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Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.
Subject(s)
Bone Neoplasms , Osteosarcoma , Humans , Prognosis , Osteosarcoma/genetics , Immunotherapy , Macrophages , Transcription Factors , Bone Neoplasms/genetics , Homeodomain Proteins , Repressor ProteinsABSTRACT
BACKGROUND: Immune cell infiltration and neuroinflammation are heavily associated with spinal cord injury (SCI). C-C motif chemokine ligand 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis has been identified as a critical role player during the invasion of immune cells to lesions in many diseases. γδ T cells, a subgroup of T cells, manage the course of inflammation response in various diseases; however, it remains unknown whether γδ T cells are recruited to injury site through CCL2/CCR2 signaling and exert the regulation effect on neuroinflammation after SCI. METHODS: Basso Mouse Scale (BMS), regularity index, cadence, max contact area, and motor-evoked potential testing (MEP) were measured to determine the neurological function recovery after spinal cord injury. Nissl staining was performed to identify the number of surviving motor neurons at lesion epicenter. Immunofluorescence, Western blot, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time polymerase chain reaction (QRT-PCR) also were employed to evaluate the expression of associated proteins and genes. RESULTS: In this study, we demonstrated that TCRδ-/- mice present improved neurological recovery after SCI. γδ T cell recruitment to the SCI site was significantly reduced and motor functional improvement enhanced in CCL2-/- and CCR2-/- mouse strains. Furthermore, reconstitution of TCRδ-/- mice with γδ T cells extracted from CCR2-/- mice also showed similar results to CCL2 and CCR2 deficient mice. CONCLUSIONS: In conclusion, γδ T cell recruitment to SCI site promotes inflammatory response and exacerbates neurological impairment. CCL2/CCR2 signaling is a vital recruitment mechanism of γδ T cells to the SCI site, and it may be taken as a novel therapeutic target for future SCI.
Subject(s)
Chemokine CCL2/immunology , Receptors, CCR2/immunology , Signal Transduction/immunology , Spinal Cord Injuries/immunology , T-Lymphocytes/immunology , Animals , Chemokine CCL2/metabolism , Chemotaxis, Leukocyte/immunology , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Antigen, T-Cell, gamma-delta/immunology , Receptors, CCR2/metabolism , Spinal Cord Injuries/pathology , T-Lymphocytes/metabolismABSTRACT
The structural evolutions and electronic properties of AulPtm (l + m ≤ 10) clusters are investigated by using the first-principles methods. We use the inverse design of materials using the multi-objective differential evolution (IM2ODE) package to globally search the equilibrium structures and investigate the evolving trend from a two-dimensional structure to a three-dimensional structure on horizontal extension and vertical extension for AulPtm (l + m ≤ 10) clusters. The three-dimensional stable geometry of Au8Pt and Au8Pt2 is discovered for the first time in our work. We also notice that the equilibrium structures of AulPtm (l + m = 10 and l ≤ 8) tend to form a tetrahedral geometry and can be obtained by replacing the Au atom in the most stable structure of Aul+1Ptm-1 with the Pt atom, where Pt atoms assemble together and occupy the center of clusters and Au atoms prefer to lie on the vertex or edge position. The average binding energy (Eb) is mostly decided by Pt-Pt bond numbers, namely the numbers of Pt atoms, followed by Au-Pt bond numbers. The second-order energy difference (Δ2Ev and Δ2Eh) and the nearest-neighbor energy difference (Δ4Enn) show that Au6Pt, Au4Pt2, Au3Pt3, Au2Pt4 and AuPt7 clusters exhibit high relative physical stability, so we suggest that these clusters could be defined as the magic number clusters for AulPtm (l + m ≤ 10) clusters. The HOMO-LUMO energy gap (Eg), adiabatic ionization potential (AIP) and the adiabatic electron affinity (AEA) are also investigated to elaborate the relative electronic stability of all the clusters.
ABSTRACT
A general AzePhenol dinuclear zinc catalytic system has been successfully developed and applied into the asymmetric Michael addition of 4-hydroxyl pyrones and 4-hydroxycoumarins to ß,γ-unsaturated α-keto esters. Excellent yields (up to 99%) and high enantioselectivities (up to 94% ee) are obtained for a wide range of substrates under mild conditions in the absence of additives. This bimetallic catalytic approach represents a new and effective asymmetric synthetic protocol to access a variety of bioactive compounds with pharmacological interest. The possible mechanism is proposed to explain the origin of the asymmetric induction.
Subject(s)
Azetidines/chemistry , Esters/chemistry , Heterocyclic Compounds/chemistry , Zinc/chemistry , CatalysisABSTRACT
A winter air pollution episode was observed in Hangzhou, South China, during the Second World Internet Conference, 2015. To study the pollution characteristics and underlying causes, the Weather Research and Forecasting with Chemistry model was used to simulate the spatial and temporal evolution of the pollution episode from December 8 to 19, 2015. In addition to scenario simulations, analysis of the atmospheric trajectory and synoptic weather conditions were also performed. The results demonstrated that control measures implemented during the week preceding the conference reduced the fine particulate matter (PM2.5) pollution level to some extent, with a decline in the total PM2.5 concentration in Hangzhou of 15% (7%-25% daily). Pollutant long-range transport, which occurred due to a southward intrusion of strong cold air driven by the Siberia High, led to severe pollution in Hangzhou on December 15, 2015, accounting for 85% of the PM2.5 concentration. This study provides new insights into the challenge of winter pollution prevention in Hangzhou. For adequate pollution prevention, more regional collaborations should be fostered when creating policies for northern China.
Subject(s)
Air Pollutants/analysis , Air Pollution/prevention & control , Environmental Monitoring/methods , Models, Theoretical , Particulate Matter/analysis , China , Computer Simulation , Congresses as Topic , Particle Size , Seasons , WeatherABSTRACT
The catalytic properties of the magic gold-platinum bimetallic clusters (Au4Pt2 and Au6Pt) for the reduction of SO2 by CO, without or with preadsorbing CO molecules, are firstly investigated using density functional theory calculations. We find that the catalytic activities improve effectively with the preadsorption of CO onto the catalysts and that the catalytic activities of Au6Pt(CO)n are better than those of Au4Pt2(CO)n as more CO molecules are adsorbed onto the catalysts. During the reaction process, the Au4Pt2(CO)n clusters always keep two-dimensional morphologies except for when n = 5 and the Au6Pt(CO)n clusters have three-dimensional geometries except for when n = 0. The most stable adsorption site for SO2 molecules on the catalysts is the site of preadsorbing the next CO molecule on the corresponding catalysts. The largest activation energy (E) is related to the metal 5d (M-5d) band center and the charge transfer (Ct) as well as the bond length (Rb) between COS and the catalyst contribute to the desorption energy (Ed) of COS corporately. We propose that Au6Pt(CO)6 is a cost-effective gold-platinum bimetallic catalyst for the reduction of SO2 by CO.
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Water samples were collected in summer, autumn, winter, and spring in Beihai Lake for the analysis of water quality and microbial community structure. It was found that the water quality in summer and autumn was worse than in winter and spring, and TN and TP were the most important factors affecting the water quality. The microbial community structure was investigated using MiSeq high-throughput sequencing. It was found that the phyla Cyanobacteria, Proteobacteria, Actinobacteria, and Bacteroidetes were abundant in all the samples, whereas their relative abundances differed among the four seasons. In summer and autumn, the microbial diversities were higher, and the phylum Cyanobacteria was most abundant, with the genus Synechococcus dominant. In winter, the phylum Proteobacteria was dominant. In spring, Actinobacteria and Bacteroidetes were abundant, accounting for 51.5%-64.3% of the bacterial community. The redundancy analysis (RDA) results showed that the microbial communities were mostly affected by water temperature in Beihai Lake. Overall, the water quality of Beihai Lake was qualified for the use of landscape water. However, the abundance of Synechococcus in summer may lead to algal blooms. Thus, it is necessary to strengthen the monitoring and estimation of water quality in Beihai Lake.