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Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.
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Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Doenças Inflamatórias Intestinais/tratamento farmacológico , Administração Oral , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Catequina/análogos & derivados , Catequina/química , Catequina/administração & dosagem , Catequina/farmacologia , Gálio/química , Gálio/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Colite/tratamento farmacológico , Humanos , Espécies Reativas de Nitrogênio/metabolismoRESUMO
Objectives: This study seeks to investigate the willingness of medical professionals to embrace training in sports medicine integrated talents, as well as the factors that influence their decision-making process. By utilizing technology acceptance models, the objective is to gain a comprehensive understanding of this phenomenon and provide valuable recommendations to facilitate the development of proficient integration of sports and medicine (ISM) talents. Methods: The questionnaire was developed through a comprehensive review of relevant literature and consultation with experts in the field. A cluster sampling method was employed to select medical professionals from various medical institutions in Guangxi Zhuang Autonomous Region (Guangxi) who had participated in ISM talent training. The collected data were analyzed using the AMOS structural equation model, ensuring a rigorous and systematic approach to data analysis. Results: A total of 403 questionnaires were collected in this survey, and 8 out of the 9 research hypotheses formulated for the model variables were found to be supported. Perceived usefulness, perceived ease of use, subjective norm and training satisfaction were identified as significant factors influencing the behavioral intention of medical professionals to engage in ISM talent training (P < 0.05). The path coefficients for these factors were 0.17, 0.16, 0.31 and 0.24, respectively. Conclusion: In order to enhance the effectiveness of training for ISM talents, it is imperative for relevant departments to collaborate and focus on improving the perceived usefulness, perceived ease of use, and training satisfaction. By doing so, we can effectively harness the subjective initiative of medical professionals, thereby increasing their willingness to participate in training programs. This, in turn, will contribute to the cultivation of "high-quality, high-level" ISM talents that are essential for the betterment of society.
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Enzyme-based sensing platforms have undergone rapid development in the field of diagnosis and bioanalysis. Here we present a novel fluorescent artificial enzyme-based detection strategy for L-cysteine (Cys) and H2O2 by fabricating a series of Au-Ag bimetallic nanoparticles with peroxidase-like activity. Taking advantage of the enhanced performance of catalysts by optimizing the surface structure, the sensitive detection of Cys with an ultralow detection limit of 0.035 µM and accurate quantification in the range of 0.075-2 µM were achieved. It was revealed that the mechanism of the catalytic process on the Au-Ag surface follows the electron transfer mechanism rather than active species, that is the peroxidase-like catalysts work as electron transfer intermediates and the electron transfer efficiency will increase with the larger electron cloud density of active sites derived from the electronic synergistic effect between Au and Ag, contributing to the enhanced catalytic activity of peroxidase mimics. This finding could provide guidance for the structural design of high-activity peroxidase mimics.
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Nanopartículas Metálicas , Peroxidase , Colorimetria , Corantes , Cisteína/análise , Fluorescência , Ouro/química , Peróxido de Hidrogênio/química , Nanopartículas Metálicas/química , Peroxidase/química , Peroxidases/químicaRESUMO
Detection of heavy metal ions (HMIs) in water is an important topic in the field of analytical chemistry and environmental science. Fluorescence spectroscopy is one of the most promising strategies due to its simple instrument, low investment, rapid and convenient operation. However, current fluorescence probes for detecting HMIs are typically selective for certain ions. Herein we reported the development of a novel strategy that determined the total content of HMIs in water by fluorescence spectroscopy. A novel fluorescent nitrogen, sulfur co-doped carbon quantum dots (N, S-CQDs) was prepared via graphene oxide-assisted synthesis method. The results showed that, with the fluorescence quenching strategy, N, S-CQDs exhibited a wide linear response to a series of water-soluble metal ions. The fluorescence of N, S-CQDs is stable in a wide range of pH 4-11. The detection mechanism was proved that the integration, caused by coordination interaction between S element in N, S-CQDs and the d-orbital of associated metal ions, was the main reason for fluorescence quenching. In practice, the N, S-CQDs were applied to determine total content of HMIs in water successfully. Interestingly, further experiment proved that the N, S-CQDs could effectively remove HMIs in water after centrifuging and filtering thoroughly. It was shown that the fluorescence of N, S-CQDs was obviously quenched by the multiple-ions-involved water and scavenging effect of N, S-CQDs on HMIs with centrifugal in which the concentration of individuals meets the Chinese National Standard. This indicates that the N, S-CQDs are of a wide application prospect in water quality analysis.
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Metais Pesados , Pontos Quânticos , Carbono/química , Grafite , Humanos , Íons , Nitrogênio/química , Espectrometria de Fluorescência/métodosRESUMO
Decades of extensive research efforts by scientists in the field of catalysis and nanomaterials have led to a large number of excellent bimetallic nanocatalysts. However, in many cases, the mechanism of the synergistic effect in bimetal catalyst-catalyzed reactions has been systematically neglected due to technical limitations. Herein, we use single-molecule fluorescence microscopy (SMFM) to reveal the mechanism of the synergy of the Au and Ag bimetal catalyst. Compared with that of the Ag nanocatalyst, the incorporation of Au changes the reaction pathway of Amplex Red and H2O2 from a noncompetitive to a competitive reaction mechanism, showing much higher catalytic efficiency. Additionally, the incorporation also inhibits the spontaneous surface reconstruction and facilitates the reaction-induced surface restructuring of the nanocatalyst, resulting in the enhancement of stability and reactivity. These findings provide useful insights into tailoring the reactivity of metal catalysts. This work also confirms the power of SMFM in revealing the origin of the catalytic activity of composite catalysts.
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Herein, for the first time, we introduced a novel electrochemiluminescence (ECL) luminophore based on a one-dimensional g-C3N4 nanotube using K2S2O8 as the coreactant. The g-C3N4 nanotube/K2S2O8 couple displayed very satisfactory ECL performance, i.e., an ECL efficiency (ΦECL) of 437% (vs 100% for the Ru(bpy)32+/K2S2O8 reference) and excellent ECL stability (the relative standard deviation (RSD) = 0.78%). By contrast, ΦECL and RSD of the control g-C3N4 nanosheet/K2S2O8 couple were merely 196% and 45.34%, respectively. The mechanism study revealed that the g-C3N4 nanotube features a large surface area and much lower interfacial impedance in the porous microstructure, which are beneficial for accelerating the charge transfer rate and stabilizing charge/excitons for ECL. Moreover, using the g-C3N4 nanotube/K2S2O8 system as a sensing platform, excellent Cu2+ detection capability was also achieved. Our work thus triggers a promising g-C3N4 nanomaterial system toward ECL application.
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BACKGROUND: Alzheimer disease (AD) is one of the most frequent neurodegenerative disorders that results in the progressive loss of memory and severe impairments and death. The experimental results showed that the neuroinflammation involving microglia and cytokines, especially the neuritic plaques composed of aggregates of ß-amyloid protein, also play a major risk in AD. Biglycan (BGN) is involved in the regulation of neuronal cell division that could induce the expression of proinflammatory factors. Furthermore, BGN also exerts effects on ß-amyloid-induced microglial dysfunction and contributes to AD pathogenesis. However, the mechanisms underlying the regulatory role of BGN on ß-amyloid-induced microglial activation remain unclear. This study intended to investigate whether BGN could promote ß-amyloid induced microglial activation through TLRs in immortalized murine microglial (BV2) cells. METHODS: The levels of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were detected by enzyme-linked immunosorbent assay (ELISA). The Cell Counting kit-8 (CCK8) assay was performed to detect cell viability. The expression level of a microglia marker (CD11b) was detected by immunofluorescence. The mRNA and protein expression levels of BGN and Toll-like receptor 2 (TLR2) were determined by quantitative RT-PCR and western blotting. RESULTS: BGN was upregulated in activated microglial cells. Knockdown of BGN efficiently attenuated ß-amyloid-induced microglial activation and expressions of proinflammatory factors. Furthermore, the present findings provided evidence showing that BGN could regulate ß-amyloid-induced microglial activation through TLR2 in BV2 cells. CONCLUSIONS: Our results suggested that TLR2 signaling may be involved in the regulatory role of BGN in ß-amyloid-induced microglial activation.
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Peptídeos beta-Amiloides , Receptor 2 Toll-Like , Animais , Biglicano/genética , Técnicas de Cultura de Células , Camundongos , Microglia , Receptor 2 Toll-Like/genéticaRESUMO
BACKGROUND: In response to the specific goals of carbon peaking and neutrality, remanufacture is becoming increasingly popular. With the marketplace being more and more adopted, an independent remanufacturer (IR) could sell its products via either the reselling model or the marketplace model. In order to contribute more to carbon neutrality, we investigate the optimal marketing decision for remanufacturing. We construct two models namely reselling model and the marketplace model, and further explore the effects of each marketing model on the decisions and profits of both the IR and the platform firm. METHODS: We examine a platform firm that sells new products and an IR that sells remanufactured products under two marketing models based on game theory: (1) a reselling model in which the IR sells remanufactured products to the platform firm; then the platform firm resells to consumers; (2) a marketplace model in which the IR sells remanufactured products to consumers through the platform. RESULTS: Our results show that aiming at carbon neutrality, the IR would be induced by the marketplace model to undertake remanufacturing operations and remanufacture products as many as it could still meet the market demand. Meanwhile, the marketplace model encourages the IR to rethink its work and manufacture more products under certain conditions. Furthermore, both the platform firm and the IR prefer the marketplace model to the reselling model within a Pareto zone. In addition, we find that both the platform firm and the IR could benefit from the marketplace model when they take carbon neutrality under consideration. CONCLUSIONS: This study provides managerial insight from two aspects. Remanufactures could decide their marketing model via thorough consideration of market competition, commission rate, and production cost. The government could do more to protect the marketplace environment in order to stimulate the internal vitality of the platform in the achievement march of carbon neutrality purpose. That is, this study will provide good guidance for sustainable development decision-making of remanufacturing marketing platforms, and further contributes to the achievement of the carbon neutrality goal.
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Carbono , Comércio , Financiamento Governamental , Governo , MarketingRESUMO
Diabetes mellitus is a complicated metabolic disease with symptoms of hyperglycemia, insulin resistance, chronic damage and dysfunction of tissues, and metabolic syndrome for insufficient insulin production. Evidence has indicated that exercise treatments are essential in the progression of typeÐÐ diabetes mellitus, and affect insulin resistance and activity of islet ßcells. In the present study, the efficacy and signaling mechanism of aerobic exercise on blood lipids and insulin resistance were investigated in the progression of typeÐÐ diabetes mellitus. Body weight, glucose metabolism and insulin serum levels were investigated in mouse models of typeÐÐ diabetes mellitus following experienced aerobic exercise. Expression levels of inflammatory factors, interleukin (IL)6, highsensitivity Creactive protein, tumor necrosis factorα and leucocyte differentiation antigens, soluble CD40 ligand in the serum were analyzed in the experimental mice. In addition, expression levels of tolllike receptor 4 (TLR4) were analyzed in the liver cells of experimental mice. Changes of oxidative stress indicators, including reactive oxygen species, superoxide dismutase, glutathione and catalase were examined in the liver cells of experimental mice treated by aerobic exercise. Expression levels and activity of extracellular signalregulated kinases (ERK) and AMPactivated protein kinase (AMPK) signaling pathways were investigated in the liver cells of mouse models of typeÐÐ diabetes mellitus after undergoing aerobic exercise. Aerobic exercise decreased the expression levels of inflammatory factors in the serum of mouse models of typeÐÐ diabetes mellitus. The results indicated that aerobic exercise downregulated oxidative stress indicators in liver cells from mouse models of typeÐÐ diabetes mellitus. In addition, the ERK and AMPK signaling pathways were inactivated by aerobic exercise in liver cells in mouse models of typeÐÐ diabetes mellitus. The activity of ERK and AMPK, and the function of islet ßcells were observed to be improved in experimental mice treated with aerobic exercise. Furthermore, blood lipid metabolism and insulin resistance were improved by treatment with aerobic exercise. Body weight and glucose concentration of serology was markedly improved in mouse models of typeÐÐ diabetes mellitus. Furthermore, TLR4 inhibition markedly promoted ERK and AMPK expression levels and activity. Thus, these results indicate that aerobic exercise may improve blood lipid metabolism, insulin resistance and glucose plasma concentration in mouse models of typeÐÐ diabetes mellitus. Thus indicating aerobic exercise is beneficial for improvement of blood lipid and insulin resistance via the TLR4mediated ERK/AMPK signaling pathway in the progression of typeÐÐ diabetes mellitus.