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The purpose of this study is to develop a method for highway tunnel performance evaluation using combined weight theory and fuzzy multi-criteria decision-making analysis (FMCDM). This study takes the MWP highway tunnel as the research object, and analytic hierarchy process (AHP), entropy theory (ET), game theory (GT), and FMCDM theory were used to study the tunnel performance. The evaluation index system and the classification value limits are determined, the key factors affecting the tunnel performance level were analyzed, and the subjective and objective weights of each index are calculated using AHP and ET. By applying the membership function of FMCDM theory to solve the single index membership of each index at different levels, and combining GT to obtain the comprehensive weights, and the weights of lining structure and Communication Systems is the largest among all index, 0.389 and 0.214, respectively, and in line with engineering practice. The multi-index comprehensive membership evaluation value and target comprehensive membership evaluation vector of the tunnels based on FMCDM theory at different levels are obtained. According to the principle that with the larger the value, the performance is better, the tunnel performance is comprehensively evaluated. Finally, the scientific of the evaluation method is tested in combination with the MWP tunnel case, and the deterioration model of the tunnel performance is proposed based on the structure reliability theory, and the model results are compared with actual observations during tunnel inspection. The results show that the degradation model has strong operability and high accuracy and can effectively predict and ensure the safety of the tunnel structure. The performance evaluation method has objectivity, relevance, and intuitiveness. It can identify the key links of the evaluation and enable construction planners and managers to improve the robustness and safety of the tunnels.

Due to the current deterioration of the environment, the performance degradation of reinforced concrete rainwater drainage pipes (RCRDPs) has become increasingly serious. Aiming at these pr...

Thermal management system is importance to the efficiency and durability of fuel cell vehicles, so related researches are carried out on the thermal balance test and evaluation of fuel cells. Through theoretical and technical analysis, a test and evaluation method of thermal management system applied to various extreme conditions is proposed, and the test and evaluation conditions and evaluation indicators of each system of fuel cell vehicles are formed. In this paper, the thermal balance test results of a fuel cell vehicle are analyzed. The research results show that the thermal balance of fuel cell vehicles under extreme conditions reduces power and increases temperature difference to dissipate heat

Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133.1 mAb. For RIT trials, animals were randomly divided into 4 groups of 6 per group, and injected with 131I-AC133.1 mAb (16.65 MBq/100 μl), AC133.1 mAb (173.1 μg/100 μl), saline (100 μl), or unrelated IgG1 as an isotype control. Iodine-131 was radiolabeled to AC133.1 mAb by conjugation with N-succinimidyl 3-(tri-n-butylstannyl) benzoate. The MTD of HCT116 tumor-bearing nude mice was 16.65 MBq. Both of the tumor volume doubling time and the survival time of the 131I-AC133.1 mAb group were significant longer than other groups (P < 0.001). CD133 expression was assessed by flow cytometry. Protein levels of cancer stem-like biomarkers (CD133, ALDH1, Lgr5, Vimentin, Snail1), and the proliferative rate of 131I-AC133.1 mAb group were lower than other groups (P

The aim of this study was to perform radiotheranostics with radioiodinated monoclonal antibodies (mAbs) for targeting cancer stem cells (CSCs) in human colorectal cancer xenografts and evaluate the relative advantage of a cocktail containing both [131I]CD133 mAb and [131I]CD44 mAb. Tumor-bearing mice were randomly divided into eight groups: [131I]CD133mAb, [131I]CD44 mAb, [131I]IgG isotype control, radioiodinated mAb cocktail, CD133 mAb, CD44 mAb, unradioiodinated mAb cocktail, and saline groups. In vivo single photon emission computed tomography (SPECT) imaging was used to monitor dynamically changes in the CSC population after treatment. The radioactivity uptake of tumors was quantified ex vivo. The expression of CD133 and CD44 after treatment was also assessed by immunohistochemistry and western blot. Tumor growth curves and survival curves were generated to assess treatment efficacy. Cell apoptosis and proliferation in xenografts 30 days after treatment were measured by TdT-mediated dUTP-biotin nick end labeling (aka, TUNEL) and Ki67 staining. The expression levels of biomarkers in xenografts 30 days after treatment were measured by flow cytometry. The radioimmunoimaging (RII) with in vivo SPECT showed that the CSC-targeting radioimmunotherapy (RIT) groups ([131I]CD133 mAb, [131I]CD44 mAb, and radioiodinated mAb cocktail groups) had intense accumulations of radiolabeled agents in the tumor areas. The ex vivo biodistribution confirmed these findings. In the CSC-targeting RIT groups, immunohistochemistry and western blot indicated significant reduction of specific target expression in the xenografts. The tumor growth curves and survival curves showed that the CSC-targeting RIT significantly inhibited tumor growth and prolonged mean survival, respectively. Significantly increased apoptosis and decreased proliferation in xenografts further confirmed the therapeutic efficacy of CSC-targeting RIT. Flow cytometry showed that the decreases in CSCs correlated with the presence of the corresponding antibodies. Our results suggest that the CSC-targeting RIT can effectively reduce CSCs which consequently inhibits tumor development. The radioiodinated mAb cocktail may generate enhanced CSC-targeting specificity.

Background Previous reports suggested that CD133-positive cells had biological features of cancer stem cells (CSCs). Furthermore, CD133 expression was reported as an unfavorable prognostic factor in patients. Therefore, a new radiolabeled probe, 99mTc labeled AC133 antibody which binding with CD133 specifically, was developed to noninvasively detect CSCs by SPECT in vivo. Methods CD133 expression was evaluated by flow cytometry in three colon cancer cell lines (HCT116, Lovo and DLD1). AC133 antibody and control IgG were conjugated with succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH), and then labeled with 99mTc. The new radiolabeled probe was named as 99mTc-SHNH-AC133. The vitro cell binding assays, series SPECT imaging and biodistribution analyses were performed. Flow cytometry, immunofluorescence staining of tumor tissues were carried to verify the in-vivo imaging results. Results 99mTc-SHNH-AC133 was labeled with a high radiochemical purity (97.7±2.4%, N.=3) and specific activity (4.07 MBq/µg). Cellular experiments showed that the labeled AC133 antibody retained with a high binding affinity on CD133-positive cells (HCT116 and Lovo cells). Biodistribution analyses showed high tumor uptake of the tracer in HCT116 and Lovo xenografts (8.82±0.73 and 7.37±0.26 %ID/g, respectively, N.=4) and high tumor-to-muscle ratios (13.18±2.84 and 11.13±0.53, respectively, N.=4) at 36 h after injection, resulting in high contrast SPECT images with high specific tumor uptake. However, the tumor bearing CD133-negative cell (DLD1 cells) showed no obvious uptake of 99mTc-SHNH-AC133 both in-vitro cell binding and in-vivo imaging study. Moreover, the tumor uptake of 99mTc-SHNH-AC133 in positive tumor models was significantly reduced by pre-injection of excess unlabeled AC133 antibody. Flow cytometric analysis and immunofluorescence staining confirmed the CD133 expression in tumors, which correlated well with the in-vivo results. Conclusions This study showed that 99mTc-SHNH-AC133 exhibited high uptake in CD133-positive tumors. The high specificity and good tumor targeting properties of 99mTc-SHNH-AC133 may provide a new method to track or locate CSCs.

Introduction Cancer stem cells (CSCs) are a subpopulation within a tumor, which possesses the characteristics of self-renewal, differentiation, tumorigenicity, and drug resistance. The aim of this study was to target the colorectal CSC marker CD133 with an 131 I-labeled specific monoclonal antibody (AC133 mAb) in a nude mouse xenograft model. Methods Colorectal adenocarcinoma cells (LoVo cell line) were separated into CD133(+) and CD133(−) cells by magnetic activated cell sorting. CD133(+), CD133(−), and unsorted LoVo cells were cultured and then implanted subcutaneously into the lower limbs of nude mice (n=5). AC133 mAb was labeled with 131 I by the iodogen method. Results The radiolabeled compound, 131 I-AC133 mAb, showed high stability, specificity, and immunoactivity in vitro. Obvious accumulation of 131 I-AC133 mAb was seen in nude mice bearing xenografts of CD133(+) and unsorted LoVo cells, but no uptake was found in mice bearing CD133(−) xenografts or specifically blocked xenografts. Biodistribution analysis showed that the tumor uptake of 131 I-AC133 mAb was 6.97±1.40, 1.35±0.48, 6.12±1.91, and 1.61±0.44% ID/g (n=4) at day 7 after injection of 131 I-AC133 mAb in CD133(+), CD133(−), unsorted LoVo cell and specifically blocked xenografts, respectively. The results of immunofluorescence, autoradiography, and western blotting further verified the specific binding of 131 I-AC133 mAb to CD133(+) tumors. Conclusions This study demonstrates the possibility of targeting CSCs with a radiolabeled AC133 mAb in colorectal cancer xenografts based on in vitro, ex vivo, and in vivo experiments. Our findings suggest a new method for imaging CSCs non-invasively.

Introduction EphA2, one member of the Eph receptor family, is widely expressed in multiple aggressive cancers. SWL, a small peptide identified by phage display, has high binding affinity to EphA2, suggesting that it could be exploited for targeted molecular imaging. Therefore, a novel peptide-based probe, 99m Tc-HYNIC-SWL, was developed and its potential to specifically target EphA2-positive tumors was investigated. Methods The SWL peptide was labeled with hydrazinonicotinic acid (HYNIC), followed by 99m Tc labeling. Immunofluorescence staining was carried out to detect the expression of EphA2 in A549 lung cancer cells and OCM-1 melanoma cells. Saturation binding experiments were performed by incubating A549 cells with increasing concentrations of radiolabeled peptide in vitro. To test the probe in vivo, nude mice bearing either A549 or OCM-1 derived tumors were established, injected with 99m Tc-HYNIC-SWL, and subjected to SPECT imaging. Mice injected with excess unlabeled SWL were used as a specific control. Ex vivo γ-counting of dissected tissues from the mice was also performed to evaluate biodistribution. Results Immunofluorescence staining showed that A549 cells intensively expressed EphA2, while OCM-1 cells had little expression. 99m Tc-HYNIC-SWL displayed high binding affinity with A549 cells (K D =2.6±0.7nM). From the SPECT images and the results of the biodistribution study, significantly higher uptake of the tracer was seen in A549 tumors (1.44±0.12 %ID/g) than in OCM-1 tumors (0.43±0.20 %ID/g) at 1h after injection. Pre-injection with excess unlabeled peptide in A549-bearing nude mice, significantly reduced tumor uptake of the radiolabeled probe (0.58±0.20 %ID/g) was seen. These data suggest that 99m Tc-HYNIC-SWL specifically targets EphA2 in tumors. Conclusions The expression of EphA2 can be noninvasively investigated using 99m Tc-HYNIC-SWL by SPECT imaging. The in vitro and in vivo characteristics of 99m Tc-HYNIC-SWL make it a promising probe for EphA2-positive tumor imaging.