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BACKGROUND: Hemifacial microsomia (HFM) is one of the most common congenital craniofacial condition often accompanied by masseter muscle involvement. U-Net neural convolution network for masseter segmentation is expected to achieve an efficient evaluation of masseter muscle. METHODS: A database was established with 108 patients with HFM from June 2012 to June 2019 in our center. Demographic data, OMENS classification, and 1-mm layer thick 3-dimensional computed tomography were included. Two radiologists manually segmented masseter muscles in a consensus reading as the ground truth. A test set of 20 cases was duplicated into 2 groups: an experimental group with the intelligent algorithm and a control group with manual segmentation. The U-net follows the design of 3D RoI-Aware U-Net with overlapping window strategy and references to our previous study of masseter segmentation in a healthy population system. Sorensen dice-similarity coefficient (DSC) muscle volume, average surface distance, recall, and time were used to validate compared with the ground truth. RESULTS: The mean DSC value of 0.794±0.028 for the experiment group was compared with the manual segmentation (0.885±0.118) with α=0.05 and a noninferiority margin of 15%. In addition, higher DSC was reported in patients with milder mandible deformity ( r =0.824, P <0.05). Moreover, intelligent automatic segmentation takes only 6.4 seconds showing great efficiency. CONCLUSIONS: We first proposed a U-net neural convolutional network and achieved automatic segmentation of masseter muscles in patients with HFM. It is a great attempt at intelligent diagnosis and evaluation of craniofacial diseases.
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Síndrome de Goldenhar , Humanos , Músculo Masetero , Inteligencia Artificial , Redes Neurales de la Computación , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
A 65-year-old man complained of choking and hoarseness for fifteen days, and was diagnosed with thyroid carcinoma infiltrating esophagus and trachea. Therefore, the patient underwent thyroidectomy, partial esophagectomy, and partial tracheal resection, and histopathology confirmed primary squamous cell carcinoma of the thyroid. Unfortunately, on the tenth postoperative day, an esophagogastroduodenoscopy showed a large fistula (25 mm*20 mm) in esophageal introitus, and diagnosed with tracheoesophageal fistula due to sustained choking. The patient failed to response to conservative treatment within 14 days. Consequently, endoscopic management was performed that the fistula was partly closed by purse-string suture using endoloop and hemostatic clips, then 1 ml of cyanoacrylate (Compon, China) was injected into the fistulous tract through a catheter. Interestingly, the patient's symptom was relieved after the procedure. And, esophagogastroduodenoscopy revealed healing of the fistula 14 days later.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Fístula Traqueoesofágica , Masculino , Humanos , Anciano , Cianoacrilatos/uso terapéutico , Fístula Traqueoesofágica/cirugía , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas/cirugía , Suturas , Técnicas de SuturaRESUMEN
High internal phase emulsions (HIPEs) provide a versatile platform for encapsulating large volumes of therapeutics that are immiscible in water. A stable scaffold is obtained by polymerizing the external phase, resulting in polyHIPEs. However, fabrication of polyHIPEs usually requires using a considerable quantity of surfactants along with nonbiocompatible components, which hinders their biological applications, e.g., drug-eluting devices. We describe here a straightforward method for generating porous biomaterials by using proteins as both the emulsifier and the building blocks for the fabrication of polyHIPEs. We demonstrate the versatility of this method by using different essential oils as the internal phase. After the gelation of protein building blocks is triggered by the addition of reducing agents, a stable protein hydrogel containing essential oils can be formed. These oils can be either extracted to obtain protein-based porous scaffolds or slowly released for antimicrobial applications.
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Antiinfecciosos , Aceites Volátiles , Antiinfecciosos/farmacología , Materiales Biocompatibles , Emulsiones , Hidrogeles , Aceites Volátiles/farmacología , Porosidad , Sustancias Reductoras , Tensoactivos , AguaRESUMEN
Molecularly imprinted polymers (MIPs) are chemically synthesized affinity materials with tailor-made binding cavities complementary to the template molecules in shape, size, and functionality. Recently, engineering MIP-based nanomedicines to improve cancer therapy has become a rapidly growing field and future research direction. Because of the unique properties and functions of MIPs, MIP-based nanoparticles (nanoMIPs) are not only alternatives to current nanomaterials for cancer therapy, but also hold the potential to fill gaps associated with biological ligand-based nanomedicines, such as immunogenicity, stability, applicability, and economic viability. Here, we survey recent advances in the design and fabrication of nanoMIPs for cancer therapy and highlight their distinct features. In addition, how to use these features to achieve desired performance, including extended circulation, active targeting, controlled drug release and anti-tumor efficacy, is discussed and summarized. We expect that this minireview will inspire more advanced studies in MIP-based nanomedicines for cancer therapy.
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Polímeros Impresos Molecularmente/química , Nanopartículas/química , Animales , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Humanos , Nanomedicina , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores de Superficie Celular/metabolismoRESUMEN
Prodrug and drug delivery systems are two effective strategies for improving the selectivity of chemotherapeutics. Molecularly imprinted polymers (MIPs) have emerged as promising carriers in targeted drug delivery for cancer treatment, but they have not yet been integrated with the prodrug strategy. Reported here is an MIP-based smart prodrug delivery system for specific targeting, prolonged retention time, and tumor microenvironment-triggered release. 5'-Deoxy-5-fluorocytidine (DFCR) and sialic acid (SA) were used as a prodrug and a marker for tumor targeting, respectively. Their co-imprinted nanoparticles were prepared as a smart carrier. Prodrug-loaded MIP specifically and sustainably accumulated at the tumor site and then gradually released. Unlike conventional prodrug designs, which often require in-liver bioconversion, this MIP-based prodrug delivery is liver-independent but tumor-dependent. Thus, this study opens new access to the development of smart prodrug delivery nanoplatforms.
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Sistemas de Liberación de Medicamentos/métodos , Polímeros Impresos Molecularmente/química , Profármacos/química , Humanos , Microambiente TumoralRESUMEN
BACKGROUND AND AIM: Additional simethicone (SIM) can improve adequate bowel preparation and adenoma detection rate (ADR). However, there is no consensus on the optimal dose of SIM. In this study, we compared the adequate bowel preparation rate with supplementation of split-dose 2 L polyethylene glycol (PEG) with low-dose SIM (200 mg) versus high-dose SIM (1200 mg). METHODS: This was a prospective, randomized, observer-blinded trial involving consecutive subjects undergoing colonoscopy. The primary outcome was adequate bowel preparation as assessed by Boston Bowel Preparation Scale (BBPS) score. RESULTS: Four hundred subjects were randomly allocated to low-dose SIM or high-dose SIM group. Baseline characteristics were comparable in the two groups (P > 0.05). No significant between-group differences were observed with respect to total bubble scale (BS) (8.49 ± 1.00 vs 8.39 ± 1.10, P = 0.07), total BBPS score (8.70 ± 0.81 vs 8.29 ± 1.18, P = 0.98), ADR (33.68% vs 31.79%, P = 0.69) or withdrawal time (13 [range, 10-16] min vs 13 [10-15] min, P = 0.96). The intubation time in low-dose SIM group was significantly shorter than that in high-dose SIM group (8 (4-16) min vs 10 [6-17] min, P = 0.04). In addition, BS scores as well as diminutive ADR in right colon were superior in the low-dose SIM group (2.68 ± 0.59 vs 2.52 ± 0.73, P = 0.03 and 54.29% vs 30.30%, P = 0.046, respectively). CONCLUSION: Addition of low-dose SIM to split-dose 2 L PEG was as effective as addition of high-dose SIM with respect to adequate bowel preparation, ADR and patient tolerance. However, low-dose SIM was superior with respect to intubation time, right colon BS scores, right colon diminutive ADR and cost savings.
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Catárticos/administración & dosificación , Colonoscopía/métodos , Polietilenglicoles/administración & dosificación , Simeticona/administración & dosificación , Adenoma/diagnóstico , Adulto , Catárticos/química , Colonoscopía/economía , Neoplasias Colorrectales/diagnóstico , Ahorro de Costo , Tolerancia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
In sonodynamic therapy (SDT), when Chlorin e6 (Ce6) accumulates in tumor tissues, its anti-tumor effect can be achieved by ultrasound activation. To increase the local drug concentration of Ce6 in tumor cells, we had established a novel drug delivery system, Ce6-loaded sonosensitive magnetic nanoliposome (Ce6/SML), which realized the targeting delivery by the external magnetic field. It was worth mentioning that the targeting release of Ce6/SML and the activation on Ce6 could be achieved simultaneously by ultrasound of SDT. In our study, after Ce6 was loaded into the sonosensitive magnetic nanoliposome (SML), the values of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in vitro and in vivo were determined, indicating the activation on Ce6 of ultrasound. The delivery system also displayed the tumor-targeting ability and anti-tumor activity, which associated with the determined tumor growth and expression levels of angiogenin (ANG), vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α). In conclusion, the Ce6/SML-SDT-Targeted delivery system could effectively enhance the anti-tumor activity of SDT and had a great potential application for the treatment of malignant tumors located in deep tissues.
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Fenómenos Magnéticos , Nanopartículas , Porfirinas/farmacología , Terapia por Ultrasonido/métodos , Células A549 , Animales , Clorofilidas , Sistemas de Liberación de Medicamentos , Humanos , Liposomas , Neoplasias Pulmonares/terapia , Campos Magnéticos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Porfirinas/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Surface properties are an essential feature in a wide range of functional materials. In this article, we summarize strategies developed in our group that employ nanoparticles and proteins as nanobricks to create thin-film coatings on surfaces. These coatings contain tailorable surface functionality based on the properties of the predesigned nanobricks, parlaying both the chemical and structural features of the precursor particles and proteins. This strategy is versatile, providing the rapid generation of both uniform and patterned coatings that provide "plug-and-play" customizable surfaces for materials and biomedical applications.
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Materiales Biocompatibles Revestidos/química , Nanopartículas/química , Proteínas/química , Animales , Humanos , Retratos como Asunto , Propiedades de SuperficieRESUMEN
Kinesin spindle protein (KSP) is a microtubule-associated motor protein that is specifically expressed by mitosis cells. It is highly expressed in various types of tumors including hematomalignances and solid tumors. Chemical KSP inhibition has become a novel strategy in the development of anticancer drugs. SB743921 is a selective inhibitor for KSP, which is a mitotic protein essential for cell-cycle progression. Although SB743921 has shown antitumor activities for several types of cancers and entered into clinical trials, its therapeutic effects on breast cancer and mechanisms have not been explored. In this study, we tested the antitumor activity of SB743921 in breast cancer cell lines and partly elucidated its mechanisms. KSP and denticleless E3 ubiquitin-protein ligase homolog (DTL) are overexpressed in breast cancer cells compared with no-cancer tissues. Chemical inhibition of KSP by SB743921 not only reduces proliferation but also induces cell-cycle arrest and leads to apoptosis in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 breast cancer cell lines with SB743921 results in decreased ability of colony formation in culture. SB743921 treatment also causes a KSP accumulation in protein level that is associated with cell arrest. Furthermore, we showed that SB743921 treatment significantly reduces the expression of bcl-2 and cell cycle-related protein DTL, and upregulates p53 and caspase-3 in breast cancer cells. Taken together, these data indicated that SB743921 can be expected to be a novel treatment agent for breast cancers.
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Benzamidas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Cromonas/farmacología , Cinesinas/antagonistas & inhibidores , Proteínas Nucleares/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Cinesinas/metabolismo , Células MCF-7 , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box-Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (Jss) of SIN from PLO was 146.55 ± 2.93 µg/cm(2)/h, significantly higher than that of gel (120.39 µg/cm(2)/h) and the amount of SIN deposited in skin from the PLO was 10.08 ± 0.86 µg/cm(2), significantly larger than that from gel (6.01 ± 0.04 µg/cm(2)). In vivo skin microdialysis studies showed that the maximum concentration (Cmax) of SIN from PLO in "permeation study" and "drug-deposition study" were 150.27 ± 20.85 µg/ml and 67.95 µg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73 µg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.
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Antirreumáticos/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Lecitinas/metabolismo , Morfinanos/metabolismo , Poloxámero/metabolismo , Absorción Cutánea/fisiología , Administración Cutánea , Animales , Antirreumáticos/administración & dosificación , Evaluación Preclínica de Medicamentos/métodos , Geles , Lecitinas/administración & dosificación , Masculino , Morfinanos/administración & dosificación , Técnicas de Cultivo de Órganos , Poloxámero/administración & dosificación , Ratas , Ratas Sprague-Dawley , Absorción Cutánea/efectos de los fármacosRESUMEN
A temperature-sensitive matrine-imprinted polymer was prepared in chloroform by free-radical cross-linking copolymerization of methacrylic acid at 60 °C in the presence of ethylene glycol dimethacrylate as the cross-linker, N-isopropyl acrylamide as the temperature-responsive monomer and matrine as the template molecule. Binding experiments and Scatchard analyses revealed that two classes of binding sites were formed on molecular imprinted polymer (MIP) at 50 °C. Additionally, the thermoresponsive MIP was tested for its application as a sorbent material for the selective separation of matrine from Chinese medicinal plant radix Sophorae tonkinensis. It was shown that the thermoresponsive MIP displayed different efficiency in clean-up and enrichments using the SPE protocol at different temperatures.
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Alcaloides/química , Impresión Molecular , Polímeros/química , Quinolizinas/química , Sophora/química , Temperatura , Estructura Molecular , Polímeros/síntesis química , MatrinasRESUMEN
Soft actuators made of soft materials cannot generate precisely efficient output forces compared to rigid actuators. It is a promising strategy to equip soft actuators with variable stiffness modules of layer jamming mechanism, which could increase their stiffness as needed. Inspired by the gecko's the array of setae, bionic adhesive flaps with inclined micropillars are applied in layer jamming mechanism. In this paper, after the manufacturing process of the layer jamming actuator based on the bionic adhesive flaps is described, the equivalent stiffness models of the whole actuator are established in the unjammed and jammed states. And the shear adhesive force of a single micropillar is calculated based on the Kendall viscoelastic band model. The finite element simulation results of two bionic adhesive flaps show that the interlaminar shear stress and stiffness increase with the increase of pressure. The measurement of shear adhesive force show that the critical shear adhesive force of the bionic adhesive material is 3.2 times that of polyethylene terephthalate (PET) material, and exhibit the ability of anisotropic adhesion behavior. The variable stiffness performance of the layer jamming actuator based on bionic adhesive flaps is evaluated by three test methods, and the max stiffness reaches 8.027 N mm-1, which is 1.5 times higher than the stiffness of the layer jamming actuator based on the PET flaps. All results of simulation and experiment effectively verify the validity and superiority of applying the bionic adhesive flaps to the layer jamming mechanism to enhance the stiffness.
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Adhesivos , Materiales Biomiméticos , Biónica , Diseño de Equipo , Animales , Adhesivos/química , Análisis de Elementos Finitos , Lagartos/fisiología , Simulación por Computador , Robótica/instrumentación , Biomimética/métodos , Tereftalatos Polietilenos/química , Estrés MecánicoRESUMEN
Cancer treatment is presently a significant challenge in the medical domain, wherein the primary modalities of intervention include chemotherapy, radiation therapy and surgery. However, these therapeutic modalities carry side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as promising modalities for the treatment of tumors in recent years. Phototherapy is a therapeutic approach that involves the exposure of materials to specific wavelengths of light, which can subsequently be converted into either heat or Reactive Oxygen Species (ROS) to effectively eradicate cancer cells. Due to the hydrophobicity and lack of targeting of many photoresponsive materials, the use of nano-carriers for their transportation has been extensively explored. Among these nanocarriers, liposomes have been identified as an effective drug delivery system due to their controllability and availability in the biomedical field. By binding photoresponsive materials to liposomes, it is possible to reduce the cytotoxicity of the material and regulate drug release and accumulation at the tumor site. This article provides a comprehensive review of the progress made in cancer therapy using photoresponsive materials loaded onto liposomes. Additionally, the article discusses the potential synergistic treatment through the combination of phototherapy with chemo/immuno/gene therapy using liposomes.
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Liposomas , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Animales , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Fototerapia/métodos , Terapia Fototérmica/métodosRESUMEN
The proliferation of nitrite oxidizing bacteria (NOB) still remains as a major challenge for nitrogen removal in mainstream wastewater treatment process based on partial nitrification (PN). This study investigated different operational conditions to establish mainstream PN for the fast start-up of membrane aerated biofilm reactor (MABR) systems. Different oxygen controlling strategies were adopted by employing different influent NH4+-N loads and oxygen supply strategies to inhibit NOB. We indicated the essential for NOB suppression was to reduce the oxygen concentration of the inner biofilm and the thickness of aerobic biofilm. A higher NH4+-N load (7.4 g-N/(m2·d)) induced higher oxygen utilization rate (14.4 g-O2/(m2·d)) and steeper gradient of oxygen concentration, which reduced the thickness of aerobic biofilm. Employing closed-end oxygen supply mode exhibited the minimum concentration of oxygen to realize PN, which was over 46% reduction of the normal open-end oxygen mode. Under the conditions of high NH4+-N load and closed-end oxygen supply mode, the microbial community exhibited a comparative advantage of ammonium oxidizing bacteria over NOB in the aerobic biofilm, with a relative abundance of Nitrosomonas of 30-40% and no detection of Nitrospira. The optimal fast start-up strategy was proposed with open-end aeration mode in the first 10 days and closed-end mode subsequently under high NH4+-N load. The results revealed the mechanism of NOB inhibition on the biofilm and provided strategies for a quick start-up and stable mainstream PN simultaneously, which poses great significance for the future application of MABR.
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Biopelículas , Reactores Biológicos , Nitrificación , Oxígeno , Oxígeno/metabolismo , Eliminación de Residuos Líquidos/métodos , Nitrógeno/metabolismo , Membranas Artificiales , Aguas Residuales/químicaRESUMEN
Dental pulp stem cells (DPSCs) derived from discarded orthodontic teeth are easily obtained and have become a promising source for mesenchymal stem cell-based therapy. However, the pulp tissue is limited, and long-term culture induces cell senescence. Hypoxic culture was expected to be suitable for DPSC expansion, but the results have been contradictory. The aim of this study was to verify the effect of hypoxic culture on human DPSCs (hDPSCs). hDPSCs were isolated and cultured in normoxic (ambient O2 concentration) and hypoxic (5% O2) environments from passage 3 (P3) to P6. The biological characteristics of the cells at P4 (short-term culture) and P6 (long-term culture) were evaluated, including the expression of surface markers, cellular proliferation activity, cellular senescence, and spontaneous and induced differentiation. The results showed that the morphology, phenotype, and proliferation activity of hDPSCs were not affected by hypoxic culture. Long-term normoxic culture of hDPSCs induced cell stemness loss and cell senescence, while hypoxic culture could alleviate these effects. The expression of the stemness markers STRO-1 and OCT4 was increased and the number of senescent cells and the expression of the senescence-related genes P53 and TGF-ß were reduced by long-term hypoxic culture. Spontaneous osteogenic and adipogenic differentiation did not occur during long-term normoxic culture. However, hypoxic culture suppressed the expression of the osteogenic markers ALP and RUNX-2 and the adipogenic markers PPAR-γ and FABP4. The induced osteogenic and adipogenic differentiation was apparently reduced by hypoxic culture as well. Our findings indicate that long-term hypoxia culture is beneficial to the maintenance of hDPSCs' biological characteristics and provide some insights into their large-scale expansion.
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Pulpa Dental , Células Madre Mesenquimatosas , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Humanos , Hipoxia/metabolismo , OsteogénesisRESUMEN
Compartmentalized micelles (CMs) are promising tailor-made soft matters that mimic natural designed structures and functions. Despite the structure of complex CMs, manipulating CM structures accessibly and reversibly remains elusive. Here, we report the fabrication of CMs via a generally valid noncovalent postmodification process. Starting from precursor micelles (PMs) based on one diblock copolymer, aromatic modification leads to the compartmentalization of PMs into well-defined spherical CMs. Control over compartment number, size and distribution in CMs, and segment distribution in their linear hierarchical assemblies is attained by simply tuning the postmodification degree and solvent composition. We also demonstrate the reversible transformation between PM and CMs during several heating-cooling cycles, which endows the micelles with potential in reversible functional transitions in situ close to nature's capability. Moreover, both hierarchically assembled or ill-structured micelles can rearrange into homogeneous CMs after one heating-cooling cycle, featuring the postmodification guided compartmentalization strategy with unprecedented micelle reproducibility.
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Micelas , Polímeros , Polímeros/química , Reproducibilidad de los ResultadosRESUMEN
In this paper, a new method was presented which can generate dental panoramic radiographs from the 3D CT sectional data. The dental panoramic radiograph was generated by casting ray into the 3D sectional data from a curved surface close to the dental arch. With this method, the relationship between the 3D CT sectional data and the dental panoramic radiographs was built, which helped to overcome the defects in the real X-ray panoramic radiographs, such as structure overlap and unselectable content for displaying. The technology is of certain significance in computer aided technique and surgical planning related to dentistry.
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Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional/métodos , Radiografía Panorámica/métodos , Tomografía Computarizada por Rayos X/métodos , HumanosRESUMEN
Nosocomial infections, caused by bacterial contamination of medical devices and implants, are a serious healthcare concern. We demonstrate here, the use of fluorous-cured protein nanofilm coatings for generating antimicrobial surfaces. In this approach, bacteria-repelling films are created by heat-curing proteins in fluorous media. These films are then loaded with antibiotics, with release controlled via electrostatic interactions between therapeutic and protein film building blocks to provide bactericidal surfaces. This film fabrication process is additive-free, biocompatible, biodegradable, and can be used to provide antimicrobial coatings for both three-dimensional (2D) and 3D objects for use in indwelling devices.
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Antibacterianos/farmacología , Incrustaciones Biológicas/prevención & control , Materiales Biocompatibles Revestidos/química , Preparaciones de Acción Retardada/química , Animales , Antibacterianos/química , Bovinos , Colistina/química , Colistina/farmacología , Liberación de Fármacos , Fluoresceína/química , Colorantes Fluorescentes/química , Fluorocarburos/química , Prótesis e Implantes , Pseudomonas aeruginosa/efectos de los fármacos , Rodamina 123/química , Albúmina Sérica Bovina/químicaRESUMEN
In situ generation of antibacterial and antiviral agents by harnessing the catalytic activity of enzymes on surfaces provides an effective eco-friendly approach for disinfection. The perhydrolase (AcT) from Mycobacterium smegmatis catalyzes the perhydrolysis of acetate esters to generate the potent disinfectant, peracetic acid (PAA). In the presence of AcT and its two substrates, propylene glycol diacetate and H2O2, sufficient and continuous PAA is generated over an extended time to kill a wide range of bacteria with the enzyme dissolved in aqueous buffer. For extended self-disinfection, however, active and stable AcT bound onto or incorporated into a surface coating is necessary. In the current study, an active, stable and reusable AcT-based coating was developed by incorporating AcT into a polydopamine (PDA) matrix in a single step, thereby forming a biocatalytic composite onto a variety of surfaces. The resulting AcT-PDA composite coatings on glass, metal and epoxy surfaces yielded up to 7-log reduction of Gram-positive and Gram-negative bacteria when in contact with the biocatalytic coating. This composite coating also possessed potent antiviral activity, and dramatically reduced the infectivity of a SARS-CoV-2 pseudovirus within minutes. The single-step approach enables rapid and facile fabrication of enzyme-based disinfectant composite coatings with high activity and stability, which enables reuse following surface washing. As a result, this enzyme-polymer composite technique may serve as a general strategy for preparing antibacterial and antiviral surfaces for applications in health care and common infrastructure safety, such as in schools, the workplace, transportation, etc.
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Antibacterianos/química , Antivirales/química , Proteínas Bacterianas/química , Hidrolasas/química , Indoles/química , Polímeros/química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Antivirales/metabolismo , Antivirales/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , COVID-19/patología , COVID-19/virología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/metabolismo , Materiales Biocompatibles Revestidos/farmacología , Estabilidad de Medicamentos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Hidrolasas/genética , Hidrolasas/metabolismo , Cinética , Mycobacterium smegmatis/enzimología , Ácido Peracético/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , SARS-CoV-2/efectos de los fármacosRESUMEN
Radiation therapy can cause haematopoietic damage, and mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) have been shown to reverse this damage. Our previous research showed that dental pulp stem cells (DPSCs) have a strong proliferation capacity and can produce abundant amounts of EVs to meet the requirements for use in vitro and in vivo. DPSCs derived EVs (DPSCs-EVs) are evaluated for their effect on reducing haematopoietic damage. Haematopoietic stem cell (HSC) numbers and function were assessed by flow cytometry, peripheral blood cell counts, histology and bone marrow transplantation. Epidermal growth factor (EGF) was used as a reference for evaluating the efficiency of EVs. miRNA microarray was employed to find out the changes of miRNA expression after cells being irradiated in vivo and the role they may play in mitigation the radiation caused injury. We observed the effect of DPSCs-EVs on promoting proliferation and inhibiting apoptosis of human umbilical vein endothelial cells (HUVECs) and FDC-P1 cells in vitro. We found that DPSCs-EVs and EGF could comparably inhibit the decrease in WBC, CFU count and KSL cells in vivo. We also verified that EVs could accelerate the recovery of long-term HSCs. In summary, DPSCs-EVs showed an apoptosis resistant effect on HUVECs and FDC-P1 cells after radiation injury in vitro. EVs from DPSCs were comparable to EGF in their ability to regulate haematopoietic regeneration after radiation injury in vivo. Radiation could alter the expression of some miRNAs in bone marrow cells, and EVs could correct these changes to some extent. Graphical abstract.