RESUMO
Hepatic ischemia-reperfusion (I/R) injury (HIRI) is recognized as a local aseptic inflammatory response driven by innate immunity and is considered a leading cause of early organ dysfunction and failure following liver transplantation. Etomidate (Eto), an anesthetic drug known for its ability to inhibit inflammatory response and apoptosis, was the focus of our investigation. In this study, we conducted hepatic I/R surgery in vivo on C57 mice, analyzing liver damage through histopathology. Additionally, primary hepatocytes isolated from mice were cultured and subjected to hypoxia/reoxygenation (H/R) insult in vitro, with cell activity assessed using the CCK8 assay and immunofluorescence staining employed to analyze liver inflammatory cell infiltration and apoptosis. Results showed that Eto effectively inhibited liver injury, inflammatory response, and apoptosis induced by HIRI surgery, with the greatest effect observed at an Eto concentration of 10 mg/kg. Furthermore, Eto also showed the ability to inhibit H/R-induced cell damage, inflammatory activation, and apoptosis in primary hepatocytes. Further mechanistic studies revealed that Eto could promote the activation of the Nrf2-HO-1 signaling pathway, and the protective effect of Eto on HIRI was nullified when the Nrf2 inhibitor ML385 was utilized. This study highlights the potential of Eto to protect against HIRI by promoting the Nrf2-HO-1 signaling axis.
RESUMO
BACKGROUND: Previous studies underscore the protective role of physical activity (PA) in bone health, yet the relationship between different PA categories and osteoporosis risk remains less explored. Understanding the relationships helps tailor health recommendations and policies to maximize the effects of preventing osteoporosis. METHODS: The cross-sectional study involves 488,403 UK Biobank participants with heel quantitative ultrasound-estimated bone mineral density (eBMD) data. The longitudinal cohort involves 471,394 UK Biobank participants without initial osteoporosis and with follow-up records. PA exposure categories in our study included sedentary behavior (SB), total PA (TPA), and different category-specific PA including household, leisure, and work PA. The cases of osteoporosis were assessed using the International Classification of Diseases, 10th revision (ICD-10). The linear, logistic, and Cox proportional hazard regression models were used in our study. RESULTS: In the cross-sectional study, 15,818 (3.28 %) participants had osteoporosis. TPA levels have a positive correlation with eBMD and a negative correlation with osteoporosis prevalence. Among different categories of PA, higher levels of leisure PA were correlated with increased eBMD and a lower osteoporosis risk (leisure PA: OR: 0.83, 95 % CI: 0.79 to 0.86;). In the longitudinal study, 16,058 (17.6 % male, 82.4 % female) (3.41 %) individuals developed osteoporosis during an average follow-up of 13 years. We observed consistent protective effects of high levels of PA on osteoporosis incidence risk, particularly within the category of leisure PA (TPA: HR: 0.78, 95 % CI: 0.74 to 0.82; leisure PA:HR: 0.83, 95 % CI: 0.80 to 0.87). Such associations are independent of genetic predisposition, with no evidence of gene-PA interactions, and keep steady among individuals using drugs affecting bone-density. Moreover, among different leisure PA items, strenuous sports, other exercises, and walking for pleasure conferred a substantial protective effect against osteoporosis. Additionally, non-elderly individuals and males exhibited lower osteoporosis risk from PA. CONCLUSION: This study highlights activity categories differently associated with the risk of osteoporosis. Adherence to frequent leisure PA may have a protective effect against osteoporosis. Such associations are independent of genetic susceptibility to osteoporosis and keep steady among individuals using drugs affecting bone-density. This highlights that leisure PA could be suggested as a more effective intervention in the primary prevention of osteoporosis.
Assuntos
Bancos de Espécimes Biológicos , Exercício Físico , Atividades de Lazer , Osteoporose , Humanos , Estudos Transversais , Feminino , Masculino , Osteoporose/epidemiologia , Reino Unido/epidemiologia , Exercício Físico/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Prevalência , Incidência , Idoso , Densidade Óssea/fisiologia , Adulto , Biobanco do Reino UnidoRESUMO
Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer. Among them, GNSs was functioned as transport media, Ce6 acted as the near-infrared (NIR) fluorescence imaging agent and photodynamic therapy (PDT), and CIK cells served as targeting vectors for immunotherapy, which can increase the efficiency of tumor enrichment and treatment effect. The results of cellular experiments demonstrated that GNSs-PEG@Ce6 NPs had good dispersibility, water solubility and low toxicity under physiological conditions, and the cultured CIK cells had strong anti-tumor properties. Subsequently, GNSs-PEG@Ce6-CIK could effectively inhibit the growth of A549 cells under the exposure of 633 nm laser, which showed stronger killing effect than that of GNSs-PEG@Ce6 NPs or CIK cells. In addition, they showed good tumor targeting and tumor synergistic killing activityin vivo. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.
Assuntos
Clorofilídeos , Células Matadoras Induzidas por Citocinas , Ouro , Neoplasias Pulmonares , Nanopartículas Metálicas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Ouro/química , Fotoquimioterapia/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Humanos , Animais , Porfirinas/química , Porfirinas/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas Metálicas/química , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Polietilenoglicóis/química , Células A549 , Imagem Óptica/métodos , Camundongos NusRESUMO
The reliability and safety of diesel engines gradually decrease with the increase in running time, leading to frequent failures. To address the problem that it is difficult for the traditional fault status identification methods to identify diesel engine faults accurately, a diesel engine fault status identification method based on synchro squeezing S-transform (SSST) and vision transformer (ViT) is proposed. This method can effectively combine the advantages of the SSST method in processing non-linear and non-smooth signals with the powerful image classification capability of ViT. The vibration signals reflecting the diesel engine status are collected by sensors. To solve the problems of low time-frequency resolution and weak energy aggregation in traditional signal time-frequency analysis methods, the SSST method is used to convert the vibration signals into two-dimensional time-frequency maps; the ViT model is used to extract time-frequency image features for training to achieve diesel engine status assessment. Pre-set fault experiments are carried out using the diesel engine condition monitoring experimental bench, and the proposed method is compared with three traditional methods, namely, ST-ViT, SSST-2DCNN and FFT spectrum-1DCNN. The experimental results show that the overall fault status identification accuracy in the public dataset and the actual laboratory data reaches 98.31% and 95.67%, respectively, providing a new idea for diesel engine fault status identification.
RESUMO
An analysis of how new-type urbanization in China impacts the green intensive use of land not only provides us with an important reference basis, but also helps support decision-making when promoting new-type urbanization. This paper theoretically analyzes how new-type urbanization influences the green intensive use of land and takes the implementation of China's new-type urbanization plan (2014-2020) as a quasi-natural experiment. To empirically analyze the impact and mechanism of new-type urbanization on the green intensive use of land, we take the panel data of 285 Chinese cities from 2007 to 2020 and use the Difference-in-differences method. Results show that new-type urbanization facilitates green intensive use of land, a conclusion which is verified by several robustness tests. Furthermore, the effects are heterogeneous with respect to urbanization stage and urban scale, both of which exert a stronger driving effect in the later stages of urbanization and in large cities. Further analysis of the mechanism shows that new-type urbanization can promote green intensive land use through an innovation effect, a structural effect, a planning effect and an ecological effect.
Assuntos
Urbanização , Cidades , ChinaRESUMO
Due to their ability to generate green industrial growth, green finance policies are important both in the greening of China's industries and in the promoting of further improvements to its financial system. In this paper, reform pilot zones are used as a quasi-natural experiment with select panel data from 2007 to 2019 taken from 30 provinces in China, and used the DID method to empirically measure the impact of green finance reform on industrial GTFP and its mechanism of action. The findings demonstrate that reforming green finance greatly enhances GTFP of industry during the review period. This result is still valid after carrying out robustness tests. The heterogeneity study finds that the policy plays a large part in fostering GTFP in the middle stage of industrialization but not in the late stage. Further analyses of its transmission mechanism demonstrate that green finance reform mostly fosters industrial green growth through an innovation effect and a structural effect.
Assuntos
Desenvolvimento Econômico , Indústrias , China , Eficiência , Desenvolvimento IndustrialRESUMO
The role of N-heterocyclic carbene, a well-known reactive site, in chemical catalysis has long been studied. However, its unique binding and electron-donating properties have barely been explored in other research areas, such as metal capture. Herein, we report the design and preparation of a poly(ionic liquid)-derived porous organic polycarbene adsorbent with superior gold-capturing capability. With carbene sites in the porous network as the "nanotrap", it exhibits an ultrahigh gold recovery capacity of 2.09 g/g. In-depth exploration of a complex metal ion environment in an electronic waste-extraction solution indicates that the polycarbene adsorbent possesses a significant gold recovery efficiency of 99.8%. X-ray photoelectron spectroscopy along with nuclear magnetic resonance spectroscopy reveals that the high performance of the polycarbene adsorbent results from the formation of robust metal-carbene bonds plus the ability to reduce nearby gold ions into nanoparticles. Density functional theory calculations indicate that energetically favourable multinuclear Au binding enhances adsorption as clusters. Life cycle assessment and cost analysis indicate that the synthesis of polycarbene adsorbents has potential for application in industrial-scale productions. These results reveal the potential to apply carbene chemistry to materials science and highlight porous organic polycarbene as a promising new material for precious metal recovery.
RESUMO
At present, rotating machinery is widely used in all walks of life and has become the key equipment in many production processes. It is of great significance to strengthen the condition monitoring of rotating machinery, timely diagnose and eliminate faults to ensure the safe and efficient operation of rotating machinery and improve the economic benefits of enterprises. When the state of a rotating machine deteriorates, the thermal energy that is much more than its normal operation will be generated due to the increase in the friction between the components or other factors. Therefore, using the infrared thermal camera to collect the infrared thermal images of rotating machinery and judge the health status of rotating machinery by observing the temperature distribution in the thermal images is often more rapid and effective than other technologies. Nevertheless, after decades of development, the research achievements of infrared thermography (IRT) and its application in various industrial fields are numerous and complex, and there is a lack of systematic sorting and summary of the achievements in this field. Accordingly, this paper summarizes the development and application of IRT as a non-contact and non-invasive tool for equipment condition monitoring and fault diagnosis, and introduces the basic theory of IRT, image processing technology and fault diagnosis methods of rotating machinery in detail. Finally, the review is summarized and some future potential topics are proposed, which will make the subject easier for beginners and non-experts to understand.
RESUMO
Complex two-dimensional warranty equipment is usually composed of many multi-component systems, which include several key components. During the warranty period, conducting maintenance according to the preventive maintenance plan of each component will increase the warranty costs. Opportunistic maintenance is an effective approach to combine the preventive maintenance of each individual component, which can reduce the warranty cost and improve the system availability. This study explored the optimal opportunistic maintenance scheme of multi-component systems. Firstly, the failure rate model and reliability evaluation model of the multi-component system considering failure dependence were established. Secondly, the preventive maintenance plan of each individual component was determined, with the goal of obtaining the lowest warranty cost per unit time in the component life cycle. Thirdly, the preventive maintenance work of each individual component was combined, and the two-dimensional warranty cost model of the multi-component system was established according to the reliability threshold when performing opportunistic maintenance. In the experimental verification and result analysis, the genetic algorithm was used to find the optimal opportunistic maintenance scheme for the power transmission device. The comparative analysis results show that the opportunistic maintenance scheme reduced the warranty cost by 5.5% and improved the availability by 10%, which fully verified the effectiveness of the opportunistic maintenance strategy.
Assuntos
Algoritmos , Reprodutibilidade dos TestesRESUMO
Since discovered in 2007, conjugated microporous polymers (CMPs) have been developed for numerous applications including gas adsorption, sensing, organic and photoredox catalysis, energy storage, etc. While featuring abundant micropores, the structural rigidity derived from CMPs' stable π-conjugated skeleton leads to insolubility and thus poor processability, which severely limits their applicability, e.g., in CMP-based devices. Hence, the development of CMPs whose structure can not only be controlled on the micro- but also on the macroscale have attracted tremendous interest. In conventional synthesis procedures, CMPs are obtained as powders, but in recent years various bottom-up synthesis strategies have been developed, which yield CMPs as thin films on substrates or as hybrid materials, allowing to span length scales from individual conjugated monomers to micro-/macrostructures. This review surveys recent advances on the construction of CMPs into macroscale structures, including membranes, films, aerogels, sponges, and other architectures. The focus is to describe the underlying fabrication techniques and the implications which follow from the macroscale morphologies, involving new chemistry and physics in such materials for applications like molecular separation/filtration/adsorption, energy storage and conversion, photothermal transformation, sensing, or catalysis.
RESUMO
Seawater evaporation realized by solar-thermal conversion represents one of the most sustainable and effective strategies to obtain fresh water. Many approaches have been proposed to achieve high efficiencies of solar-thermal conversion, but their practical applications are limited by the low scalability. Herein, novel porphyrin/aniline-based conjugated microporous polymers (PACMPs) are synthesized via a Buchwald-Hartwig coupling reaction, which are then integrated with polyurethane sponges via a simple dip-coating technique. The PACMP-modified sponges (PACSs) retain the high porosity of the sponge substrate and excellent solar-thermal conversion properties of PACMPs. Under standard solar irradiation (1 kW m-2), PACSs achieve a high seawater evaporation rate of 1.31 kg m-2 h-1 with a solar-thermal conversion efficiency of 86.3%. PACSs show no salt accumulation and high performance of desalination and dye decolorization, removing >99.9% salt and >99.2% dye, respectively. The self-floating characteristic, recyclability, and durable solar-thermal evaporation efficiencies enable PACSs to be promising candidate materials for seawater desalination and sewage purification.
RESUMO
Gastric cancer (GC), one of the most prevalent malignancies across the world, has an increasing incidence rate. Long non-coding RNA (lncRNA) PURPL (also referred to as LINC01021) has been demonstrated to influence malignant GC behaviors and partake in other cancers. Notwithstanding, reports pertaining to the underlying mechanism of PURPL in GC haven't been rarely seen. Presently, in-vivo and ex-vivo experiments were implemented to examine the PURPL-miR-137-ZBTB7A-PI3K-AKT-NF-κB regulatory axis in GC. Our statistics revealed that PURPL presented a high expression in GC tissues and cell lines. PURPL overexpression remarkably exacerbated colony formation, migration, and invasion and repressed apoptosis in GC cells (AGS and MNK-45). In-vivo experiments also corroborated that cell growth was boosted by PURPL up-regulation. Mechanistic investigations verified that PURPL interacted with miR-137 and lowered its profile in GC cell lines. miR-137 overexpression or ZBTB7A knockdown upended the oncogenic function mediated by PURPL. PURPL initiated the PI3K/AKT/NF-κB pathway. PI3K and NF-κB inhibition impaired the promoting impact on GC cells elicited by PURPL overexpression and contributed to PURPL down-regulation. These findings disclosed that PURPL serves as an oncogene in the context of GC via miR-137-ZBTB7A-PI3K-AKT-NF-κB axis modulation.
Assuntos
Proteínas de Ligação a DNA/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Fatores de Transcrição/genética , Regulação para Cima , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
To investigate the impact of megacities on the chemistry of surface waters, monthly sampling and monitoring were conducted in the Chengdu section of the Minjiang and Tuojiang River basin, corresponding to the upper reaches of the Yangtze River since the spring of 2019, including the influent and effluent water samples from 57 sewage treatment plants in Chengdu. All the samples were analyzed for major ions and other water chemistry parameters, and compared with the historical data of the Minjiang and Tuojiang River. The results showed that the Chengdu surface water still presented a natural chemistry with medium-low total dissolved solids(TDS), and calcium bicarbonate chemistry type, which is the natural consequence of the weathering of carbonate rocks in the basin effected by the weathering of silicates and evaporites. The natural water chemistry of the surface waters in Chengdu presented monthly variation, i.e.,the concentration of major ions and TDS was higher in the dry season compared to the wet season, reflecting the variations of point source. Spatially, the concentration of major ions and TDS downstream of the city was higher than those in the upper reaches, and the concentration in the tributary was higher than that in the mainstream, which may reflect urban influence. Further analyses, such as simulation calculations, indicated that urban activities were the major driving factor for the chemistry change in the surface waters in Chengdu, which is evidenced by the significant contribution of the sewage discharge to the elevated Cl- and Na+ and the ratio of hardness/alkalinity>1 from anthropogenic acid gas emissions. A comparison with the water chemistry of the Minjiang and Tuojiang River in the 1960s indicated that, the current Cl-/Na+ ratio has significantly increased, which has been evidenced by a salinization trend. As a megacity nearest to the source of the Yangtze River, the impact of Chengdu on the natural water chemistry of the Yangtze River system and its environmental effects deserves more attention.
Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água , Carbonatos/análise , Rios , Água , Poluentes Químicos da Água/análiseRESUMO
Urban governance is an important cornerstone in the modernization of a national governance system. The establishment of smart cities driven by digitalization will be a vital way to promote economic green and sustainable growth. By using the data of 274 prefecture-level cities in China from 2004 to 2017, we study the impact of smart city policy on economic green growth and the underlying mechanism of the impact. It is shown that the establishment of smart cities has significantly promoted the green growth of China's economy. This conclusion is further confirmed by using exogenous geographic data as instrumental variables and robustness tests, such as the quasi-experimental method of Difference in Difference with Propensity Score Matching (PAM-DID). The mechanism test shows that promoting economic growth, reducing per unit GDP energy consumption, and lowering waste emissions represent three ways for smart cities to promote green economic growth. The heterogeneity test shows that smart city policy has an obvious promotional effect on the economic green growth of both large cities and non-resource-based cities. This paper is expected to provide a reference for the urban development and economic transformation of emerging economies.
Assuntos
Desenvolvimento Econômico , Reforma Urbana , China , Cidades , PolíticasRESUMO
The traditional data envelopment analysis (DEA) model usually ignores the influence of external environmental factors and random interference. This can easily lead to deviations in efficiency estimates. In order to solve this problem, a three-stage DEA model was used to better reflect the carbon emission efficiency of Chinese construction industry (CEECI) (2006-2017) from the perspective of non-management factors. The internal influencing factors of CEECI are analyzed by the Tobit model, which provides a more accurate basis for formulating policies. It is found that the CEECI is significantly affected by the GDP, the level of industrialization, the degree of opening-up, technological innovation, and energy structure. After excluding environmental factors and random interference, the average CEECI increased by 16%. The resulting calculations are noteworthy in three aspects. First, there are significant regional differences in the CEECI. Both the multi-polarization phenomenon of CEECI and regional differences also reduced gradually over time. Second, the CEECI can be decomposed into pure carbon emission efficiency (PCEE) and scale efficiency (SE), which is mainly caused by SE. Excluding external environmental factors and random interference will have a specific impact on the CEECI. All the 30 provinces are divided into four categories to analyze the reasons and solutions of the differences in the CEECI in provinces. Third, many factors had inhibitory effects on the CEECI, PCEE, and SE; these included energy structure optimization, labor force number, total power of construct ion equipment, and construction intensity in the construction industry. Nevertheless, the development level of the construction industry did have a significant positive effect.
Assuntos
Carbono , Indústria da Construção , Carbono/análise , China , Eficiência , Desenvolvimento IndustrialRESUMO
The fiscal decentralization system under China's political centralization affects local economic and environmental policies, and thus has an important impact on environmental quality. This paper uses the panel data of 285 cities in China from 2003 to 2018 and the spatial Durbin model to empirically analyze the impact of fiscal decentralization on haze pollution and its mechanism. The results show that the increase in fiscal decentralization will significantly aggravate the haze pollution in and around the region, and this conclusion is still valid after a series of robustness tests. Moreover, the impact of fiscal decentralization on haze pollution has significant heterogeneity in the size and region of the city, and the sample period. In addition, mechanism analyses show that fiscal decentralization has aggravated haze pollution by increasing infrastructure construction, reducing environmental regulations, and intensifying market segmentation. Further analyses reveal that, on the one hand, local governments have the ability to control haze pollution in their own regions according to their own wishes and interests, but on the other hand, adjustments to environmental policies in surrounding areas will significantly inhibit the control of environmental policies in the region, thereby making local governments haze pollution has not been effectively controlled. This is essentially a "Race to bottom" phenomenon among local governments in environmental policies.
Assuntos
Poluição do Ar , Poluição Ambiental , Poluição do Ar/análise , China , Cidades , Política Ambiental , Poluição Ambiental/análise , PolíticaRESUMO
Organic phase change materials (PCMs) have attracted considerable attention for thermal energy storage applications because of their non-toxicity, suitable working temperature range and excellent thermal/chemical stability. However, most traditional organic PCMs have small molecular structures and are prone to leakage during fusion. To address this problem and enhance the shape-stability of organic PCMs, nanosphere-shaped porphyrin-ferrocenyl conjugated microporous polymers (PFCMPs) with high porosity (~ 650 m2/g) were solvothermally synthesized using a Diels-Alder reaction between 1,1'-ferrocenedicarboxaldehyde and pyrrole in the presence of glacial acetic acid and anhydrous Lewis acids (FeCl3, AlCl3, and CuCl2). The PFCMPs were then encapsulated with PCMs, that is, 1-octadecanol (ODA), to prepare the composite materials of ODA@PFCMPs. The optimized composite exhibited a high latent heat (up to 153.8 J/g), excellent reversibility (negligible change in latent heat upon 100 cycles of heating-cooling), good shape stability, and long heat storage durability (425 s), making it a promising candidate for solar thermal energy engineering and management.
RESUMO
To reveal the Beijing-Hangzhou Grand Canal natural water chemistry characteristics and the influence of human activities, river samples from Xuzhou to Jiaxing were collected in 2019-2020. Simultaneously, the water chemistry data of the canal from 1959 to 1962 and 1975 to 1977 in the Suzhou, Wuxi, and Changzhou sections and the recent social and economic data of the major cities along the canal were collected and analyzed. The results showed that the type of hydrochemistry in the study area was mainly influenced by the weathering of carbonate rocks in the basin, but K++Na+ accounted for 40.39% of the cation equivalent concentration, which was higher than that in ordinary surface water, thereby indicating that the natural hydrochemistry of the canal had been significantly affected by human factors. Spatially, the major ion mass concentrations, total hardness, and total alkalinity of the Grand Canal from Xuzhou station to the downstream area tended to decrease overall, but the parameters at Wuxi and Suzhou stations increased significantly. It was found that Na+ and SO42- were increased by approximately 16 and 12 times and total dissolved solids was increased by nearly 3 times by analyzing the 60 years of water chemistry of the Suzhou, Wuxi, and Changzhou sections. The current (Ca2++Mg2+)/HCO3- ratio in the Suzhou, Wuxi, and Changzhou sections is generally greater than 1, which is significantly higher than that from 1959 to 1962, thereby reflecting the results of human activities. According to the analysis of the social and economic development of the Grand Canal, this change was the result of the accelerated weathering of carbonate rocks in the basin caused by the sulfur oxides discharged by human activities. Further statistical analysis showed that urban domestic sewage and industrial wastewater discharge were the main driving factors causing chemical salinization of natural water in the Grand Canal. This study can provide a scientific basis for coordinating urban development and protecting the water ecological environment of the Grand Canal Basin.
RESUMO
INTRODUCTION: Osteosarcoma, the most prevalent primary malignancy of the bone, is often presented with high-grade subclinical metastatic disease that metastasizes at very early stages. Exosomes, as molecular information carriers, may play a potent role in the occurrence and development of tumors through oncogenic molecular reprogramming of tumor-associated macrophages (TAMs). In this study, we will investigate the effect of osteosarcoma-derived exosomes on the polarization of TAMs and decipher its underlying molecular mechanism. MATERIAL AND METHODS: Osteosarcoma-derived exosomes from MG63 cells were isolated and characterized by transmission electron microscopy, and nano-particle size analysis. Double fluorescence staining was performed to confirm the macrophages phagocytosis of exosomes. Western blot, qRT-PCR, and transwell assays were conducted to assess the effect of exosomes on migration, invasion, and macrophage differentiation. The mouse model of osteosarcoma was established to evaluate the effects of exosomes on lung metastasis in vivo. RESULTS: MG63 exosomes were successfully isolated and verified to be phagocytized by macrophages through fluorescence confocal microscopy. The results revealed that osteosarcoma cells could induce M2 type differentiation of macrophages largely through Tim-3 mediated by exosomes, which in turn could promote the migration, invasion, epithelial-mesenchymal transition (EMT), and lung metastasis of osteosarcoma cells through the secretion of cytokines including IL-10, TGF-ß, and VEGF. CONCLUSIONS: Our results demonstrated that osteosarcoma-derived exosomes induced M2 polarization of macrophages and promoted the invasion and metastasis of tumors through Tim-3; besides, the study also suggests a novel therapeutic target for future studies.