Efficient energy transport throughout conical implosions.

The double-cone ignition (DCI) scheme has been proposed as one of the alternative approaches to inertial confinement fusion, based on direct-drive and fast-ignition, in order to reduce the requirement for the driver energy. To evaluate the conical implosion energetics from the laser beams to the plasma flows, a series of experiments have been systematically conducted. The results indicate that 89%-96% of the laser energy was absorbed by the target, with moderate stimulated Raman scatterings. Here 2%-6% of the laser energy was coupled into the plasma jets ejected from the cone tips, which was mainly restricted by the mass reductions during the implosions inside the cones. The supersonic dense jets with a Mach number of 4 were obtained, which is favorable for forming a high-density, nondegenerated plasma core after the head-on collisions. These findings show encouraging results in terms of energy transport of the conical implosions in the DCI scheme.

Analysis of the quality of tunnel roof topography by automatic cutting control under the coupling of multiple factors.

The automatic cutting of coal and rock surface morphology modeling based on the actual geological environment of coal mine underground excavation and mining is of great significance for improving the surface quality of coal and rock after cutting and enhancing the safety and stability of advanced support. To this end, using the principle of coordinate transformation, the kinematic trajectory of the cutting head of the tunneling machine is established, and the contour morphology of the cutting head under variable cutting technology is obtained. Then, based on the regenerative vibration theory of the cutting head, a dynamic model of the cutting head coal wall is established, and the coordinate relationship of the cutting head in the tunnel coordinate system under vibration induction is analyzed. Based on fractal theory and Z-MAP method, a simulation method for the surface morphology of coal and rock after cutting is proposed, which is driven by the cutting trajectory Under the coupling effect of cutting vibration induction and random fragmentation of coal and rock, simulation of the surface morphology of comprehensive excavation tunnels was conducted, and relevant experiments were conducted to verify the results. A 1:3 similarity experimental model of EBZ160 tunneling machine was used to build a cutting head coal and rock system cutting experimental platform for comparative experiments of cutting morphology. Furthermore, statistical methods were used to compare and evaluate the simulated roof with the actual roof. The results show that the relative errors between the maximum range of peaks and valleys, the peak skewness coefficient of height standard deviation, and the kurtosis coefficient of the actual roof are 1.3%, 24.5%, 16%, and 2.9%, respectively. Overall, this indicates that the surface morphology distribution characteristics of the simulated roof and the actual roof are similar, verifying the effectiveness of the modeling and simulation method proposed in this paper, and providing theoretical support for the design and optimization of advanced support in the future.

Rapamycin Inhibits Senescence and Improves Immunomodulatory Function of Mesenchymal Stem Cells Through IL-8 and TGF-ß Signaling.

Mesenchymal stromal cells (MSCs) grown in high-density monolayers (sheets) are promising vehicles for numerous bioengineering applications. When MSC sheets are maintained in prolonged cultures, they undergo rapid senescence, limiting their downstream efficacy. Although rapamycin is a potential agent that can inhibit senescence in cell cultures, no study has investigated rapamycin's effect on MSCs grown in high-density culture and its effect on downstream target gene expression. In this study, placental-derived MSCs (PMSCs) were seeded at high density to generate PMSC sheets in 24 hours and were then treated with rapamycin or vehicle for up to 7 days. Autophagy activity, cell senescence and apoptosis, cell size and granularity, and senescence-associated cytokines (IL-6 and IL-8) were analyzed. Differential response in gene expression were assessed via microarray analysis. Rapamycin significantly increased PMSC sheet autophagy activity, inhibited cellular senescence, decreased cell size and granularity at all timepoints. Rapamycin also significantly decreased the number of cells in late apoptosis at day 7 of sheet culture, as well as caspase 3/7 activity at all timepoints. Notably, while rapamycin decreased IL-6 secretion, increased IL-8 levels were observed at all timepoints. Microarray analysis further confirmed the upregulation of IL-8 transcription, as well as provided a list of 396 genes with 2-fold differential expression, where transforming growth factor-ß (TGF-ß) signaling were identified as important upregulated pathways. Rapamycin both decreased senescence and has an immunomodulatory action of PMSCs grown in sheet culture, which will likely improve the chemotaxis of pro-healing cells to sites of tissue repair in future bioengineering applications.

Effects of stacking breeding on the methylome and transcriptome profile of transgenic rice with glyphosate tolerance.

MAIN CONCLUSION: Transcriptomics and methylomics were used to identify the potential effects resulting from GM rice breeding stacks, which provided scientific data for the safety assessment strategy of stacked GM crops in China. Gene interaction is one of the main concerns for stacked genetically modified crop safety. With the development of technology, the combination of omics and bioinformatics has become a useful tool to evaluate the unintended effects of genetically modified crops. In this study, transcriptomics and methylomics were used as molecular profiling techniques to identify the potential effects of stack through breeding. Stacked transgenic rice En-12 × Ec-26 was used as material, which was obtained through hybridization using parents En-12 and Ec-26, in which the foreign protein can form functional EPSPS protein by intein-mediated trans-splitting. Differentially methylated region (DMR) analysis showed that the effect of stacking breeding on methylation was less than that of genetic transformation at the methylome level. Differentially expressed gene (DEG) analysis showed that the DEGs between En-12 × Ec-26 and its parents were far fewer than those between transgenic rice and Zhonghua 11 (ZH11), and no unintended new genes were found in En-12 × Ec-26. Statistical analysis of gene expression and methylation involved in shikimic acid metabolism showed that there was no difference in gene expression, although there were 16 and 10 DMR genes between En-12 × Ec-26 and its parents (En and Ec) in methylation, respectively. The results indicated that the effect of stacking breeding on gene expression and DNA methylation was less than the effect of genetic transformation. This study provides scientific data supporting safety assessments of stacked GM crops in China.

Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications.

Although the complex mechanism by which skeletal tissue heals has been well described, the role of reactive oxygen species (ROS) in skeletal tissue regeneration is less understood. It has been widely recognized that a high level of ROS is cytotoxic and inhibits normal cellular processes. However, with more recent discoveries, it is evident that ROS also play an important, positive role in skeletal tissue repair, specifically fracture healing. Thus, dampening ROS levels can potentially inhibit normal healing. On the same note, pathologically high levels of ROS cause a sharp decline in osteogenesis and promote nonunion in fracture repair. This delicate balance complicates the efforts of therapeutic and engineering approaches that aim to modulate ROS for improved tissue healing. The physiologic role of ROS is dependent on a multitude of factors, and it is important for future efforts to consider these complexities. This review first discusses how ROS influences vital signaling pathways involved in the fracture healing response, including how they affect angiogenesis and osteogenic differentiation. The latter half glances at the current approaches to control ROS for improved skeletal tissue healing, including medicinal approaches, cellular engineering, and enhanced tissue scaffolds. This review aims to provide a nuanced view of the effects of ROS on bone fracture healing which will inspire novel techniques to optimize the redox environment for skeletal tissue regeneration.

Transient activation of notch signaling enhances endogenous stromal cell expansion and subsequent bone defect repair.

BACKGROUND: Following traumatic bone loss or removal of bone tumors, the failure of bone allograft transplantation for large bone defect repair remains a significant problem in orthopedics. Therefore, new strategies that can efficiently enhance allograft healing and long-term incorporation are critically needed. METHOD: In this study, we first injected Notch-activating Jagged1 peptide to mice and then isolated bone marrow tissues and cells for proliferation and differentiation assays. Femur bone allograft surgery was also performed in Jagged1 pre-treated mice, and bone defect healing process were monitored by histology, Micro-CT and biomechanical testing. RESULT: Our results showed that Jagged1 therapeutic injection is sufficient to maximally activate Notch and promote bone marrow stromal cell proliferation in vivo, while no effects on bone structure were observed. More importantly, Jagged1 pre-treatment significantly promoted bone callus formation and increased bone mechanical strength during allograft healing in a femur bone defect mouse model. CONCLUSION: This study reveals that Notch in vivo activation can be induced by injection of Jagged1 peptide for expansion of local native stromal cells that will significantly enhance bone callus formation. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The clinical uses of this therapeutic strategy would be immediately applicable for chronic long bone defect repair. More importantly, this devised strategy for expansion of endogenous BMSCs can also be applied to enhance other tissue and organ repair.

Comparative transcriptomic analysis reveals the coordinated mechanisms of Populus × canadensis 'Neva' leaves in response to cadmium stress.

Cadmium (Cd), a heavy metal element has strong toxicity to living organisms. Excessive Cd accumulation directly affects the absorption of mineral elements, inhibits plant tissue development, and even induces mortality. Populus × canadensis 'Neva', the main afforestation variety planted widely in northern China, was a candidate variety for phytoremediation. However, the genes relieving Cd toxicity and increasing Cd tolerance of this species were still unclear. In this study, we employed transcriptome sequencing on two Cd-treated cuttings to identify the key genes involved in Cd stress responses of P. × canadensis 'Neva' induced by 0 (CK), 10 (C10), and 20 (C20) mg/L Cd(NO3)2 4H2O. We discovered a total of 2,656 (1,488 up-regulated and 1,168 down-regulated) and 2,816 DEGs (1,470 up-regulated and 1,346 down-regulated) differentially expressed genes (DEGs) between the CK vs C10 and CK vs C20, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses in response to the Cd stress indicated that many DEGs identified were involved in the catalytic activity, the oxidoreductase activity, the transferase activity, and the biosynthesis of secondary metabolites. Based on the enrichment results, potential candidate genes were identified related to the calcium ion signal transduction, transcription factors, the antioxidant defense system, and transporters and showed divergent expression patterns under the Cd stress. We also validated the reliability of transcriptome data with the real-time PCR. Our findings deeper the understanding of the molecular responsive mechanisms of P. × canadensis 'Neva' on Cd tolerance and further provide critical resources for phytoremediation applications.

Effect of Overexpression of JERFs on Intracellular K+/Na+ Balance in Transgenic Poplar (Populus alba × P. berolinensis) Under Salt Stress.

Salt stress is one of the main factors that affect both growth and development of plants. Maintaining K+/Na+ balance in the cytoplasm is important for metabolism as well as salt resistance in plants. In the present study, we monitored the growth (height and diameter) of transgenic Populus alba × P. berolinensis trees (ABJ01) carrying JERF36s gene (a tomato jasmonic/ethylene responsive factors gene) over 4 years, which showed faster growth and significant salt tolerance compared with non-transgenic poplar trees (9#). The expression of NHX1 and SOS1 genes that encode Na+/H+ antiporters in the vacuole and plasma membranes was measured in leaves under NaCl stress. Non-invasive micro-test techniques (NMT) were used to analyse ion flux of Na+, K+, and H+ in the root tip of seedlings under treatment with100 mM NaCl for 7, 15, and 30 days. Results showed that the expression of NHX1 and SOS1 was much higher in ABJ01 compared with 9#, and the Na+ efflux and H+ influx fluxes of root were remarkable higher in ABJ01 than in 9#, but K+ efflux exhibited lower level. All above suggest that salt stress induces NHX1 and SOS1 to a greater expression level in ABJ01, resulting in the accumulation of Na+/H+ antiporter to better maintain K+/Na+ balance in the cytoplasm of this enhanced salt resistant variety. This may help us to better understand the mechanism of transgenic poplars with improving salt tolerance by overexpressing JERF36s and could provide a basis for future breeding programs aimed at improving salt resistance in transgenic poplar.

Wnt Signaling Inhibits High-Density Cell Sheet Culture Induced Mesenchymal Stromal Cell Aging by Targeting Cell Cycle Inhibitor p27.

Mesenchymal stromal cell senescence and apoptosis have been identified as critical molecular hallmarks in aging. In this study, we used stromal cell sheet culture as an in vitro model to study the progressive changes of cellular senescence, apoptosis and underlying mechanism in Wnt3a treated cells. Our results showed fresh bone marrow mesenchymal stromal cells (BMSCs) become senescent and undergo apoptosis with increased inflammatory profile and Reactive Oxygen Species (ROS) in high-density cell sheet cultures. The gene expression level of senescence related proteins and key regulators of apoptosis in cell sheet cultures was significantly increased in older BMSCs at Days 4 and 7 cultures compared with younger cells at Day 1 cultures. More importantly, Wnt signaling activation significantly reduced senescence in cell sheet cultures by direct regulation of cell cycle inhibitor p27. This study not only characterized the cellular and molecular features of aging stromal cells in short-term cell sheet cultures, but also identified the downstream target responsible for Wnt inhibition of cell senescence.

Absolute x-ray calibration of an Amersham imaging plate scanner.

The absolute response of the GE Amersham Typhoontm imaging plate scanner is studied in this paper. The sensitivity function of the scanner with different photomultiplier tube voltages was obtained by using a pre-calibrated Cu Kα x-ray tube. The results showed that the sensitivity function decreases exponentially with higher voltage and is also affected by the scanning pixel size. The spatial resolution and the fading effect of the imaging plate system on x rays were also investigated and compared with the previous scanner models.

The application of gene splitting technique for controlling transgene flow in rice.

Controlling transgene flow in China is important, as this country is part of the center of origin of rice. A gene-splitting technique based on intein-mediated trans-splicing represents a new strategy for controlling transgene flow via biological measures. In this study, the G2-aroA gene which provides glyphosate tolerance was split into an N-terminal and a C-terminal region, which were then fused to intein N and intein C of the Ssp DnaE intein, ultimately forming EPSPSn:In and Ic:EPSPSc fusion genes, respectively. These fusion genes were subsequently transformed into the rice cultivar Zhonghua 11 via the Agrobacterium-mediated method. The two split gene fragments were then introduced into the same rice genome by genetic crossings. Glyphosate tolerance analysis revealed that the functional target protein was reconstituted by Ssp DnaE intein-mediated trans-splicing and that the resultant hybrid rice was glyphosate tolerant. The reassembly efficiency of the split gene fragments ranged from 67 to 91% at the molecular level, and 100% of the hybrid F1 progeny were glyphosate tolerant. Transgene flow experiments showed that when the split gene fragments are inserted into homologous chromosomes, the gene-splitting technique can completely avoid the escape of the target trait to the environment. This report is the first on the reassembly efficiency and effectiveness of transgene flow containment via gene splitting in rice. This study provides not only a new biological strategy for controlling rice transgene flow but also a new method for cultivating hybrid transgenic rice.

Notch Signaling in Osteogenesis, Osteoclastogenesis, and Angiogenesis.

Skeletal tissue development and regeneration in mammals are intricate, multistep, and highly regulated processes. Various signaling pathways have been implicated in the regulation of these processes, including Notch. Notch signaling is a highly conserved, intercellular signaling pathway that regulates cell proliferation and differentiation, determines cell fate decision, and participates in cellular process in embryonic and adult tissue. Here, we review recent data showing the regulation of Notch signaling in osteogenesis, osteoclastogenesis, and angiogenesis. These processes are cell-context-dependent via direct or indirect mechanisms. Furthermore, Notch signaling may be highly beneficial for efficient coupling of osteogenesis and angiogenesis for tissue engineering and skeletal repair, which is critical to develop clinically therapeutic options.

Notch ligand Jagged1 promotes mesenchymal stromal cell-based cartilage repair.

Placenta-derived mesenchymal stromal cells (PMSCs) provide a promising cell source for tissue regeneration. However, rapid induction of PMSC chondrogenic differentiation during therapeutic transplantation remains extremely challenging. Here we undertook a study to determine if Notch inhibition by soluble Jagged1 (JAG1) peptides could be utilized to accelerate PMSC-induced cartilage regeneration in a mouse post-traumatic osteoarthritis (PTOA) model. Our results showed that treatment of PMSCs with soluble JAG1 significantly enhanced chondrogenesis in culture as shown by increased alcian blue staining and decreased Notch target Hes1 expression when compared to those in lgG-treated control cells. Importantly, significantly enhanced cartilage formation and decreased joint inflammation were observed when JAG1-treated PMSCs were injected into mouse PTOA knee joints. Finally, in vivo cell tracing showed that more JAG1-treated PMSCs remained in knee joint tissues and that JAG1-treated PMSCs exhibited greater PMSC chondrogenic differentiation than lgG-treated control PMSCs at 4 weeks after injection. These data indicate that transient Notch inhibition by soluble JAG1 could be used to enhance PMSC survival and chondrogenic differentiation, thereby increasing the therapeutic potential of PMSCs for cartilage regeneration.

Comparative Metabolomic Analysis of the Cambium Tissue of Non-transgenic and Multi-Gene Transgenic Poplar (Populus × euramericana 'Guariento').

Poplar, a model for woody plant research, is the most widely distributed tree species in the world. Metabolites are the basis of phenotypes, allowing an intuitive and effective understanding of biological processes and their mechanisms. However, metabolites in non-transgenic and multi-gene transgenic poplar remains poorly characterized, especially in regards of the influences on quantity and in the analysis of the relative abundance of metabolites after the introduction of multi stress-related genes. In this study, we investigated the cambium metabolomes of one non-transgenic (D5-0) and two multi-gene (vgb, SacB, ERF36, BtCry3A, and OC-I) transgenic lines (D5-20 and D5-21) of hybrid poplar (Populus × euramericana 'Guariento') using both gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We aimed to explore the effects of the exogenous genes on metabolite composition and to screen out metabolites with important biological functions. Finally, we identified 239 named metabolites and determined their relative abundance. Among these, 197 metabolites had a different abundance across the three lines. These methabolites spanned nine primary and 44 secondary metabolism pathways. Arginine and glutamate, as substrates and intermediates in nitrogen metabolism, and important in growth and stress-related processes, as well as sucrose, uridine diphosphate glucose, and their derivatives, precursors in cell wall pathways, and catechol, relevant to insect resistance, differed greatly between the genetically modified and non-transgenic poplar. These findings may provide a basis for further study of cambium metabolism, and fully understand metabolites associated with stress response.

The naturally derived small compound Osthole inhibits osteoclastogenesis to prevent ovariectomy-induced bone loss in mice.

OBJECTIVE: This study was to determine the bone protective effects and underlying mechanisms of Osthole (OT) in ovariectomized (OVX) mice. We found that the inhibitory effects of OT on receptor activator of nuclear factor kappa-B ligand (RANKL)-activated osteoclastogenesis are responsible for its bone protective effects in OVX mice. METHODS: Eight-week-old mice were ovariectomized and OT (10 mg/kg/d) was intraperitoneally administrated to OVX mice 7 days after the surgery and were sacrificed at the end of the 3 months. Osteoclasts were generated from primary bone marrow macrophages (BMMs) to investigate the inhibitory effects of OT. The activity of RANKL-activated signaling was simultaneously analyzed in vitro and in vivo using immunohistochemistry, Western blot, and PCR assays. RESULTS: OT dose dependently inhibited RANKL-mediated osteoclastogenesis in BMM cultures. OT administration attenuated bone loss (mg Ha/cm: 894.68 ±â€Š33.56 vs 748.08 ±â€Š19.51, P < 0.05) in OVX mice. OT inhibits osteoclastogenesis (Oc.N/per view area: 72 ±â€Š4.3 vs 0.8 ±â€Š0.4, P < 0.05) and bone resorption activity (bone resorbed percentages %, 48.56 ±â€Š7.25 vs 3.25 ±â€Š1.37, P < 0.05) from BMMs. Mechanistically, OT inhibited the expressions of nuclear factor of activated T-cells c1 (NFATc1) and c-Fos. Moreover, OT suppressed the expression of RANKL-induced osteoclast marker genes, including matrix metalloproteinase 9 (MMP9), Cathepsin K (Ctsk), tartrate-resistant acid phosphatase (TRAP), and carbonic anhydrase II (Car2). CONCLUSIONS: OT inhibits RANKL-mediated osteoclastogenesis and prevents bone loss in OVX mice. Our findings revealed that OT is a potential new drug for treating postmenopausal osteoporosis.

Regulatory effects of root pruning on leaf nutrients, photosynthesis, and growth of trees in a closed-canopy poplar plantation.

A plantation of 5-year-old poplar Populus × euramericana cv. 'Neva' was used to study the regulatory effects of root pruning on nutrients, photosynthetic characteristics, and water-use efficiency (WUE) of leaves and growth rates of diameter at breast height (DBH; 1.3 m), tree height, and volume. Six root-pruning treatments were conducted with different combinations of intensity (at a distance of six, eight or ten times DBH from the trunk) and orientation (on two or four sides of the trees). Results showed that the N, P, K, photosynthetic rate, transpiration rate, and stomatal conductance of leaves were all significantly decreased by root pruning over the initial period following root pruning (30 days), but increased in the subsequent investigations. The values of the above indexes peaked in 8-2 treatment (i.e., eight times DBH distance on two sides). The leaf WUE in 8-2 treatment, and average growth rates of DBH, tree height and volume, were the highest among all treatments within 3 years of root pruning. The results indicated that the root pruning based on the appropriate selection of intensity and orientation had significant positive effects on leaf nutrients, photosynthesis, and growth of trees in a closed-canopy poplar plantation.

Oleanolic acid exerts bone protective effects in ovariectomized mice by inhibiting osteoclastogenesis.

Postmenopausal osteoporosis (POP) is quite prevalent and many new drugs are under development to obtain better therapeutic outcomes. Oleanolic acid (OA) has been reported to prevent bone loss in ovariectomized (OVX) rats by stimulating osteoblastogenesis. One previous study has demonstrated that acetate of OA suppressed lipopolysaccharides (LPS)-induced bone loss in mice. However, the role of OA in the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis is still not elucidated. Here we show that OA dose-dependently inhibits RANKL-mediated osteoclastogenesis and the formation of functional osteoclasts without impairing the viability and osteoclastic potential in bone marrow macrophages (BMMs). Moreover, OA administration attenuates bone loss in OVX mice by inhibiting osteoclast's densities. Mechanistically, OA does not affect RANKL-induced activation of the NF-кB, JNK, p38, ERK and Akt pathways, but inhibits the expression of the nuclear factor of activated T-cells c1(NFATc1) and c-Fos. Moreover, OA significantly suppresses the expression of RANKL-activated osteoclast genes encoding matrix metalloproteinase 9 (MMP9), Cathepsin K(Ctsk), tartrate-resistant acid phosphatase (TRAP) and carbonic anhydrase II (Car2). This work has elucidated the molecular mechanism of OA in RANKL-mediated osteoclastogenesis and revealed the promising potential of OA to be further developed as a new drug to prevent and treat POP.

Notch activation promotes osteoblast mineralization by inhibition of apoptosis.

Notch activator Jagged1 (JAG1) plays a critical role in the regulation of osteoblast differentiation and bone metabolism. In this study, JAG1-induced osteoblast proliferation, differentiation, and mineralization has been analyzed in primary osteoblasts for up to 7 days. Alkaline phosphatase and Alizarin red staining showed an enhanced osteoblast maturation and mineralization in JAG1 treated cells, as well as higher mRNA levels of late osteoblast differentiation markers. In contrast, Notch inhibitor DAPT and deletion of Runx2 totally blocked JAG1 effects on osteoblast mineralization. Flow cytometry data further showed a significantly higher cell proliferation in early stages of culture at day 3, and lower levels of osteoblast apoptosis in late stages of culture at day 7. More importantly, activation of anti-apoptotic factor BCL-2 was enhanced, while pro-apoptotic factor Caspase3 was reduced in JAG1 treated osteoblasts. Therefore, we conclude that cell mineralization is enhanced via anti-apoptotic actions of Notch signaling within the osteoblast cells.

Oleanolic acid induces osteosarcoma cell apoptosis by inhibition of Notch signaling.

Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in several tumor cell lines. Although the inhibition effects of OA on proliferation and survival in human cancers have been confirmed, the potential mechanism underlying OA-induced osteosarcoma cell death has not yet been fully elucidated. Our results in this study showed that OA inhibits proliferation and viability of osteosarcoma cells in a dose-dependent manner. Flow cytometry assays revealed that apoptosis in osteosarcoma cells was significantly induced by OA treatment, while this induction was blocked by Jagged1-mediated activation of Notch signaling. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. More importantly, our data revealed that OA treatment interrupted the balance between pro-apoptotic factors and anti-apoptotic factors in osteosarcoma cells by inhibition of the Notch signaling pathway. These data suggest that OA induces osteosarcoma cell apoptosis by targeting mitochondria in a Notch signaling-dependent manner. Thus, OA may be a promising drug for adjuvant chemotherapy in osteosarcoma.