RESUMO
A targeted strategy for treating cancer is antibody-directed enzyme prodrug therapy, where the enzyme attached to the antibody causes conversion of an inactive small-molecule prodrug into an active drug. A limitation may be the diffusion of the active drug away from the antibody target site. A related strategy with radiotherapeutics entails enzymatically promoted conversion of a soluble to insoluble radiotherapeutic agent, thereby immobilizing the latter at the target site. Such a molecular brachytherapy has been scarcely investigated. In distinct research, the advent of molecular designs for aggregation-induced emission (AIE) suggests translational use in molecular brachytherapy. Here, several 2-(2-hydroxyphenyl)benzothiazole substrates that readily aggregate in aqueous solution (and afford AIE) were elaborated in this regard. In particular, (1) the 2-(2-hydroxyphenyl) unit was derivatized to bear a pegylated phosphodiester that imparts water solubility yet undergoes enzymatic cleavage, and (2) a p-phenol unit was attached to the benzo moiety to provide a reactive site for final-step iodination (here examined with natural abundance iodide). The pegylated phosphodiester-iodinated benzothiazole undergoes conversion from aqueous-soluble to aqueous-insoluble upon treatment with a phosphatase or phosphodiesterase. The aggregation is essential to molecular brachytherapy, whereas the induced emission of AIE is not essential but provides a convenient basis for research development. Altogether, 21 compounds were synthesized (18 new, 3 known via new routes). Taken together, blending biomedical strategies of enzyme prodrug therapy with materials chemistry concerning substances that undergo AIE may comprise a step forward on the long road toward molecular brachytherapy.
Assuntos
Braquiterapia , Pró-Fármacos , Benzotiazóis , PolietilenoglicóisRESUMO
Plasmonic polymers consisting of metallic nanoparticles (NPs) are able to squeeze light into the deep-subwavelength space and transfer along a highly confined nanoscale path in long range. DNA nanotechnology, particularly benefiting from the molecular programmability of DNA origami, has provided otherwise nearly impossible platforms for constructing plasmonic nanoparticle polymers with designer configurations and nanoscale gaps. Here, we design and assemble a DNA origami hashtag tile that is able to polymerize into one-dimensional chains with high rigidity. The DNA origami hashtag chains are used as frames to enable robust, versatile, and precise arrangement of metallic NPs into micrometer-long chiral and magnetic plasmonic polymers, which are capable of efficiently transporting plasmonic angular momentum and magnetic surface plasmonic polaritons at the deep-subwavelength scale. Our work provides a molecular platform for the fabrication of long, straight, and structurally complex nanoparticle polymers with emerging plasmonic properties that are appealing to a variety of fields.
Assuntos
Ouro , Nanopartículas Metálicas , DNA , Nanotecnologia , PolímerosRESUMO
Amphiphilic DNA block copolymers have been utilized in preparing self-assembled amphiphilic structures in aqueous solution. These block copolymers usually contain specifically designed hydrophobic regions, and typically assemble under near-physiological conditions. Here, we report self-assembly of spherical micelles and one-dimensional nanorods under acidic conditions from cholesterol-conjugated DNA strands (Cholesterol-DNA). Further study also revealed that the nanorods were hierarchically assembled from the micelle nanostructures. The morphology of the nanorod assemblies can be tuned by altering solution condition and the design of Cholesterol-DNA. The self-assembly of Cholesterol-DNA nanostructures under acidic conditions and the discovery of the relationship between the nanorods and the micelles can provide new insights for future design of self-assemblies of amphiphilic DNA block copolymers.
Assuntos
Colesterol/química , DNA/química , Nanotubos/química , Interações Hidrofóbicas e Hidrofílicas , Micelas , Polímeros/químicaRESUMO
The digestive physiology of Chinese loach (Paramisgurnus dabryanus) was studied by assessing the specific and total activities of different pancreatic (trypsin, chymotrypsin, amylase and lipase), gastric (pepsin) and intestinal (alkaline phosphatase and leucine-aminopeptidase) enzymes from hatching to 40 days after hatching (DAH). Larvae were reared at 24.4 ± 0.4 °C and fed with rotifers from mouth opening (4 DAH) to 15 DAH, from 10 to 35 DAH with Cladocera and from 30 to 40 DAH with compound diet. Enzyme activities for trypsin, chymotrypsin, amylase and lipase were detected before the onset of exogenous feeding, indicating that these enzymes were genetically pre-programmed. Most of the pancreatic enzyme specific activities increased until 20 DAH and decreased thereafter. The pepsin activity of Chinese loach was firstly detected at 30 DAH, indicating the appearance of functional gastric gland. Alkaline phosphatase specific activity was detected from hatching onward, showed marked increase and reached the second peak at 20 DAH, while a gradual increase in specific leucine-aminopeptidase activity was observed until the end of the experiment. Accordingly, the larvae of Chinese loach possess a functional digestive system before the onset of exogenous feeding and the digestive capacity gradually increases as development progresses. The abrupt increase in intestinal enzyme activities between 10 and 20 DAH demonstrates onset of juvenile-like digestive mode in Chinese loach larvae. The increase in pepsin activity after 30 DAH indicates the shift from alkaline to acidic digestion in Chinese loach larvae, which may be considered as the onset of weaning.
Assuntos
Cipriniformes/crescimento & desenvolvimento , Digestão , Intestinos/enzimologia , Pâncreas/enzimologia , Fosfatase Alcalina/metabolismo , Amilases/metabolismo , Animais , Quimotripsina/metabolismo , Larva/crescimento & desenvolvimento , Leucil Aminopeptidase/metabolismo , Lipase/metabolismo , Pepsina A/metabolismo , Tripsina/metabolismoRESUMO
The use of waste polyethylene (WPE) in modified asphalt is frequently employed to reduce environmental pollution and improve asphalt properties. However, research has shown that using WPE alone as a modifier does not effectively enhance the low-temperature flexibility of asphalt. This study aims to investigate the potential of utilizing WPE and waste cooking oil (WCO) as composite modifiers to enhance the properties of virgin asphalt under both high and low-temperature conditions. The contents of WPE and WCO were used, and the preparation process for the modified asphalt was optimized through an orthogonal experiment. The experimental results indicate that the optimal formulation for the WPE/WCO composite modified asphalt (WPE/WCO-A) is obtained with an additive dosage of 8% and 1% by mass of virgin asphalt for WPE and WCO, respectively, as well as the maintenance process at a temperature of 140 °C and a duration of 2 h. Dynamic shear rheometer (DSR) results reveal that WPE/WCO composite modifier can greatly improve the high-temperature deformation resistance of asphalt. Bending beam rheometer (BBR) tests confirm that WPE adversely affects the low-temperature flexibility of asphalt, while the addition of WCO can improve it. WPE/WCO-A has even better low-temperature properties than virgin asphalt (VA). The Fourier transform infrared spectroscopy (FT-IR) results suggest that the composite modification of asphalt by WPE/WCO modifiers is dominated by physical action. Furthermore, the fluorescence microscopy test results demonstrate that WCO can promote WPE swelling in asphalt. This study offers a novel approach to improve the comprehensive properties of asphalt through composite modification using WPE and WCO.
Assuntos
Hidrocarbonetos , Polietileno , Polietileno/química , Hidrocarbonetos/químicaRESUMO
Hydrogels are functional materials that are similar to human skin and have received much attention in recent years for biomedical applications. However, the preparation of nontoxic, highly adhesive, and antimicrobial hydrogels in an efficient way remains a great challenge. Inspired by adhesive mussel foot proteins (mfps) which consist of abundant catecholic amino acids and lysine (Lys) residues, gallic acid-modified ε-poly-L-lysine (EPL/GA) was synthesized, and an active functional monomer (AA-EPL/GA) was then created through a reaction with acrylic acid (AA). The polymerization of AA-EPL/GA occurred rapidly (30-160 s) under blue light (λ = 405 nm) irradiation to produce a biomimetic PAA-EPL/GA hydrogel under mild conditions. The biomimetic pyrogallol-Lys distribution endowed the PAA-EPL/GA hydrogels with superior adhesion in humid environments (with an adhesive strength of 50.02 kPa toward wet porcine skin) and tunable mechanical and self-healing properties. Additionally, the PAA-EPL/GA hydrogels exhibited outstanding antibacterial ability due to the inherent characteristics of GA and EPL. In a mouse model, PAA-EPL/GA adhered firmly around the wound tissues. Photographs of the wound and the histological results demonstrated the ability of the hydrogel to promote wound healing, control wound infection, and suppress scar formation. Moreover, the hydrogel had a good hemostatic effect on liver bleeding. Our results highlighted the promising application potential of GA-based hydrogels, which were easily, harmlessly, and efficiently fabricated by blue light irradiation.
Assuntos
Hemostáticos , Hidrogéis , Adesivos/farmacologia , Animais , Antibacterianos/farmacologia , Biônica , Hemostáticos/farmacologia , Humanos , Hidrogéis/farmacologia , Camundongos , Pirogalol/química , Cimentos de Resina , Suínos , CicatrizaçãoRESUMO
Deterministic assembly of metallic nanoparticles (e.g. gold nanoparticles) into prescribed configurations has promising applications in many fields such as biosensing and drug delivery. DNA-directed bottom-up assembly has demonstrated unparalleled capability to precisely organize metallic nanoparticles into assemblies of designer configurations. However, the fabrication of assemblies comprising delicate nanoparticle arrangements, especially across large dimensions (e.g. micron size), has remained challenging. In this report, we have designed DNA origami hexagon tiles that are capable of assembling into higher-order networks of honeycomb arrays or tubes with dimensions up to several microns. The versatile addressability of the unit tile enables precise and periodic positioning of nanoparticles onto these higher-order DNA origami frame structures. Overall, we have constructed a series of 9 gold nanoparticle architectures with programmable configurations ranging from nanometer-sized clusters to micrometer-sized lattices. We believe these architectures shall hold great application potential in numerous biomedical fields.
Assuntos
Ouro/química , Nanopartículas Metálicas/química , Materiais Biocompatíveis/química , DNA/química , Tamanho da PartículaRESUMO
The motive of this study was to investigate the interaction between polymorphisms in the MDR1 gene and anesthetic effects following pediatric tonsillectomy. In total, 240 children undergoing tonsillectomy with preoperative propofol-remifentanil anesthesia were selected. Genomic DNA was extracted from the peripheral blood of children after operation, and the MDR1 gene polymorphisms of 2677 G>T/A, 1236 C>T and 3435 C>T were detected by direct sequencing. We tested mean arterial pressure, diastolic blood pressure, systolic blood pressure, and heart rate at several time-points: T0 (5 mins after the repose), T1 (0âmin after tracheal intubation), T2 (5 mins after the tracheal intubation), T3 (0âmin after the tonsillectomy), T4 (0âmin after removal of the mouth-gag) and T5 (5âmin after the extubation). The visual analog scale, the face, legs, activity, cry, and consolability pain assessment, and the Ramsay sedation score were recorded after the patients regained consciousness. Adverse reactions were also recorded. The time of induction, respiration recovery, eye-opening, and extubation of children with the CC genotype were found to be shorter compared to the CTâ+âTT genotype of MDR1 1236Câ>âT (all Pâ<.05). The mean arterial pressure, diastolic blood pressure, systolic blood pressure, and heart rate were significantly reduced at T5 in children with the CC genotype (all Pâ<.05). The visual analog scale at 1, 2, 4, and 8âhours post-operation, and the Ramsay sedation score at 5, 10, and 30 min after the extubation were decreased, while the face, legs, activity, cry, and consolability pain assessment score increased (all Pâ<0.05). There was no statistically significant difference in the adverse reaction of MDR1 mutations (P> 0.05). It could be concluded that anesthetic effect following pediatric tonsillectomy in patients with the MDR1 1236Câ>âT CC genotype was stronger than in those carrying the CTâ+âTT genotype.
RESUMO
OBJECTIVES: Because females are under-represented in coronary trials, this study sought to assess the relative safety and efficacy of Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) and the Xience everolimus-eluting stent in females compared with males. BACKGROUND: The Absorb everolimus-eluting BVS provides drug delivery and mechanical support similar to a metallic drug-eluting stent, followed by resorption and restoration of more normal vascular structure with the potential to improve late clinical outcomes. METHODS: The ABSORB II, ABSORB III, ABSORB Japan, and ABSORB China trials were pooled. Baseline clinical, angiography, procedural variables, and 2-year outcomes were analyzed by sex and device. RESULTS: Among 3,384 randomized patients, 932 (27.5%) were female. Females were older, more often had diabetes and hypertension, but had less everolimus-eluting stent, 3-vessel disease, and smoking compared with males (all p≤0.001). The 2-year rates of target lesion failure with BVS versus everolimus-eluting stent in females were 8.9% versus 6.2% (study-level adjusted hazard ratio: 1.47; 95% confidence interval [CI]: 0.88 to 2.46) and 8.9% versus 6.4% in males (HR: 1.40; 95% CI: 1.02 to 1.92; pinteraction = 0.85). There were no significant interactions between sex and device type for any of the components of target lesion failure. CONCLUSIONS: The relative treatment effects of BVS and everolimus-eluting stent for the 2-year rates of target lesion failure and other cardiovascular outcomes were consistent in females and males.
Assuntos
Implantes Absorvíveis , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Stents Farmacológicos , Everolimo/administração & dosagem , Intervenção Coronária Percutânea/instrumentação , Idoso , Fármacos Cardiovasculares/efeitos adversos , Distribuição de Qui-Quadrado , Angiografia Coronária , Everolimo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Intervenção Coronária Percutânea/efeitos adversos , Modelos de Riscos Proporcionais , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
[reaction: see text] A synthetic route to select cyclooctane-1,2,3-triols and 1,2,3,4,5-pentaols has been defined. The starting materials are d-glucose or d-arabinose, and the key steps consist of a zirconocene-promoted ring contraction, a [3,3] sigmatropic rearrangement, and more extended functionalization of the resulting cyclooctadienone.
Assuntos
Carboidratos/química , Polímeros/química , Arabinose/química , Boroidretos , Glucose/química , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Compostos Organometálicos/química , Estereoisomerismo , Zircônio/químicaRESUMO
AIM: To evaluate the effects of surfactants on the pharmacokinetics and distribution in rats after intravenous administration of SOD liposomes. METHODS: The liposomes were prepared by reverse phase evaporation method. The activity of SOD was assayed by method of xanthine oxidase. RESULTS: The T1/2 of SOD solution, common SOD liposome, SOD liposomes modified by DSPE-PEG2000 and Tween 80 were 0.25, 0.34, 0.66 and 0.41 h, respectively; AUC were 12.48, 24.66, 41.16 and 33.02 microg x h x mL(-1), respectively. Compared with the common liposome, the liposomes modified by DSPE-PEG and Tween 80 decreased the content of SOD in liver and spleen, but increased in brain. CONCLUSION: The three kinds of liposomes could increase T1/2 and AUC in some extent, especially in PEG-L group. Tween-L could increase the SOD content in brain, and PEG-L could decrease the SOD content in the liver and spleen compared with the common liposome.
Assuntos
Encéfalo/enzimologia , Superóxido Dismutase/administração & dosagem , Superóxido Dismutase/farmacocinética , Animais , Área Sob a Curva , Injeções Intravenosas , Lipossomos , Fígado/enzimologia , Masculino , Polissorbatos/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Baço/enzimologia , Tensoativos/farmacologia , Distribuição TecidualRESUMO
Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial "closed-loop" system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days.
Assuntos
Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Glucose/metabolismo , Insulina/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Alginatos/química , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Quitosana/química , Dextranos/química , Diabetes Mellitus Tipo 1/tratamento farmacológico , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Injeções , Insulina/química , Insulina/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVES: To more efficiently determine the subcritical crack growth (SCG) parameters of dental ceramics, the effects of stressing rate and choice of statistical regression model on estimates of SCG parameters were assessed. METHODS: Two dental ceramic materials, a veneering material having a single critical flaw population (S) and a framework material having partially concurrent flaw populations (PC), were analyzed using constant stress-rate testing, or "dynamic fatigue", with a variety of testing protocols. For each material, 150 rectangular beam specimens were prepared and tested in four-point flexure according to ISO6872 and ASTM1368. A full-factorial study was conducted on the following factors: material, stress rate assumed vs. calculated, number of stress rates, and statistical regression method. RESULTS: The proportion of specimens for which the statistical models over-estimated reliability was not significantly different based on regression method for Material S (P = 0.96, power = 94%) and was significantly different based on regression method for Material PC (P < 0.001). The standard method resulted in SCG parameters, n and l nB, of 35.9 and -11.1 MPa(2)s for Material S and 12.4 and 9.61 MPa(2)s for Material PC, respectively. SIGNIFICANCE: The method of calculation that uses only the median strength value at each stress rate provided the most robust SCG parameter estimates. Using only two stress rates resulted in fatigue parameters comparable to those estimated using four stress rates having the same range. The stress rate of each specimen can be assumed to be the target stress rate with negligible difference in SCG parameter estimates.
Assuntos
Porcelana Dentária/química , Algoritmos , Óxido de Alumínio/química , Silicatos de Alumínio/química , Análise do Estresse Dentário/estatística & dados numéricos , Facetas Dentárias , Previsões , Vidro/química , Humanos , Teste de Materiais/estatística & dados numéricos , Maleabilidade , Compostos de Potássio/química , Análise de Regressão , Estresse Mecânico , Propriedades de Superfície , Zircônio/químicaRESUMO
STATEMENT OF PROBLEM: Dental technicians use a variety of techniques when condensing dental porcelains. It is unclear whether these techniques affect the total porosity and translucency of dental porcelains. PURPOSE: The objective of this study was to determine whether varying the powder/liquid ratio during condensation affects porosity and translucency of porcelains. Material and methods Duceram LFC dentin, Duceram LFC incisal, IPS Eris dentin, and IPS Eris incisal porcelains were studied. For each specimen, 1.0 g of porcelain powder was mixed with 1 of 3 different volumes of deionized water to form a slurry with a thin, medium, or thick consistency. The slurries were condensed in a plastic syringe mold, fired, and polished to a 3-microm finish to form 12 groups of 4 specimens each (14-mm diameter, 1.10-mm thickness). The apparent density (g/mL) of each specimen was measured using Archimedes method, and the porosity (%) calculated. Each specimen was coupled to standard ceramic tiles using an immersion liquid, and the color shade was measured in CIE Yxy coordinates using a tristimulus colorimeter. Translucency was assessed by calculating the contrast ratio of shade value (Y) in front of black versus white backgrounds. Two-way analysis of variance and Tukey's multiple comparison tests (alpha = .05) were used to test for significant effects of factors. RESULTS: Porcelain type and powder/liquid ratio had a significant interactive effect on the apparent density (P < .001) and on total porosity (P = .003); however, there was no consistent trend. The powder/liquid ratio did not significantly affect translucency (P = .28), but porcelain type had a significant effect on translucency (P < .001). CONCLUSION: In this in vitro study, total porosity of specimens prepared using 4 porcelains was found to be sensitive to powder/liquid ratio; whereas translucency was found to be insensitive to powder/liquid ratio.
Assuntos
Porcelana Dentária/química , Análise de Variância , Cerâmica/química , Cor , Colorimetria , Polimento Dentário , Temperatura Alta , Humanos , Teste de Materiais , Óptica e Fotônica , Porosidade , Pós , Propriedades de Superfície , ÁguaRESUMO
OBJECTIVE: To study the bonding characteristic of Titanium and RG experiment porcelain. METHODS: 5 specimens with a size of 10 mm x 5 mm x 1.4 mm were cast from pure titanium. Then 1 mm of RG experiment opaque and body porcelain were fused on the surface of the titanium specimens. The interface of titanium and porcelain was analyzed with a scanning electron microscope with energy-despersive spectrometry; 6 metal specimens with the size of 25 mm x 3 mm x 0.5 mm were cast from Ni-Cr alloy and a uniform thickness of 1 mm of VMK 99 porcelain was veneered on the central area of 8 mm x 3 mm 18 metal specimens as the same size were cast from pure titanium. The uniform thickness of 1 mm of VITA TITANKERAMIK porcelain, of Noritake super porcelain Ti-22 and of RG experiment porcelain were veneered on every 6 specimens respectively in the central area of 8 mm x 3 mm. The specimens were subjected to a three-point bending test on a load-test machine with a span of 20 mm, then the failure loads were recorded and statistically analysised. The RG porcelain/titanium crown was fabricated by fusing RG opaque porcelain and body porcelain to cast titanium substrate crown. RESULTS: The SEM results show no porosity and crackle were found in the interface. The energy-dispersive spectrometry show that there are Si, Ti and O in the 1 micro m layer between porcelain and titanium, which suggesting titanium and experiment porcelain bonding well. The three point test showed the fracture force for the combinations of titanium/VITA TITANKERAMIK porcelain, titanium/Noritake super porcelain Ti-22 and titanium/RG experiment porcelain were (7.233 +/- 2.539) N, (5.533 +/- 1.199) N and (6.316 +/- 1.433) N respectively. There were not statistically significant differences among them (t test, P < 0.01). The fracture force for the Ni-Cr alloy/VMK99 porcelain combination (12.733 +/- 3.297) N was significantly greater than those of the cast titanium/porcelain (t test, P > 0.05). The crown was translucent with no crack. CONCLUSION: RG porcelain is well compatible with titanium.