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Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that recognize invading pathogens and activate downstream signaling pathways. The number of 10 Tolls is found in Litopenaeus vannamei but have not yet been identified as the corresponding Toll homologue of model animal. In this study, we predicted the three-dimensional (3D) structures of 10 LvTolls (LvToll1-10) with AlphaFold2 program. The per-residue local distance difference test (pLDDT) scores of LvTolls showed the predicted structure of LvTolls had high accuracy (pLDDT>70). By structural analysis, 3D structures of LvToll2 and LvToll3 had high similarity with Drosophila melanogaster Toll and Toll7, respectively. 3D structure of LvToll7 and LvToll10 were not similar to that of other LvTolls. Moreover, we also predicted that LvSpätzle4 had high structural similarity to DmSpätzle. There were 9 potential hydrogen bonds in LvToll2-LvSpätzle4 complex. Importantly, co-immunoprecipitation assay showed that LvToll2 could bind with LvSpätzle4. Collectively, this study provides new insight for researching invertebrate immunity by identifying the protein of model animal homologue.
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Penaeidae , Receptores Toll-Like , Animales , Penaeidae/inmunología , Receptores Toll-Like/metabolismo , Receptores Toll-Like/genética , Drosophila melanogaster/inmunología , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Modelos Moleculares , Secuencia de Aminoácidos , Inmunidad Innata , Unión Proteica , Filogenia , Transducción de Señal , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Conformación ProteicaRESUMEN
Toll-like receptor 4 (TLR4) plays an essential role in the activation of innate immunity by recognizing diverse pathogenic components of bacteria. Six Tolls were found in Eriocheir sinensis but have not yet been identified as mammalian TLR4 homolog. For this purpose, we predicted three-dimensional (3D) structures of EsTolls (EsToll1-6) with AlphaFold2. 3D structure of LRRs and TIR most had high accuracy (pLDDT >70). By structure analysis, 3D structures of EsToll6 had a high overlap with HsTLR4. Moreover, we also predicted potential 11 hydrogen bonds and 3 salt bridges in the 3D structure of EsToll6-EsML1 complex. 18 hydrogen bonds and 7 salt bridges were predicted in EsToll6-EsML2 complex. Co-immunoprecipitation assay showed that EsToll6 could interact with EsML1 and EsML2, respectively. Importantly, TAK242 (a mammalian TLR4-specific inhibitor) could inhibit the generation of ROS stimulated by lipopolysaccharides (LPS) in EsToll6-EsML2-overexpression Hela cells. Collectively, these results implied that EsToll6 was a mammalian TLR4 homolog and provided a new insight for researching mammalian homologs in invertebrates.
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Braquiuros , Inmunidad Innata , Lipopolisacáridos , Receptor Toll-Like 4 , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Animales , Humanos , Braquiuros/inmunología , Células HeLa , Lipopolisacáridos/inmunología , Proteínas de Artrópodos/metabolismo , Proteínas de Artrópodos/genética , Especies Reactivas de Oxígeno/metabolismo , Unión Proteica , SulfonamidasRESUMEN
In low-permeability coal reservoirs, utilizing the organic solvent N-methyl-2-pyrrolidone (NMP) has emerged as an effective approach to improving the coal pore structure and enhancing coalbed methane productivity. However, the exact mechanisms of how solvent erosion alters functional groups and develops pores remain incompletely understood. This study utilized Fourier transform infrared spectroscopy and low-field nuclear magnetic resonance to assess the impact of NMP on the functional groups and pore structures of lignite, bituminous coal, and anthracite. The results indicate that a 6 h treatment with NMP led to an increased proportion of oxygen-containing functional groups in all coal samples, accompanied by a decrease in hydroxyls and aliphatic hydrocarbons. The aromaticity of the coal samples was enhanced to varying degrees, most notably for lignite. In terms of pore modification, the porosity of lignite and bituminous coal increased by 84.82 and 43.56%, while anthracite experienced a porosity increase of 3.04%, indicating a diminished effectiveness of NMP as the coal rank increased. These findings suggest that NMP selectively dissolves specific organic molecules in coals, thereby enhancing pore connectivity and promoting a transition from micro- to meso- and macropores. These findings highlight the potential of NMP in enhancing coalbed methane production and advance our understanding of the mechanisms behind solvent erosion.
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To study the effect of the inert gas mixture concentration and ratio on the spontaneous combustion reaction of gas coal, a combination of experimental research and theoretical analysis was used to study the pyrolysis and combustion kinetics characteristics of gas coal and further explore the influence of inert gas on the inerting characteristics of gas coal. Research has shown that during the entire heating reaction process of gas coal, the concentration of inert gases has little effect on the drying and desorption stages, but there is a significant lag phenomenon in the characteristic temperature points of active decomposition and degassing stages. Under the same concentration of mixed inert gases, the higher the relative percentage content of CO2, the more significant the change and the better the inhibitory effect. The higher the volume fraction of the inert gas, the higher the cross-temperature point. In the late stage of rapid heating of coal samples, when the volume fraction of inert gas is 40%, the rate of temperature rise increases rapidly. In a pure air environment, CO begins to be released at 80 °C, and when the temperature rises to 130 â¼ 140 °C, the concentration of CO begins to rapidly increase. Under inert conditions, the higher the relative percentage content of inert gas is, the higher the temperature point at which CO is generated. When the experimental conditions are a mixture of 30% N2 and 10% CO2 as inert gas, the optimal inerting effect has been achieved. The research results provide a theoretical basis for determining the optimal ratio of inert gas inerting concentrations to achieve fire prevention and extinguishing.
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Lung cancer, ranking second globally in both incidence and high mortality among common malignant tumors, presents a significant challenge with frequent occurrences of drug resistance despite the continuous emergence of novel therapeutic agents. This exacerbates disease progression, tumor recurrence, and ultimately leads to poor prognosis. Beyond acquired resistance due to genetic mutations, mounting evidence suggests a critical role of epigenetic mechanisms in this process. Numerous studies have indicated abnormal expression of Histone Methyltransferases (HMTs) in lung cancer, with the abnormal activation of certain HMTs closely linked to drug resistance. HMTs mediate drug tolerance in lung cancer through pathways involving alterations in cellular metabolism, upregulation of cancer stem cell-related genes, promotion of epithelial-mesenchymal transition, and enhanced migratory capabilities. The use of HMT inhibitors also opens new avenues for lung cancer treatment, and targeting HMTs may contribute to reversing drug resistance. This comprehensive review delves into the pivotal roles and molecular mechanisms of HMTs in drug resistance in lung cancer, offering a fresh perspective on therapeutic strategies. By thoroughly examining treatment approaches, it provides new insights into understanding drug resistance in lung cancer, supporting personalized treatment, fostering drug development, and propelling lung cancer therapy into novel territories.
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Safety management is a key issue in the railroad industry that needs to be continuously focused on. And it is essential to study causes of accidents for preventing accidents. However, there is a limited academic discussion on the systematic study of organizations and accidents, as well as their safety-related interactions and accidents, as opposed to human-caused disasters. Thus, the model of China's railway safety supervision and management system by sorting out the existing organizations involved in management in China is established in this paper. Firstly, social forces and auxiliary enterprises are specifically added to the model. And then, the relationship between organizations and accidents, as well as the relationship between safety interactions among organizations and accidents are explored by analyzing 224 accident reports, which led to 4 principles for accident prevention. Finally, based on these principles, measures to secure organizational nodes, as well as measures to promote safe interactions among organizations are proposed. The results showed that: (1) China Railway node is not only the most critical node in the safety supervision and management system but also the most vulnerable to the influence of other nodes. (2) The accident occurred due to the simultaneous occurrence of an accident at the China Railway node and the social force node. (3) When there are often safety risks in auxiliary enterprises and social forces simultaneously, the government's management is likely to be defective. The findings in this study can provide helpful references not only for improvement of safety management system structure and supervision and management mechanism but also for the formulation of safety supervision and management policies in China and other countries.
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Prevención de Accidentes , Administración de la Seguridad , Humanos , Administración de la Seguridad/métodos , Prevención de Accidentes/métodos , Accidentes , China , OrganizacionesRESUMEN
BACKGROUND: Non-small cell lung cancer (NSCLC) is a major pathological type of lung cancer. However, its pathogenesis remains largely unclear. MRPL35 is a regulatory subunit of the mitoribosome, which can regulate the assembly of cytochrome c oxidases and plays an important role in the occurrence of NSCLC. METHODS: The expression of MRPL35 in NSCLC was detected by tissue microarray and immunohistochemistry. H1299 cells were infected with lentivirus to knockdown MRPL35, and the cells were subjected to crystal violet staining to assess the results of colony formation assays. A549 cells were infected by lentiviral particles-expressing shMRPL35 or shControl, and then subcutaneously injected into nude mice. Tumorigenesis in mice was detected by in vivo imaging. The potential pathway of MRPL35 in NSCLC was assessed by Western blotting. RESULTS: MRPL35 was over-expressed in NSCLC tissue compared to para-cancerous and normal tissues. Knockdown of MRPL35 suppressed cell proliferation and decreased NSCLC progression both in vitro and in vivo. The possible molecular mechanisms were also clarified, which indicated that MRPL35 could be involved in cell apoptosis and proliferation by modulating the expression levels of CDK1, BIRC5, CHEK1, STMN1 and MCM2. Knockdown of MRPL35 activated p53 signaling pathway and inhibited cell cycle regulation. CONCLUSIONS: The oncogenic role of MRPL35 in NSCLC was potentially mediated through the cell cycle regulatory genes such as BIRC5, STMN1, CDK1, CHEK1 and MCM2, as well as activation of P53 signaling pathway.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/patología , Ratones Desnudos , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Utilizing biogas as a fuel for heating and power generation usually requires desulfurization pretreatment. In this study, the biogas utilization without desulfurization pretreatment in a bioelectrochemical system (BES) was explored. The results showed that the biogas-fueled BES was successfully started up within 36 d and the presence of hydrogen sulfide promoted both methane consumption and electricity generation. The optimal performance (i.e., a methane consumption of 0.523 ± 0.004 mmol/d, a peak voltage of 577 ± 1 mV, a coulomb production of 37.86 ± 0.43C/d, a coulombic efficiency of 9.37 ± 0.06 % and the maximum power density of 2.070 W/m3) was obtained under bicarbonate buffer solution and 40 °C conditions. The addition of 1 mg/L sulfide and 5 mg/L L-cysteine facilitated methane consumption and electricity generation. In the anode biofilm, the dominant bacteria were Sulfurivermis, unclassified_o__Ignavibacteriales and Lentimicrobium, while Methanobacterium, Methanosarcina and Methanothrix were the predominant archaea. Besides, the metagenomics profiles reveal that anaerobic methane oxidation and electricity generation were closely related to sulfur metabolism. These findings provide a novel approach for utilizing biogas without desulfurization pretreatment.
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Archaea , Biocombustibles , Archaea/metabolismo , Electricidad , Bacterias/metabolismo , Metano/metabolismo , Anaerobiosis , Reactores Biológicos/microbiologíaRESUMEN
CH4 can be separated from low-concentration coal bed methane (LCCBM) by using the hydrate-based gas separation (HBGS) method. To study the contribution of different cyclic organic compounds to the separation of CH4 in LCCBM, an LCCBM hydrate model was constructed. Based on the Monte Carlo and molecular dynamics theory, we simulated the effect of three cyclic organic compounds-cyclopentane (CP), cyclopentanone (CP-one), and cyclopentanol (CP-ol)-on the stability of the LCCBM hydrate at P = 2 MPa, various temperatures, and discussed the structural stability of the hydrate in depth in terms of final snapshots, radial distribution function, mean square displacement, diffusion coefficient, and potential energy change. The results showed that for the CH4-N2 LCCMM gas mixture, CP showed the best facilitation effect compared to the other two cyclic compounds by maintaining the stability of the LCCBM hydrate well at T = 293 K. The promotion effect of CP-one is between CP and CP-ol, and when the temperature increases to T = 293 K, the oxygen atoms in the water molecule can maintain the essential stability of the hydrate structure, although the orderliness decreases significantly. Moreover, the structure of the hydrate model containing CP-ol is destroyed at T = 293 K, and the eventual escape of CH4 and N2 molecules in solution occurs as bubbles. The research results are important for further exploration of the mechanism of action of cyclic promoter molecules with LCCBM hydrate molecules and promoter preferences.
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Dióxido de Carbono , Metano , Dióxido de Carbono/química , Metano/química , Agua/química , Simulación de Dinámica Molecular , Ciclopentanos , Carbón Mineral , OxígenoRESUMEN
Spexin (SPX) is an evolutionarily conserved neuropeptide, which was first identified in human proteome by data mining. Two orthologs (SPX1 and SPX2) are present in some non-mammalian species, including teleosts. It has been demonstrated that SPX1 is involved in reproduction and food intake, whereas the functional role of SPX2 is still absent in any vertebrate. The aim of the current study was to evaluate the actions of intraperitoneal injection of endogenous SPX2 peptide on the expression levels of some key reproductive genes of the brain-pituitary axis in half-smooth tongue sole. Our data showed an inhibitory action of SPX2 on brain gnih, spx1, tac3 and pituitary gthα, lhß mRNA levels. However, SPX2 had no significant effect on brain gnihr, gnrh2, gnrh3, kiss2, kiss2r, spx2 expression or pituitary gh expression. On the other hand, SPX2 induced an increase in pituitary fshß expression. Taken together, our results provide initial evidence for the involvement of SPX2 in the regulation of reproduction in vertebrates, which is in accordance with previous studies on SPX1.
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Hipófisis , Reproducción , Animales , Encéfalo/metabolismo , Peces/genética , Humanos , Hipófisis/metabolismo , ARN Mensajero/genética , Reproducción/genéticaRESUMEN
Spontaneous coal combustion is the primary cause of coal mine fires. During the production process, spontaneous coal combustion in the goaf is often affected by air leakage, which weakens or annuls the effect of inhibitors and leads to secondary oxidation. However, the action mechanism of inhibitors on secondary oxidation spontaneous coal combustion remains unclear. Thus, this study analyzes the influence of moisture evaporation on the performance of a high-water-content physical inhibitor (HWPI) using the Carbolite temperature-programmed experiment, differential scanning calorimetry, scanning electron microscopy, and a MINI MR test. The results demonstrate that as the moisture content of the inhibitor decreased, after being treated with the HWPI and drying for 24 h, the concentrations of O2, CO, and CO2 were found to be lower than the gas concentration of raw coal, which showed that although the moisture content is reduced, the treated coal sample still has a lower spontaneous combustion tendency than the raw coal. The apparent activation energy was reduced, and the heat absorption per unit time decreased, which eventually weakened or annulled the effect of the HWPI. Future research should further improve existing inhibitor types to reduce the impact of secondary oxidation on spontaneous coal combustion caused by water evaporation.
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Micropores are the primary sites for methane occurrence in coal. Studying the regularity of methane occurrence in micropores is significant for targeted displacement and other yield-increasing measures in the future. This study used simplified graphene sheets as pore walls to construct coal-structural models with pore sizes of 1 nm, 2 nm, and 4 nm. Based on the Grand Canonical Monte Carlo (GCMC) and molecular dynamics theory, we simulated the adsorption characteristics of methane in pores of different sizes. The results showed that the adsorption capacity was positively correlated with the pore size for pure gas adsorption. The adsorption capacity increased with pressure and pore size for competitive adsorption of binary mixtures in pores. As the average isosteric heat decreased, the interaction between the gas and the pore wall weakened, and the desorption amount of CH4 decreased. In ultramicropores, the high concentration of CO2 (50-70%) is more conducive to CH4 desorption; however, when the CO2 concentration is greater than 70%, the corresponding CH4 adsorption amount is meager, and the selected adsorption coefficient SCO2/CH4 is small. Therefore, to achieve effective desorption of methane in coal micropores, relatively low pressure (4-6 MPa) and a relatively low CO2 concentration (50-70%) should be selected in the process of increasing methane production by CO2 injection in later stages. These research results provide theoretical support for gas injection to promote CH4 desorption in coal pores and to increase yield.
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Low-grade ores, tailings, and solid wastes contain small amounts of valuable heavy metals. Improper disposal of these substances results in the waste of resources and contamination of soil or groundwater. Accordingly, the treatment and recycling of low-grade ores, tailings, and solid wastes attracted much attention recently. Bioelectrochemical system, an innovative technology for the removal and recovery of heavy metals, has been further developed and applied in recent years. In the current study, the low-grade chalcopyrite was bioleached with the assistance of microbial fuel cells. Copper extraction along with electricity generation from the low-grade chalcopyrite was achieved in the column bioleaching process assisted by MFCs. Results showed that after 197 days bioleaching of low-grade chalcopyrite, 423.9 mg copper was extracted from 200 g low-grade chalcopyrite and the average coulomb production reached 1.75 C/d. The introduction of MFCs into bioleaching processes promoted the copper extraction efficiency by 2.7 times (3.62% vs. 1.33%), mainly via promoting ferrous oxidation, reducing ORP, and stimulating bacterial growth. This work provides a feasible method for the treatment and recycling of low-grade ores, tailings, and solid wastes. But balancing energy consumption of aeration and circulation frequency and chemical consumption of acid to improve the copper extraction efficiency need further investigation.
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Fuentes de Energía Bioeléctrica , Metales Pesados , Cobre/química , Residuos SólidosRESUMEN
In order to study differences in the methane adsorption characteristics of coal pores of different metamorphic degrees, 4 nm pore structure models based on three typical coal structure models with different metamorphic degrees were constructed. Based on the molecular mechanics and dynamics theory, the adsorption characteristics of methane in different coal rank pores were simulated by the grand canonical Monte Carlo (GCMC) and molecular dynamics methods. The isothermal adsorption curve, Van der Waals energy, concentration distribution, and diffusion coefficient of methane under different conditions were analyzed and calculated. The results showed that at the same pore size, the adsorption capacity of CH4 is positively correlated with pressure and metamorphic degree of coal, and the adsorption capacity of CH4 in high metamorphic coal is more affected by temperature. The relative concentration of CH4 in high-order coal pores is low, and the relative concentration at higher temperature and pressure conditions is high. The CH4 diffusion coefficient in high-rank coal is low, corresponding to the strong Van der Waals interaction between CH4 and coal. The research results are of great significance for further exploration of the interaction mechanism between CH4 and coal with different metamorphic degrees and can provide theoretical support for the selection of gas extraction parameters.
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Metal halide perovskite materials have opened up a great opportunity for high-performance optoelectronic devices owing to their extraordinary optoelectronic properties. More than lead halide ones, stable and nontoxic bismuth halide perovskites exhibit more promise in their future commercialization. In this work, we developed for the first time photodetectors based on full-inorganic Cs3Bi2I9-xBrx perovskites and modulate their performance by varying x in the composition systematically. Among those self-powered photodetectors, those based on Cs3Bi2I6Br3 shows the best performance with excellent photosensitivity of 4.1 × 104 at zero bias as well as the responsivity and detectivity reaching 15 mA/W and 4.6 × 1011 Jones, respectively. More strikingly, the full-inorganic perovskite photodetectors exhibit excellent stability in the ambient environment and can maintain over 96% of the initial value after 100 days owing to the high stability of the core perovskite film. The paper definitely paves an alternative and promising strategy for the design of future commercial photodetectors that are self-powered, stable, nontoxic, etc.
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The recent emerging progress of quantum dot ink (QD-ink) has overcome the complexity of multiple-step colloidal QD (CQD) film preparation and pronouncedly promoted the device performance. However, the detrimental hydroxyl (OH) ligands induced from synthesis procedure have not been completely removed. Here, a halide ligand additive strategy was devised to optimize QD-ink process. It simultaneously reduced sub-bandgap states and converted them into iodide-passivated surface, which increase carrier mobility of the QDs films and achieve thicker absorber with improved performances. The corresponding power conversion efficiency of this optimized device reached 10.78%. (The control device was 9.56%.) Therefore, this stratege can support as a candidate strategy to solve the QD original limitation caused by hydroxyl ligands, which is also compatible with other CQD-based optoelectronic devices.
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The promising tin perovskite solar cells (PSCs) suffer from the oxidation of Sn2+ to Sn4+ , leading to a disappointing conversion efficiency along with poor stability. In this work, phenylethylammonium bromide (PEABr) was employed to form an ultrathin, low-dimensional perovskite layer on the surface of the FASnI3 (FA=formamidinium) absorber film to improve the interface of perovskite/PCBM ([6,6]-phenyl-C61 -butyricacid methyl) in the inverted planar device structure of the ITO (indium-doped tin oxide)/PEDOT:PSS [poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate]/perovskite/[6,6]-phenyl-C61 -butyricacid methyl (PCBM)/BCP (2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline) electrode. The device efficiency was enhanced from 4.77 to 7.86 % by this PEABr treatment. A series of characterizations proved that this modification could improve the crystallinity of the FASnI3 perovskite by incorporating Br and forming an ultrathin, low-dimensional perovskite layer at the interface, which led to the effective suppression of Sn2+ oxidation, improved band level alignment, and decreased defect density. These effects contributed to the clear enhancement of conversion efficiency. Moreover, this treatment also led to remarkably enhanced device stability, with approximately 80 % of the initial efficiency retained after 350â h light soaking, whereas the control device failed within 140â h. This work deepens our understanding of the suppression effect of PEABr on the oxidation of Sn2+ and paves a new way to fabricate promising tin halide PSCs by facile interface engineering.
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MicroRNA (miR)-199b-5p has been reported to be upregulated in human osteosarcoma tissues and participate in the Notch signaling in osteosarcoma cells. This study was aimed to investigate the associations of miR-199b-5p expression with tumor progression of primary osteosarcoma, and to deepen the understanding of its involvement in carcinogenesis. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to detect expression levels of miR-199b-5p in 98 osteosarcoma and corresponding adjacent normal tissues. Then, the correlations of its expression with clinicopathological characteristics and patient prognosis were statistically analyzed. Moreover, in vitro assays were performed to assess the effects of miR-199b-5p on the proliferation, migration and invasion of two human osteosarcoma cell lines MG63 and U2OS. Compared to normal controls, miR-199b-5p expression was significantly upregulated in osteosarcoma tissues (P < 0.001). In addition, the expression levels of miR-199b-5p in osteosarcoma patients with high tumor grade (P = 0.008), positive metastasis (P = 0.001) and positive recurrence (P = 0.001) were markedly higher than those with low tumor grade, negative metastasis and negative recurrence. Moreover, osteosarcoma patients with high miR-199b-5p expression showed shorter overall survival (P < .001) and shorter disease-free survival (P < 0.001) than those with low expression. Furthermore, the inhibition of miR-199b-5p significantly suppressed cell proliferation, and reduced the migratory and invasive abilities of osteosarcoma cells. This study offer the convincing evidence for the first time that the increased expression of miR-199b-5p may play crucial roles in aggressive progression and poor prognosis of human osteosarcoma. miR-199b-5p may function as an oncogene by positively regulating the malignant potentials of this neoplasm.