Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α.

Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-γ-dependent transcriptional activation of hypoxia-inducible factor-2α. Finally, utilizing a genetic murine GBM model, we show that EC-specific knockout of IL-6 inhibits macrophage alternative activation and improves survival in the GBM-bearing mice. These findings illustrate a vascular niche-dependent mechanism for alternative macrophage activation and cancer progression, and suggest that targeting endothelial IL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors

Roles of phosphotase 2A in nociceptive signal processing

Abstract Multiple protein kinases affect the responses of dorsal horn neurons through phosphorylation of synaptic receptors and proteins involved in intracellular signal transduction pathways, and the consequences of this modulation may be spinal central sensitization. In contrast, the phosphatases catalyze an opposing reaction of de-phosphorylation, which may also modulate the functions of crucial proteins in signaling nociception. This is an important mechanism in the regulation of intracellular signal transduction pathways in nociceptive neurons. Accumulated evidence has shown that phosphatase 2A (PP2A), a serine/threonine specific phosphatase, is implicated in synaptic plasticity of the central nervous system and central sensitization of nociception. Therefore, targeting protein phosphotase 2A may provide an effective and novel strategy for the treatment of clinical pain. This review will characterize the structure and functional regulation of neuronal PP2A and bring together recent advances on the modulation of PP2A in targeted downstream substrates and relevant multiple nociceptive signaling molecules

Experimental study of a novel subcooling method based on liquid desiccant dehumidification for vapor-compression refrigeration systems

Refrigerant subcooling could increase the refrigerating capacity and potentially improve the performance of refrigeration systems. In this paper, a novel subcooling method is experimentally studied for the first time in a hybrid vapor compression refrigeration system. In this system, condensation heat (~40 °C) is used to drive an integrated subcooling cycle to subcool the refrigerant leaving the condenser, which significantly increases the system performance. Changes in system performance are measured as functions of the following variables: the mass flow rates of the dehumidification air, ambient air, dehumidification solution, regeneration solution, and spraying water. Comparisons are made between the proposed system and the traditional water-cooled chiller. The proposed system can achieve a larger degree of subcooling (15–20 °C); what’s more, it shows much higher performances than the traditional water-cooled chiller: COP and exergy efficiency of the chiller are improved by 18.6% and 27.9%, respectively. Performance of the integrated subcooling cycle is also evaluated; it has a low COP, with the maximum value of 0.13, due to the low-grade condensation heat; however, it has a pretty high exergy efficiency, with the maximum value of 0.28, which indicates the effective use of the low-grade heat. In addition, an economic analysis of the integrated subcooling cycle is made with a project life cycle of 15 years; the payback period varies from 2.4 to 3.2 years based on different electricity tariffs, and the savings to investment ratio is between 1.3 and 2.1, which indicates that the project is profitable

Image post-processing techniques of 64-slice CT in the diagnosis of external cardiac malformations

Abstract: Objective To discuss the value of Image post-processing techniques of 64-slice CT in the diagnosis of external cardiac malformations．Materials and methods Retrospective reviews of imaging data base were done which consisted of 59 patients with congenital cardiovascular malformations who presented to our hospital. The scanning data were carried on multiple planar reformation (MPR), maximum intensity projection (MIP) and volume rendering (VR) as needed. The operation results were taken as diagnostic standard to evaluate the diagnostic accuracy of 64-slice spiral CT. Results 69 external cardiac malformations (cardiovascular connection department and peripheral vascular malformations) were confirmed by operation in all 59 patients. 67 malformations correctly diagnosed and 2 malformations were incorrecty diagnos in 64-slice spiral CT. The accuracy in diagnosing cardiovascular connection department and peripheral vascular malformations were 97.10% (67/69). There was no significant difference in image scores compared with the three image post-processing techniques (P value were 0.612, 0.902 and 0.815, respectively). Conclusions 64-slice spiral CT may be used as a primary technique and as a substitute for the diagnosis imaging portion of cardiovascular connection and peripheral vascular malformations

Multi‐Scale Microstructural Thermoelectric Materials: Transport Behavior, Non‐Equilibrium Preparation, and Applications

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137226/1/adma201602013_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137226/2/adma201602013.pd

Blocking Ion Migration Stabilizes the High Thermoelectric Performance in Cu2Se Composites

The applications of mixed ionic–electronic conductors are limited due to phase instability under a high direct current and large temperature difference. Here, it is shown that Cu2Se is stabilized through regulating the behaviors of Cu+ ions and electrons in a Schottky heterojunction between the Cu2Se host matrix and in‐situ‐formed BiCuSeO nanoparticles. The accumulation of Cu+ ions via an ionic capacitive effect at the Schottky junction under the direct current modifies the space‐charge distribution in the electric double layer, which blocks the long‐range migration of Cu+ and produces a drastic reduction of Cu+ ion migration by nearly two orders of magnitude. Moreover, this heterojunction impedes electrons transferring from BiCuSeO to Cu2Se, obstructing the reduction reaction of Cu+ into Cu metal at the interface and hence stabilizes the β‐Cu2Se phase. Furthermore, incorporation of BiCuSeO in Cu2Se optimizes the carrier concentration and intensifies phonon scattering, contributing to the peak figure of merit ZT value of ≈2.7 at 973 K and high average ZT value of ≈1.5 between 400 and 973 K for the Cu2Se/BiCuSeO composites. This discovery provides a new avenue for stabilizing mixed ionic–electronic conduction thermoelectrics, and gives fresh insights into controlling ion migration in these ionic‐transport‐dominated materials.The space‐charge region between Cu2Se host matrix and in‐situ‐formed BiCuSeO under a direct current causes drastic suppression of the Cu+ ion migration in such composites and obstructs the reduction reaction of Cu+ into Cu metal. This, together with the effective regulation of carrier concentration as well as enhanced interfacial phonon scattering, greatly stabilizes the improved thermoelectric performance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163457/2/adma202003730-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163457/3/adma202003730_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163457/1/adma202003730.pd

PERK-Mediated Cholesterol Excretion from IDH Mutant Glioma Determines Anti-Tumoral Polarization of Microglia

Isocitrate dehydrogenase (IDH) mutation, a known pathologic classifier, initiates metabolic reprogramming in glioma cells and has been linked to the reaction status of glioma-associated microglia/macrophages (GAMs). However, it remains unclear how IDH genotypes contribute to GAM phenotypes. Here, it is demonstrated that gliomas expressing mutant IDH determine M1-like polarization of GAMs, while archetypal IDH induces M2-like polarization. Intriguingly, IDH-mutant gliomas secrete excess cholesterol, resulting in cholesterol-rich, pro-inflammatory GAMs without altering their cholesterol biosynthesis, and simultaneously exhibiting low levels of tumoral cholesterol due to expression remodeling of cholesterol transport molecules, particularly upregulation of ABCA1 and downregulation of LDLR. Mechanistically, a miR-19a/LDLR axis-mediated novel post-transcriptional regulation of cholesterol uptake is identified, modulated by IDH mutation, and influencing tumor cell proliferation and invasion. IDH mutation-induced PERK activation enhances cholesterol export from glioma cells via the miR-19a/LDLR axis and ABCA1/APOE upregulation. Further, a synthetic PERK activator, CCT020312 is introduced, which markedly stimulates cholesterol efflux from IDH wild-type glioma cells, induces M1-like polarization of GAMs, and consequently suppresses glioma cell invasion. The findings reveal an essential role of the PERK/miR-19a/LDLR signaling pathway in orchestrating gliomal cholesterol transport and the subsequent phenotypes of GAMs, thereby highlighting a novel potential target pathway for glioma therapy

Dental resin monomer enables unique NbO2/carbon lithium‐ion battery negative electrode with exceptional performance

Niobium dioxide (NbO2) features a high theoretical capacity and an outstanding electron conductivity, which makes it a promising alternative to the commercial graphite negative electrode. However, studies on NbO2 based lithium-ion battery negative electrodes have been rarely reported. In the present work, NbO2 nanoparticles homogeneously embedded in a carbon matrix are synthesized through calcination using a dental resin monomer (bisphenol A glycidyl dimethacrylate, Bis-GMA) as the solvent and a carbon source and niobium ethoxide (NbETO) as the precursor. It is revealed that a low Bis-GMA/NbETO mass ratio (from 1:1 to 1:2) enables the conversion of Nb (V) to Nb (IV) due to increased porosity induced by an alcoholysis reaction between the NbETO and Bis-GMA. The as-prepared NbO2/carbon nanohybrid delivers a reversible capacity of 225 mAh g−1 after 500 cycles at a 1 C rate with a Coulombic efficiency of more than 99.4% in the cycles. Various experimental and theoretical approaches including solid state nuclear magnetic resonance, ex situ X-ray diffraction, differential electrochemical mass spectrometry, and density functional theory are utilized to understand the fundamental lithiation/delithiation mechanisms of the NbO2/carbon nanohybrid. The results suggest that the NbO2/carbon nanohybrid bearing high capacity, long cycle life, and low gas evolution is promising for lithium storage applications