RESUMEN
A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 µm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.
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Técnicas Fotoacústicas , Polímeros , Semiconductores , Técnicas Fotoacústicas/métodos , Animales , Ratones , Polímeros/química , Quinoxalinas/química , Femenino , Humanos , Tiadiazoles/química , Rayos Infrarrojos , Ratones Desnudos , Ratones Endogámicos BALB C , Medios de Contraste/químicaRESUMEN
The secondary structures of polypeptides, such as an α-helix and a ß-sheet, often impart specific properties and functions, making the regulation of their secondary structures of great significance. Particularly, water-soluble polypeptides bearing a ß-sheet conformation are rare and challenging to achieve. Here, a series of oligo(ethylene glycol)-modified lysine N-carboxylic anhydrides (EGmK-NCA, where m = 1-3) and the corresponding polymers EGmKn are synthesized, with urethane bonds as the linker between the side-chain EG and lysine. The secondary structure of EGmKn is delicately regulated by both m and n, the length (number of repeating units) of EG and the degree of polymerization (DP), respectively. Among them, EG2Kn adopts a ß-sheet conformation with good water solubility at an appropriate DP and forms physically cross-linked hydrogels at a concentration as low as 1 wt %. The secondary structures of EG1Kn can be tuned by DP, exhibiting either a ß-sheet or an α-helix, whereas EG3Kn appears to a adopt pure and stable α-helix with no dependence on DP. Compared to previous works reporting EG-modified lysine-derived polypeptides bearing exclusively an α-helix conformation, this work highlights the important and unexpected role of the urethane connecting unit and provides useful case studies for understanding the secondary structure of polypeptides.
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Péptidos , Conformación Proteica en Lámina beta , Solubilidad , Agua , Péptidos/química , Agua/química , Polietilenglicoles/química , Lisina/química , Hidrogeles/química , Glicol de Etileno/química , Estructura Secundaria de Proteína , PolimerizacionRESUMEN
Near-infrared (NIR)-triggered shape memory hydrogels with promising mechanical strength hold immense potential in the field of biomedical applications and soft actuators. However, the optical and mechanical properties of currently reported hydrogels usually suffer from limited solubility and dispersion of commonly used photothermal additives in hydrogels, thus restricting their practical implementations. Here,, a set of NIR-responsive shape memory hydrogels synthesized by polyaddition of diisocyanate-terminated poly(ethylene glycol), imidazolidinyl urea (IU), and p-benzoquinone dioxime (BQDO) is reported. The introduction of IU, a hydrogen bond reinforcing factor, significantly enhances the mechanical properties of the hydrogels, allowing for their tunable ranges of the ultimate tensile strength (0.4-2.5 MPa), elongation at break (210-450%), and Young's modulus (190-850 kPa). The unique hydrogels exhibit an intrinsic photothermal effect because of the covalently incorporated photothermal moiety (BQDO), and the photothermal supramolecular hydrogel shows controllable shape memory capabilities characterized by rapid recovery speed and high recovery ratio (>90%). This design provides new possibilities for applying shape memory hydrogels in the field of soft actuators.
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Hidrogeles , Rayos Infrarrojos , Hidrogeles/química , Hidrogeles/síntesis química , Polietilenglicoles/química , Estructura Molecular , Resistencia a la Tracción , Urea/química , Sustancias Macromoleculares/química , Sustancias Macromoleculares/síntesis química , Materiales Inteligentes/químicaRESUMEN
Preparation of materials that possess highly strong and tough properties simultaneously is a great challenge. Thermosetting resins as a type of widely used polymeric materials without synergistic strength and toughness limit their applications in some special fields. In this report, an effective strategy to prepare thermosetting resins with synergistic strength and toughness, is presented. In this method, the soft and rigid microspheres with dynamic hemiaminal bonds are fabricated first, followed by hot-pressing to crosslink at the interfaces. Specifically, the rigid or soft microspheres are prepared via precipitation polymerization. After hot-pressing, the resulting rigid-soft blending materials exhibit superior strength and toughness, simultaneously. As compared with the precursor rigid or soft materials, the toughness of the rigid-soft blending films (RSBFs) is improved to 240% and 2100%, respectively, while the strength is comparable to the rigid precursor. As compared with the traditional crushing, blending, and hot-pressing of rigid or soft materials to get the nonuniform materials, the strength and toughness of the RSBFs are improved to 168% and 255%, respectively. This approach holds significant promise for the fabrication of polymer thermosets with a unique combination of strength and toughness.
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Polimerizacion , Resinas Sintéticas/química , Microesferas , Polímeros/química , Temperatura , Ensayo de Materiales , Propiedades de Superficie , Tamaño de la PartículaRESUMEN
Poly(amic acid) (PAA) materials as the precursor of polyimide generally show remarkably poor mechanical properties, thus limiting their application as the engineering plastics. In this study, it is demonstrated that the mechanical properties of PAA materials can be improved significantly for tens of folds with breaking strength >50 MPa, Young's modulus >400 MPa, and elongation at break >300% by incorporation of 20% (mol%) poly(propylene glycol) (PPO) soft segments. The optimization for suitable hard-soft composition with 20% PPO and the existence of various hydrogen bonds with different binding energies can dissipate energies efficiently, which simultaneously improve the material strength and toughness. In addition, PAA82 films exhibit excellent tolerance toward cyclic stretch, and have the capability to resist various harsh conditions including solar radiation testing (1 sun), heat (85 °C), alkalinity (pH 10), and acidity (pH 4) over one month. Noted that PAA82 films can be laminated with Kapton films, which show excellent resistance to ultrahigh (200 °C) and ultralow temperature (-196 °C). The laminated film also exhibits bulletproof property with a thickness of 6 mm. The strategy via modulation of hard-soft compositions and hydrogen bonds in PAA materials shows great potentials to improve the mechanical properties of polymeric materials.
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Plásticos , Polímeros , Enlace de Hidrógeno , Polímeros/química , Temperatura , CalorRESUMEN
Polymer blending is an efficient way to obtain extraordinary polymeric materials. However, once permanently cross-linked thermosets are involved in blending, there are challenges in designing and optimizing the structures and interfacial compatibility of blends. Vitrimer with dynamic covalent polymer networks provides an innovative opportunity for blending thermoplastics and thermosets. Herein, a reactive blending strategy is proposed to develop thermoplastic-thermoset blend with enhanced compatibility on the basis of dynamic covalent chemistry. Specifically, polybutylene terephthalate (PBT) and polymerized epoxy vitrimer can be directly melt blended to obtain tough and thermostable blends with desirable microstructures and interfacial interaction. Bond exchange facilitates the grafting of PBT and epoxy vitrimer chains, thus enhancing the interfacial compatibility and thermal stability of blends. The obtained blend balances the strength and stretchability of PBT and epoxy vitrimer, resulting in enhanced toughness. This work offers a new way of designing and fabricating new polymeric materials by blending thermoplastics and thermosets. It also suggests a facile direction towards upcycling thermoplastics and thermosets.
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Poliésteres , Polímeros , Resinas Epoxi , PolimerizacionRESUMEN
Polymer alloys (PAs) are mixtures of two or more types of polymers to enhance the properties of polymeric materials. However, thermosets with crosslinked structures are immiscible and cannot be prepared PAs. Herein, two immiscible covalent adaptable networks containing phenoxy carbamate bonds are explored as the typical polymeric materials to prepare the hard-soft thermoset alloy (HSTA) by the interpenetrated dynamic crosslinked interface (IDCI) to enhance the toughness. Specifically, two types of polyurethane covalent adaptable networks with either high stiffness (thermoset) or extensibility (elastomer) are prepared, respectively. The granules of thermoset and elastomer are mixed and hot-pressed to prepare the HSTA. The HSTA shows improved mechanical properties with a toughness of 22.8 MJ m-3 which is 14 times higher than that of hard thermoset. In addition, the HSTA shows excellent impact-resistance property after 1000 punctures. Moreover, the obtained HSTA via addition of carbon nanotubes can significantly decrease the electric resistance over six orders of magnitudes as compared to the blending method, which is due to the distribution of the carbon nanotubes at the interfaces of the two networks.
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Nanotubos de Carbono , Nanotubos de Carbono/química , Polímeros/química , Elastómeros , Conductividad EléctricaRESUMEN
Inspired by protein polymerizations, much progress has been made in making "polymer-like" supramolecular structures from small synthetic subunits through non-covalent bonds. A few regulation mechanisms have also been explored in synthetic platforms to create supramolecular polymers and materials with dynamic properties. Herein, a type of reactive regulator that facilitates the dimerization of the monomer precursors through dynamic bonds to trigger the supramolecular assembly from small molecules in an aqueous solution is described. The supramolecular structures are crystalline in nature and the reaction coupled assembly strategy can be extended to a supramolecular assembly of aromatic amide derivatives formed in-situ. The method may be instructive for the development of supramolecular nanocrystalline materials with desired physical properties.
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Compuestos Heterocíclicos , Polímeros , Sustancias Macromoleculares , Polimerizacion , AguaRESUMEN
The fabrication of block copolymer (BCP) vesicles with controlled membrane permeability and promising stability remains a considerable challenge. Herein, a new type of pH-responsive and self-crosslinked vesicle based on a hydrolytically hindered urea bond is reported. This kind of vesicle is formed by the self-assembly of a pH-responsive and hydrolytically self-crosslinkable copolymer poly(ethylene glycol)-block-poly[2-(3-(tert-butyl)-3-ethylureido)ethyl methacrylate-co-2-(diethylamino)ethyl methacrylate] (PEG-b-P(TBEU-co-DEA)). The BCP can be easily synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(3-(tert-butyl)-3-ethylureido)ethyl methacrylate (TBEU) and 2-(diethylamino)ethyl methacrylate (DEA) using PEG-based macro-chain transfer agent. The copolymer could self-assemble into stable vesicles by the hydrophobic interaction and in situ cross-linking between amines and isocyanates after the hydrolysis of the hindered urea bonds without any catalyst. Dynamic light scattering (DLS) studies show that the vesicles exhibit enhanced stability against the dilution of organic solvent, and the size can be adjusted through the change of pH values. Moreover, the alkaline phosphatase-loaded vesicles can act as nano-reactor and enable free diffusion of small molecules into the vesicles, followed by the significantly improved fluorescence intensity of phosphate-caged fluorescein. This self-crosslinking and pH-sensitive vesicles may serve as a smart platform in controlled drug delivery and molecular reactor.
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Reactivos de Enlaces Cruzados/síntesis química , Polímeros/síntesis química , Reactivos de Enlaces Cruzados/química , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Molecular , Tamaño de la Partícula , Polímeros/química , Propiedades de SuperficieRESUMEN
Encapsulation of small-molecule drugs in hydrophobic polymers or amphiphilic copolymers has been extensively used for preparing polymeric nanoparticles (NPs). The loadings and loading efficiencies of a wide range of drugs in polymeric NPs, however, tend to be very low. In this Communication, we report a strategy to prepare polymeric NPs with exceptionally high drug loading (>50%) and quantitative loading efficiency. Specifically, a dimeric drug conjugate bearing a trigger-responsive domain was designed and used as the core-constructing unit of the NPs. Upon co-precipitation of the dimeric drug and methoxypoly(ethylene glycol)-block-polylactide (mPEG-PLA), NPs with a dimeric drug core and a polymer shell were formed. The high-drug-loading NPs showed excellent stability in physiological conditions. No premature drug or prodrug release was observed in PBS solution without triggering, while external triggering led to controlled release of drug in its authentic form.
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Dimerización , Portadores de Fármacos/química , Liberación de Fármacos , Nanopartículas/química , Poliésteres/química , Polietilenglicoles/química , Interacciones Hidrofóbicas e Hidrofílicas , Modelos MolecularesRESUMEN
Flexible biosensors made from conductive hydrogels have shown tremendous potential in health management and human-machine interfaces. Nevertheless, it remains challenging to fabricate conductive hydrogels with robust resilience and long-term stability. Herein, we report a nanocomposite conductive hydrogel prepared through one-pot radical polymerization of 3-acrylamidophenylboronic acid (APBA) and acrylamide (AM) in the presence of LAPONITE® XLG nanosheet (XLG) stabilized carbon nanotubes (CNTs). Owing to the existence of various non-covalent interactions within the network (B-N coordination, hydrogen bond, and polymer chain entanglement), the hydrogels feature splendid mechanical properties with a tensile strength of 252-323 kPa, fracture strain of 880-1200%, Young's modulus of 48-50 kPa and fracture energy of 911-1078 J m-2, and exhibit robust elasticity and fatigue resistance during 1000 consecutive tensile and compressive cycles. The hydrogels show remarkable sensing performances (gauge factor up to 9.43) and a broad sensing range of strain (1-300%) and pressure (1-80 kPa), enabling reliable and accurate monitoring of large and tiny motions in daily human life. Moreover, the conductive hydrogels could not only accelerate skin incision healing but also act as smart wearable sensors to monitor the skin wound healing process by detection of local temperature changes.
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Fracturas Óseas , Nanotubos de Carbono , Humanos , Nanogeles , Elasticidad , HidrogelesRESUMEN
Development of polymeric hydrogels with multiple functions (adhesiveness, self-healability, anti-oxidation efficiency, etc.) through one-step green polymerization of naturally occurring small molecules in water is critical for various biomedical applications and clinical transformation. In this work, benefiting from the dynamic disulfide bond in α-lipoic acid (LA), we directly obtain an advanced hydrogel (poly(lipoic acid-co-sodium lipoate) (PLAS)) through heat and concentration-induced ring-opening polymerization of LA with the addition of NaHCO3 in an aqueous solution. The presence of COOH, COO- and disulfide bonds endows the resulting hydrogels with comprehensive mechanical properties, facile injectability, fast self-healability and adequate adhesiveness. Moreover, the PLAS hydrogels show promising antioxidative efficiency, inherited from naturally occurring LA, and can efficiently eliminate intracellular reactive oxygen species (ROS). We also verify the advantage of PLAS hydrogels in a rat spinal injury model. Through the regulation of ROS and in situ inflammation, our system can promote the recovery of spinal cord injury. Owing to the natural origin and inherent anti-oxidative capability of LA, and a green preparation method, our hydrogel should be beneficial for clinical transformation and may be a good candidate for various biomedical applications.
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Traumatismos de la Médula Espinal , Ácido Tióctico , Ratas , Animales , Hidrogeles/química , Antioxidantes/farmacología , Antioxidantes/química , Polímeros/química , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Ácido Tióctico/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , DisulfurosRESUMEN
Identification and quantification of synthetic polymers in complex biological milieu are crucial for delivery, sensing and scaffolding functions, but conventional techniques based on imaging probe labellings only afford qualitative results. Here we report modular construction of precise sequence-defined amphiphilic polymers that self-assemble into digital micelles with contour lengths strictly regulated by oligourethane sequences. Direct sequence reading is accomplished with matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry, facilitated by high-affinity binding of alkali metal ions with poly(ethylene glycol) dendrons and selective cleavage of benzyl-carbamate linkages. A mixture of four types of digital micelles could be identified, sequence-decoded and quantified by MALDI and MALDI imaging at cellular, organ and tissue slice levels upon in vivo administration, enabling direct comparison of biological properties for each type of digital micelle in the same animal. The concept of digital micelles and encoded amphiphiles capable of direct sequencing and high-throughput label-free quantification could be exploited for next-generation precision nanomedicine designs (such as digital lipids) and protein corona studies.
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Micelas , Animales , Polietilenglicoles/química , Polímeros/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
Osteomyelitis is a difficult-to-treat infectious disease. Treatment, which includes controlling the infection and removing necrotic tissues, is challenging. Considering the side effects and drug resistance of systemic antibiotics, local drug delivery systems are being explored. Antibiotic-loaded bone cement is the main treatment strategy; however, it has several disadvantages. Thus, based on its thermosensitive gelation properties, poly(D, L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer was used as a sustained-release drug carrier by calibrating its synthesis parameters. We prepared and characterized vancomycin@PLGA-PEG-PLGA/hydroxyapatite (HA) thermosensitive hydrogel with an LA/GA ratio of 15:1. The rheological characteristics, sol-gel phase-transition properties, and critical micelle concentration value of the PLGA-PEG-PLGA/HA complex confirmed that it undergoes a temperature-sensitive sol-gel phase transition. Furthermore, the HA in the composite increased the storage modulus of the system. FT-IR, XRD, and TEM findings showed that HA could be dispersed uniformly in the PLGA-PEG-PLGA polymer. Moreover, HA neutralized acidity during polymer degradation, improving in vitro cytocompatibility. In vitro and in vivo antibacterial experiments showed that the composite sustained-release system exhibited good bone repair characteristics owing to its efficacy in infection treatment. Therefore, vancomycin@PLGA-PEG-PLGA/HA allows sustained release of antibiotics and promotes bone tissue repair, showing potential for wide clinical applicability.
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Durapatita , Osteomielitis , Humanos , Preparaciones de Acción Retardada , Vancomicina , Micelas , Hidrogeles , Espectroscopía Infrarroja por Transformada de Fourier , Cementos para Huesos , Polietilenglicoles , Materiales Biocompatibles , Polímeros , Osteomielitis/tratamiento farmacológico , Portadores de Fármacos , Antibacterianos/farmacologíaRESUMEN
The clinical management of chronic periodontitis with diabetes mellitus (CPDM) is a long-standing thorny issue. The excessive production of reactive oxygen species (ROS) is one of the important implications in CPDM. In the present study, oxidized dextran (OD) and phenylboronic acid-functionalized poly (ethylene imine) (PBA-PEI) were used to develop a novel injectable local drug delivery system (LDDS) which could simultaneously improve drug loading efficiency (doxycycline (Doxy) and metformin (Met)) through B-N coordination and achieve ROS-triggered drug release locally. The injectable LDDS exhibited appropriate adhesiveness to gingival tissue, good biocompatibility, and remarkable antibacterial effect against S. aureus, E. coli, and P. gingivalis. Furthermore, the favorable synergistic effect of Doxy and Met was also verified in vivo in a CPDM rat model through the morphometry and histological observations of alveolar bone, immunohistochemistry staining, and the detection of the expression level of immune-inflammatory mediators in gingival tissue. The results show that the double drug-loaded PBA-PEI/OD hydrogel, as a novel promising therapeutic agent, may be a favorable potential candidate for the CPDM management in the dental clinic.
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Periodontitis Crónica , Diabetes Mellitus Experimental , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Doxiciclina , Liberación de Fármacos , Escherichia coli/metabolismo , Hidrogeles , Ratas , Especies Reactivas de Oxígeno/metabolismo , Staphylococcus aureus/metabolismoRESUMEN
The botulinum neurotoxins (BoNTs) produced by different strains of the bacterium Clostridium botulinum are responsible for the disease botulism and include a group of immunologically distinct serotypes (A, B, E, and F) that are considered to be the most lethal natural proteins known for humans. Two BoNT serotypes, C and D, while rarely associated with human infection, are responsible for deadly botulism outbreaks afflicting animals. Also associated with animal infections is the BoNT C-D mosaic protein (BoNT/CD), a BoNT subtype that is essentially a hybrid of the BoNT/C (â¼two-third) and BoNT/D (â¼one-third) serotypes. While the amino acid sequence of the heavy chain receptor binding (HCR) domain of BoNT/CD (BoNT/CD-HCR) is very similar to the corresponding amino acid sequence of BoNT/D, BoNT/CD-HCR binds synaptosome membranes better than BoNT/D-HCR. To obtain structural insights for the different membrane binding properties, the crystal structure of BoNT/CD-HCR (S867-E1280) was determined at 1.56 Å resolution and compared to previously reported structures for BoNT/D-HCR. Overall, the BoNT/CD-HCR structure is similar to the two sub-domain organization observed for other BoNT HCRs: an N-terminal jellyroll barrel motif and a C-terminal ß-trefoil fold. Comparison of the structure of BoNT/CD-HCR with BoNT/D-HCR indicates that K1118 has a similar structural role as the equivalent residue, E1114, in BoNT/D-HCR, while K1136 has a structurally different role than the equivalent residue, G1132, in BoNT/D-HCR. Lysine-1118 forms a salt bridge with E1247 and may enhance membrane interactions by stabilizing the putative membrane binding loop (K1240-N1248). Lysine-1136 is observed on the surface of the protein. A sulfate ion bound to K1136 may mimic a natural interaction with the negatively changed phospholipid membrane surface. Liposome-binding experiments demonstrate that BoNT/CD-HCR binds phosphatidylethanolamine liposomes more tightly than BoNT/D-HCR.
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Toxinas Botulínicas/química , Lisina/química , Animales , Toxinas Botulínicas/genética , Toxinas Botulínicas/metabolismo , Membrana Celular/metabolismo , Cristalografía por Rayos X , Humanos , Liposomas/química , Lisina/genética , Datos de Secuencia Molecular , Mutación , Fosfatidiletanolaminas/química , Fosfolípidos/química , Estructura Terciaria de ProteínaRESUMEN
Poly(N-isopropylacrylamide) (PNIPAM) oligomer containing one adamantyl (AD) and two ß-cyclodextrin (ß-CD) moieties at the chain terminals, AD-PNIPAM-(ß-CD)(2), was synthesized by atom transfer radical polymerization (ATRP) and successive click reactions. In aqueous solution, AD-PNIPAM-(ß-CD)(2) spontaneously forms supramolecular thermoresponsive hyperbranched polymers via molecular recognition between AD and ß-CD moieties. To the best of our knowledge, this work represents the first report of the construction of supramolecular thermoresponsive hyperbranched polymers from well-defined polymeric AB(2) building units.
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Acrilamidas/química , Resinas Acrílicas/química , Adamantano/química , Polímeros/química , beta-Ciclodextrinas/química , Resinas Acrílicas/síntesis química , Radicales Libres/química , Polimerizacion , Termodinámica , beta-Ciclodextrinas/síntesis químicaRESUMEN
BACKGROUND: Paroxysmal tonic upgaze (PTU) is an infantile-onset paroxysmal neurological disorder that is characterized by episodes of sustained conjugate upward eye deviation. The paroxysmal abnormal eye movements need to be differentiated from seizures. We report a case of PTU with occipital discharge on electroencephalography (EEG), which made the diagnosis more complicated. CASE PRESENTATION: A 6-month-old girl presented with paroxysmal upward deviation or left strabismus of the eyes, with a bowed head, lowered jaw, raised eyebrows, closed lips, and slight grin. Each episode lasted for a few seconds, and episodes occurred multiple times per day. EEG showed spike waves in the right occipital region, and the girl was initially misdiagnosed with epilepsy. After further analysis using video EEG, we corrected her diagnosis as PTU and stopped the administration of an antiepileptic drug. CONCLUSION: PTU accompanied by discharge on EEG may lead to a misdiagnosis. Video EEG monitoring, and especially the analysis of EEG traces synchronized with attacks, can provide evidence to distinguish between seizures and non-epileptic events.
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Epilepsia , Trastornos de la Motilidad Ocular , Anticonvulsivantes/uso terapéutico , Electroencefalografía , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Lactante , Trastornos de la Motilidad Ocular/tratamiento farmacológico , Alta del PacienteRESUMEN
Endo/lysosome entrapment is the key barrier for gene delivery using synthetic polycations. Although the introduction of a membrane-lytic peptide into polycations could facilitate efficient endo/lysosome release and improve gene delivery efficiency, it is always accompanied by serious safety concerns. In this work, the widely used polycations, poly(2-dimethylaminoethyl methacrylate (PDMAEMA), poly(l-lysine) (PLL) and polyethylenimine (PEI), are modified with a pH-sensitive peptide (C6M3) with selective lytic activity to produce three functional polycations to address the issue of endo/lysosome entrapment and facilitate efficient gene transfer. Hemolysis study shows that the functionalized polycations show good biocompatibility toward red blood cells at neutral pH, and exhibit potent membrane lysis activity under acidic conditions, which are both on-demand for the ideal gene carriers. In vitro transfection studies demonstrate that the peptide modified polycations mediate promising gene delivery efficiency with the luciferase plasmid and the green fluorescence protein plasmid in HeLa cells compared to the parent polycations. Owing to the facile preparation and selective lysis activity of the C6M3 modified polycations, these smart gene vectors may be good candidates for the transfer of various nucleic acids and further clinical gene therapy.
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Técnicas de Transferencia de Gen , Polietileneimina , Terapia Genética , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Péptidos , Polielectrolitos , TransfecciónRESUMEN
Preformed crowns are preferred to reduce the failure risk of restoration of primary teeth, but some drawback of conventional material is still a main barrier for their clinical use. Polyether etherketone (PEEK), a tooth colored, high-performance thermoplastic polymer, has been recognized as a promising alternative to manufacture the restoration of primary teeth. However, the hydrophobic surface and low surface energy of PEEK make it hard to establish a strong and durable adhesion. In this study, we have evaluated a modification method of polydopamine (PDA) coating with plasma pretreatment for the PEEK films by physical and chemical characterization, bonding properties, and biocompatibility. The surface properties of PEEK were well-characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). The adhesive strength of the PEEK films was greatly improved without significant reduction of the proliferation rate of human gingival fibroblast cells in MTT and Live/Dead assays. Therefore, PDA coating with plasma pretreatment may give a new solution for effective clinical application of PEEK in primary performed crowns.