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The outstanding chemical and physical properties of 2D materials, together with their atomically thin nature, make them ideal candidates for metaphotonic device integration and construction, which requires deep subwavelength light-matter interaction to achieve optical functionalities beyond conventional optical phenomena observed in naturally available materials. In addition to their intrinsic properties, the possibility to further manipulate the properties of 2D materials via chemical or physical engineering dramatically enhances their capability, evoking new science on light-matter interaction, leading to leaped performance of existing functional devices and giving birth to new metaphotonic devices that were unattainable previously. Comprehensive understanding of the intrinsic properties of 2D materials, approaches and capabilities for chemical and physical engineering methods, the resulting property modifications and novel functionalities, and applications of metaphotonic devices are provided in this review. Through reviewing the detailed progress in each aspect and the state-of-the-art achievement, insightful analyses of the outstanding challenges and future directions are elucidated in this cross-disciplinary comprehensive review with the aim to provide an overall development picture in the field of 2D material metaphotonics and promote rapid progress in this fast emerging and prosperous field.
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Óptica y Fotónica , HumanosRESUMEN
Chemical modifications of enzymes excel in the realm of enzyme engineering due to its directness, robustness, and efficiency; however, challenges persist in devising versatile and effective strategies. In this study, we introduce a supramolecular modification methodology that amalgamates a supramolecular polymer with Candida antarctica lipaseâ B (CalB) to create supramolecular enzymes (SupEnzyme). This approach features the straightforward preparation of a supramolecular amphiphilic polymer (ß-CD@SMA), which was subsequently conjugated to the enzyme, resulting in a SupEnzyme capable of self-assembly into supramolecular nanoparticles. The resulting SupEnzyme nanoparticles can form micron-scale supramolecular aggregates through supramolecular and electrostatic interactions with guest entities, thus enhancing catalyst recycling. Remarkably, these aggregates maintain 80 % activity after seven cycles, outperforming Novozym 435. Additionally, they can effectively initiate photobiocatalytic cascade reactions using guest photocatalysts. As a consequence, our SupEnzyme methodology exhibits noteworthy adaptability in enzyme modification, presenting a versatile platform for various polymer, enzyme, and biocompatible catalyst pairings, with potential applications in the fields of chemistry and biology.
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Nanopartículas , Polímeros , Polímeros/química , Catálisis , Nanopartículas/químicaRESUMEN
Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a persistent infectious disease with significant global impact. Amidst the challenges presented by tuberculosis, optimizing infection control and management for acute and critically ill patients remains imperative. This study addresses this need by investigating the efficacy of standardized risk management in enhancing care outcomes. Objective: The study aims to investigate the impact of standardized risk management on infection control and the management of acute and critically ill patients in a tuberculosis clinic. Design: A randomized controlled experiment was employed for this study. Setting: The research took place at Qingdao Haici Medical Group. Participants: A total of 96 patients with acute and severe tuberculosis treated in the outpatient department from January 2020 to December 2022 were randomly assigned to the control group (CG) and the observation group (OG), with 48 cases in each group. Interventions: Patients in the CG received conventional management, while those in the OG underwent standardized risk management. Primary Outcome Measures: (1) incidence of infection events; (2) quality of management; (3) outpatient health indicators; and (4) patient satisfaction. Results: The OG exhibited a lower incidence of infection events compared to the CG (P < .05). Quality management scores were higher in the OG (P < .05). The OG demonstrated a higher qualified rate in air quality, disinfectant standards, hand hygiene, and mechanical use compared to the CG (P < .05). Patient satisfaction was higher in the OG (χ2=7.21, P < .05). Conclusions: The application of standardized risk management in infection control and management of acute and critically ill patients in tuberculosis clinics significantly reduced the incidence of infection events and improved patient satisfaction with nursing. This approach is considered worthy of widespread implementation.
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Competition from hydrogen/oxygen evolution reactions and low solubility of N2 in aqueous systems limited the selectivity and activity on nitrogen fixation reaction. Herein, we design an aerobic-hydrophobic Janus structure by introducing fluorinated modification on porous carbon nanofibers embedded with partially carbonized iron heterojunctions (Fe3 C/Fe@PCNF-F). The simulations prove that the Janus structure can keep the internal Fe3 C/Fe@PCNF-F away from water infiltration and endow a N2 molecular-concentrating effect, suppressing the competing reactions and overcoming the mass-transfer limitations to build a robust "quasi-solid-gas" state micro-domain around the catalyst surface. In this proof-of-concept system, the Fe3 C/Fe@PCNF-F exhibits excellent electrocatalytic performance for nitrogen fixation (NH3 yield rate up to 29.2â µg h-1 mg-1 cat. and Faraday efficiency (FE) up to 27.8 % in nitrogen reduction reaction; NO3 - yield rate up to 15.7â µg h-1 mg-1 cat. and FE up to 3.4 % in nitrogen oxidation reaction).
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The outbreak of Coronavirus Disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered great global public health concern. Face masks are essential tools to reduce the spread of SARS-CoV-2 from human to human. However, there are still challenges to prolong the serving life and maintain the filtering performance of the current commercial mask. Filters composed of ultrafine fibers with diameter down to tens of nanometers have the potential to physically block viruses. With adjustable composition and nanostructures, the electrospun ultrafine fiber filter is possible to achieve other necessary functions beyond virus blocking, such as antiviral, transparent, and degradable, making it an important part of fighting the epidemic. In this review, beginning with the basic information of the viruses, we summarize the knowledge of masks and respirators, including the filtering mechanism, structure, classification, and standards. We further present the fabrication method, filtering performance, and reusable potential of electrospun ultrafine fiber-based masks. In the end, we discuss the development directions of ultrafine fibers in protective devices, especially their new functional applications and possible contributions in the prevention and control of the epidemic.
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BACKGROUND/AIMS: C reactive protein (CRP) levels are elevated in many diseases, including malignant tumors and cardiovascular disorders. In this study, the protein interaction network for CRP was evaluated to determine the importance of CRP and its interacting proteins in the molecular pathogenesis of hepatocellular carcinoma (HCC). METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometry were used to identify CRP interacting proteins in SMMC7721 cells. Moreover, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to evaluate enriched genes and pathways for differentially expressed genes using DAVID and WebGestalt. Co-immunoprecipitation and western blot analyses were employed to assess interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. RESULTS: In total, 52 proteins that interact with CRP were identified. A GO analysis suggested that most of the interacting proteins were involved in CRP complexes and regulated metabolic processes. A KEGG pathway analysis suggested that most CRP-interacting proteins contribute to the TRAIL signaling pathway, Class I PI3K/Akt signaling pathway, plasma membrane estrogen receptor signaling, Nectin adhesion pathway, and S1P1 pathway. Immunoprecipitation and western blot analyses revealed interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. CONCLUSIONS: iTRAQ based proteomic profiling revealed the network of CRP interacting proteins. This network may activate the PI3K/Akt signaling pathway, thereby contributing to the pathogenesis of HCC.
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Proteína C-Reactiva/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteómica , Anexina A2/metabolismo , Proteína C-Reactiva/antagonistas & inhibidores , Proteína C-Reactiva/genética , Carcinoma Hepatocelular/metabolismo , Perfilación de la Expresión Génica , Humanos , Queratina-8/metabolismo , Neoplasias Hepáticas/metabolismo , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Nectinas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Mapas de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismoRESUMEN
BACKGROUND: Liuweiwuling tablets (LWWL) are an herbal product that exerts remarkable effects on liver protection and aminotransferase levels, and they have been approved by the Chinese State Food and Drug Administration (CFDA). Clinical studies have found that LWWL can inhibit collagen production and reduce the levels of liver fibrosis markers in the serum. Thus, LWWL is expected to have beneficial effects in the treatment of liver fibrosis. The purpose of this study was to evaluate the pharmacological effects of LWWL. METHODS: Hepatic fibrosis was induced in rats via carbon tetrachloride (CCl4) treatment. The rats were treated twice weekly for 8 weeks with either 2 mL·kg- 1 body weight of a 50% solution of CCl4 in olive oil or olive oil alone by oral gavage. A subset of rats received daily intraperitoneal injections of either colchicine (0.2 mg/kg per day), LWWL (0.4, 1.6, or 6.4 g/kg per day), or vehicle (N = 12 for all groups) during weeks 9-12. The rats were sacrificed after 12 weeks. Pathological changes in hepatic tissue were examined using hematoxylin and eosin (H&E) and Sirius Red staining. Immunohistochemistry was performed to observe α-smooth muscle actin (α-SMA) and collagen type I (collagen I) protein expression. Western blotting was also used to detect α-SMA protein expression. Real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect transforming growth factor-1 (TGF-ß1), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinase-1 (TIMP1), and tissue inhibitor of metalloproteinase-2 (TIMP2) mRNA expression. RESULTS: LWWL significantly reversed histological fibrosis and liver injury, reduced the hydroxyproline content in liver tissue, and decreased α-SMA and collagen I expression. LWWL also suppressed hepatic stellate cell (HSC) activation by reducing the expression of the profibrogenic factors TGF-ß1 and PDGF. The expression levels of TIMP1 and TIMP2, which regulate extracellular matrix (ECM) degradation, were decreased after CCl4 injury in LWWL-treated rats. CONCLUSIONS: These data suggest that LWWL may serve as a promising therapeutic agent to reduce fibrogenesis.
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Medicamentos Herbarios Chinos/administración & dosificación , Cirrosis Hepática/tratamiento farmacológico , Animales , Tetracloruro de Carbono/efectos adversos , Humanos , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Comprimidos/administración & dosificación , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
This paper was aimed to investigate the protective effects of luteolin (Lut) against acetaminophenï¼APAPï¼-induced damage in L02 liver cells. CCK-8 was used to detect the cell activation of L02 cells treated by different Lut. The concentration and time of APAP induced L02 cell damage was screened. The effect of Lut on APAP induced apoptosis of L02 cells was detected by cell morphological observation, CCK-8 assay and flow cytometry. The contents of MDA, GSH and SOD activity in cell supernatant were detected by colorimetric assay. The expression of apoptosis-related genes Bax, Bcl-2 and caspase-3 was detected by RT-PCR. The results showed that Lut in 2.5-40 µmolâ¢L⻹ range does not affect the activity of L02 cells; 12 mmolâ¢L⻹ APAP incubated with L02 cell 12 h to establish damage model. Compared with the model group, the cell status of Lut group was significantly improved, the cell body was increased, the adherence ability was recovered, and the apoptosis rate was obviously decreased. MDA content decreased significantly (P<0.05, P<0.01), GSH and SOD activity significantly increased (P<0.05, P<0.01), at the same time, it could up-regulate expression of Bcl-2 mRNA and down-regulate the expression of Bax and caspase-3 mRNA. In conclusion,Lut has protective effect on APAP induced L02 cell injury, and its mechanism may be related to the reduction of oxidative stress and inhibition of apoptosis.
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Acetaminofén/toxicidad , Hepatocitos/efectos de los fármacos , Luteolina/farmacología , Sustancias Protectoras/farmacología , Apoptosis , Caspasa 3/metabolismo , Línea Celular , Humanos , Hígado , Malondialdehído/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Superóxido Dismutasa/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Glomerella leaf spot (GLS) caused by Glomerella cingulata is a newly emergent disease that results in severe defoliation and fruit spots. Currently, GLS is not effectively controlled in China due to a lack of understanding of its epidemiology. Therefore, the effects of temperature, wetness duration, and moisture on conidial germination, infection, and the disease incubation period of GLS were examined by inoculating cv. Gala apple leaves with a conidial suspension and performing in vitro germination assays. Conidia could germinate and form appressoria at temperatures ranging from 5 to 35°C, with an optimum temperature of 27.6°C. The germination of conidia required free water or a nearly saturated relative humidity, with only a few conidia germinating and forming appressoria when the RH was less than 99%. The conidial germination dynamics at 10, 25, and 30°C were well represented by three logistic models. The infection of cv. Gala apple leaves by conidia occurred at temperatures ranging from 15 to 35°C. The minimum wetness duration required for infection by conidia at different temperatures was described using a polynomial equation, and the lowest minimum wetness duration was 2.76 h, which occurred at 27.6°C according to the polynomial. Successful infection by conidia was represented by the number of lesions per leaf, which increased with extended wetness durations at the conidial infection stage for six tested temperatures, with the exception of 10°C, when the minimum wetness durations were satisfied. The associations of successfully infected conidia with wetness duration at temperatures of 15, 20, 25, and 30°C were described by four logistic models. Conidia infections developed into visible lesions at temperatures ranging from 15 to 30°C, and the shortest incubation period of 2 days was observed at 25°C. These data and models can be used to construct forecasting models and develop effective control systems for Glomerella leaf spot.
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Due to the pressure of the ecological environment and government, it is incumbent for enterprises to undertake corporate social responsibility (CSR). However, during the recycling process, awareness of equity concerns due to the distribution of benefits among members has intensified, and it is crucial to resolve channel conflicts and design a reasonable cooperation model to recycle used power batteries. Therefore, this paper constructs a closed-loop supply chain composed of power battery manufacturer, retailer and third-party collector based on the consideration of cascade utilization, in order to study the impact of the level of CSR and the degree of fairness concern on the decision-making of channel participants. Our research shows that: (1) Fairness concern behavior adversely affects the supply chain, which raises the sales price and reduces the collecting rate and the utility of the supply chain as a whole. (2) Undertaking CSR is beneficial to the development of the power battery market, and also helps to reduce the sense of unfairness among third-party recycling companies. (3) The cost-sharing contract effectively coordinates the distribution of supply chain benefits and improves the recycling rate. Finally, we further verify the correctness of the conclusions through numerical studies.
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Acorus tatarinowii Schott is a traditional Chinese medicine used to treat memory and cognitive dysfunction. Because of their efficacy and lower toxic effects, research on α- and ß-asarone, the phytoconstituents, has attracted attention owing to their remarkable pharmacological activities. Silver ion coordination complexation high-speed counter-current chromatography was used to separate these isomers from A. tatarinowii extract, coupled with accelerated solvent extraction. Accelerated solvent extraction parameters were investigated with single-factor and orthogonal testing. A two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (2:1:2:1, v/v) with 0.50 mol/L silver ions was selected for separation. From 2.0 g crude extract, 1.4 g of ß-asarone and 0.09 g of α-asarone were obtained with purities over 98% by sequential sample loading in 20 h. The isolated compounds were identified by electrospray ionization mass spectrometry, 1H and 13C NMR. Silver ions significantly increased the separation factor and retention of the stationary phase. The chromatographic behavior indicated that cis-configuration was more strongly complexed with the silver ion. This was further demonstrated with the help of computational analysis. In conclusion, the established method could be employed to separate other cis-trans or E/Z isomers that form coordination complexes.
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Acorus/química , Anisoles/análisis , Distribución en Contracorriente/métodos , Acorus/metabolismo , Derivados de Alilbenceno , Anisoles/aislamiento & purificación , Teoría Funcional de la Densidad , Isomerismo , Extracción Líquido-Líquido , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Plata/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
In this work a novel, relatively simple, and fast method for patterning of gold nanoparticles (Au NPs) on poly(ethylene glycol) (PEG)-based hydrogels is presented. In the hereby exploited reactive micro-contact printing (reactive-µ-CP) process, the surface of a micro-relief patterned PDMS-stamp is first functionalized with an amino-silane self-assembled monolayer (SAM), which is then inked with Au NPs. The stamp is subsequently brought into conformal contact with thiol-functionalized PEG-based hydrogel films. Due to the strong gold-thiol interactions the Au NPs are adequately and easily transferred onto the surfaces of these soft, multifunctional PEG hydrogels. In this way, defined µ-patterns of Au NPs on PEG hydrogels are achieved. These Au NPs patterns allow specific biomolecular interactions on PEG surfaces, and cell adhesion has been studied. Cells were found to effectively adhere only on Au NPs micro-patterns and to avoid the anti-adhesive PEG background. Besides the cell adhesion studies, these Au NPs µ-patterns can be potentially applied as biosensors in plasmon-based spectroscopic devices or in medicine, e.g., for drug delivery systems or photothermal therapies.
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Phytophthora fruit rot, caused by Phytophthora cactorum, is an important disease of apple in China, often causing more than 50% fruit rot in rainy years. We examined the effects of temperature and moisture on the development of the disease and effects of the variables on zoospore release and germination, infection, and lesion development. In vitro, a temperature range of 5 to 20°C had no significant effects on zoospore release dynamics but did significantly affect the quantities of released zoospores. The largest quantity of zoospores was released at 9.9°C according to a fitted model. Zoosporangia released zoospores within 15 min at the test temperatures (0 to 20°C), which peaked at the fourth hour. Zoospores germinated in vitro, requiring free water, at temperatures from 5 to 35°C. The optimum germination temperature was 25.1°C according to a fitted model. The minimum wetness duration required for zoospores to complete the infection process and induce visible lesions on Fuji fruit was 0.40 h at the optimal temperature of 23.0°C according to the fitted model, whereas observed values were 4.5, 1.5, 0.5, 1.5 and 8.5 h at 10, 15, 20, 25, and 30°C, respectively. The number of zoospore infections on fruit at various temperatures and wetness durations were well fitted by the modified Weibull model; based on the model, the optimal temperature for zoospore infections was 23.0°C. Young apple fruit infected by zoospores developed visible lesions from 10 to 30°C, with a predicted optimum of 23.5°C; no lesions developed at 5 or 35°C. The shortest incubation period of the disease was 4 days. These results can be used to develop disease forecasting models for improved fungicide control.
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Malus/parasitología , Phytophthora/fisiología , Enfermedades de las Plantas/parasitología , Frutas/parasitología , Phytophthora/crecimiento & desarrollo , Raíces de Plantas/parasitología , Temperatura , AguaRESUMEN
The network structure of hydrogels is a vital factor to determine their physical properties. Two network structures within hydrogels based on eight-arm star-shaped poly(ethylene glycol)(8PEG) have been obtained; the distinction between the two depends on the way in which the macromonomers were crosslinked: either by (i) commonly-used photo-initiated chain-growth polymerization (8PEGâ»UV), or (ii) Michael addition step-growth polymerization (8PEGâ»NH3). The crystallization of hydrogels is facilitated by a solvent drying process to obtain a thin hydrogel film. Polarized optical microscopy (POM) results reveal that, while in the 8PEGâ»UV hydrogels only nano-scaled crystallites are apparent, the 8PEGâ»NH3 hydrogels exhibit an assembly of giant crystalline domains with spherulite sizes ranging from 100 to 400 µm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses further confirm these results. A model has been proposed to elucidate the correlations between the polymer network structures and the crystallization behavior of PEG-based hydrogels.
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This study was aimed to investigate the effect of Forkhead Box G1 (FOXG1) on the epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells and the underlying mechanism. For this purpose, FOXG1 lentiviral interference (shRNA) plasmid and expression plasmid were constructed. Western blotting was used to analyze the expression of FOXG1 protein in five CRC cells, namely RKO, SW480, SW620, LoVo and DLD-1. The shRNA fragment of FOXG1 (shFOXG1) was designed and synthesized. Recombinant plasmids were obtained with the aid of DNA recombination technique. Double digestion and sequencing were used to identify the recombinant plasmids, and then lentivirus packaging, purification and stable transfection were carried out. Additionally, stable CRC cell lines were screened out. The changes of FOXG1 knockdown and overexpression efficiency, E-cadherin, Vimentin, Fibronectin, Snail, Twist mRNA and protein were investigated respectively by Western blotting and qRT-PCR analysis. Furthermore, the changes of cell morphology after knockdown and cell migration ability were evaluated respectively with optical microscopy, scratch test and Transwell assay. FOXG1 had the highest protein expression in RKO and the lowest in DLD-1 among the five CRC cells. Compared with those of the control group, the cell morphology in FOXG1 knockdown RKO group was changed from spindle into round or polygonal shape, cell polarization was enhanced and tight junction assembly was acclerated while cell migration distance was noticeably decreased. Moreover, the number of cells invaded and migrated through chambers was significantly reduced. Among these key factors of EMT, the expression of E-cadherin was increased while the expressions of Vimentin, Fibronectin, Snail and Twist were decreased. The opposite was the case in the overexpressed FOXG1 group. The overexpression of FOXG1 in CRC promoted the invasion and metastasis of CRC cells and played a crucial role in regulating the EMT. Thus, FOXG1 might be a novel therapeutic target in CRC treatment.
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Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal , Factores de Transcripción Forkhead/metabolismo , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteínas del Tejido Nervioso/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , HumanosRESUMEN
We report on a versatile and easy approach to micro-pattern gold nanoparticles (Au NPs) on 8-arm poly(ethylene glycol)-vinyl sulfone thiol (8PEG-VS-SH) hydrogels, and the application of these patterned Au NPs stripes in controlling cell adhesion. Firstly, the Au NPs were patterned on silicon wafers, and then they were transferred onto reactive, multifunctional 8PEG-VS-SH hydrogels. The patterned, micrometer-sized Au NPs stripes with variable spacings ranging from 20 µm to 50 µm were created by our recently developed micro-contact deprinting method. For this micro-contact deprinting approach, four different PEG-based stamp materials have been tested and it was found that the triblock copolymer PEG-PPG-PEG-(3BC) stamp established the best transfer efficiency and has been used in the ongoing work. After the successful creation of micro-patterns of Au NPs stripes on silicon, the patterns can be transferred conveniently and accurately to 8PEG-VS-SH hydrogel films. Subsequently these Au NPs patterns on 8PEG-VS-SH hydrogels have been investigated in cell culture with murine fibroblasts (L-929). The cells have been observed to adhere to and spread on those nano-patterned micro-lines in a remarkably selective and ordered manner.
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Oxymatrine (OMT) is able to effectively protect against hepatic fibrosis because of its anti-inflammatory property, while the underlying mechanism remains incompletely understood. In this study, forty rats were randomly divided into five groups: control group, model group (carbon tetrachloride, CCl4) and three OMT treatment groups (30, 60, 120mg/kg). After CCl4 alone, the fibrosis score was 20.2±0.8, and the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline content, and collagen I expression was elevated, but OMT blunted these parameters. Treatment with OMT prevented CCl4-induced increases in expression of pro-inflammatory and pro-fibrotic cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α, meanwhile OMT promoted the expression of anti-inflammatory and anti-fibrotic factors such as interleukin (IL)-10 and bone morphogenetic protein and activin membrane-bound inhibitor (Bambi). Moreover, lipopolysaccharides (LPS) and high mobility group box-1 (HMGB1), which activates Toll-like receptor 4 (TLR4) and modulate hepatic fibrogenesis through hepatic stellate cells (HSCs) or Kupffer cells, were significantly decreased by OMT treatment. These results were further supported by in vitro data. First, OMT suppressed the expression of TLR4 and its downstream pro-inflammatory cytokines, lowered the level of HMGB1, TGF-ß1 in macrophages. Then, OMT promoted Bambi expression and thereby inhibited activation of HSCs mediated by transforming growth factor (TGF)-ß1. In conclusion, this study showed that OMT could effectively attenuate the CCl4-induced hepatic fibrosis, and this effect may be due to modulation of TLR4-dependent inflammatory and TGF-ß1 signaling pathways.
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Alcaloides/uso terapéutico , Antiinflamatorios/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Células Estrelladas Hepáticas/efectos de los fármacos , Hígado/efectos de los fármacos , Macrófagos/efectos de los fármacos , Quinolizinas/uso terapéutico , Receptor Toll-Like 4/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Alanina Transaminasa/sangre , Animales , Tetracloruro de Carbono/toxicidad , Línea Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocinas/metabolismo , Fibrosis , Células Estrelladas Hepáticas/inmunología , Humanos , Hígado/metabolismo , Hígado/patología , Macrófagos/inmunología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
In this study, a mask-less laser-assisted patterning method is used to fabricate well-defined cell-adhesive microdomains delimited by protein-repellent poly(ethylene glycol) (PEG) microstructures prepared from multiarm (8-PEG) macromonomers. The response of murine fibroblasts (L-929) toward these microdomains is investigated, revealing effective cell confinement within the cell-adhesive areas surrounded by nonadhesive 8-PEG microstructures. Moreover, the spatial positioning of cells in microdomains of various sizes and geometries is analyzed, indicating control of cell density, size, and elongated cell shape induced by the size of the microdomains and the geometric confinement.
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Cellular responses to various gels fabricated by photoinitiated crosslinking using acrylated linear and multi-arm poly(ethylene glycol) (PEG)-based and poly(propylene glycol)-b-poly(ethylene glycol) precursors were investigated. While no protein adsorption and cell adhesion were observed on the hydrophilic PEG-based gels, protein adsorption and cell adhesion did occur on the more hydrophobic gel generated from the block copolymer precursor. Murine fibroblast viability on the poly(ethylene glycol)-based gels was studied in the course of 72 h and the results indicated no cytotoxicity. In a systematic study, extra- and intracellular metabolites of the murine fibroblasts cultured on these PEG-based gels were examined by GC-MS. Distinct intra- and extracellular changes in primary metabolism, namely amino acid metabolism, glycolysis and fatty acid metabolism, were observed. Cells cultured on the polymeric gels induced more intense intracellular changes in the metabolite profile by means of higher metabolite intensities with time in comparison to cells cultured on the reference substrate (tissue culture polystyrene). In contrast, extracellular changes of metabolite intensities were comparable.
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To improve the biocompatibility of a gene vector and to avoid its being eliminated by the immune system, polyethylenimine (PEI) was modified with poly(ethylene glycol) (PEG) before G250 monoclonal antibody (mAb) conjugation. G250-PEI-PEG was capable of forming complexes with DNA in the right size distribution, and the G250 mAb modification significantly improved PEI transfection of G250-positive cells. The highest transfection efficiency was seen in HeLa cells as determined by flow cytometry after transfection with the gene encoding green fluorescent protein: 2-fold higher compared with the transfection of HepG2 cells. Blocking the surface antigen on the cell membrane of HeLa cells by incubation with free G250 mAb, or by downregulating G250 expression by small interfering RNA transfection, resulted in a remarkable decrease in transfection efficiency. These data indicate the targeting effect of G250 antibody modification. The presence of serum decreased transfection efficiency in a concentration-dependent manner. However, the transfection of HeLa cells with G250-PEI-PEG remained significant in the presence of 30% serum. In an in vivo study, G250-PEI-PEG exhibited high transfection efficiency in tumors. In addition, pathological analysis did not show obvious toxicity caused by the materials used. These suggest that PEG- and G250 mAb-modified PEI could be a useful nonviral gene vector for in vivo study.