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Maneuver of conducting polymers (CPs) into lightweight hydrogels can improve their functional performances in energy devices, chemical sensing, pollutant removal, drug delivery, etc. Current approaches for the manipulation of CP hydrogels are limited, and they are mostly accompanied by harsh conditions, tedious processing, compositing with other constituents, or using unusual chemicals. Herein, a two-step route is introduced for the controllable fabrication of CP hydrogels in ambient conditions, where gelation of the shape-anisotropic nano-oxidants followed by in-situ oxidative polymerization leads to the formation of polyaniline (PANI) and polypyrrole hydrogels. The method is readily coupled with different approaches for materials processing of PANI hydrogels into varied shapes, including spherical beads, continuous wires, patterned films, and free-standing objects. In comparison with their bulky counterparts, lightweight PANI items exhibit improved properties when those with specific shapes are used as electrodes for supercapacitors, gas sensors, or dye adsorbents. The current study therefore provides a general and controllable approach for the implementation of CP into hydrogels of varied external shapes, which can pave the way for the integration of lightweight CP structures with emerging functional devices.
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Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein (ABI3BP) on vesicular stomatitis virus (VSV) genome replication and innate immune signaling pathway.Methods The small interfering RNA (siRNA) was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells. VSV-green fluorescent protein (VSV-GFP)-infected cell model was established. The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining. The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection; western blotting was performed to detect the changes in interferon regulatory factor 3 (IRF3) and TANK-binding kinase 1 (TBK1) phosphorylation levels.Results The VSV-GFP-infected BJ-5ta cell model was successfully established. Efficient knockdown of ABI3BP in BJ-5ta cells was achieved. Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown. Compared with the control group, the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2 - 3.5 times (P<0.01) and 2.2 - 4.0 times (P<0.01) respectively when infected with VSV of multiplicity of infection 0.1 and 1. The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection. The activation of type-I interferon pathway, as determined by phosphorylated IRF3 and phosphorylated TBK1, was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection.Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure. ABI3BP gene deletion promotes RNA virus replication, and ABI3BP is an important molecule that maintains the integrity of type I interferon pathway.
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Estomatite Vesicular , Animais , Humanos , Estomatite Vesicular/metabolismo , Actinas/genética , Actinas/metabolismo , Faloidina/metabolismo , Vírus da Estomatite Vesicular Indiana/genética , Antivirais , Proteínas da Matriz Extracelular/metabolismo , Proteínas de TransporteRESUMO
Considering that typically more than two pin diodes or other tunable elements are required in the unit cell of polarization-insensitive reconfigurable metasurfaces (RMs), this paper proposes a new approach to design a polarization-insensitive RM unit using only one VO2 chip. A polarization-insensitive phase-modulated metasurface (PMM) using single VO2 chip is presented. The surface layer is composed of an outer ring and an inner cross, with a VO2 chip loaded at the connection of the cross. As the VO2 chip can be connected with the metal patch on all sides, only one VO2 chip is used in this polarization-insensitive design. By thermally controlling VO2 chips switch between low-resistance and high-resistance states, the PMM achieves a 1-bit phase shift within 180° ± 37° from 7.85 to 15â GHz. A prototype is fabricated and measured, and the measured results have verified the correction of the design and analysis of the designed PMM.
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The fibrillation process of human insulin (HI) is closely related to the therapy for type II diabetes (T2D). Due to changes in the spatial structure of HI, the fibrillation process of HI takes place in the body, which leads to a significant decrease in normal insulin levels. L-Lysine CDs with a size of around 5 nm were synthesized and used to adjust and control the fibrillation process of HI. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CDs showed the role of HI fibrillation from the perspective of the kinetics of HI fibrillation and regulation. Isothermal titration calorimetry (ITC) was used to explore the regulatory mechanism of CDs at all stages of HI fibrillation from the perspective of thermodynamics. Contrary to common sense, when the concentration of CDs is less than 1/50 of the HI, CDs will promote the growth of fibres, while a high concentration of CDs will inhibit the growth of fibres. The experimental results of ITC clearly prove that different concentrations of CDs will correspond to different pathways of the combination between CDs and HI. CDs have a strong ability to combine with HI during the lag time, and the degree of combination has become the main factor influencing the fibrillation process.
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Diabetes Mellitus Tipo 2 , Pontos Quânticos , Humanos , Lisina , Pontos Quânticos/química , Carbono/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , InsulinaRESUMO
Triboelectric nanogenerators (TENGs) are devices that can harvest energy from mechanical motions; such devices can be used to power wearable sensors and various low-power electronics. To increase the lifetime of the device, scientists mainly use the method of making TENG in a hard skeleton to simplify the complex possible relative movements between two triboelectric parts. However, the hard skeletons cannot be embedded in soft and lightweight clothing. To make matters worse, the materials used in the garments must be able to withstand high mechanical forces when worn, such as the pressure of more than 100 KPa exerted by body pressure or everyday knocks. Notably, the TENGs are usually made of fragile materials, such as vacuum-evaporated metal electrodes and nano-sized coatings, on the contact interface; these electrodes and coatings often chip or wear off under the action of external loads. In this work, we succeeded in creating a thin, light-weight, but extremely robust garment-integrated triboelectric nanogenerator (G-TENG) that can be embedded in clothing and pass the water wash test. First, we chemically deposited a durable electrode with flexible properties for G-TENG using a novel technique called polymer-assisted metal deposition (PAMD). The as-formed metal electrodes are firmly bonded to the plastic substrate by a sub-10 nm adhesive polymer brush and can withstand a pressure of 22.5 MPa and a tear force of 0.7 MPa. We then removed the traditionally used fragile nanoparticle materials and the non-durable poly-dimethylsiloxane (PDMS) layer at the triboelectric interface, and then used a cost-effective, durable and slightly flowable pressure-sensitive adhesive to form a plastic contact interface. Such a soft plastic interface can ensure full contact of the triboelectric materials, which is excellent in complex environments and ultimately improves the power generation efficiency of the devices. The as-formed low-cost energy harvesting device could become an industry standard for future smart clothing.
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This study constructed the recombinant plasmid of a TonB-dependent receptor from V. parahaemolyticus and evaluated the immunogenicity of the recombinant protein in mice. The TonB-dependent receptor gene (GI: 28901321) was obtained by PCR amplification and cloned into plasmid pET-32a (+). The recombinant plasmids were transformed into Escherichia coli BL21, and the protein expression was induced by isopropyl-ß-d-thiogalactopyranoside (IPTG). The 6 × His-tagged TonB-dependent receptor inclusion bodies were purified by Ni-NTA Agarose column and renatured by gradient urea dialysis. The soluble and inclusion bodies of the TonB-dependent receptor were emulsified with Freund's adjuvant and subcutaneously injected into BALB/c mice. The serum titers with seven V. parahaemolyticus strains, eight Vibrio species, and nine other bacteria were studied by enzyme-linked immunosorbent assay and immunoblotting. The results showed that the serum homogenously bound the target protein in the V. parahaemolyticus cell lysates. The titers against the immunized protein were above 89K, while the titer against whole cells of seven V. parahaemolyticus strains ranged from 4.12K to 12.5K. However, the titers were higher for the soluble TonB-dependent receptor. The serums reacted with E. coli strains but did not cross-react with eight Vibrio species and Photobacterium damselae. These results showed that the TonB-dependent receptor proteins in this study were immunogenic, and the serums showed adequate specificity for V. parahaemolyticus. However, the availability of the TonB-dependent receptor on V. parahaemolyticus cells is probably limited.
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Vibrio parahaemolyticus , Animais , Proteínas de Transporte/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Camundongos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Diálise Renal , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismoRESUMO
A semiconductor nano-material was prepared, and its degradation efficiency of zearalenone (ZEN) was studied. The photocatalytic material graphitic carbon nitride (g-C3 N4 ) was synthesized by the traditional method of hot cracking. Its structure was characterized by X-ray diffraction (XRD), Fourier-transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The photocatalytic degradation experiment showed that under the irradiation of ultraviolet (UV) lamp (254 nm, including 185 nm), g-C3 N4 could induce photocatalytic effect, which provided a new method for the degradation of ZEN in real powder samples. The experimental conditions of photocatalytic degradation of the primary reference material of ZEN and ZEN in real powder samples were explored. And the degradation products of ZEN were analyzed after high-performance liquid chromatography-mass spectrometry (HPLC-MS). Under each optimal experimental conditions, the degradation rate on primary reference material of ZEN and ZEN in real powder samples was 96.0% and 50.0%, respectively. The results in this work provide a theoretical reference and practical basis for the photocatalytic degradation of mycotoxin in real powder samples by g-C3 N4 .
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Grafite , Zearalenona , Catálise , Luz , Compostos de NitrogênioRESUMO
Conducting polymer nanocoatings render plastics to possess interesting optical, chemical, and electrical properties. It nevertheless remains technically challenging to deposit uniform conducting polymer nanocoatings on ambient plastic substrates ascribed to the inert and varied chemical properties of plastics and the notorious processability of conducting polymers. Previous studies have made progress in delivering various conducting polymer thin films via oxidative chemical vapor deposition. Herein, we develop a solution-based approach to polyaniline (PANI) and PEGylated PANI nanocoatings on multiple engineering plastics followed by evaluating their antifouling performance. The procedure relies on the formation of uniform, lyotropic V2O5·nH2O thin films on plastics assisted by a surfactant-sodium N-lauroylsarcosinate. Next, in situ, oxidative polymerization causes the formation of nanofibrous PANI nanocoatings. Finally, interfacial functionalization leads to PEGylated PANI nanocoatings, and the steric nanolayer effectively repels the adsorption of bovine serum albumin and the attachment of the bacterium Pseudoalteromonas sp. on the surface. It is worth noting that the antifouling properties rely mainly on the presence of PEGylated PANI nanocoatings, irrespective of the type of plastic substrates underneath. The current study therefore opens an avenue for the solution-based delivery of conducting polymer-based, functional nanocoatings on hydrophobic substrates in a controllable manner with the availability of further modification.
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Keyin Pills is a kind of traditional Chinese medicine for the treatment of psoriasis, but it has been reported that it can cause serious liver injury. In this paper, we used the integrated evidence chain method to retrieve and reevaluate the adverse drug reaction database, CNKI literature and cases of liver injury relating to Keyin Pills in specialist hepatology hospitals. We screened out 23 cases with the causal relationship of the possible grade and above. Among them, 11 cases showed the positive causal relationship only with Keyin Pills, accounting for 47.83%, suggesting that there was objective liver injury caused by Keyin Pills. The incubation period of liver injury caused by Keyin Pills is 1-90 days, and the cumulative dosage span is 20-1 800 g. There were obvious individual diffe-rences. There was no relationship between liver injury as well as dose and course of treatment, suggesting that Keyin Pills could induce immune idiosyncratic liver injury. Furthermore, based on the liver injury model induced by immunological stress, it was confirmed that Keyin Pills could induce acute liver injury in a dose-dependent manner in rats with immunological stress. The toxic dose(14 g·kg~(-1)) of a single dose was 6.7 times of the clinical equivalent dose, and had no significant effect on the biochemical index of liver function and histopathology in normal rats. Decomposition experiments showed that Dictamnus dasycarpus in Keyin Pills is the main medicinal flavor that causes special liver injury, and the other three medicines had neither liver injury nor compatibility attenuation effect. The results suggest that clinical medication shall pay attention to the risk of liver injury caused by Keyin Pills in patients with immunological stress.
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Doença Hepática Induzida por Substâncias e Drogas , Dictamnus , Medicamentos de Ervas Chinesas , Psoríase , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Fígado , Medicina Tradicional Chinesa , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , RatosRESUMO
PURPOSE: Prophylactic release of the ulnar nerve to reduce the incidence of postoperative nerve symptoms in stiff elbows has been recommended. However, the necessity for routine anterior transposition remains unclear. In this study, we aim to gain an insight into the value of routine transposition in open release of stiff elbows. METHODS: We retrospectively reviewed 94 patients suffering from elbow stiffness with no pre-operative ulnar nerve symptoms. Simple decompression (with in situ decompression or epicondylectomy) and subcutaneous anterior transposition were chronologically performed in 53 and 37 patients, respectively. Another four patients were treated by a single lateral approach with no intervention of the ulnar nerve. Pre- and postoperative range of motion and incidence of ulnar nerve symptoms were recorded. The function of ulnar nerve was measured by Amadio rating scale. RESULTS: The incidence of ulnar nerve dysfuction was 18.9% (ten of 53) and 8.1% (three of 37) in the simple decompression and transposition groups, respectively. The mean Amadio scores were 7.62 and 8.22, respectively. All these data showed a statistically significant difference (P < 0.05). In the lateral approach group, 50 % (two of four) of patients developed nerve symptoms with a mean Amadio score of 6.50. CONCLUSIONS: The transposition group exhibited a superior nervous outcomes compared with the simple decompression group. No comparison was conducted between the transposition and lateral approach groups because of too few patients in the latter. According to related literature and our experience, we conclude that routine transposition is necessary to prevent postoperative nerve symptoms.
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Articulação do Cotovelo/cirurgia , Procedimentos Neurocirúrgicos/métodos , Nervo Ulnar/cirurgia , Adolescente , Adulto , Criança , Descompressão Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Amplitude de Movimento Articular/fisiologia , Estudos Retrospectivos , Resultado do Tratamento , Nervo Ulnar/transplante , Neuropatias Ulnares/prevenção & controle , Adulto JovemRESUMO
Fibrillation process of human insulin (HI) is closely related to type 2 diabetes (T2D). In the present work, Carbon Polymer Dots (CPDs) was synthesized by Bodipy to control the process of insulin fibrillation. The inhibition process of insulin fibrillation with the existence of CPDs was completed investigated. The hydrophobic interaction of CPDs and insulin was used to inhibit the change of insulin's secondary structure in the lag phase and growth period. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CPDs were used to explore the kinetics of insulin fibrillation and regulation process by CPDs. Isothermal titration calorimetry (ITC) was applied to explore the regulatory mechanism by CPDs at all stages of the insulin fibrillation process. ThT was used to complete the chemical modification of CPDs by Friedel-Crafts alkylation, which made the CPDs maintain the characteristics of photothermal effect and also obtain the ability to bind specifically to the fibers. Finally, the process of defibrillation of human insulin fibers under the Near-infrared light's irradiation was realized. In this work, we clarified the mechanism of the regulation process by Bodipy CPDs and made CPDs able to defibrillate the insulin fibers by chemical modification.
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Diabetes Mellitus Tipo 2 , Polímeros , Humanos , Polímeros/farmacologia , Polímeros/química , Carbono/química , Insulina/química , CalorimetriaRESUMO
CD39 is associated with diverse physiological and pathological processes, including cell proliferation and differentiation. Adenosine triphosphate (ATP) is hydrolysed to adenosine by different enzymes including ecto-nucleoside triphosphate diphosphohydrolase-1/ENTPD1 (CD39) and ecto-5'-nucleotidase (CD73), regulating many physiological and pathological processes in various diseases, but these changes and functions in alcoholic liver disease are generally unknown. In this study, an alcoholic liver disease model in vivo was induced by ethanol plus carbon tetrachloride(CCl4) administered to C57BL/6 mice, who were the intraperitoneally injected with the CD39 inhibitor sodium polyoxotungstate (POM1) or colchicine from the 5th week to the 8th week. Meanwhile, hepatic stellate cells were stimulated by acetaldehyde to replicate alcoholic liver fibrosis models in vitro. Exogenous ATP and POM1 were added in turn to the culture system. Pharmacological blockade of CD39 largely prevents liver damage and collagen deposition. We found that blockade or silencing of CD39 prevented acetaldehyde-induced proliferation of HSC-T6 cells and the expression of fibrogenic factors. Moreover, blockade or silencing of CD39 could block the activation of the adenosine A2A and adenosine A2B receptors and the TGF-ß/Smad3 pathway, which are essential events in HSC activation. Thus, blockade of CD39 to inhibit the transduction of ATP to adenosine may prevent HSC activation, alleviating alcoholic hepatic fibrosis. The findings from this study suggest ATP-adenosine signalling is a novel therapeutic and preventive target for alcoholic liver disease.
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Trifosfato de Adenosina/metabolismo , Adenosina/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Células Estreladas do Fígado/metabolismo , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Acetaldeído/toxicidade , Animais , Antígenos CD/genética , Apirase/antagonistas & inibidores , Apirase/genética , Tetracloreto de Carbono/toxicidade , Colchicina/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol/toxicidade , Técnicas de Silenciamento de Genes , Humanos , Hepatopatias Alcoólicas/patologia , Camundongos Endogâmicos C57BL , Cultura Primária de Células , Ratos , Receptor A2A de Adenosina/metabolismo , Receptor A2B de Adenosina/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Compostos de Tungstênio/farmacologiaRESUMO
BACKGROUND: In recent years, ER+ and HER2- breast cancer of adjuvant therapy has made great progress, including chemotherapy and endocrine therapy. We found that the responsiveness of breast cancer treatment was related to the prognosis of patients. However, reliable prognostic signatures based on ER+ and HER2- breast cancer and drug resistance-related prognostic markers have not been well confirmed, This study in amied to establish a drug resistance-related gene signature for risk stratification in ER+ and HER2- breast cancer. METHODS: We used the data from The Cancer Genoma Atlas (TCGA) breast cancer dataset and gene expression database (Gene Expression Omnibus, GEO), constructed a risk profile based on four drug resistance-related genes, and developed a nomogram to predict the survival of patients with I-III ER+ and HER2- breast cancer. At the same time, we analyzed the relationship between immune infiltration and the expression of these four genes or risk groups. RESULTS: Four drug resistance genes (AMIGO2, LGALS3BP, SCUBE2 and WLS) were found to be promising tools for ER+ and HER2- breast cancer risk stratification. Then, the nomogram, which combines genetic characteristics with known risk factors, produced better performance and net benefits in calibration and decision curve analysis. Similar results were validated in three separate GEO cohorts. All of these results showed that the model can be used as a prognostic classifier for clinical decision-making, individual prediction and treatment, as well as follow-up.
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There are multiple causes of liver fibrosis, common ones include ethanol, toxins, and cholestasis. However, whether these different etiologies lead to the same pathological outcomes contain common genetic targets or signaling pathways, the current research has not attracted widespread attention. GSE40041 and GSE55747 were downloaded from the Gene Expression Omnibus (GEO) database. GSE40041 and GSE55747 represent the differential expression profiles in the liver of mice with bile duct ligation (BDL) and carbon tetrachloride (CCl4) induced liver fibrosis models, respectively. By using GEO2R, 701 differential expression genes (DEGs) in GSE40041 and 6540 DEGs in GSE55747 were identified. 260 co-DEGs were shared and extracted for gene ontology (GO) analysis. Through GO analysis, it was found that the regulation of cell migration in biological processes (BPs) was closely related to the pathogenesis of liver fibrosis, and the genes involved in this process include a key gene, chemokine (C-X-C motif) ligand 14 (CXCL14). Subsequently, further bioinformatic analysis showed that CXCL14 may be regulated by miR-122 to participate in the progression of liver fibrosis. Then real-time PCR and western blotting were performed to validate the expression of CXCL14 in liver tissue after liver fibrosis caused by different etiologies (ethanol, CCl4). The expression of CXCL4 in liver fibrosis induced by BDL was verified in another GEO dataset. Basically consistent with our bioinformatics results, our experimental results showed that the expression of CXCL14 was most significantly increased in alcoholic liver fibrosis model, followed by CCl4-induced liver fibrosis, which was also significantly increased in the BDL-induced model. Thus, CXCL14 can act as a common potential genetic target for different liver fibrosis diseases.
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Quimiocinas CXC/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Cirrose Hepática/metabolismo , MicroRNAs/metabolismo , Consumo de Bebidas Alcoólicas , Animais , Células Cultivadas , Quimiocinas CXC/genética , Biologia Computacional , Bases de Dados Genéticas , Etanol/toxicidade , Células Estreladas do Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , RatosRESUMO
Xiamen is one of China's five major special economic zones and is the core city of Haixi Economic Zone, with a high level of urbanization. Monitoring and driving force analysis of impervious surfaces can increase our understanding of urbanization process and have important significance for urban landscape pattern research and urban ecological environment construction. We used the Landsat remote sensing image data from 1978 to 2018 to reveal the temporal and spatial variation characteristics of the impervious surface landscape in Xiamen in the past 40 years, using the full-restricted least squares method, landscape pattern analysis, slope gradient analysis and correlation analysis. We further analyzed its relationship with social and economic factors. The results showed that, during 1978-2018, the impervious surface of Xiamen increased by 348.96 km2, with a mean annual increase of 8.72 km2. The impervious surface dynamics reached a maximum of 9.0% in 2005-2010. More than 86.6% of the impervious surface of Xiamen was distributed within 6° of slope, with a tendency to expand to a greater slope in 2010-2018. With the increases of slope, the proportion of impervious surface decreased, the density of plaque decreased with the shape tending to be regular and continuous, the degree of fragmentation of the impervious surface increased. The increases of impervious surface in Xiamen was significantly related to the regional economic aggregate and population. In the study period, the spatial pattern of impervious surface in Xiamen significantly altered. In the future urban planning process, the extent and speed of impervious surface expansion should be coordinated to avoid ecological problems caused by excessive impervious surface to meet the need for sustainable development of Xiamen.
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Planejamento de Cidades , Urbanização , China , Cidades , EcologiaRESUMO
Hepatic fibrosis is the most common pathological feature of most chronic liver diseases, and its continuous deterioration gradually develops into liver cirrhosis and eventually leads to liver cancer. At present, there are many kinds of drugs used to treat liver fibrosis. However, Western drugs tend to only target single genes/proteins and induce many adverse reactions. Most of the mechanisms and active ingredients of traditional Chinese medicine (TCM) are not clear, and there is a lack of unified diagnosis and treatment standards. Natural products, which are characterized by structural diversity, low toxicity, and origination from a wide range of sources, have unique advantages and great potential in anti-liver fibrosis. This article summarizes the work done over the previous decade, on the active ingredients in natural products that are reported to have anti-hepatic fibrosis effects. The effective anti-hepatic fibrosis ingredients identified can be generally divided into flavonoids, saponins, polysaccharides and alkaloids. Mechanisms of anti-liver fibrosis include inhibition of liver inflammation, anti-lipid peroxidation injury, inhibition of the activation and proliferation of hepatic stellate cells (HSCs), modulation of the synthesis and secretion of pro-fibrosis factors, and regulation of the synthesis and degradation of the extracellular matrix (ECM). This review provides suggestions for the development of anti-hepatic fibrosis drugs.
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Produtos Biológicos/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Animais , Produtos Biológicos/farmacologia , Humanos , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologiaRESUMO
Inflammation plays a central role in the progression of alcoholic liver disease. ATP-P2Y2R signaling and CD39 play an important role in various diseases, but little is known about their role in alcoholic liver steatosis and inflammation. As a transmembrane hydrolase, CD39 hydrolyzes ATP, while the mutual regulation of CD39 and ATP-P2Y2R in alcoholic steatohepatitis is poorly understood. Here, we found that the expression of ATP, P2Y2R, and CD39 is increased significantly both in the liver of alcohol-fed mice and alcohol-induced RAW264.7 cell lines. In this study, C57BL/6 mice were intrapretationally injected with P2Y2R inhibitor suramin from day 4 until day 10 during the induction of a chronic/binge drinking model. Pharmacological blockade of P2Y2R largely prevents liver damage, lipid accumulation, and inflammation, with concomitant down-expression of CD39 in liver. We found that the inhibition of P2Y2R in vitro reduces inflammation via down-expression of interleukin 6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α), and the expression of CD39 was reduced, whereas the activation of P2Y2R showed an opposite effect. Silencing of CD39 promoted the expression of ATP and P2Y2R. These results indicate that CD39 attenuates alcohol-induced steatohepatitis by scavenging extracellular ATP to indirectly regulate the expression of P2Y2R. Interestingly, P2Y2R paradoxically boosts CD39 activity. Thus, blockade of the extracellular ATP-P2Y2R signalling represents a potential therapeutic approach against alcoholic liver disease, and CD39 is a potential therapeutic target.
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Trifosfato de Adenosina/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Fígado Gorduroso Alcoólico/metabolismo , Receptores Purinérgicos P2Y2/metabolismo , Animais , Citocinas/genética , Fígado Gorduroso Alcoólico/genética , Inflamação/genética , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7RESUMO
Cocaine,as a widely abused and highly addictive drug,has a serious impact on the physical and mental health of individuals and carries a certain degree of social harm and economic burden.Acupuncture can assist in the treatment of cocaine addiction with fewer side effects.However,a well-defined mode of stimulation is an important factor in elucidating the various mechanisms by which acupuncture treats disease.This paper summarizes the problems in the mechanism of cocaine addiction,such as different parameters of stimulation,unstable depth of acupuncture,different acupoint selection,and different lengths of acupuncture time.To standardize the intervention measures of acupuncture experiments,it is suggested that in future research,the stimulation method should explore the best parameters,the selection of acupoints should be based on clinical practice,the timing of acupuncture should be objective,and the treatment course should consider the effects of acupuncture.
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Objective To analyze the diagnostic efficacy and clinical significance of magnifying endoscopy combined with narrow-band imaging(ME-NBI),acetate-indigo rouge staining and multi-slice spiral CT for early gastric cancer and precancerous lesions.Methods 202 patients with suspected early gastric cancer and precancerous lesions from February 2019 to March 2022 were regarded as the subjects of this study,all the patients underwent ME-NBI,acetate-indigo rouge staining,and multi-slice spiral CT examination;The diagnostic value of different examination methods for early gastric cancer and precancerous lesions was analyzed using the receiver operator characteristic curve(ROC curve),using the pathological results of gastric cancer as the gold standard,the diagnostic value of ME-NBI,acetate-indigo rouge staining combined with multi-slice spiral CT and their combination in early gastric cancer and precancerous lesions was analyzed using a four grid table.Results The image quality of ME-NBI and acetate-indigo rouge staining combined examinations was significantly higher than that of their respective independent examinations(P<0.05).There was significant difference in the degree of differentiation in the clinical features of patients with early gastric cancer and precancerous lesions(P<0.05).The area under the curve(AUC)of ME-NBI for the diagnosis of early gastric cancer and precancerous lesions was 0.853,the accuracy was 85.64%,the sensitivity was 88.37%,and the specificity was 83.62%.The AUC of acetate-indigo rouge staining for the diagnosis of early gastric cancer and precancerous lesions was 0.814,the accuracy was 81.68%,the sensitivity was 83.72%,and the specificity was 80.17%.The AUC of multi-slice spiral CT for the diagnosis of early gastric cancer and precancerous lesions was 0.804,with an accuracy of 80.69%,a sensitivity of 82.56%,and a specificity of 79.31%.And the AUC of the three methods combined to diagnose early gastric cancer and precancerous lesions was 0.893,with an accuracy of 89.60%,a sensitivity of 93.02%,and a specificity of 87.07%.Conclusion ME-NBI,acetate-indigo rouge staining combined with multi-slice spiral CT has high diagnostic efficacy in early gastric cancer and precancerous lesions,and can be used in clinical practice.
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AIM To explore the effects of Rosa roxburghii Radix on ulcerative colitis(UC)in rats based on pyroptosis and neutrophil extracellular traps(NETs).METHODS Rats were randomly divided into the normal group and the model group.The successfully established UC rat models by trinitrobenzene sulfonic acid(TNBS)/ethanol enema were then randomly divided into the model group,the sulfasalazine group(0.3 g/kg)and the low,medium and high dose R.roxburghii Radix groups(2,4,8 g/kg),followed by dosing of corresponding drugs by gavage.21 days later,the rats had their disease activity index(DAI)score calculated;their pathological changes of colon tissue observed by HE staining;their levels of serum interleukin(IL)-18,IL-1β and myeloperoxidase(MPO)detected by ELISA;and their protein expressions of NE,MPO,NLRP3,caspase-1 and GSDMD in colon tissue detected by Western blot and immunohistochemistry.RESULTS Compared with the normal group,the model group displayed increased DAI score(P<0.01),increased serum levels of IL-1β,IL-18 and MPO(P<0.01),and increased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P<0.01).Compared with the model group,the groups intervened with sulfasalazine,or medium,or high dose R.roxburghii Radix demonstrated with decreased DAI scores(P<0.05,P<0.01),decreased serum levels of IL-1β,IL-18 and MPO(P<0.01),and decreased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P<0.05,P<0.01).CONCLUSION R.roxburghii Radix may alleviate the inflammatory reaction in a rat model of UC and improve its pathological injury of colon via regulating pyroptosis and NETs.