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Malignant transformation of cells leads to enhanced glucose uptake and the conversion of a larger fraction of pyruvate into lactate, even under normoxic conditions; this phenomenon of aerobic glycolysis is largely known as the Warburg effect. This metabolic reprograming serves to generate biosynthetic precursors, thus facilitating the survival of rapidly proliferating malignant cells. Extracellular lactate directs the metabolic reprograming of tumor cells, thereby serving as an additional selective pressure. Besides tumor cells, stromal cells are another source of lactate production in the tumor microenvironment, whose role in both tumor growth and the antitumor immune response is the subject of intense research. In this review, we provide an integral perspective of the relationship between lactate and the overall tumor microenvironment, from lactate structure to metabolic pathways for its synthesis, receptors, signaling pathways, lactate-producing cells, lactate-responding cells, and how all contribute to the tumor outcome. We discuss the role of lactate as an immunosuppressor molecule that contributes to tumor evasion and we explore the possibility of targeting lactate metabolism for cancer treatment, as well as of using lactate as a prognostic biomarker.

Acute ocular chemical burns are ophthalmic emergencies requiring immediate diagnosis and treatment as they may lead to permanent impairment of vision. The clinical manifestations of such burns are produced by exacerbated innate immune response via the infiltration of inflammatory cells and activation of stromal fibroblasts. New therapies are emerging that are dedicated to repair mechanisms that improve the ocular surface after damage; for example, transplantation of stem cells (SC) has been successfully reported for this purpose. The pursuit of easily accessible, noninvasive procedures to obtain SC has led researchers to focus on human tissues such as amniotic membrane. Human amniotic mesenchymal SC (hAM‐MSC) inhibits proinflammatory and fibrotic processes in different diseases. hAM‐MSC expresses low levels of classical MHC‐I and they do not express MHC‐II, making them suitable for regenerative medicine. The aim of this study was to evaluate the effect of intracameral injection of hAM‐MSC on the clinical manifestations, the infiltration of inflammatory cells, and the activation of stromal fibroblasts in a corneal alkali‐burn model. We also determined the in vitro effect of hAM‐MSC conditioned medium (CM) on α‐SMA+ human limbal myofibroblast (HLM) frequency and on release of neutrophil extracellular traps (NETs). Our results show that intracameral hAM‐MSC injection reduces neovascularization, opacity, stromal inflammatory cell infiltrate, and stromal α‐SMA+ cells in our model. Moreover, in in vitro assays, CM from hAM‐MSC decreased the quantity of α‐SMA+ HLM and the release of NETs. These results suggest that intracameral hAM‐MSC injection induces an anti‐inflammatory and anti‐fibrotic environment that promotes corneal wound healing. Stem Cells Translational Medicine 2018;7:906–917 A novel route of administration of mesenchymal stem cells obtained from human amnion in corneal alkali‐burn ameliorates corneal inflammation and fibrosis; also, these stem cells secrete soluble factors that improve corneal wound healing by reducing inflammation and inhibiting α‐SMA myofibroblasts differentiation and suppress neutrophils activation.

This work was supported by European Union FEDER funds and Fondo de Investigaciones Sanitarias PI12/00523 MECD AP2010-1614 Sociedad Española de Reumatologia (ES). J.R.-C. is a recipient of a FPU grant from the Ministerio de Educación (AP2010-1614)

The study of reliability, availability and control of industrial manufacturing machines is a constant challenge in the industrial environment. This paper compares the results offered by several maintenance strategies for multi-stage industrial manufacturing machines by analysing a real case of a multi-stage thermoforming machine. Specifically, two strategies based on preventive maintenance, Preventive Programming Maintenance (PPM) and Improve Preventive Programming Maintenance (IPPM) are compared with two new strategies based on predictive maintenance, namely Algorithm Life Optimisation Programming (ALOP) and Digital Behaviour Twin (DBT). The condition of machine components can be assessed with the latter two proposals (ALOP and DBT) using sensors and algorithms, thus providing a warning value for early decision-making before unexpected faults occur. The study shows that the ALOP and DBT models detect unexpected failures early enough, while the PPM and IPPM strategies warn of scheduled component replacement at the end of their life cycle. The ALOP and DBT strategies algorithms can also be valid for managing the maintenance of other multi-stage industrial manufacturing machines. The authors consider that the combination of preventive and predictive maintenance strategies may be an ideal approach because operating conditions affect the mechanical, electrical, electronic and pneumatic components of multi-stage industrial manufacturing machines differently.

2-deoxyglucose is a glucose analog that impacts many aspects of cellular physiology. After its uptake and its phosphorylation into 2-deoxyglucose-6-phosphate (2DG6P), it interferes with several metabolic pathways including glycolysis and protein N-glycosylation. Despite this systemic effect, resistance can arise through strategies that are only partially understood. In yeast, 2DG resistance is often associated with mutations causing increased activity of the yeast 5’-AMP activated protein kinase (AMPK), Snf1. Here we focus on the contribution of a Snf1 substrate in 2DG resistance, namely the alpha-arrestin Rod1 involved in nutrient transporter endocytosis. We report that 2DG triggers the endocytosis of many plasma membrane proteins, mostly in a Rod1-dependent manner. Rod1 participates in 2DG-induced endocytosis because 2DG, following its phosphorylation by hexokinase Hxk2, triggers changes in Rod1 post-translational modifications and promotes its function in endocytosis. Mechanistically, this is explained by a transient, 2DG-induced inactivation of Snf1/AMPK by protein phosphatase 1 (PP1). We show that 2DG-induced endocytosis is detrimental to cells, and the lack of Rod1 counteracts this process by stabilizing glucose transporters at the plasma membrane. This facilitates glucose uptake, which may help override the metabolic blockade caused by 2DG, and 2DG export—thus terminating the process of 2DG detoxification. Altogether, these results shed a new light on the regulation of AMPK signaling in yeast and highlight a remarkable strategy to bypass 2DG toxicity involving glucose transporter regulation.

With the development of new technologies, some concepts become relevant in the economic area, as is the case with cryptocurrencies, in general, or Bitcoin and Ethereum, in particular. Due to the impact of these tools, a detailed bibliometric study that allows us to obtain all information about cryptocurrencies must be conducted. This study will help scientific production by specifying the development and lines of related research that have been followed and are currently being followed. We have used Tableau, R (Bibliometrix R Package), and VOSviewer software to analyze the information. These have been combined to create and review unified metadata from the Web of Science (WoS) and Scopus databases. The bibliometric analysis shows 771 articles on the WoS database and 648 articles on Scopus published between 2010 and early 2019. They present the most relevant articles, research areas, countries, institutions, authors, journals, and trends during the last few years. In conclusion, the number of publications has grown in the last 3 years. The analysis shows the evolution of blockchain technology used in this type of cryptocurrency. The review of this period marks a possible end to the historical part of cryptocurrencies, thereby opening the current topic to its multiple applications.

Abstract Objective The need for measuring emotional functioning in patients with chronic pain was recognized decades ago. The Initiative on Methods, Measures, and Pain Assessment in Clinical Trials (IMMPACT) proposed the Profile of Mood States for this purpose. However, to date, its factor structure has not been confirmed in these patients. Methods We set out to use confirmatory factor analysis to test the theoretical structure of seven factors: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, Confusion-Bewilderment, and Friendliness. Participants The sample consisted of 588 Spanish adult patients with chronic pain. Results The original structure could not be verified according to the obtained fit indices (e.g., root-mean-square error of approximation = 0.11). For this reason, we carried out a second study that relied on exploratory factor analysis to evaluate the structure in half of the cases and confirmatory factor analysis to validate it in the other half. The factor structure detected in the exploratory factor analysis was not satisfactory, nor could it be validated with confirmatory factor analysis (e.g., normed fit index between 0.54 and 0.56). Conclusions The factor structure of the Profile of Mood States could not be satisfactorily confirmed. Consequently, other mood measures and shorter, optimized versions of the POMS are discussed as possible alternatives.

(1) Background: This article seeks to shed a light on the innovation, digitalisation, and teleworking processes that have occurred because of the coronavirus crisis. (2) Methods: To this end, we analyse data from Eurostat (2020), the European Companies Survey (2013; 2019) and the Living, Working and COVID-19 Dataset (2020), the latter two gathered by Eurofound. (3) Results: Our main findings reveal that COVID-19 has accelerated a process of digitalisation that has produced relevant changes in labour relations and, consequently, in companies’ organisation. (4) Conclusions: In short, home confinement has had a profound impact on work and occupational risks.

Background The Mediterranean Diet (MD) is recognized as heart-healthy, but the economic cost associated with this type of diet has scarcely been studied. The objective of the present study is to explore the cost and adherence of a low-income region population to the MD and its relationship with income. Methods A population-based study was carried out on 2,833 subjects between 25 and 79 years of age, 54% women, selected at random from the municipalities of Vegas Altas, La Siberia and La Serena in the province of Badajoz, Extremadura (Spain). Average monthly cost of each product included in the MD was computed and related to adherence to the MD using the Panagiotakos Index and average disposable income. Results The monthly median cost was 203.6€ (IQR: 154.04-265.37). Food-related expenditure was higher for men (p<0.001), age cohort between 45 and 54 years (p<0.013) and those living in urban areas (p<0.001). A positive correlation between food-related expenditure and the MD adherence was found. Monthly median cost represents 15% of average disposable income, ranging between 11% for the group with low MD adherence and 17% for the group with high MD adherence. Conclusions The monthly cost of the MD was positively correlated with the degree of adherence to this dietary pattern. Given that the estimated monthly cost is similar to that of other Spanish regions with a higher income level, the economic effort required to be able to afford the Mediterranean diet is higher. This may represent a barrier to access, which should be analyzed in detail by public decision-makers.

Host cell metabolism is essential for the viral replication cycle and, therefore, for productive infection. Energy (ATP) is required for the receptor-mediated attachment of viral particles to susceptible cells and for their entry into the cytoplasm. Host cells must synthesize an array of biomolecules and engage in intracellular trafficking processes to enable viruses to complete their replication cycle. The tricarboxylic acid (TCA) cycle has a key role in ATP production as well as in the synthesis of the biomolecules needed for viral replication. The final assembly and budding process of enveloped viruses, for instance, require lipids, and the TCA cycle provides the precursor (citrate) for fatty acid synthesis (FAS). Viral infections may induce host inflammation and TCA cycle metabolic intermediates participate in this process, notably citrate and succinate. On the other hand, viral infections may promote the synthesis of itaconate from TCA cis-aconitate. Itaconate harbors anti-inflammatory, anti-oxidant, and anti-microbial properties. Fumarate is another TCA cycle intermediate with immunoregulatory properties, and its derivatives such as dimethyl fumarate (DMF) are therapeutic candidates for the contention of virus-induced hyper-inflammation and oxidative stress. The TCA cycle is at the core of viral infection and replication as well as viral pathogenesis and anti-viral immunity. This review highlights the role of the TCA cycle in viral infections and explores recent advances in the fast-moving field of virometabolism.