Neutrophils in glioma microenvironment: from immune function to immunotherapy.

Glioma is a malignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important member of the tumor microenvironment (TME), are widely distributed in circulation. Recently, the discovery of cranial-meningeal channels and intracranial lymphatic vessels has provided new insights into the origins of neutrophils in the CNS. Neutrophils in the brain may originate more from the skull and adjacent vertebral bone marrow. They cross the blood-brain barrier (BBB) under the action of chemokines and enter the brain parenchyma, subsequently migrating to the glioma TME and undergoing phenotypic changes upon contact with tumor cells. Under glycolytic metabolism model, neutrophils show complex and dual functions in different stages of cancer progression, including participation in the malignant progression, immune suppression, and anti-tumor effects of gliomas. Additionally, neutrophils in the TME interact with other immune cells, playing a crucial role in cancer immunotherapy. Targeting neutrophils may be a novel generation of immunotherapy and improve the efficacy of cancer treatments. This article reviews the molecular mechanisms of neutrophils infiltrating the central nervous system from the external environment, detailing the origin, functions, classifications, and targeted therapies of neutrophils in the context of glioma.

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways.

BACKGROUND: In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. METHODS: Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. RESULTS: Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß, and caused further DNA damage and promoted the apoptosis rate of tumor cells. CONCLUSIONS: Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.

Thiosalicylic-Acid-Mediated Coordination Structure of Nickel Center via Thermodynamic Modulation for Aqueous Ni-Zn Batteries.

Uniquely functional nanocomplexes with rich coordination environments are critical in energy storage. However, the construction of structurally versatile nanocomplexes remains challenging. In this study, a nickel-based complex with structural variations is designed via thermodynamic modulation using a dual-ligand synthesis strategy. A nickel-based nanomaterial (NiSA-SSA-160) with a large specific surface area is synthesized around the competing coordination of the host and guest molecules that differ in terms of the chemical properties of the O and S elements. Concurrently, the coordination environment of NiSA-SSA-160 is investigated via X-ray absorption fine structure spectroscopy. The thiol functional groups synergistically induced an electron-rich Ni structure, thus increasing the electron density of the central atom. The electrochemical performance of an assembled NiSA-SSA-160//Zn@CC battery is shown to improve significantly, with a maximum energy density of 0.54 mWh cm-2 and a peak power density of 49.49 mW cm-2. This study provides a new perspective regarding coordination transformations and offers an idea for the design of functionally rich nanomaterials.

Case report: a case report of excision of giant lipoma in the posterior neck.

Lipomas, benign tumors originating from the anomalous proliferation of adipocytes, predominantly emerge in regions rich in adipose tissue. However, their presence in the head and neck areas remains rare, constituting approximately 13% of all diagnosed lipoma cases. This study presents a case involving a substantial subcutaneous lipoma located at the posterior neck, measuring about 20 cm × 19 cm × 10 cm. The patient presented with swelling and pain in the back of the neck. And the considerable dimensions of this lipoma significantly impacted the patient's quality of life and aesthetic appearance. Concurrently, the patient exhibited symptoms indicative of degenerative cervical spine disease and cervical disc herniation. After admission, a comprehensive examination, including ultrasound, CT scan, and MRI, was conducted. Given the clinical complexity, the decision for surgical intervention was deemed essential. The surgical strategy entailed a meticulous total excision of the tumor through an incision made in the posterior cross-neck, coupled with the strategic removal of excess skin. To facilitate wound healing, postoperative management included the use of negative pressure drainage. Pathological examination conclusively identified the mass as a lipoma. Postoperative follow-ups indicated successful recovery, as evidenced by the restoration of the neck's aesthetic contour and the complete resolution of the previously observed restrictions in sagittal neck movement.

The mechanism of extracellular CypB promotes glioblastoma adaptation to glutamine deprivation microenvironment.

Glioblastoma, previously known as glioblastoma multiform (GBM), is a type of glioma with a high degree of malignancy and rapid growth rate. It is highly dependent on glutamine (Gln) metabolism during proliferation and lags in neoangiogenesis, leading to extensive Gln depletion in the core region of GBM. Gln-derived glutamate is used to synthesize the antioxidant Glutathione (GSH). We demonstrated that GSH levels are also reduced in Gln deficiency, leading to increased reactive oxygen species (ROS) levels. The ROS production induces endoplasmic reticulum (ER) stress, and the proteins in the ER are secreted into the extracellular medium. We collected GBM cell supernatants cultured with or without Gln medium; the core and peripheral regions of human GBM tumor tissues. Proteomic analysis was used to screen out the target-secreted protein CypB. We demonstrated that the extracellular CypB expression is associated with Gln deprivation. Then, we verified that GBM can promote the glycolytic pathway by activating HIF-1α to upregulate the expression of GLUT1 and LDHA expressions. Meanwhile, the DRP1 was activated, increasing mitochondrial fission, thus inhibiting mitochondrial function. To explore the specific mechanism of its regulation, we constructed a si-CD147 knockout model and added human recombinant CypB protein to verify that extracellular CypB influenced the expression of downstream p-AKT through its cell membrane receptor CD147 binding. Moreover, we confirmed that p-AKT could upregulate HIF-1α and DRP1. Finally, we observed that extracellular CypB can bind to the CD147 receptor, activate p-AKT, and upregulate HIF-1α and DRP1 in order to promote glycolysis while inhibiting mitochondrial function to adapt to the Gln-deprived microenvironment.

Streamlined synthesis of superstructure Ni-benzimidazole MOFs: Glucose electrochemical analysis.

The design and synthesis of efficient electrochemical sensors are crucial transformation technologies in electrochemistry. We successfully synthesize a three-dimensional Ni-metal-organic framework (MOF) nanostructured material with a superior architecture using benzimidazole and nickel nitrate as precursors at room temperature which is being applied in glucose electrochemical sensors. The reaction mechanism of M-6 during glucose detection is thoroughly studied using various characterization techniques, such as in situ Raman spectroscopy, in situ ultraviolet-visible spectrophotometry, synchrotron radiography, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The research findings demonstrate that the M-6 material exhibits high sensitivity for glucose detection, with a sensitivity of 2199.88 mA M-1 cm-2. This study provides an important reference for designing more efficient electrochemical reaction systems and optimizing material performance. Furthermore, the superstructural design offers new ideas and possibilities for the development and application of similar materials.

SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma.

Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. Patients with NF1 often have complications with tumors, such as neurofibroma. In order to investigate the pathogenesis of human neurofibroma, a systematic comparison of protein expression levels between Schwann cell-like sNF96.2 cells, which originated from malignant peripheral nerve sheath tumors (MPNST), and normal Schwann cells was performed using 4-D label-free proteomic analysis. In addition, the expression levels and localization of dysregulated proteins were confirmed using a Gene Expression Omnibus (GEO) transcriptomic dataset, Western blot analysis, and immunofluorescence labeling. The effects of SRY-box transcription factor 9 (SOX9) in the neurofibroma and surrounding microenvironment were evaluated in vivo using a tumor transplantation model. The present study observed that SOX9 and procollagen C-endopeptidase enhancer (PCOLCE) were significantly altered. NF1 mutation promoted the nuclear translocation and transcriptional activity of SOX9 in neurofibromas. SOX9 increased collagen VI secretions by enhancing the activation of PCOLCE in neurofibroma cells. These findings might provide new perspectives on the pathophysiological significance of SOX9 in neurofibromas and elucidate a novel molecular mechanism underlying neurofibromas.

Bisphenol A: Unveiling Its Role in Glioma Progression and Tumor Growth.

Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial-mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology.

Exploring the therapeutic mechanisms and prognostic targets of Biochanin A in glioblastoma via integrated computational analysis and in vitro experiments.

Glioblastoma (GBM) is the most aggressive brain tumor and is characterized by a poor prognosis and high recurrence and mortality rates. Biochanin A (BCA) exhibits promising clinical anti-tumor effects. In this study, we aimed to explore the pharmacological mechanisms by which BCA acts against GBM. Network pharmacology was employed to identify overlapping target genes between BCA and GBM. Differentially expressed genes from the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database were visualized using VolcaNose. Interactions among these overlapping genes were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Protein-protein interaction networks were constructed using Cytoscape 3.8.1. The Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Survival analyses for these genes were performed using the GEPIA2 database. The Chinese Glioma Genome Atlas database was used to study the correlations between key prognostic genes. Molecular docking was confirmed using the DockThor database and visualized with PyMol software. Cell viability was assessed via the CCK-8 assay, apoptosis and the cell cycle stages were examined using flow cytometry, and protein expression was detected using western blotting. In all, 63 genes were initially identified as potential targets for BCA in treating GBM. Enrichment analysis suggested that the pharmacological mechanisms of BCA primarily involved cell cycle inhibition, induction of cell apoptosis, and immune regulation. Based on these findings, AKT1, EGFR, CASP3, and MMP9 were preliminarily predicted as key prognostic target genes for BCA in GBM treatment. Furthermore, molecular docking analysis suggested stable binding of BCA to the target protein. In vitro experiments revealed the efficacy of BCA in inhibiting GBM, with an IC50 value of 98.37 ± 2.21 µM. BCA inhibited cell proliferation, induced cell apoptosis, and arrested the cell cycle of GBM cells. Furthermore, the anti-tumor effects of BCA on U251 cells were linked to the regulation of the target protein. We utilized integrated bioinformatics analyses to predict targets and confirmed through experiments that BCA possesses remarkable anti-tumor activities. We present a novel approach for multi-target treatment of GBM using BCA.

Record high external quantum efficiency of 20% achieved in fully solution-processed quantum dot light-emitting diodes based on hole-conductive metal oxides.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has been widely used as a hole injection material in quantum dot (QD) light-emitting diodes (QLEDs). However, it degrades the organic materials and electrodes in QLEDs due to its strong hydroscopicity and acidity. Although hole-conductive metal oxides have a great potential to solve this disadvantage, it is still a challenge to achieve efficient and stable QLEDs by using these solution-processed metal oxides. Herein, the state-of-the-art QLEDs fabricated by using hole-conductive MoOx QDs are achieved. The α-phase MoOx QDs exhibit a monodispersed size distribution with clear and regular crystal lattices, corresponding to high-quality nanocrystals. Meanwhile, the MoOx film owns an excellent transmittance, suitable valence band, good morphology and impressive hole-conductivity, demonstrating that the MoOx film could be used as a hole injection layer in QLEDs. Moreover, the rigid and flexible red QLEDs made by MoOx exhibit peak external quantum efficiencies of over 20%, representing a new record for the hole-conductive metal oxide based QLEDs. Most importantly, the MoOx QDs afford their QLEDs with a longer T95 lifetime than these devices made by PEDOT:PSS. As a result, we believe that the MoOx QDs could be used as efficient and stable hole injection materials used in QLEDs.

Composites of (NH2)-MIL-53(Al) and CBB as bifunctional electrocatalysts for overall electrochemical water splitting in all pH solutions.

Electrochemical water splitting is one of the most active areas of energy research, yet the benchmark electrocatalysts used for this area are based on expensive noble metals and transition metals, thus mainly reactions in alkaline solution. MOFs and halide perovskite are novel electrochemical catalysts but unstable in water basically. Here we report a study on composites of (NH2)-MIL-53(Al) MOFs and CBB halide perovskite (Cs3Bi2Br9), which exhibit obvious activity for overall electrochemical water splitting for long-term stability with little deactivation after 10 h in all pH solutions.

Enhancing Zn2+ Storage Performance by Constructing the Interfaces Between VO2 and Co-N-C Layers.

Vanadium oxides have aroused attention as cathode materials in aqueous zinc-ion batteries (AZIBs) due to their low cost and high safety. However, low ion diffusion and vanadium dissolution often lead to capacity decay and deteriorating stability during cycling. Herein, vanadium dioxides (VO2) nanobelts are coated with a single-atom cobalt dispersed N-doped carbon (Co-N-C) layer via a facile calcination strategy to form Co-N-C layer coated VO2 nanobelts (VO2@Co-N-C NBs) for cathodes in AZIBs. Various in-/ex situ characterizations demonstrate the interfaces between VO2 layers and Co-N-C layers can protect the VO2 NBs from collapsing, increase ion diffusion, and enhance the Zn2+ storage performance. Additional density functional theory (DFT) simulations demonstrate that Co─O─V bonds between VO2 and Co-N-C layers can enhance interfacial Zn2+ storage. Moreover, the VO2@Co-N-C NBs provided an ultrahigh capacity (418.7 mAh g-1 at 1 A g-1), outstanding long-term stability (over 8000 cycles at 20 A g-1), and superior rate performance.

Innate immune response restarts adaptive immune response in tumors.

The imbalance of immune response plays a crucial role in the development of diseases, including glioblastoma. It is essential to comprehend how the innate immune system detects tumors and pathogens. Endosomal and cytoplasmic sensors can identify diverse cancer cell antigens, triggering the production of type I interferon and pro-inflammatory cytokines. This, in turn, stimulates interferon stimulating genes, enhancing the presentation of cancer antigens, and promoting T cell recognition and destruction of cancer cells. While RNA and DNA sensing of tumors and pathogens typically involve different receptors and adapters, their interaction can activate adaptive immune response mechanisms. This review highlights the similarity in RNA and DNA sensing mechanisms in the innate immunity of both tumors and pathogens. The aim is to enhance the anti-tumor innate immune response, identify regions of the tumor that are not responsive to treatment, and explore new targets to improve the response to conventional tumor therapy and immunotherapy.

Exploring the Role of the Plant Actin Cytoskeleton: From Signaling to Cellular Functions.

The plant actin cytoskeleton is characterized by the basic properties of dynamic array, which plays a central role in numerous conserved processes that are required for diverse cellular functions. Here, we focus on how actins and actin-related proteins (ARPs), which represent two classical branches of a greatly diverse superfamily of ATPases, are involved in fundamental functions underlying signal regulation of plant growth and development. Moreover, we review the structure, assembly dynamics, and biological functions of filamentous actin (F-actin) from a molecular perspective. The various accessory proteins known as actin-binding proteins (ABPs) partner with F-actin to finely tune actin dynamics, often in response to various cell signaling pathways. Our understanding of the significance of the actin cytoskeleton in vital cellular activities has been furthered by comparison of conserved functions of actin filaments across different species combined with advanced microscopic techniques and experimental methods. We discuss the current model of the plant actin cytoskeleton, followed by examples of the signaling mechanisms under the supervision of F-actin related to cell morphogenesis, polar growth, and cytoplasmic streaming. Determination of the theoretical basis of how the cytoskeleton works is important in itself and is beneficial to future applications aimed at improving crop biomass and production efficiency.

Efficacy of TTFields in high-grade gliomas: a protocol for systematic review and meta-analysis.

INTRODUCTION: Despite their recent FDA(Food and Drug Administration) approval, tumour treatment fields (TTFields) have not seen acceptance as part of standard of care (SOC) for the treatment of high-grade gliomas (HGGs). Few studies have reported the clinical effect of simultaneous or sequential use of TTFields with the current SOC. However, whether TTFields are beneficial over the standard treatment remains to be established with a meta-analysis. Therefore, we here performed a systematic review and meta-analysis to understand the benefit of TTFields for patients with HGGs. METHODS AND ANALYSIS: We registered this systematic review with the PROSPERO network (registration number: CRD42023398972) and aimed to follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in the study. All articles related to TTFields in glioma will be systematically searched for in the following databases since their inception until November 2023: the China National Knowledge Infrastructure, Embase, Cochrane Library, Wanfang Database, China Science Journal Database, China Biomedical Documentation Database, VIP database, Web of Science and PubMed. Article screening and data extraction will be done independently by the authors and cross-checked by two of the authors on completion. The Cochrane risk of bias assessment tool will be used for quality assessment of the included studies. Review Manager V.5.3 (Cochrane Collaboration) will be used to perform the meta-analysis. ETHICS AND DISSEMINATION: Ethical approval is not required because the data used will be obtained from published studies, and there will be no concerns about privacy. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023398972.

SUPPRESSOR OF MAX2 LIKE 6, 7, and 8 Interact with DDB1 BINDING WD REPEAT DOMAIN HYPERSENSITIVE TO ABA DEFICIENT 1 to Regulate the Drought Tolerance and Target SUCROSE NONFERMENTING 1 RELATED PROTEIN KINASE 2.3 to Abscisic Acid Response in Arabidopsis.

SUPPRESSOR OF MAX2-LIKE 6, 7, and 8 (SMXL6,7,8) function as repressors and transcription factors of the strigolactone (SL) signaling pathway, playing an important role in the development and stress tolerance in Arabidopsis thaliana. However, the molecular mechanism by which SMXL6,7,8 negatively regulate drought tolerance and ABA response remains largely unexplored. In the present study, the interacting protein and downstream target genes of SMXL6,7,8 were investigated. Our results showed that the substrate receptor for the CUL4-based E3 ligase DDB1-BINDING WD-REPEAT DOMAIN (DWD) HYPERSENSITIVE TO ABA DEFICIENT 1 (ABA1) (DWA1) physically interacted with SMXL6,7,8. The degradation of SMXL6,7,8 proteins were partially dependent on DWA1. Disruption of SMXL6,7,8 resulted in increased drought tolerance and could restore the drought-sensitive phenotype of the dwa1 mutant. In addition, SMXL6,7,8 could directly bind to the promoter of SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASE 2.3 (SnRK2.3) to repress its transcription. The mutations in SnRK2.2/2.3 significantly suppressed the hypersensitivity of smxl6/7/8 to ABA-mediated inhibition of seed germination. Conclusively, SMXL6,7,8 interact with DWA1 to negatively regulate drought tolerance and target ABA-response genes. These data provide insights into drought tolerance and ABA response in Arabidopsis via the SMXL6,7,8-mediated SL signaling pathway.

Regulating Intramolecular Electron Transfer of Nickel-Based Coordinations through Ligand Engineering for Aqueous Batteries.

The integration of electronic effects into complexes for the construction of novel materials has not yet attracted significant attention in the field of energy storage. In the current study, eight one-dimensional (1D) nickel-based salicylic acid  complexes (Ni-XSAs, X = pH, pMe, pMeO, mMe, pBr, pCl, pF, and pCF3 ), are prepared by ligand engineering. The coordination environments in the Ni-XSAs are explored using X-ray absorption fine structure spectroscopy. The charge transfer of the complexes is modulated according to the difference in the electron-donating ability of the substituents, in combination with frontier orbital theory. Furthermore, density functional theory is used to investigate the effect of the substituent position on the electronic properties of the complexes. Ni-mMeSA exhibits better electrical conductivity than Ni-pMeSA. The electrochemical performance of Ni-mMeSA as an aqueous battery cathode is remarkably improved with a maximum energy density of 0.30 mWh cm-2 (125 Wh kg-1 ) and a peak power density of 33.72 mW cm-2 (14.03 kW kg-1 ). This study provides ideas for the application of new coordination chemistry in the field of energy materials science.

AtHSPR functions in gibberellin-mediated primary root growth by interacting with KNAT5 and OFP1 in Arabidopsis.

KEY MESSAGE: AtHSPR forms a complex with KNAT5 and OFP1 to regulate primary root growth through GA-mediated root meristem activity. KNAT5-OFP1 functions as a negative regulator of AtHSPR in response to GA. Plant root growth is modulated by gibberellic acid (GA) signaling and depends on root meristem maintenance. ARABIDOPSIS THALIANA HEAT SHOCK PROTEIN-RELATED (AtHSPR) is a vital regulator of flowering time and salt stress tolerance. However, little is known about the role of AtHSPR in the regulation of primary root growth. Here, we report that athspr mutant exhibits a shorter primary root compared to wild type and that AtHSPR interacts with KNOTTED1-LIKE HOMEOBOX GENE 5 (KNAT5) and OVATE FAMILY PROTEIN 1 (OFP1). Genetic analysis showed that overexpression of KNAT5 or OFP1 caused a defect in primary root growth similar to that of the athspr mutant, but knockout of KNAT5 or OFP1 rescued the short root phenotype in the athspr mutant by altering root meristem activity. Further investigation revealed that KNAT5 interacts with OFP1 and that AtHSPR weakens the inhibition of GIBBERELLIN 20-OXIDASE 1 (GA20ox1) expression by the KNAT5-OFP1 complex. Moreover, root meristem cell proliferation and root elongation in 35S::KNAT5athspr and 35S::OFP1athspr seedlings were hypersensitive to GA3 treatment compared to the athspr mutant. Together, our results demonstrate that the AtHSPR-KNAT5-OFP1 module regulates root growth and development by impacting the expression of GA biosynthetic gene GA20ox1, which could be a way for plants to achieve plasticity in response to the environment.

Quantitation of macropinocytosis in glioblastoma based on high-content analysis.

BACKGROUND: Macropinocytosis is a pathway utilized for the internalization of extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging in the past because the combination of manual acquisition and visual evaluation of images is laborious, making this type of assessment difficult for high-throughput applications. Therefore, there is a need to develop sensitive and specific macropinocytosis evaluation methods. METHODS: This paper proposed a quantitative and time-saving method for macropinocytosis detection based on high-content analysis (HCA). Additionally, cell proliferation was evaluated using CCK8 test. RESULTS: The term "macropinosome index" was defined to estimate macropinocytosis and allow comparisons between different cell lines and treatments. Furthermore, we demonstrated that macropinocytosis can promote glioblastoma (GBM) cell survival under L-glutamine (L-Gln)-deficient conditions that resemble the tumour microenvironment. CONCLUSIONS: HCA represents a novel, nonsubjective and high-throughput assay for macropinocytosis assessment. In addition, L-Gln deprivation increased the macropinosome index in GBM cells, suggesting that this process may be used to design GBM therapies. AVAILABILITY OF DATA AND MATERIALS: The datasets supporting the conclusions of this article are included within the article and its supplementary materials.

EEF1E1 promotes glioma proliferation by regulating cell cycle through PTEN/AKT signaling pathway.

The cell cycle, a pivotal regulator of cell proliferation, can be significantly influenced by the phosphatase and tensin homolog (PTEN)/AKT signaling pathway's modulation of cyclin-related proteins. In our study, we discovered the crucial role of EEF1E1 in this process, as it appears to downregulate PTEN expression. Furthermore, our findings affirmed that EEF1E1 modulates downstream cell cycle-related proteins by suppressing the PTEN/AKT pathway. Cell cycle assay results revealed that EEF1E1 downregulation stunted the advancement of glioma cells in both the G1 and S phases. A suite of assays-Cell Counting Kit-8, colony formation, and ethyl-2'-deoxyuridine-substantiated that the EEF1E1 downregulation markedly curtailed glioma proliferation. We further validated this phenomenon through animal studies and coculture experiments on brain slices. Our comprehensive investigation indicates that EEF1E1 knockdown can effectively inhibit the glioma cell proliferation by regulating the cell cycle via the PTEN/AKT signaling pathway. Consequently, EEF1E1 emerges as a potential therapeutic target for glioma treatment, signifying critical clinical implications.