The neglected liaison: Targeting cancer cell metabolic reprogramming modifies the composition of non‐malignant populations of the tumor microenvironment

Metabolic reprogramming is a well‐known hallmark of cancer, whereby the development of drugs that target cancer cell metabolism is gaining momentum. However, when establishing preclinical studies and clinical trials, it is often neglected that a tumor mass is a complex system in which cancer cells coexist and interact with several types of microenvironment populations, including endothelial cells, fibroblasts and immune cells. We are just starting to understand how such populations are affected by the metabolic changes occurring in a transformed cell and little is known about the impact of metabolism‐targeting drugs on the non‐malignant tumor components. Here we provide a general overview of the links between cancer cell metabolism and tumor microenvironment (TME), particularly focusing on the emerging literature reporting TME‐specific effects of metabolic therapies

Editorial: Mitochondria as a hub in cellular signaling

Editorial on the Research Topic Mitochondria as a hub in cellular signalin

Extremely high He isotope ratios in MORB-source mantle from the proto-Iceland plume

The high <sup>3</sup>He/<sup>4</sup>He ratio of volcanic rocks thought to be derived from mantle plumes is taken as evidence for the existence of a mantle reservoir that has remained largely undegassed since the Earth's accretion. The helium isotope composition of this reservoir places constraints on the origin of volatiles within the Earth and on the evolution and structure of the Earth's mantle. Here we show that olivine phenocrysts in picritic basalts presumably derived from the proto-Iceland plume at Baffin Island, Canada, have the highest magmatic <sup>3</sup>He/<sup>4</sup>He ratios yet recorded. A strong correlation between <sup>3</sup>He/<sup>4</sup>He and <sup>87</sup>Sr/<sup>86</sup>Sr, <sup>143</sup>Nd/<sup>144</sup>Nd and trace element ratios demonstrate that the <sup>3</sup>He-rich end-member is present in basalts that are derived from large-volume melts of depleted upper-mantle rocks. This reservoir is consistent with the recharging of depleted upper-mantle rocks by small volumes of primordial volatile-rich lower-mantle material at a thermal boundary layer between convectively isolated reservoirs. The highest <sup>3</sup>He/<sup>4</sup>He basalts from Hawaii and Iceland plot on the observed mixing trend. This indicates that a <sup>3</sup>He-recharged depleted mantle (HRDM) reservoir may be the principal source of high <sup>3</sup>He/<sup>4</sup>He in mantle plumes, and may explain why the helium concentration of the 'plume' component in ocean island basalts is lower than that predicted for a two-layer, steady-state model of mantle structure

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Oxidative function during exercise was evaluated in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (RTA, body mass 102.67.3 kg, meanSD) and 11 controls (CTRL, body mass 77.86.0). Pulmonary O2 uptake (V\u27O2) and vastus lateralis muscle fractional O2 extraction (by near-infrared spectroscopy) were determined during an incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers obtained by biopsy. Quadriceps femoris muscle cross sectional area, volume (determined by magnetic resonance imaging) and strength were greater in RTA vs. CTRL (by ~40%, ~33% and ~20%, respectively). V\u27O2peak during CE was higher in RTA vs. CTRL (4.050.64 L min-1 vs. 3.560.30)no difference between groups was observed during KE. The O2 cost of CE exercise was not different between groups. When divided per muscle mass (for CE) or quadriceps muscle mass (for KE) V\u27O2peak was lower (by 15-20%) in RTA vs. CTRL. Vastus lateralis fractional O2 extraction was lower in RTA vs. CTRL at all work rates, both during CE and KE. RTA had higher ADP-stimulated mitochondrial respiration (56.723.7 pmolO2s-1mg-1 ww) vs. CTRL (35.710.2), and a tighter coupling of oxidative phosphorylation. In RTA the greater muscle mass and maximal force, and the enhanced mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O2 diffusion. The net results are an enhanced whole body oxidative function at peak exercise, and unchanged efficiency and O2 cost at submaximal exercise, despite a much greater body mas

Software design for the control system for Small-Size Telescopes with single-mirror of the Cherenkov Telescope Array

The Small-Size Telescope with single-mirror (SST-1M) is a 4 m Davies-Cotton telescope and is among the proposed telescope designs for the Cherenkov Telescope Array (CTA). It is conceived to provide the high-energy ($>$ few TeV) coverage. The SST-1M contains proven technology for the telescope structure and innovative electronics and photosensors for the camera. Its design is meant to be simple, low-budget and easy-to-build industrially. Each device subsystem of an SST-1M telescope is made visible to CTA through a dedicated industrial standard server. The software is being developed in collaboration with the CTA Medium-Size Telescopes to ensure compatibility and uniformity of the array control. Early operations of the SST-1M prototype will be performed with a subset of the CTA central array control system based on the Alma Common Software (ACS). The triggered event data are time stamped, formatted and finally transmitted to the CTA data acquisition. The software system developed to control the devices of an SST-1M telescope is described, as well as the interface between the telescope abstraction to the CTA central control and the data acquisition system.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis

Summary: Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNKT) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNKT cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNKT cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNKT cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNKT cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNKT cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination

Simple SummaryEmerging evidence has suggested that cancer-derived extracellular vesicles (EVs) have a crucial role in mediating directional metastasis to the peritoneal surface in colorectal cancer (CRC). We investigated the EV-mediated crosstalk between tumor and mesothelial cells which may drive remodeling of the premetastatic niche to allow tumor spread to the peritoneal surface. Our findings demonstrated that cancer-derived EVs triggered apoptosis and reduced mesothelial cell invasiveness and mesothelial-to-mesenchymal transition. On the other hand, mesothelial cells actively supported tumor invasion by releasing EVs, which induced upregulation of the major pro-invasive system in tumor cells. For the first time, we provide evidence of EV-driven mechanisms of CRC progression in patient-derived models, highlighting the crucial role of EVs in the reprogramming of mesothelial and tumor cells to establish the metastatic process.Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-beta 1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients

Assessment of the Psychometric Characteristics of the Italian Version of the Nurse Manager Actions Scale

Nurse managers play a vital role in healthcare organizations, wielding the ability to substantially enhance work environments, foster nurses’ autonomy, and bolster retention within workplaces. In this context, this study focuses on the Nurse Manager Actions scale, aiming to evaluate its items’ scalability as well as the scale’s validity and reliability among nurses and nurse managers operating within the Italian healthcare context. The study protocol was not registered. To ensure linguistic and cultural alignment, an iterative and collaborative translation process was undertaken. Subsequently, a multi-center cross-sectional design was adopted. Using a web-survey approach, data were collected among 683 nurses and 188 nurse managers between August 2022 and January 2023. The Nurse Manager Actions scale was found to be a valid and reliable instrument in Italian after a Mokken Scale Analysis. For nurses (HT = 0.630, Molenaar–Sijtsma rho = 0.890), the scale included 6 items, while 11 items were confirmed for nurse managers (HT = 0.620, Molenaar–Sijtsma rho = 0.830). Nurse Manager Actions scale scores were correlated with increased satisfaction and decreased intention to leave for both nurses and nurse managers. The employed validation process enhanced the scale validity for use in Italy and provided a model for other researchers to follow when assessing similar measures in different populations. Measuring and empowering nurse manager actions in work contexts is essential to improve the general well-being and retention of nurses, especially in the current nursing shortage

DigiCam - Fully Digital Compact Read-out and Trigger Electronics for the SST-1M Telescope proposed for the Cherenkov Telescope Array

The SST-1M is one of three prototype small-sized telescope designs proposed for the Cherenkov Telescope Array, and is built by a consortium of Polish and Swiss institutions. The SST-1M will operate with DigiCam - an innovative, compact camera with fully digital read-out and trigger electronics. A high level of integration will be achieved by massively deploying state-of-the-art multi-gigabit transmission channels, beginning from the ADC flash converters, through the internal data and trigger signals transmission over backplanes and cables, to the camera's server link. Such an approach makes it possible to design the camera to fit the size and weight requirements of the SST-1M exactly, and provide low power consumption, high reliability and long lifetime. The structure of the digital electronics will be presented, along with main physical building blocks and the internal architecture of FPGA functional subsystems.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589