PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3)

Review on PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3), with data on DNA, on the protein encoded, and where the gene is implicated

PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2)

Review on PFKFB2, with data on DNA/RNA, on the protein encoded and where the gene is implicated

C12orf5 (chromosome 12 open reading frame 5)

Review on C12orf5, with data on DNA/RNA, on the protein encoded and where the gene is implicated

BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

NRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRAS(Q61)-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRAS(Q61) mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRAS(Q61)-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib. Targeted therapeutic options for NRAS-mutant melanoma are limited. Here, the authors show that under metabolic stress NRAS-mutant melanoma cells activate a BRAF-dependent glycolysis pathway for survival, leading to improve efficacy of sorafenib when combined with glycolysis inhibitors

Prospective observational cohort study of the association between antiplatelet therapy, bleeding and thrombosis in patients with coronary stents undergoing noncardiac surgery

Background: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). Methods: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. Results: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93–3.88), P=0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31–3.46), P=0.96. Bleeding was more frequent with DAPT 6.55 (2.3–17.96) P=0.0002. In a propensity matched analysis of 177 patients who received DAPT and 177 monotherapy patients, the risk ratio for MACE with DAPT was 1.83 (0.69–4.85), P=0.32. The risk of bleeding was significantly greater in the DAPT group 4.00 (1.15–13.93), P=0.031. Conclusions: OBTAIN showed an increased risk of bleeding with DAPT and found no evidence for protective effects of DAPT from perioperative MACE in patients who have undergone previous PCI

Electro-fluidic timer for event control in paper-based devices

In this paper, we present a simple yet smart electro-fluidic platform that enables automatic time control in a very affordable and simple manner. The system is based on the electric detection of a fluid front when it crosses a particular area of a paper strip. The detection can be used to trigger the sequential activation or deactivation of different electronic modules (heating of molecular diagnostics, time interval detection, or readout of test results) with an accuracy within the range of minutes. The whole system is implemented with a few number of discrete electronic components such as transistors, resistors and capacitors that, if required, can be totally fabricated using printed electronics technology. This platform opens new possible applications for paper-based point-of care (POC) diagnostic devices and enables the possibility of these devices to introduce time control functions without the need for any external instrumentation and human action

An Organic Redox Flow Cell‐Inspired Paper‐Based Primary Battery

A portable paper‐based organic redox flow primary battery using sustainable quinone chemistry is presented. The compact prototype relies on the capillary forces of the paper matrix to develop a quasi‐steady flow of the reactants through a pair of porous carbon electrodes without the need of external pumps. Co‐laminar capillary flow allows operation Under mixed‐media conditions, in which an alkaline anolyte and an acidic catholyte are employed. This feature enables higher electrochemical cell voltages during discharge operation and the utilization of a wider range of available species and electrolytes and provides the advantage to form a neutral or near‐neutral pH as the electrolytes neutralize at the absorbent pad, which allows a safe disposal after use. The effects of the device design parameters have been studied to enhance battery features such as power output, operational time, and fuel utilization. The device achieves a faradaic efficiency of up to 98 %, which is the highest reported in a capillary‐based electrochemical power source, as well as a cell capacity of up to 11.4 Ah L−1 cm−2, comparable to state‐of‐the‐art large‐scale redox flow cells.The funding for this research provided through the Science for Solving Society's Problems Challenge by the Electrochemical Society and the Bill & Melinda Gates Foundation is highly appreciated. P.A. acknowledges support from CONACyT through a scholarship to pursue postgraduate studies. N.S. is thankful for financial support received from ERC Consolidator Grant (SUPERCELL—GA.648518). Additional support from the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundation for Innovation (CFI) and British Columbia Knowledge Development Fund (BCKDF) is also acknowledged. E.K. acknowledges support from the Canada Research Chairs program.Peer reviewe

Procedimiento de cuantificación de la concentración de analitos en una celda electroquímica

La invención se refiere a un procedimiento de cuantificación de la concentración de analitos, que hace uso de un dispositivo que comprende una celda electroquímica (1) que contiene el analito, una carga (4,5) que se conecta en paralelo con la celda electroquímica (1), y un elemento de lectura (3), que se conecta en paralelo con la carga (4,5) y que comprende las etapas de cuantificación de la concentración de analitos, transferencia de carga de la celda electroquímica (1) a la carga (4, 5), determinación de la tensión de la carga (4, 5) y determinación de la concentración de analito a partir de la relación que existe entre esta y la tensión de la carga (4, 5).Peer reviewedConsejo Superior de Investigaciones Científicas (España), Fundació Privada Institució Catalana de Recerca i Estudis Avançats - ICREAA1 Solicitud de patente con informe sobre el estado de la técnic