297 research outputs found
Numerical Analysis of Partial Abrasion of the Straddle-type Monorail Vehicle running Tyre
The finite element model of the running tyre and the pre-stressed concrete (PC) track beam are created in the study. The wheel-rail contact status under the conditions such as acceleration or braking, lateral deviation, and roll is analysed. The wear law of the running tyre under the operating condition of driving on winding roads is discussed. The results show that the running tyre will unevenly wear when driving on the winding road; the smaller curve radius and the faster speed result in heavier and more uneven wear. There is a larger slip between the running tyre on the inner side of the curve and the rail surface, and this tyre has more uneven wear than the running tyre on the outer side of the curve. The research findings provide a theoretical basis for solving the problem of reducing the uneven wear of the running tyre
Conservation tillage increases soil bacterial diversity in the dryland of northern China
International audienceAbstractAgricultural practices change soil’s physical and chemical properties, therefore modifying soil microbial communities. Conservation tillage is widely used to improve the soil texture and nutrient status in the dryland regions of northern China. However, little is known about the influence of soil properties on microbes, in particular on the effect of conservation tillage on soil bacterial communities. Here, we studied the effect of a 5-year tillage treatment on soil properties and soil bacterial communities in the dryland regions of northern China using a high-throughput sequencing technology and quantitative PCR of 16S rRNA genes. We compared the changes in soil bacterial diversity, and composition was measured for conservation tillage, including zero plow or chisel plow, and for conventional tillage using plow. Our results show that conservation tillage increased the Simpson index by 378 % and exhibited significantly dissimilar polygenetic diversity, with r of 1, and taxonomic diversity, of r higher than 0.49, compared to conventional tillage. This finding demonstrates that conservation tillage modifies soil bacterial diversity. Chisel plow and zero tillage increase the abundance of the genus Bacillus, including 85 % of the phylum Firmicutes, and of Rhizobiales belonging to the Alphaproteobacteria. Overall conservation tillage increased the abundance of profitable functional bacteria species
IL-17B Can Impact on Endothelial Cellular Traits Linked to Tumour Angiogenesis
IL-17B is a member of the IL-17 cytokine family which have been implicated in inflammatory response and autoimmune diseases such as rheumatoid arthritis. The founding member of this family, IL-17 (or IL-17A), has also been implicated in promoting tumour angiogenesis through the induction of other proangiogenic factors. Here we examine the potential of recombinant human IL-17B to contribute to the angiogenic process. In vitro rhIL-17B was able to inhibit HECV endothelial cell-matrix adhesion and cellular migration and also, at higher concentrations, could substantially reduce tubule formation compared to untreated HECV cells in a Matrigel tubule formation assay. This data suggests that IL-17B may act in an antiangiogenic manner
Metagenomics reveals the abundance and accumulation trend of antibiotic resistance gene profile under long-term no tillage in a rainfed agroecosystem
Widespread soil resistance can seriously endanger sustainable food production and soil health. Conservation tillage is a promising practice for improving soil structure and health. However, the impact of long-term no-tillage on the presence of antibiotic resistance genes in agricultural soils remains unexplored. Based on the long-term (>11 yr) tillage experimental fields that include both conservation tillage practices [no tillage (ZT)] and conventional tillage practices [plough tillage (PT)], we investigated the accumulation trend of antibiotic resistance genes (ARGs) in farmland soils under long-term no-tillage conditions. We aimed to provide a scientific basis for formulating agricultural production strategies to promote ecological environment safety and human health. In comparison to PT, ZT led to a considerable reduction in the relative abundance of both antibiotic resistance genes and antibiotic target gene families in the soil. Furthermore, the abundance of all ARGs were considerably lower in the ZT soil. The classification of drug resistance showed that ZT substantially decreased the relative abundance of Ethambutol (59.97%), β-lactams (44.87%), Fosfomycin (35.82%), Sulfonamides (34.64%), Polymyxins (33.67%), MLSB (32.78%), Chloramphenicol (28.57%), Multi-drug resistance (26.22%), Efflux pump (23.46%), Aminoglycosides (16.79%), Trimethoprim (13.21%), Isoniazid (11.34%), Fluoroquinolone (6.21%) resistance genes, compared to PT soil. In addition, the abundance of the bacterial phyla Proteobacteria, Actinobacteria, Acidobacteria, and Gemmatimonadetes decreased considerably. The Mantel test indicated that long-term ZT practices substantially increased the abundance of beneficial microbial flora and inhibited the enrichment of ARGs in soil by improving soil microbial diversity, metabolic activity, increasing SOC, TN, and available Zn, and decreasing pH. Overall, long-term no-tillage practices inhibit the accumulation of antibiotic resistance genes in farmland soil, which is a promising agricultural management measure to reduce the accumulation risk of soil ARGs
Assessment of Mucin 13 (MUC13) as an Imaging Target for Guiding Colorectal Cancer Treatment: A Pathway Towards Theranostic Development
Background: A theranostic strategy combining diagnostic imaging and targeted therapy in a single regimen is proposed for improved management and treatment of colorectal cancer (CRC). Increased specificity in detection by the noninvasive imaging technique positron emission tomography (PET) can be achieved by radiolabeling antibodies (Abs) designed to target tumor-associated antigens with increased expression post-translational modifications present in cancer cells. In this study, an Ab designed to target the transmembrane glycoprotein mucin 13 (MUC13) was radiolabeled with the positron-emitting radionuclide zirconium-89 (89Zr) for PET imaging of a xenograft mouse model of CRC. Specified uptake of this radioimmunoconjugate was observed in the presence of increased MUC13 expression was observed through imaging along with in vitro and ex vivo analyses.
Methods:
Radiochemistry: The MUC13-targeting Ab C14 conjugated with desferrioxamine (DFO) was radiolabeled with 89Zr alongside isotype control Ab MOPC-21 (IgG) at a 59 kBq/µg (1.6 µCi/µg) ratio, producing [89Zr]Zr-DFO-C14 and [89Zr]Zr-DFO-IgG. Radiochemical purity (RCP) was determined using radio-iTLC and radio-SEC. Radiochemical yield (RCY) was determined with a well-type dose calibrator.
Cellular Binding and Internalization: Cultured human CRC cell lines T84 (MUC13+) and SW480 (MUC13-) were incubated with either [89Zr]Zr-DFO-C14 or [89Zr]Zr-DFO-IgG. At 2 and 24h, cell membranes were separated and radioactivity measured to compare membrane-bound and cell-internalized activity. To determine binding specificity of radiolabeled C14, cells were co-incubated with excess unmodified Ab.
µPET/CT Imaging: T84 and SW480 cells were introduced subcutaneously in athymic nude mice. Once palpable tumors were detected, mice were placed in the following treatment groups for 1.9 MBq (50 µCi) injection: T84+[89Zr]Zr-DFO-C14 (n=5), T84+[89Zr]Zr-DFO-C14 with 350 µg C14 (n=2), SW480+[89Zr]Zr-DFO-C14 (n=5), and T84+[89Zr]Zr-DFO-IgG (n=4). PET imaging was performed 24, 48, and 120h post-injection (p.i.) alongside computational tomography (CT) imaging to provide anatomical context. After 120h, mice were euthanized and blood, organs, and tissues were collected to measure radioactivity biodistribution and radioimmunoconjugate distribution in tumor tissue.
Results: Radiolabeled C14 and IgG were successfully produced with RCY\u3e83% (n.d.c.) and RCP\u3e95%. Reflecting rapid internalization observed in vitro (57.9±13% [89Zr]Zr-DFO-C14 uptake in T84 at 2h compared to 6.57±0.6% uptake in SW480 (p89Zr]Zr-DFO-IgG uptake (p89Zr]Zr-DFO-C14 at 24h p.i. through 120h p.i. compared to that measured in SW480 xenografts (5.5±0.7% ID/cc vs. 2.8±0.5% ID/cc at 24h p.i., p89Zr]Zr-DFO-IgG (1.9±0.2% ID/cc at 24h p.i., p89Zr]Zr-DFO-C14 within the tumor. Furthermore, co-injection with excess C14 resulted in reduced PET signal (2.7±0.1% ID/cc, p=0.0002), supporting the targeting specificity of [89Zr]Zr-DFO-C14. Ex vivo biodistribution comparison confirmed high, persistent [89Zr]Zr-DFO-C14 uptake in T84-derived tumor (18.5% ID/g at 120h p.i.).
Conclusion: MUC13 expression was clearly represented by PET/CT imaging in a xenograft mouse model of CRC using a 89Zr-labeled MUC13-targeting Ab, which also demonstrated target specificity both in vitro and ex vivo. These promising results justify further exploration into developing a theranostic platform for CRC treatment. Future work will test the therapeutic efficacy of the MUC13-targeting Ab radiolabeled with a beta particle-emitting radionuclide
NMR-based Metabolic Profiling of Pancreatic Cancer and Response to Glutamine Transport Inhibition
https://openworks.mdanderson.org/sumexp21/1227/thumbnail.jp
Feasibility of [18F]FSPG PET for Early Response Assessment to Combined Blockade of EGFR and Glutamine Metabolism in Wild-Type KRAS Colorectal Cancer
Early response assessment is critical for personalizing cancer therapy. Emerging therapeutic regimens with encouraging results in the wild-type (WT) KRAS colorectal cancer (CRC) setting include inhibitors of epidermal growth factor receptor (EGFR) and glutaminolysis. Towards predicting clinical outcome, this preclinical study evaluated non-invasive positron emission tomography (PET) with (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) in treatment-sensitive and treatment-resistant WT KRAS CRC patient-derived xenografts (PDXs). Tumor-bearing mice were imaged with [18F]FSPG PET before and one week following the initiation of treatment with either EGFR-targeted monoclonal antibody (mAb) therapy, glutaminase inhibitor therapy, or the combination. Imaging was correlated with tumor volume and histology. In PDX that responded to therapy, [18F]FSPG PET was significantly decreased from baseline at 1-week post-therapy, prior to changes in tumor volume. In contrast, [18F]FSPG PET was not decreased in non-responding PDX. These data suggest that [18F]FSPG PET may serve as an early metric of response to EGFR and glutaminase inhibition in the WT KRAS CRC setting
- …