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2021 ◽  
Yuchong Zhao ◽  
Yun Wang ◽  
Wei Chen ◽  
Shuya Bai ◽  
Wang Peng ◽  

Abstract Background: Due to the lack of effective interference options, early metastasis remains a major cause of pancreatic ductal adenocarcinoma (PDAC) recurrence and mortality. However, the molecular mechanism of early metastasis is largely unknown. We characterize the function of eukaryotic translation initiation factors (eIFs) in Pancreatic cancer cell epithelial mesenchymal-transition (EMT) and metastasis, to investigate whether it is effective to inhibit EMT and metastasis by joint interference of eIFs and downstream c-MYC. Methods: We used the data of The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) to analyze the expression level of eIF4A1 in PDAC tissues, and further validated in a microarray containing 53 PDAC samples. Expression regulation and pharmacological inhibition of eIF4A1/c-MYC was performed to determine their role in migration, invasion, and metastasis in pancreatic cancer cells in vitro and in vivo.Results: Elevated expression of eIF4A1 was positively correlated with lymph node infiltration, tumor size, and indicated a poor prognosis. eIF4A1 decreased E-cadherin expression through c-MYC/miR-9 axis. Ablation of eIF4A1 and c-MYC decreased the EMT and metastasis capabilities of pancreatic cancer cells. Upregulation of eIF4A1 could attenuate the inhibition of EMT and metastasis induced by c-MYC downregulation. Single-use of eIF4A1 inhibitor Rocaglamide (RocA) or c-MYC inhibitor Mycro3 and joint intervention all significantly the EMT level of pancreatic cancer cells in vitro. However, the efficiency and safety of RocA single-use were not inferior to joint use in vivo. Conclusion: The results demonstrated that overexpression of eIF4A1 downregulated E-cadherin through c-MYC/miR-9 axis, which promoted EMT and metastasis of pancreatic cancer cells. Despite the potential loop between eIF4A1 and c-MYC existing, RocA single strategy was a promising therapy for the inhibition of eIF4A1 induced PDAC metastasis.

Dependability ◽  
2021 ◽  
Vol 21 (3) ◽  
pp. 3-12
Yu. P. Pokhabov

Aim. To consider matters of dependability of highly critical non-recoverable space products with short operation life, whose failures are primarily caused by design and process engineering errors, manufacturing defects in the course of single-unit or small-scale production, as well as to define the methodological approach to ensuring the required reliability.Methods. Options were analysed for improving the dependability of entities with short operation life using the case study of single-use mechanical devices and the statistical approaches of the modern dependability theory, special methods of dependability of actuated mechanical assemblies, FMEA, Stage-Gate and ground experiments on single workout equivalents for each type of effect. Results. It was concluded that additional procedures need to be conducted for the purpose of predicting, mitigation and (or) eliminating possible failures as part of the design process using exactly the same approaches that cause failures, i.e., those of design and process engineering. The engineering approaches to dependability are based on early identification of possible causes of failures, which requires a qualified and systemic analysis aimed at identifying the functionality, performance and dependability of an entity, taking into account critical output parameters and probabilistic indicators that affect the performance of the required functions with the allowable probability of failure. The solution is found using a generalized parametric model of operation and design engineering analysis of dependability.Conclusion. For highly critical non-recoverable space entities with short operation life, the reliability requirements should be considered primarily in terms financial, economic, safetyrelated and reputational risks associated with the loss of spacecraft. From a design engineer’s standpoint, the number of nines after the decimal point (rounded to a smaller number of nines for increased confidence) should be seen as the indicator for the application of the appropriate approaches to ensuring the required reliability at the stage of product design. In case of two nines after the decimal point it is quite acceptable to use analytical and experimental verification techniques common to the aerospace industry, i.e., dependability calculations using the statistical methods of the modern dependability theory and performance indicators, FMEA and Stage-Gate, ground experiments on single workout equivalents for each type of effect. As the required number of nines grows, it is advisable to also use early failure prevention methods, one of which is the design engineering analysis of dependability that enables designers to adopt substantiated design solutions on the basis of engineering disciplines and design and process engineering methods of ensuring quality and dependability. The choice of either of the above dependability strategies is determined solely by the developer’s awareness and understanding of potential hazards, which allows managing the risk of potential rare failures or reasonably refusing to do so.

Vox Sanguinis ◽  
2021 ◽  
Nadine Schossee ◽  
Gabriele Veit ◽  
Julia Gittel ◽  
Johannes Viebahn ◽  
Marius Niklaus ◽  

2021 ◽  
Vol 22 (7) ◽  
pp. 769-773
Fouad Salama ◽  
Mannaa K Aldowsari ◽  
Mohamed H Al-Agamy ◽  
Sultan A Alquraishi ◽  
Faisal S Alsaif ◽  

2021 ◽  
Forbes McGain ◽  
Nicole Sheridan ◽  
Kasun Wickramarachchi ◽  
Simon Yates ◽  
Brandon Chan ◽  

Background Health care itself contributes to climate change. Anesthesia is a “carbon hotspot,” yet few data exist to compare anesthetic choices. The authors examined the carbon dioxide equivalent emissions associated with general anesthesia, spinal anesthesia, and combined (general and spinal anesthesia) during a total knee replacement. Methods A prospective life cycle assessment of 10 patients in each of three groups undergoing knee replacements was conducted in Melbourne, Australia. The authors collected input data for anesthetic items, gases, and drugs, and electricity for patient warming and anesthetic machine. Sevoflurane or propofol was used for general anesthesia. Life cycle assessment software was used to convert inputs to their carbon footprint (in kilogram carbon dioxide equivalent emissions), with modeled international comparisons. Results Twenty-nine patients were studied. The carbon dioxide equivalent emissions for general anesthesia were an average 14.9 (95% CI, 9.7 to 22.5) kg carbon dioxide equivalent emissions; spinal anesthesia, 16.9 (95% CI, 13.2 to 20.5) kg carbon dioxide equivalent; and for combined anesthesia, 18.5 (95% CI, 12.5 to 27.3) kg carbon dioxide equivalent. Major sources of carbon dioxide equivalent emissions across all approaches were as follows: electricity for the patient air warmer (average at least 2.5 kg carbon dioxide equivalent [20% total]), single-use items, 3.6 (general anesthesia), 3.4 (spinal), and 4.3 (combined) kg carbon dioxide equivalent emissions, respectively (approximately 25% total). For the general anesthesia and combined groups, sevoflurane contributed an average 4.7 kg carbon dioxide equivalent (35% total) and 3.1 kg carbon dioxide equivalent (19%), respectively. For spinal and combined, washing and sterilizing reusable items contributed 4.5 kg carbon dioxide equivalent (29% total) and 4.1 kg carbon dioxide equivalent (24%) emissions, respectively. Oxygen use was important to the spinal anesthetic carbon footprint (2.8 kg carbon dioxide equivalent, 18%). Modeling showed that intercountry carbon dioxide equivalent emission variability was less than intragroup variability (minimum/maximum). Conclusions All anesthetic approaches had similar carbon footprints (desflurane and nitrous oxide were not used for general anesthesia). Rather than spinal being a default low carbon approach, several choices determine the final carbon footprint: using low-flow anesthesia/total intravenous anesthesia, reducing single-use plastics, reducing oxygen flows, and collaborating with engineers to augment energy efficiency/renewable electricity. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Thi-Kim Chi Do ◽  
Sunil Herat ◽  
Le Van Khoa ◽  
Prasad Kaparaju

This study aims to determine the composition and the weight of individual single-use items (SUIs) generated in the selected fast-food restaurants (FFRs) in Ho Chi Minh City (HCMC), Vietnam. A semi-structured questionnaire was used to collect data of SUIs consumed per day from 126 FFRs covering six popular fast food companies (FFCs). At the same time, waste from 30 FFRs was collected, and its composition and weight were determined. Consequently, the amount and composition of the waste varied among the studied FFCs and is dependent on the food menu, the number of franchises for each FFC, customer number, size, and the type of SUIs used at these restaurants. Total waste collected across the six FFCs was 6 t.d-1 and was equivalent to 1560 t.yr-1 in HCMC. Of which, single-use plastic items (SUPIs) waste and single-use paper items (SUPaIs) waste accounted for 39% and 28%, respectively. The total weight of unnecessary SUPIs (condiment containers, straws, and forks) generated was about 44 t.yr-1. The results suggest that the necessity of standardizing the type and size of the SUIs used at the FFRs, phasing out the use of unnecessary SUPIs, improving the local waste management practices through material recovery and recycling.

2021 ◽  
pp. 117578
Ioannis C. Ioannidis ◽  
Ioannis Anastopoulos ◽  
Ioannis Pashalidis

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