Mechanism Of Activation Research Articles

Reinvestigation of the mechanism of the enamine-mediated dioxygen activation

The reaction of cyclohexylidene-2-carbamylcyclohex-1-enylamines with molecular oxygen does not undergo a [4+2] cycloaddition reactions but leads mainly to a dimer via single electron transfer (SET) from the enamine to 3O2, proton transfer (PT) and consecutive radical C–C coupling, an addition to the formation of hydroperoxide byproduct.

Efficient removal of 4-chlorophenol by activation of peroxymonosulfate with synthesized high-performance MnOx/CBC catalysts

Effective activation of peroxymonosulfate (PMS) is critical to remove chlorophenols (CPs) in the well-used sulfate radical advanced oxidation processes (SR-AOPs). Though manganese oxides (MnOx) have shown remarkable performance in activating PMS in SR-AOPs, the ease of agglomeration and relatively low crystallinity of MnOx can seriously decreases their activation efficiency. In this study, Camellia oleifera shell-based biochar (CBC) was employed as the support to load MnOx to prevent agglomeration, using the so-called co-precipitation approach. At the same time, low-temperature carbothermal reduction was utilized to increase crystallinity of MnOx while still maintaining promising surface structure of CBC. Using 4-chlorophenol (4-CP) as a representative for CPs, the synthesized MnOx/CBC showed high performance in activating PMS for degradation of 4-CP, with removal percentage up to 84.28%. Furthermore, the effects of roasting time, mass ratio between biochar and Mn, and roasting temperature on synthesis of MnOx/CBC were systematically investigated through the response surface methodology, and the obtained quadratic multinomial regression model can well predict the optimal synthesis condition. Finally, the underlined PMS activation mechanism by MnOx/CBC was explored, where main reactive oxygen species involved in degradation were found to be SO4•−, •OH, 1O2 and O2•−, and a possible routine was proposed. Overall, this work demonstrates the great potential of MnOx/CBC for activation of PMS for removing CPs.

Surface- and substrate-coated catalytic membrane for mitigating interference of water matrix species in intensified micropollutant confinement oxidation

The integration of advanced oxidation processes (AOPs) with membrane technology offers benefits for catalyst recovery and reducing membrane fouling. However, the application of the hybrid process could be hampered by the background species in water matrix. This study addresses this challenge by developing catalytic ceramic membranes (CCMs) with dual mechanisms to intensify acetaminophen (ACT) removal in water. The CCMs effectively activated peroxymonosulfate (PMS), achieving ACT degradation of 85% and 93% in real water matrices (reverse osmosis retentate and settled water, respectively) and 99% in MQ water. The CCMs demonstrated consistent performance across multiple operational cycles, even in the presence of humic acid (HA) (96% ACT reduction). The CCM design features Co3O4 catalytic layer on CCM surface, facilitating surface oxidation, reducing fouling, and TiO2 intermediate rejection layers serving as barrier for bulk organic pollutants, achieving 50% HA removal through rejection and 70% with 1.5mM PMS. This design facilitates catalytic degradation at the membrane surface, allowing retention and degradation of bulk organic pollutants and intermediates, while ACT permeates into CCM substrate. The surface oxidation and rejection enhanced confinement oxidation within the Co3O4-coated macropores, minimizing interference from background species. LC-QTOF analysis identified multiple degradation pathways, including hydroxylation, acetyl-amino group cleavage, side chain oxidation and benzene ring cleavage, with intermediates showing reduced toxicity. Reactive oxygen species involved in the system were identified and PMS activation mechanism was proposed. This research highlights the potential of the hybrid process, enhancing micropollutant removal by mitigating interference from background species, providing practical implications in water treatment applications.

A non-canonical mechanism of GPCR activation.

The goal of designing safer, more effective drugs has led to tremendous interest in molecular mechanisms through which ligands can precisely manipulate the signaling of G-protein-coupled receptors (GPCRs), the largest class of drug targets. Decades of research have led to the widely accepted view that all agonists-ligands that trigger GPCR activation-function by causing rearrangement of the GPCR's transmembrane helices, opening an intracellular pocket for binding of transducer proteins. Here we demonstrate that certain agonists instead trigger activation of free fatty acid receptor 1 by directly rearranging an intracellular loop that interacts with transducers. We validate the predictions of our atomic-level simulations by targeted mutagenesis; specific mutations that disrupt interactions with the intracellular loop convert these agonists into inverse agonists. Further analysis suggests that allosteric ligands could regulate the signaling of many other GPCRs via a similar mechanism, offering rich possibilities for precise control of pharmaceutically important targets.

Intrinsic Activity: A Critical Challenge of Alkaline Hydrogen Oxidation Reaction

AbstractAnion exchange membrane fuel cells (AEMFCs) are advantageous for reducing or even eliminating the dependency on platinum resources, as the alkaline environment allows the use of non‐precious metal catalysts for oxygen reduction reaction at the cathode. However, the intrinsic activity of hydrogen oxidation reaction (HOR) catalysts in alkaline environments is 2 to 4 orders of magnitude lower than in acidic environments, which becomes the major challenge for AEMFCs. This review examines the current developments in the intrinsic activity of alkaline HOR catalysts and systematically summarizes the hydrogen activation mechanism with a focus on potential influencing factors and enhancement strategies. Furthermore, it offers insights into the prospects for developing more efficient alkaline HOR catalysts.

A Comprehensive Exploration of the Synergistic Relationship between DMSO and Peroxide in Organic Synthesis.

In the realm of organic synthesis, reagents can serve not only as solvents but also as synthons. Dimethyl sulfoxide (DMSO) is recognized for its efficiency in this dual capacity, enabling diverse chemical transformations. DMSO can generate various synthons, including methyl, methylene, methine, oxygen, and methyl sulfoxide, broadening the accessible compound repertoire. Activation of DMSO as a reagent relies heavily on synergies with secondary agents like peroxide, persulfate, or iodine. Recent years have witnessed a surge in innovative synthetic techniques harnessing the synergistic interplay of DMSO and peroxide, leading to environmentally friendly and cost-effective reactions with mild conditions. This review highlights the synergistic effects of DMSO and peroxides (up to 2023), detailing their activation mechanisms and the generation of various synthons, along with numerous reported derivatives. Although this topic has received considerable attention in recent years, there are numerous discrepancies and a plethora of possibilities yet to be explored. We anticipate that this review will significantly support researchers in advancing their innovations to a greater extent in the future.

Gibbs states and Brownian models for coexisting haze and cloud droplets.

Cloud microphysics studies include how tiny cloud droplets grow and become rain. This is crucial for understanding cloud properties like size, life span, and impact on climate through radiative effects. Small weak-updraft clouds near the haze-to-cloud transition are especially difficult to measure and understand. They are abundant but hard to capture by satellites. Köhler's theory explains initial droplet growth but struggles with large particle groups. Here, we present a stochastic, analytical framework building on Köhler's theory to account for (monodisperse) aerosols and cloud droplet interaction through competitive growth in a limited water vapor field. These interactions are modeled by sink terms, while fluctuations in supersaturation affecting droplet growth are modeled by nonlinear white noise terms. Our results identify hysteresis mechanisms in the droplet activation and deactivation processes. Our approach allows for multimodal cloud's droplet size distributions supported by laboratory experiments, offering a different perspective on haze-to-cloud transition and small cloud formation.

Multiorgan involvement and circulating IgG1 predict hypocomplementaemia in IgG4-related disease

ObjectivesHypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease.MethodsWe performed a...

Epigenetics behind CD8+ T cell activation and exhaustion.

CD8+ T cells play a critical role in specific immunity. In recent years, cell therapy has been emerging rapidly. The specific cytotoxic capabilities of these cells enable them to precisely identify and kill cells presenting specific antigens. This has demonstrated promise in the treatment of autoimmune diseases and cancers, with wide-ranging applications and value. However, in some diseases, such as tumors and chronic infections, T cells may adopt an exhausted phenotype, resulting in a loss of cytotoxicity and limiting their further application. Epigenetics plays a significant role in the differentiation and regulation of gene expression in cells. There is extensive evidence indicating that epigenetic remodeling plays an important role in T cell exhaustion. Therefore, further understanding its role in CD8+ T cell function can provide insights into the programmatic regulation of CD8+ T cells from a genetic perspective and overcome these diseases. We attempted to describe the relationship between the activation, function, and exhaustion mechanisms of CD8+ T cells, as well as epigenetics. This understanding makes it possible for us to address the aforementioned issues.

Exposure to copper and copper-based nanoparticles induces hepatopancreatic mitochondrial dysfunction by triggering mtROS mediated apoptosis and mitophagy in Eriocheir sinensis.

Copper (Cu) is an important metal pollutant commonly found in aquatic environment owing to its inherent bioaccumulation and biomagnification potentials and long-term persistence in environmental compartments. The application of novel fabricated copper nanoparticles (Cu-NPs) has led to cytotoxicity in aquatic animals. However, the differences in underlying toxicity mechanisms between Cu-NPs and waterborne Cu (such as CuSO4) remain unelucidated. Herein, the mechanisms underlying the CuSO4/Cu-NPs-mediated perturbation of the hepatopancreatic mitochondrial function at different concentrations were investigated and compared. After exposing Eriocheir sinensis to 0 (control), 5, 50, and 500 μg/L CuSO4 and 10 μg/L Cu-NPs for 21 days, hepatopancreases were retrieved. The results revealed that Cu-NPs or CuSO4 (50 and 500 μg/L) induced ultrastructural damage following a time-dose effect, as indicated by swelling and degeneration of the lumen of hepatic tubules. Excess CuSO4 or Cu-NPs exposure decreased the antioxidative capacity and led to the over-accumulation of mitochondrial ROS. Moreover, the mitochondrial membrane potential (ΔΨm) was reduced and apoptosis induced. Additionally, both CuSO4 and Cu-NPs increased the numbers of mitophagosomes and the mRNA and protein levels of LC3B, and triggered mitophagy through PRKN-independent pathway; however, mostly the BNIP3L/Beclin1 pathway was involved in excess CuSO4-induced mitophagy. Altogether, this study provides a basis for exploring Cu-mediated potential mitochondrial autophagy activation mechanisms and their effects on environmental toxicity.

KOH Activation Mechanism in the Preparation of Brewer’s Spent Grain-Based Activated Carbons

Understanding the mechanism of KOH activation in the preparation of activated carbon (AC) enables more efficient utilization of biomass. In this study, brewer’s spent grains (BSGs) were carbonized at 500 °C to produce biochar (BC), followed by KOH activation under different activation conditions. The gas and solid products generated during the activation process were analyzed by gas chromatography (GC), X-ray diffraction (XRD), Raman analysis, a surface area and pore size analyzer, and X-ray photoelectron spectroscopy (XPS). The results show that increasing the KOH/BC ratio or the activation temperature could both promote gas production. XPS results indicated that the activator reacted first with -COOH and then with -OH of ACs, with AC5-700 having the highest C-OH content (50.04%). As the KOH/BC ratio increased, more aromatic structures were destroyed, and the porosity of ACs was significantly enhanced, with AC7-700 having the highest Brunauer–Emmett–Teller (BET) specific surface area (SBET) (2997.69 m2/g). At low temperatures, KOH reacted with the active groups of BC and carbon at the edge of the aromatic structure. At high temperatures, the activator (KOH, K2O, and K2CO3) reacted with carbon in the aromatic structure to generate a large number of pores on ACs and expand them. ACs exhibited more pores with higher KOH addition, and a higher activation temperature did not generate more new pores, but expanded the pores more significantly than high KOH addition.

TMIC-78. CHEMOTHERAPY INDUCED IMMUNOGENIC RESPONSE IN GLIOMA AND IMPLICATIONS FOR THERAPEUTIC STRATEGIES

Abstract INTRODUCTION Many glioblastoma (GBM) treatments fail because they treat tumor cells in isolation and ignore the surrounding microenvironment. In our phase 1b clinical trial of delivery of Topotecan (TPT) via Convection Enhanced Delivery (CED) in glioma, we demonstrated effective tumor cell elimination accompanied by a robust inflammatory response. We hypothesized that TPT induces an immunogenic response resulting in an unfavorable inflammatory landscape. METHODS To characterize chemotherapy’s effect on myeloid cells, we analyzed pre- and post-treatment biopsies from our trial using bulk RNA sequencing to measure canonical myeloid markers. We validated survival benefit of CED in vivo in our tumor model and characterized post-treatment tissue using single cell RNA sequencing (scRNA seq) after 7 days of treatment. We treated slice cultures generated from surgical samples of GBM with TPT and performed scRNA seq and histologic analysis to assess microenvironment changes after 24 hours of treatment. We used several in vitro assays to characterize the direct and indirect mechanisms of myeloid activation. RESULTS Bulk RNA sequencing of post treatment biopsies demonstrates upregulation of markers associated with activated and exhausted immune cell populations such as IBA1, CD68, MSR1, MARCO and loss of markers associated with homeostatic microglia such as P2RY12 and TMEM119. Similar results are found within 7 days of treatment in vivo, however, are not found in human derived samples treated acutely. Treatment of in vitro mono and co-culture systems demonstrate a tumor cell death dependent activation of myeloid cell populations via immunogenic molecules. CONCLUSIONS Chemotherapies eliminate proliferating glioma cells but also induce inflammation. While many investigators have tried to leverage this activation, our results suggest that chronic inflammation contributes to poor prognosis and recurrence. The identification of molecules responsible for this activation point to new therapeutic targets aimed at controlling treatment-induced inflammation, as part of a combinatorial approach to treat GBM.

Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway

Fibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF.

CSIG-34. TYROSINE PHOSPHORYLATION OF NON-CANONICAL NF-ΚB P52 PROMOTES GLIOMA GROWTH AND CHEMORESISTANCE IN GBM

Abstract p52 is a nuclear factor-κB (NF-κB) transcription factor that comprises the non-canonical NF-κB pathway. The impact and mechanism of non-canonical NF-κB signaling remains understudied in glioblastoma (GBM). Subunit post-translational modification is a known mechanism of NF-κB activation, however phosphorylation of p52 has never been demonstrated. Elevated tyrosine kinase activity is a known-feature of GBM and portends worse survival. Further, p52 has been shown to upregulate factors that likely promote invasion of GBM, thereby reducing survival. Activation of p52 may serve as a link between increased kinase activity and poor survival in GBM. p52-knockout cell lines were generated using the CRISPR-Cas9 system and assessed for growth and survival differences in vitro and in syngeneic murine glioma models. Public glioma datasets and an institutional cohort were surveyed to corroborate p52-dependent survival differences in GBM. To determine whether p52 is post-translationally modified, we performed tandem mass spectrometry on p52 in GBM cells. Interacting factors were also analyzed and tested for site-specific modification of p52 via co-IP studies. We then generated PTM-null, knock-in glioma cell lines using CRISPR-CAS9 editing to demonstrate the functional significance of p52 PTMs, which were assessed using assays of relative cell growth, stemness, chemosensitivity and survival. Finally, we performed unbiased analysis of the p52 PTM-dependent transcriptome via RNA-seq. p52 loss significantly reduced glioma growth rate in vitro and improves murine survival. Retrospective analysis of GBM in patients suggests that p52 levels are negatively prognostic. Mass spectrometry identified multiple p52 PTMs with tyrosine phosphorylation sites as top hits. Identified phospho-tyrosine residues specifically interact with SRC-family kinases. PTM site editing significantly reduces glioma cell growth and stemness while enhancing chemosensitivity, reflecting broad transcriptome level changes. In sum, p52 activity enhances GBM growth and chemoresistance, which is partially modulated by tyrosine-specific phosphorylation. p52 warrants investigation as a therapeutic target in GBM, possibly in combination with kinase inhibitors and standard alkylating chemotherapy.

TMIC-36. EVALUATING PHARMACOLOGICAL INHIBITION OF LSD1 IN MODELS OF DIFFUSE MIDLINE GLIOMA AND EFFECTS ON IMMUNE MICROENVIRONMENT SIGNALING

Abstract BACKGROUND Diffuse midline glioma (DMG) is the leading cause of death for pediatric brain tumor patients. DMG is remarkably immunologically senescent, even in comparison to other “immune-cold” tumors like adult glioblastoma. Lysine specific demethylase-1 (LSD1) is a histone demethylase exerting context-specific mechanisms of gene repression and activation and can be inhibited pharmacologically. We found LSD1 regulates the expression of inflammatory cytokines such as Interleukin 18 (IL18) and immune signaling receptors in DMG. Here, we investigated whether IL18 is transcriptionally regulated by LSD1 in vitro and in vivo using clinically relevant small molecule inhibitors. METHODS LSD1 binding to the IL-18 promoter was evaluated using chromatin immunoprecipitation. Transcript and protein expression using qRT-PCR and western blotting assessed the impact of LSD1 inhibition on IL18-related pathways and immune signaling pathways. LSD1 inhibitors (IMG-7289 or GSKLSD1) were evaluated patient-derived xenograft models. Results. We found elevated LSD1 binding on the IL18 promoter in DIPG VI cells. Subsequent qRT-PCR and western blot analyses demonstrated increased IL18 protein levels following treatment with GSKLSD1 or IMG-7289 in DIPG VI cells, alongside heightened IL18 mRNA expression compared to DMSO-treated cells. Either GSKLSD1 or IMG-7289 treatment in DIPG IV cells also led to significantly elevated IL18 binding protein mRNA levels. Orthotopic xenografts using DIPG IV bearing mice dosed with LSD1 inhibitors over the course of 35 days several weeks showed a decrease in IL-18R, and an increase in IL-18 BP transcript levels alongside a significant increase in Slamf7 transcript levels. Some evidence of tumor inhibition was seen in male but not female mice treated with GSKLSD1. CONCLUSIONS Our investigation revealed IL18 as a direct target of LSD1 specifically in DIPG VI, and gender specific effects of GSKLSD1 treatment in vivo. Future studies will prioritize validating and elucidating the underlying mechanisms the therapeutic potential of LSD1 inhibition in DMG.

EXTH-76. REDIRECTING STROMAL CELLS TO IGNITE ANTI-TUMOR IMMUNITY AGAINST GLIOBLASTOMA

Abstract BACKGROUND The dismal prognosis of high-grade gliomas demands novel treatment approaches. Through the development of a novel mRNA lipid particle aggregate (RNA-LPA) vaccine, our lab has shown anti-tumor efficacy in preclinical murine studies and promising immunological responses in canine glioma models and human studies (Cell. 2024 May 9;187(10):2521-2535.e21). The translational potential necessitates further investigating the immune activation mechanism to allow greater applicability of this therapy in the future. OBJECTIVE We sought to unravel mechanistic cross-talk for immune initiation following intravenous administration of RNA-LPAs. METHODS We used Ai14 reporter mice to determine RNA-LPA transfected cellular subsets and dual reporter mice to assess cellular infiltration into murine glioma models. Murine gliomas were generated via implantation of K2 or KR158b-luc cell lines. RESULTS Following intravenous administration, we found fibroblastic reticular cells in secondary lymphoid organs take up RNA-LPAs. We show that FRCs have direct contact with antigen presenting cells and mediate release of full-length proteins following RNA-LPA transfection. Similar to the periphery, there is transfection of stromal cells in the brain tumor microenvironment (TME) and recruitment of infiltrating leukocytes. In response to RNA-LPAs, transfected stromal cells release type I interferon (IFN-I), which is requisite for anti-tumor efficacy. IFN-I mediates upregulation of CD69 on lymphocytes leading to sequestration following co-localization with RNA-LPAs. IFN-I is necessary for LFA-I expression on T cells, which is important for T cell trafficking across the blood-brain barrier. In preclinical models to track antigen specific immunity, we find systemic RNA administration elicits an increase in tumor reactive T cells with decreased S1P1 expression suggestive of a ‘locked-in’ response within the TME. CONCLUSION While stromal cells are regulatory niches in glioblastoma ecosystems, we show they can be leveraged for immunologic cross-talk that facilitates T cell recruitment, trafficking and sequestration in the TME critical for immunologic reprogramming and long-lasting immunotherapy.

Structure-Activity-Relationships of the Stability of six Pentathiepins towards Glutathione: Possible Correlations with Biological Activities.

The biological properties of pentathiepins have been intensively studied in recent years. Although the proposed mechanism of action requires activation by intracellular thiols, the dependence of activity on the stability of pentathiepins towards glutathione (GSH) has not been directly investigated. Here, we determined the structure-related stability of six different pentathiepins with four different scaffolds in the presence of GSH by using reversed-phase high-performance liquid chromatography (RP-HPLC) and UV-vis spectroscopy over a wide range of GSH concentrations. We found significant differences in compound stability depending on the pentathiepin scaffold; these differences were reflected in their cytotoxic activities. However, we found no substantial differences in their inhibition of glutathione peroxidase 1 (GPx-1). While the intact pentathiepin ring is necessary for the antiproliferative activity of pentathiepins, the depletion of intracellular GSH content with dl-buthionine-(S,R)-sulfoximine (BSO) led to a significant increase in cytotoxicity of the tested substances. In view of the increased cytotoxicity following artificial GSH depletion, this calls into question the sole role of GSH in the intracellular activation mechanism.

IMMU-22. TWIST1-MEDIATED ENDOTHELIAL PLASTICITY DRIVES GLIOBLASTOMA RESISTANCE TO CAR T IMMUNOTHERAPY

Abstract Glioblastoma (GBM) is the most common and most aggressive malignant primary brain tumor in adults. Among the most lethal human malignancies, GBM is highly resistant to cytotoxic treatments and molecularly targeted therapies, and also generally refractory to T cell–based immunotherapies, largely due to their immunologically cold nature, i.e., characterized by a paucity of tumor T cell infiltrates that result from the immunosuppressive microenvironment. Here, we identify a distinct mechanism driven by spatiotemporal interaction of leukocytes with tumor stromal cells, namely, mesenchymal-like population of endothelial cells (ECs) form an immunosuppressive vascular niche that regulates macrophage polarization and induces GBM resistance to CAR T immunotherapy. Our single-cell transcriptome analyses of human and mouse GBM tumors identify a subpopulation of ECs acquire robust immunosuppressive phonotypes to drive alternative macrophage polarization. These ECs are spatially localized proximately to immunosuppressive macrophages and selectively express Twist1. Furthermore, we reveal a Twist1/SATB1-mediated sequential transcriptional activation mechanism, through which Twist1+ tumor ECs produce osteopontin to locally promote immunosuppressive macrophage phenotypes. Genetic or pharmacological ablation of Twist1 reverses macrophage-mediated immunosuppression and enhances T cell infiltration and activation, leading to reduced GBM growth and extended mouse survival. Importantly, pharmacological inhibition and lipid nanoparticle-mediated targeted inactivation of Twist1 overcome GBM resistance to Egfrviii CAR T cell immunotherapy. Thus, these findings uncover a spatially restricted mechanism controlling vasculature-mediated tumor immunity and suggest that targeting endothelial Twist1 may offer exciting opportunities for GBM immunotherapy.

Involvement of PDGFR-integrin interactions in the regulation of anoikis resistance in glioblastoma progression.

The interactions between platelet-derived growth factor/PDGF receptor and integrin signaling are crucial for cells to respond to extracellular stimuli. Integrin interactions with PDGFR within the lipid rafts activate downstream cellular signaling pathways that regulate cell proliferation, cell migration, cell differentiation, and cell death processes. The mechanisms underlying PDGFR activation mediated receptor internalization, interactions with other cell-surface receptors, particularly extracellular matrix receptors, integrins, and how these cellular mechanisms switch on anchorage-independent cell survival, leading to anoikis resistance are discussed. The role of regulatory molecules such as noncoding RNAs, that can modulate several molecular and cellular processes, including autophagy, in the acquisition of anoikis resistance is also discussed. Overall, the review provides a new perspective on a complex interplay of regulatory cellular machineries involving autophagy, noncoding RNAs and cellular mechanisms of PDGFR activation, PDGFR-integrin interactions, and involvement of lipids rafts in the acquisition of anoikis resistance that regulates glioblastoma progression along with potential future strategies to develop novel therapeutics for glioblastoma multiforme.

Sodium and Potassium Storage Behaviour in AgNbO3 Perovskite

AbstractIn this work, we report on the investigation the perovskite‐type AgNbO3 as a model negative electrode for sodium and potassium systems. We demonstrated that during the initial discharge, regardless of the inserted cation, the material undergoes an activation mechanism that induces a crystalline‐to‐amorphous transition. This transition, in turn, leads to an enhancement of the electrode capacity. At 5 A g−1 sodium‐ion AgNbO3 and Potassium‐ion AgNbO3 display capacities of 81 mAh g−1 and 60 mAh g−1, respectively. Furthermore, both electrodes display good cycling stability and efficiency over 350 cycles at 1 A g−1.