoing a sham UUO surgery and untreated UUO mice were used as disease controls, and mice administered plasmid alone, plasmid with ultrasound treatment and microbubbles and plasmid without ultrasound were used as treatment controls. Mice were treated once and then evaluated at day 14. CTGF in the kidney was measured by quantitative reverse transcription polymerase chain reaction and Western blot. Expression of CTGF, transforming growth factor ß1, α smooth muscle actin and type I collagen in the obstructed kidney was evaluated by immunohistochemistry. The cohort treated with plasmid-carrying microbubbles and ultrasound exhibited reduced mRNA and protein expression of CTGF (p < 0.01). Furthermore, CTGF gene silencing decreased the interstitial deposition of transforming growth factor ß1, α smooth muscle actin and type I collagen as assessed in immunohistochemistry, as well as reduced renal fibrosis in pathologic alterations (p < 0.01). No significant changes in target mRNA, protein expression or disease pathology were observed in the control cohorts. A single treatment of ultrasound-targeted microbubble destruction is able to deliver sufficient shRNA to inhibit the expression of CTGF and provide a meaningful reduction in disease severity. This technique may be a potential therapy for treatment of renal fibrosis.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/metabolismo , Nefropatias/terapia , Microbolhas , RNA Interferente Pequeno/metabolismo , Terapia por Ultrassom/métodos , Animais , Western Blotting , Fator de Crescimento do Tecido Conjuntivo/genética , Modelos Animais de Doenças , Feminino , Fibrose/terapia , Nefropatias/genética , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , RNA Interferente Pequeno/genética
16.
Ultrasound Med Biol ; 40(6): 1250-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24613557

RESUMO

Previous studies have reported that microbubbles bearing targeting ligands to molecular markers of angiogenesis can be successfully detected by ultrasound imaging in various animal models of solid cancer. In the present study, we sought to investigate the activity of microbubbles targeted to vascular endothelial growth factor receptor 2 (VEGFR2) in an orthotopic model of renal cell carcinoma (RCC). Microbubbles conjugated to an anti-VEGFR2 antibody (MBV) were compared with microbubbles conjugated to an isotype control antibody (MBC) or naked microbubbles (MBN). An orthotopic mouse model of human RCC was established by surgically implanting an established tumor within the renal capsule in mice. Tumor growth and blood flow were verified by B-mode and color Doppler ultrasound imaging. VEGFR2 expression within the tumor and renal parenchyma was detected by immunohistochemistry. The duration of contrast enhancement of MBV was much longer than those of MBN and MBC when assessed over 10 min. The baseline-subtracted contrast intensity within the tumor was higher for MBV than for MBC and MBN (p < 0.01). Additionally, the contrast intensity for MBV was significantly higher in the tumor region than in normal parenchyma (p < 0.01). Microbubbles targeting VEGFR2 exhibit suitable properties for imaging angiogenesis in orthotopic models of renal cell carcinoma, with potential applications in life science research and clinical medicine.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Imagem Molecular/métodos , Neovascularização Patológica/diagnóstico por imagem , Animais , Meios de Contraste/farmacocinética , Modelos Animais de Doenças , Humanos , Interpretação de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Microbolhas , Ultrassonografia Doppler em Cores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
17.
Biotechnol Biofuels ; 6(1): 7, 2013 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-23351660

RESUMO

BACKGROUND: Acetoin is an important bio-based platform chemical. However, it is usually existed as a minor byproduct of 2,3-butanediol fermentation in bacteria. RESULTS: The present study reports introducing an exogenous NAD+ regeneration sysytem into a 2,3-butanediol producing strain Klebsiella pneumoniae to increse the accumulation of acetoin. Batch fermentation suggested that heterologous expression of the NADH oxidase in K. pneumoniae resulted in large decreases in the intracellular NADH concentration (1.4 fold) and NADH/NAD+ ratio (2.0 fold). Metabolic flux analysis revealed that fluxes to acetoin and acetic acid were enhanced, whereas, production of lactic acid and ethanol were decreased, with the accumualation of 2,3-butanediol nearly unaltered. By fed-batch culture of the recombinant, the highest reported acetoin production level (25.9 g/L) by Klebsiella species was obtained. CONCLUSIONS: The present study indicates that microbial production of acetoin could be improved by decreasing the intracellular NADH/NAD+ ratio in K. pneumoniae. It demonstrated that the cofactor engineering method, which is by manipulating the level of intracellular cofactors to redirect cellular metabolism, could be employed to achieve a high efficiency of producing the NAD+-dependent microbial metabolite.

18.
Radiol Oncol ; 46(3): 198-206, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23077458

RESUMO

BACKGROUND: To evaluate the usefulness of the routine sonographic evaluation of the pattern of fluctuate portal velocity tracings and the hepatic veins for the diagnosis of arterioportal fistula (APF) and cardiogenic trans-sinusoidal shunting (CTS). MATERIALS AND METHODS.: Color Doppler flow imaging and pulsed-wave Doppler (PW) examinations of the portal vein were performed in 282 subjects. The waveforms of the velocity tracings in the portal main trunk and its branches were determined to infer APF or CTS. Suspected cases of APFs or CTSs were always confirmed by echocardiography, contrast-enhanced ultrasound, computed tomography, or digital subtraction angiography findings. The portal maximum velocity (V(max)), minimum velocity(V(min)), V(max)/V(min), arterial peak systolic velocity and resistance index, and venous reverse and forward velocities were used to estimate their haemodynamics. RESULTS: The waveform of the velocity tracing for the draining portal vein of APF was typically arterial-like or diphase, as indicated by a systolic hepatofugal dwarf peak and a diastolic hepatopetal low flat shape. The flow in the affected portal vein was always hepatofugal in an intrahepatic patient, whereas a hepatopetal flow was observed in an extrahepatic APF patient. The waveform of the velocity tracing for the portal vein of CTS patients, especially its intrahepatic branches, showed a typical hump-like shape with or without a transitory hepatofugal tracing. The PW results displayed an increase in the retrograde phase of the hepatic venous flow with increased velocities in the two phases. CONCLUSIONS: Portal velocity tracings should be evaluated during routine detecting for APF or CTS, especially in patients with gastrointestinal upsets.

19.
Appl Biochem Biotechnol ; 168(6): 1516-27, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23054814

RESUMO

Defined medium for arachidonic acid (ARA) production by Mortierella alpina was optimized for its metabolomics study. For this purpose, a visualization method (VM) was applied for the first time. Experiments were designed according to the uniform design with four factors (concentrations of glucose, NaNO(3), KH(2)PO(4) and MgSO(4)·7H(2)O) for each at nine levels. Dry cell weight (DCW), ARA yield in DCW [percent (w/w)] and ARA content in total fatty acids [percent (w/w)] were considered as the three objectives. Optimization of single-objective function and multi-objective function of two objectives and three objectives was attempted. Optimal DCW, ARA yield and ARA content were predicted to occur in a medium that contained (grams per litre): glucose 35, NaNO(3) 1, KH(2)PO(4) 7.5 and MgSO(4)·7H(2)O 2.6. Upon verification, the average tested DCW (12.95 g/l), ARA yield (18.89 %) and ARA content (42.36 %) were fairly close to the predicted values (12.88 g/l, 9.68 % and 35.57 %, respectively). Moreover, DCW, ARA yield and ARA content from the optimum medium increased by 35.68, 47.23 and 30.90 % compared with control, respectively, indicating that VM had succeeded in exploiting the biomass growth and ARA production by M. alpina.


Assuntos
Ácido Araquidônico/metabolismo , Meios de Cultura/metabolismo , Técnicas de Cultura/métodos , Mortierella/crescimento & desenvolvimento , Biomassa , Meios de Cultura/química , Técnicas de Cultura/instrumentação , Fermentação , Glucose/metabolismo , Mortierella/metabolismo , Micélio/crescimento & desenvolvimento , Micélio/metabolismo
20.
Radiol Oncol ; 45(2): 82-90, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22933940

RESUMO

BACKGROUND: The aim of the study was to trace the peripheral artery velocity with ultrasound in pigs and provide inference on diagnosis of the type, location and severity of vascular diseases. MATERIALS AND METHODS: Limb tightening, adrenaline administration and arterial wall pinching were performed independently in six pigs, and then the evolution of the external iliac artery or femoral artery velocity tracing were monitored. RESULTS: With the increase of the extents of hindlimb tightening, peak systolic velocity (PSV) of ipsilateral external iliac artery turned from 36.33±1.77 cm/s to 59.72±2.67 cm/s, minimum post-principal wave velocity (MPV from 13.68±1.11 cm/s to -7.48±0.82 cm/s, peak diastolic velocity (PDV) from 19.31±0.86 cm/s to 8.98±0.45 cm/s, and, end diastolic velocity (EDV) from 13.2±0.45 cm/s to 0. With the increase of the dose of the epinephrine injection, PSV increased from 36.33±1.77 cm/s to 43.97±2.15 cm/s but then decreased to 35.43±3.01 cm/s, and MPV negatively increased to -23.53±0.82 cm/s after decreasing from 13.68±1.11 cm/s to 0. PDV and EDV gradually decreased to zero. With the increase of the stenosis severity in the abdominal aortic wall pinching, PSV was reduced and had a linearly negative correlation with the stenosis severity (R=0.983, R2=0.967). MPV gradually increased, and its direction reversed when the stenosis severity increased, then diminished when the blood flow was occluded by more than 2/3. CONCLUSIONS: The formation of peripheral artery velocity is the result of concurrent effects of cardiac ejection, vascular resistance, effective circulating blood volume and elastic recoil. Vascular resistance exerts pronounced effects on the diastolic waveform, and the occurrence of backward wave indicates that the downstream circulation resistance significantly increases.

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