SLUG is activated by nuclear factor kappa B and confers human alveolar epithelial A549 cells resistance to tumor necrosis factor-alpha-induced apoptosis

BACKGROUND: The role of tumor necrosis factor alpha (TNF-α) in cancer is complex with both apoptotic and anti-apoptotic roles proposed. However the mechanism is not clear. In the study, we designed to investigate the effect of TNF-α on the activation and expression of nuclear factor kappa B (NF-κB)/p65/SLUG/PUMA/Bcl-2 levels in human lung cancer A549 cell line, and in conditions of TNF-α-induced apoptosis. METHODS: We have engineered three A549 cell lines that were transiently transfected with PUMA siRNA, SLUG siRNA and Bcl-2 siRNA, respectively. We have measured the in vitro effects of siRNA on apoptosis, and sensitivity to 20 ng/ml of TNF-α treatment for 24–48 h. RESULTS: We found the NF-κB activity and PUMA mRNA/protein was significantly increased after treatment of TNF-α for 24 h in untreated A549 cells, and led to a significant increase in TNF-α-induced apoptosis, no significant increase of SLUG and Bcl-2 level was shown. However, after treatment of TNF-α for 48 h in untreated A549 cells, SLUG and Bcl-2 level was significant increased, and PUMA level was significant decreased, and TNF-α-induced apoptosis was significantly decreased compared to the apoptosis level after treatment of TNF-α for 24 h. Inhibition of the NF-κB activity could effectively decrease the PUMA level and increase the SLUG and Bcl-2 level. PUMA silencing by siRNA led to a significant decrease in TNF-α-induced apoptosis after treatment of TNF-α for 24 h. Bcl-2 and SLUG silencing by siRNA led to a significant increase in TNF-α-induced apoptosis for 48 h. Furthermore, SLUG silencing increased PUMA level and decreased Bcl-2 level. CONCLUSIONS: The findings suggested that TNF-α treatment promoted apoptosis via the NF-κB-dependent PUMA pathway. The anti-apoptotic role of TNF-α was via NF-κB-dependent SLUG and Bcl-2 pathway at a later time

Evaluation Method for Probability of Blowout after the Failure of Offshore Well Killing

249-259With the development of offshore oil industry, the influx and blowout are inevitable. Well control methods have been well researched, but how to recognize the failure of well control earlier and how to evaluate the probability of blowout for taking steps to avoid are imperfect. Based on the two-phase gas-liquid flow, the characteristic of well killing curve before and after killing are analyzed. Then the method for recognizing the failure of well killing is established by the probabilistic and covariance processing method. Then the blowout due to the failure of well killing is studied and the build-up pressure template is established. According to this, three evaluation methods for blowout probability are established, the shut-off pressure, the standing and casing pressure, formation parameters and underbalanced level varying methods. Final, four hardware systems and one evaluation system are recommended for decreasing or avoiding the risk during the failure of well killing

Architecture of Heptagonal Metallo-macrocycles via Embedding Metal Nodes Into Its Rigid Backbone

Metal-organic macrocycles have received increasing attention not only due to their versatile applications such as molecular recognition, compounds encapsulation, anti-bacteria and others, but also for their important role in the study of structure-property relationship at nano scale. However, most of the constructions utilize benzene ring as the backbone, which restricts the ligand arm angle in the range of 60, 120 and 180 degrees. Thus, the topologies of most metallo-macrocycles are limited as triangles and hexagons, and explorations of using other backbones with large angles and the construction of metallo-macrocycles with more than six edges are very rare. In this study, we present a novel strategy for self-assembly two giant heptagonal metallo-macrocycles with an inner diameter of 5 nm, by embedding metal nodes into the ligand backbone and regulating the ligand arm angle. By complexing with metal ions, the angle between two arms at the 4,4” position of the central terpyridine (tpy) was extended, resulting in ring expansion of the metallo-macrocycle. This approach enabled the construction of giant and more complex metallo- macrocycles that could not be achieved with traditional benzene ring backbones. The characterization of complex molecules often requires the use of multiple techniques, such as multi-dimensional and multinuclear NMR and multidimensional mass spectrometry analysis. Here, we also utilized transmission electron microscopy (TEM) and ultra-high vacuum (∼E-10 torr) low-temperature (∼77 K) scanning tunneling microscopy (UHV-LT-STM) to characterize complex supramolecules. The resulting metallo-macrocycles formed hierarchical self-assembled nanotube structures at larger densities, which is observed by TEM, while UHV-LT-STM was used for direct visualization of individual complex supramolecules deposited on an Au(111) substrate. Our findings indicate that UHV-LT-STM is an effective methodology for characterizing supramolecules at a single molecule level, providing more details of the molecular structure that is difficult to resolve by the resolution of TEM.https://digitalcommons.odu.edu/gradposters2023_sciences/1005/thumbnail.jp

Experimental Study on the Down-Speed of Conductor Pipe Influenced by Jetting Displacement in Deepwater Drilling

Based on the theory of jet drilling technology and displacement optimization, a set of experimental equipment about jet drilling is devised. The laws of conductor pipe down-speed influenced by pump displacement were studied by laboratory experiments. According to the experimental results and analysis, the following conclusions can be drawn. The down-speed of conductor pipe increases with the increasing of displacement, also the drilling speed is boosted. But the unstableness of borehole wall is augmented as well. And this will result in the increasing of waiting time for borehole formation. In the process of conductor pipe jetting, the conductor pipe down-speed and the waiting time of soil returning to a certain bearing capacity should be considered together in order to shorten the entirety drilling time. The research can provide certain references for expensive offshore operation and have important significance to improve the economic benefits of deepwater drilling

Efficacy and safety of immunotherapy combined with single-agent chemotherapy as second- or later-line therapy for metastatic non-small cell lung cancer

ObjectiveThis study sought to assess the efficacy and safety of immunotherapy combined with single-agent chemotherapy as a second- or later-line setting for metastatic non-small cell lung cancer (NSCLC) and to provide clinical evidence for this treatment regimen. The predictive value of extracellular vesicle (EV) membrane proteins was explored in patients who underwent this treatment.MethodsClinical data from patients diagnosed with metastatic NSCLC who received immunotherapy plus single-agent chemotherapy as a second- or later-line setting were retrospectively collected between March 2019 and January 2022. A total of 30 patients met the inclusion criteria, and all were pathologically confirmed to have NSCLC. Short-term efficacy, progression-free survival (PFS), EV markers for response prediction, and adverse events were assessed.ResultsEfficacy data were available for all 30 patients and included a partial response in 5 patients, stable disease in 18 patients, and disease progression in 7 patients. The objective response rate was 16.7%, the disease control rate was 76.7%, and the median PFS was 3.2 months. Univariate analysis showed that PFS was not associated with sex, age, smoking status, treatment lines, prior use of immunotherapy, or prior use of antiangiogenic drugs. The EV membrane proteins MET proto-oncogene, receptor tyrosine kinase (c-MET), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptor 2 (VEGFR2) at baseline were associated with poor prognosis and correlated with the efficacy of immunotherapy plus chemotherapy. According to the receiver operating characteristics and Kaplan–Meier curve analyses, patients with high c-MET, EGFR, and VEGFR2 expression at baseline had significantly shorter PFS than those with low expression. In addition, VEGFR2 expression was increased after combined immunotherapy in responders, which was decreased in non-responders. The most common grade 2 or higher adverse events were neutropenia, gastrointestinal reactions, and thyroid dysfunction, all of which were tolerated.ConclusionsImmunotherapy plus single-agent chemotherapy as a second- or later-line treatment is safe, effective, and tolerable for metastatic NSCLC. EV markers can be used as predictive markers of efficacy in patients with metastatic NSCLC treated with immunotherapy plus chemotherapy to help monitor treatment efficacy and guide treatment decisions

BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer

[Context]: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined. [Objective]: To study whether BRAF V600E affected LNM-associated mortality in PTC. [Design, Setting, and Participants]: We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months. [Results]: Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism. [Conclusions]: LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.This work was supported partly by the following funding at the individual participating centers: Polish National Center of Research and Development MILESTONE Project—molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant No. STRATEGMED2/267398/4/ NCBR/2015 (Poland, AC, BJ); Grants No. PID2019-105303RB-I00 (AEI from MICINN), GCB14142311CRES (AECC Foundation), and B2017/BMD-3724 TIRONET2-CM (Spain; PS and GR-E); Grant No. AZV 16-32665A and MH CZ-DRO (Institute of Endocrinology-EU, 00023761) (Czech Republic; BB, VS); NIH/ National Institute on Aging Grant No. 5R03AG042334-02 (LY); and grants from the Qingdao Science and Technology Project for People’s Livelihood No.13-1-3-58-nsh (China; FW) and the Innovative Platform Project of Qingdao No.12-1-2-15-jch (China; YW)

The Morbidity of Multivariable Grey Model MGM(1,m)

This paper proposes the morbidity of the multivariable grey prediction MGM(1,m) model. Based on the morbidity of the differential equations, properties of matrix, and Gerschgorin Panel Theorem, we analyze the factors that affect the morbidity of the multivariable grey model and give a criterion to justify the morbidity of MGM(1,m). Finally, an example is presented to illustrate the practicality of our results

Slurry rheology in wet ultra-fine grinding of industrial minerals: A review

Wet ultrafine grinding has been increasingly used for production of ultrafine powders in various industries. It has been known that slurry rheology significantly influences the grindability of industrial minerals in wet ultrafine grinding. This review represents some previous work with respect to slurry rheology in ultrafine grinding. In this review, some methods for the characterization of the slurry rheology and some empirical equations modelling rheological behaviours of slurries were presented. The semiempirical model incorporating slurry rheology, solids concentration, particle size and slurry temperature was described. In addition, on-line measurement for the slurry rheology control was also discussed. In the case of ultrafine grinding, various parameters (such as solid concentration, particle size and distribution, particle shape, temperature, rotation and pH, use of dispersants), which affect the slurry rheology, have been described. It was revealed that the optimization of the rheological behaviours of slurry in ultrafine grinding could increase throughput, energy efficiency and product fineness as well. It is suggested to further study the mechanisms of slurry rheology in the presence of chemical dispersants in wet ultrafine grinding. It is desired to develop a model, which can represent a relation among slurry rheology, comminution parameters, amount of dispersant, energy efficiency and particle size characterization

Parameter effects on wet ultrafine grinding of limestone through slurry rheology in a stirred media mill

Wet ultra-fine grinding of a limestone powder ( 0.991) to the grinding results under the experimental conditions investigated