Ligustrazine Inhibits the Migration and Invasion of Renal Cell Carcinoma

Ligustrazine is a Chinese herb (Chuanxiong) approved for use as a medical drug in China. Recent evidence suggests that ligustrazine has promising antitumor properties. Our preliminary results showed that ligustrazine could inhibit the growth of human renal cell carcinoma (RCC) cell lines. However, the complicated molecular mechanism has not been fully revealed. Therefore, the purpose of this study to investigate the mechanism of ligustrazine resistance in human RCC cells. Cell proliferation, migration, invasion, and colony-formation ability of RCC cells A498 were detected by MTT assay, clonal formation rates, and transwell chamber assay in vitro. The expression of epithelial–mesenchymal transition (EMT)–related proteins were analyzed using western blot test. The effect of ligustrazine on the growth of A498 cells in nude mice was investigated in vivo. Our results showed that ligustrazine could significantly inhibit the proliferation, migration, and invasion of A498 both in vivo and vitro. Western blot analysis showed that the expressions of EMT-related, N-cadherin, snail, and slug proteins were significantly decreased in A498 in the ligustrazine treatment group. This study indicated that ligustrazine could significantly inhibit the malignant biological behaviors of RCC cell lines, possibly by inhibiting the EMT process

Optimisation of Mobile Communication Networks - OMCO NET

The mini conference “Optimisation of Mobile Communication Networks” focuses on advanced methods for search and optimisation applied to wireless communication networks. It is sponsored by Research & Enterprise Fund Southampton Solent University. The conference strives to widen knowledge on advanced search methods capable of optimisation of wireless communications networks. The aim is to provide a forum for exchange of recent knowledge, new ideas and trends in this progressive and challenging area. The conference will popularise new successful approaches on resolving hard tasks such as minimisation of transmit power, cooperative and optimal routing

Safety in magnetic resonance units: an update

The number of anaesthetists who are involved in magnetic resonance (MR) units is increasing. Magnetic resonance systems are becoming more powerful and interventional procedures are now possible. This paper updates information relating to safety terminology, occupational exposure, reactions to gadolinium-based contrast agents and the risk of nephrogenic systemic fibrosis. Magnetic resonance examinations of patients with pacemakers are still generally contra-indicated but have been carried out in specialist centres under strictly controlled conditions. As availability of MR increases, so the education of anaesthetists, who are occasionally required to provide a service, must be considered

The aetiology of social deficits within mental health disorders:The role of the immune system and endogenous opioids

The American National Institute for Mental Health (NIMH) has put out a set of research goals that include a long-term plan to identify more reliable endogenous explanations for a wide variety of mental health disorders (Insel, 2013). In response to this, we have identified a major symptom that underlies multiple mental health disorders – social bonding dysfunction. We suggest that endogenous opioid abnormalities can lead to altered social bonding, which is a symptom of various mental health disorders, including depression, schizophrenia and ASD. This article first outlines how endogenous opioids play a role in social bonding. Then we show their association with the body’s inflammation immune function, and review recent literature linking inflammation to mental health ‘immunophenotypes’. We finish by explaining how these immunophenotypes may be caused by alterations in the endogenous opioid system. This is the first overview of the role of inflammation across multiple disorders where we provide a biochemical explanation for why immunophenotypes might exist across diagnoses. We propose a novel mechanism of how the immune system may be causing ‘sickness-type’ behaviours (fatigue, appetite change, social withdrawal and inhibited motivation) in those who have these immunophenotypes. We hope that this novel aetiology can be used as a basis for future research in mental health

Trigger versus Substrate: Multi-Dimensional Modulation of QT-Prolongation Associated Arrhythmic Dynamics by a hERG Channel Activator

Background: Prolongation of the QT interval of the electrocardiogram (ECG), underlain by prolongation of the action potential duration (APD) at the cellular level, is linked to increased vulnerability to cardiac arrhythmia. Pharmacological management of arrhythmia associated with QT prolongation is typically achieved through attempting to restore APD to control ranges, reversing the enhanced vulnerability to Ca²⁺-dependent afterdepolarisations (arrhythmia triggers) and increased transmural dispersion of repolarisation (arrhythmia substrate) associated with APD prolongation. However, such pharmacological modulation has been demonstrated to have limited effectiveness. Understanding the integrative functional impact of pharmacological modulation requires simultaneous investigation of both the trigger and substrate. Methods: We implemented a multi-scale (cell and tissue) in silico approach using a model of the human ventricular action potential, integrated with a model of stochastic 3D spatiotemporal Ca²⁺ dynamics, and parameter modification to mimic prolonged QT conditions. We used these models to examine the efficacy of the hERG activator MC-II-157c in restoring APD to control ranges, examined its effects on arrhythmia triggers and substrates, and the interaction of these arrhythmia triggers and substrates. Results: QT prolongation conditions promoted the development of spontaneous release events underlying afterdepolarisations during rapid pacing. MC-II-157c applied to prolonged QT conditions shortened the APD, inhibited the development of afterdepolarisations and reduced the probability of afterdepolarisations manifesting as triggered activity in single cells. In tissue, QT prolongation resulted in an increased transmural dispersion of repolarisation, which manifested as an increased vulnerable window for uni-directional conduction block. In some cases, MC-II-157c further increased the vulnerable window through its effects on INa. The combination of stochastic release event modulation and transmural dispersion of repolarisation modulation by MC-II-157c resulted in an integrative behavior wherein the arrhythmia trigger is reduced but the arrhythmia substrate is increased, leading to variable and non-linear overall vulnerability to arrhythmia. Conclusion: The relative balance of reduced trigger and increased substrate underlies a multi-dimensional role of MC-II-157c in modulation of cardiac arrhythmia vulnerability associated with prolonged QT interval

Cellular, circuit and transcriptional framework for modulation of itch in the central amygdala

Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of the cells and neural circuits that organize this information remains elusive. Here, we show the necessity and sufficiency of chloroquine-activated neurons in the central amygdala (CeA) for both itch sensation and associated aversion. Further, we show that chloroquine-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of chloroquine-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral tracing experiments demonstrate that these neurons send projections to the ventral periaqueductal gray that are critical in modulation of itch. These findings reveal a cellular and circuit signature of CeA neurons orchestrating behavioral and affective responses to pruritus in mice

Membrane Interactome of a Recombinant Fragment of Human Surfactant Protein D Reveals GRP78 as a Novel Binding Partner in PC3, a Metastatic Prostate Cancer Cell Line

ICMR- National Institute for Research in Reproductive Health ICMR-NIRRH (Accession no. 921); ICMR- National Institute for Research in Reproductive Health ICMR-NIRRH-JRF; ICMR- National Institute for Research in Reproductive Health ICMR-SRF; Researchers Supporting Project (RSP-2020/26) King Saud University, Riyadh

Scientific access into Mercer Subglacial Lake: scientific objectives, drilling operations and initial observations

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Priscu, J. C., Kalin, J., Winans, J., Campbell, T., Siegfried, M. R., Skidmore, M., Dore, J. E., Leventer, A., Harwood, D. M., Duling, D., Zook, R., Burnett, J., Gibson, D., Krula, E., Mironov, A., McManis, J., Roberts, G., Rosenheim, B. E., Christner, B. C., Kasic, K., Fricker, H. A., Lyons, W. B., Barker, J., Bowling, M., Collins, B., Davis, C., Gagnon, A., Gardner, C., Gustafson, C., Kim, O-S., Li, W., Michaud, A., Patterson, M. O., Tranter, M., Ryan Venturelli, R., Trista Vick-Majors, T., & Elsworth, C. Scientific access into Mercer Subglacial Lake: scientific objectives, drilling operations and initial observations. Annals of Glaciology, 62(85–86), (2021): 340–352, https://doi.org/10.1017/aog.2021.10.The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.This material is based upon work supported by the US National Science Foundation, Section for Antarctic Sciences, Antarctic Integrated System Science program as part of the interdisciplinary (Subglacial Antarctic Lakes Scientific Access (SALSA): Integrated study of carbon cycling in hydrologically-active subglacial environments) project (NSF-OPP 1543537, 1543396, 1543405, 1543453 and 1543441). Ok-Sun Kim was funded by the Korean Polar Research Institute. We are particularly thankful to the SALSA traverse personnel for crucial technical and logistical support. The United States Antarctic Program enabled our fieldwork; the New York Air National Guard and Kenn Borek Air provided air support; UNAVCO provided geodetic instrument support. Hot water drilling activities, including repair and upgrade modifications of the WISSARD hot water drill system, for the SALSA project were supported by a subaward from the Ice Drilling Program of Dartmouth College (NSF-PLR 1327315) to the University of Nebraska-Lincoln. J. Lawrence assisted with manuscript preparation. Finally, we are grateful to C. Dean, the SALSA Project Manager, and R. Ricards, SALSA Project Coordinator at McMurdo Station, for their organizational skills, and B. Huber of Lamont-Doherty Earth Observatory for providing the SBE39 PT sensors and the Nortek Aquadopp current meter and assisting with interpretation of the data. B. Huber also provided helpful input on programing and calibrating the SBE19PlusV2 6112 CTD

Biogenic nano-magnetite and nano-zero valent iron treatment of alkaline Cr(VI) leachate and chromite ore processing residue

Highly reactive nano-scale biogenic magnetite (BnM), synthesized by the Fe(III)-reducing bacterium Geobacter sulfurreducens, was tested for the potential to remediate alkaline Cr(VI) contaminated waters associated with chromite ore processing residue (COPR). The performance of this biomaterial, targeting aqueous Cr(VI) removal, was compared to a synthetic alternative, nano-scale zero valent iron (nZVI). Samples of highly contaminated alkaline groundwater and COPR solid waste were obtained from a contaminated site in Glasgow, UK. During batch reactivity tests, Cr(VI) removal from groundwater was inhibited by ~25% (BnM) and ~50% (nZVI) when compared to the treatment of less chemically complex model pH 12 Cr(VI) solutions. In both the model Cr(VI) solutions and contaminated groundwater experiments the surface of the nanoparticles became passivated, preventing complete coupling of their available electrons to Cr(VI) reduction. To investigate this process, the surfaces of the reacted samples were analyzed by TEM-EDX, XAS and XPS, confirming Cr(VI) reduction to the less soluble Cr(III) on the nanoparticle surface. In groundwater reacted samples the presence of Ca, Si and S was also noted on the surface of the nanoparticles, and is likely responsible for earlier onset of passivation. Treatment of the solid COPR material in contact with water, by addition of increasing weight % of the nanoparticles, resulted in a decrease in aqueous Cr(VI) concentrations to below detection limits, via the addition of ≥5% w/w BnM or ≥1% w/w nZVI. XANES analysis of the Cr K edge, showed that the % Cr(VI) in the COPR dropped from 26% to a minimum of 4-7% by the addition of 5% w/w BnM or 2% w/w nZVI, with higher additions unable to reduce the remaining Cr(VI). The treated materials exhibited minimal re-mobilization of soluble Cr(VI) by re-equilibration with atmospheric oxygen, with the bulk of the Cr remaining in the solid fraction. Both nanoparticles exhibited a considerable capacity for the remediation of COPR related Cr(VI) contamination, with the synthetic nZVI demonstrating greater reactivity than the BnM. However, the biosynthesized BnM was also capable of significant Cr(VI) reduction and demonstrated a greater efficiency for the coupling of its electrons towards Cr(VI) reduction than the nZVI

Room temperature coherent control of coupled single spins in solid

Coherent coupling between single quantum objects is at the heart of modern quantum physics. When coupling is strong enough to prevail over decoherence, it can be used for the engineering of correlated quantum states. Especially for solid-state systems, control of quantum correlations has attracted widespread attention because of applications in quantum computing. Such coherent coupling has been demonstrated in a variety of systems at low temperature1, 2. Of all quantum systems, spins are potentially the most important, because they offer very long phase memories, sometimes even at room temperature. Although precise control of spins is well established in conventional magnetic resonance3, 4, existing techniques usually do not allow the readout of single spins because of limited sensitivity. In this paper, we explore dipolar magnetic coupling between two single defects in diamond (nitrogen-vacancy and nitrogen) using optical readout of the single nitrogen-vacancy spin states. Long phase memory combined with a defect separation of a few lattice spacings allow us to explore the strong magnetic coupling regime. As the two-defect system was well-isolated from other defects, the long phase memory times of the single spins was not diminished, despite the fact that dipolar interactions are usually seen as undesirable sources of decoherence. A coherent superposition of spin pair quantum states was achieved. The dipolar coupling was used to transfer spin polarisation from a nitrogen-vacancy centre spin to a nitrogen spin, with optical pumping of a nitrogen-vacancy centre leading to efficient initialisation. At the level anticrossing efficient nuclear spin polarisation was achieved. Our results demonstrate an important step towards controlled spin coupling and multi-particle entanglement in the solid state