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Background A better understanding of the molecular mechanism involving lncRNA-miRNA-mRNA network underlying glioma genesis is beneficial to the treatment of glioma. This study was designed to investigate the role of lncRNA NEAT1, miR-132 and SOX2 interaction in glioma. Methods Microarray analysis was conducted to identify the differentially expressed lncRNAs in glioma tissues. The expression levels of NEAT1, miR-132 and SOX2 were determined by qRT-PCR and western blot. Proliferation of glioma cells was detected by MTT assay, while migration and invasion were determined by transwell assay. The target relationships were predicted by miRcode algorithm, and confirmed by dual luciferase reporter gene assay. Results NEAT1 was up-regulated in glioma. Knockdown of NEAT1 inhibited glioma cells’ viability, migration and invasion. MiR-132 was down-regulated while SOX2 was up-regulated in glioma cells. NEAT1 negatively regulated the expression of miR-132 in glioma while miR-132 targeted SOX2 to down-regulate its expression. Conclusion NEAT1 promoted glioma development by promoting SOX2 expression through suppressing miR-132.

Background Glioblastoma is one of the malignant tumors of the central nervous system with high lethality, high disability and low survival rate. Effective induction of its death is one of the existing challenges. In recent studies, heat shock protein 27 (HSP27) has been shown to be associated with ferroptosis; therefore, targeting HSP27 may be a potential therapeutic approach for GBM. Methods Immunohistochemistry and western blot analysis were used to detect the expression of HSP27 in GBM tissues. CCK8, plate clone formation assay, EdU proliferation assay for cell proliferation ability, PI, LDH release assay for cell viability. Reactive oxygen, iron levels, and mitochondrial potential for HSP27 silencing were assayed for ferrotosis in vitro. Western blotting and IP were used to verify the relationship between HSP27 and ACSL4. The effect of knockdown of HSP27 on tumor growth capacity was assessed in an intracranial xenograft model. Results HSP27 was significantly highly expressed in GBM. In vitro experiments, knockdown of HSP27 significantly induced ferroptosis in GBM cells. IP and western blot demonstrated a sumo-ization link between HSP27 and ACSL4. In vivo experiments, HSP27 deficiency retarded tumor growth rate by promoting ferroptosis. Conclusions HSP27 deficiency promotes GBM ferroptosis. Targeting HSP27 may serve as a new direction for GBM treatment.

Waste heat air-source heat pump water heater (WH-ASHPWH) systems have been widely used to provide water heating in buildings due to their advantages of high efficiency and low environmental impact. It is important to determine reasonable operating conditions for WH-ASHPWH systems to improve their heating efficiency, especially for systems using industrial waste heat. In this study, a semiempirical parametric model of a WH-ASHPWH system was established to simulate heating performance under different working conditions and determine the optimum operating range of the system. A new discrete model for a tube-in-tube condenser was also generated. Taking the equipment of a pharmaceutical factory as an example, the heat exchanger model was first calibrated; then, the global model was used to study the effects of different air-side and condenser-side waste heat conditions on the heating performance of the system. According to the simulation results, the coefficient of performance (COP) reached a maximum value of 4.5 under the optimum working conditions. The deviation between the COP simulation data and experimental values was less than 8.28%, and the simulation time was less than 8 min. These metrics indicate that the model is reasonable and efficient.

Background Glioblastoma (GBM) is an immunosuppressive, universally lethal cancer driven by glioblastoma stem cells (GSCs). The interplay between GSCs and immunosuppressive microglia plays crucial roles in promoting the malignant growth of GBM; however, the molecular mechanisms underlying this crosstalk are unclear. This study aimed to investigate the role of POSTN in maintaining GSCs and the immunosuppressive phenotype of microglia. Methods The expression of POSTN in GBM was identified via immunohistochemistry, quantitative real-time PCR, and immunoblotting. Tumorsphere formation assay, Cell Counting Kit-8 assay and immunofluorescence were used to determine the key role of POSTN in GSC maintenance. ChIP-seq and ChIP-PCR were conducted to confirm the binding sequences of β-catenin in the promoter region of FOSL1. Transwell migration assays, developmental and functional analyses of CD4 + T cells, CFSE staining and analysis, enzyme-linked immunosorbent assays and apoptosis detection tests were used to determine the key role of POSTN in maintaining the immunosuppressive phenotype of microglia and thereby promoting the immunosuppressive tumor microenvironment. Furthermore, the effects of POSTN on GSC maintenance and the immunosuppressive phenotype of microglia were investigated in a patient-derived xenograft model and orthotopic glioma mouse model, respectively. Results Our findings revealed that POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway. In addition to its intrinsic effects on GSCs, POSTN can recruit microglia and upregulate CD70 expression in microglia through the αVβ3/PI3K/AKT/NFκB pathway, which in turn promotes Treg development and functionality and supports the formation of an immunosuppressive tumor microenvironment. In both in vitro models and orthotopic mouse models of GBM, POSTN depletion disrupted GSC maintenance, decreased the recruitment of immunosuppressive microglia and suppressed GBM growth. Conclusion Our findings reveal that POSTN plays critical roles in maintaining GSCs and the immunosuppressive phenotype of microglia and provide a new therapeutic target for treating GBM.

In high-temperature, high-pressure, and corrosive industrial environments, frictional wear of metallic components stands as a critical determinant governing the long-term operational reliability of mechanical systems. To address the challenge of traditional lubricating coating failure under a broad temperature range (−50 to 500 °C), this study developed a phosphate-based composite lubricating coating. Through air-spraying technology and orthogonal experimental optimization, the optimal formulation was determined as follows: binder/filler ratio = 6:4, 5% graphite, 15% MoS2, and 10% aluminum powder. Experimental results demonstrated that at 500 °C, the coating forms an Al–O–P cross-linked network structure, with MoS2 oxidation generating MoO3 and aluminum powder transforming into Al2O3, significantly enhancing density and oxidation resistance. Friction tests revealed that the composite coating achieves a friction coefficient as low as 0.12 at room temperature with a friction time of 260 min. At 500 °C, the friction coefficient stabilizes at 0.24, providing 40 min of effective protection. This technology not only resolves the high-temperature instability of traditional coatings but also ensures an environmentally friendly preparation process with no harmful emissions, offering a technical solution for the protection of high-temperature equipment such as thermal power plant boiler tubes and petrochemical reactors.

A phase field model was established to simulate the grain growth of Al2O3-based composite ceramic tool materials containing second phase nanoparticles and pores. The free energy parameters of the model are directly related to the surface and grain boundary energies of Al2O3 such that the grain growth process can be quantitatively analysed. The model was used to investigate the effects of the volume fraction and size of second phase particles on grain growth in Al2O3 with a certain initial pore volume fraction. Findings show that pores and second phase particles jointly hinder grain growth. When the radii of second phase nanoparticles are the same, as the number of particles increase, most of the grain boundaries occur as straight lines in the microstructure, and grain size decreases. It is beneficial to obtain fine and uniform microstructure. However, when the particles content reaches a certain level, the second phase particles tend to agglomerate at the grain boundary of matrix grains, which will result in a decrease in the properties of nanocomposite ceramic tool materials. The study also found that, at a constant volume fraction of particles, with the decrease of particle radius, the grain size decreases. When the second phase particle size is reduced to 50 nm, relatively more intragranular microstructure was observed, which is considered to be the main reason for increasing the toughness of nano composite ceramic tool materials. Through analyzing the simulation results, the optimal combination of the content and size of the second phase particles can provide theoretical guidance for Al2O3 nano composite ceramic tool materials design and preparation.

Glioma is the most common primary malignant tumor of the central nervous system, which results in both a poor prognosis and outcome because of the aggressive progression of disease, growth and resistance to surgery, chemotherapy, and radiotherapy. MiR-140-5p is a small, non-coding single-stranded RNA molecule, which was previously studied in the settings of human tongue cancer, hepatocellular carcinoma, and colorectal cancer. However, detailed data that formally demonstrate the contribution of miR-140-5p to glioma development are missing. Similarly, relatively little is known about the relationship of miR-140-5p, vascular endothelial growth factor A, and matrix metalloproteinase-2 in glioma progression. In this study, we found that miR-140-5p expression was significantly decreased in glioma tissues and in the glioma cell-lines U87 and U251 as compared with non-cancerous brain tissues by quantitative real-time polymerase chain reaction. In addition, miR-140-5p inhibited glioma cell proliferation and invasion and promoted glioma cell apoptosis both in vivo and in vitro. Interestingly, while the expression levels of miR-140-5p were higher in glioma cells, the messenger RNA or protein expression levels of vascular endothelial growth factor A and matrix metalloproteinase-2 were lower in glioma cells as determined by quantitative real-time polymerase chain reaction, western blot assay, and immunohistochemistry. By contrast, downregulation in the expression levels of miR-140-5p augmented the messenger RNA and protein expression levels of both vascular endothelial growth factor A and matrix metalloproteinase-2. These findings suggested that miR-140-5p inhibited glioma proliferation and invasion by regulating the vascular endothelial growth factor A/matrix metalloproteinase-2 signaling pathway both in vitro and in vivo.

Background Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a short median overall survival. Effective induction of GBM cell death is difficult because the GBM cell population is genetically unstable, resistant to chemotherapy and highly angiogenic. In recent studies, ubiquitin-specific protease 7 (USP7) is shown to scavenge ubiquitin from oncogenic protein substrates, so effective inhibition of USP7 may be a potential key treatment for GBM. Methods Immunohistochemistry and western blotting were used to detect the expression of USP7 in GBM tissues. In vitro apoptosis assay of USP7 inhibition was performed by western blotting, immunofluorescence, and flow cytometry. Anti-apoptotic substrates of USP7 were defined by Co-IP and TMT proteomics. Western blotting and IP were used to verify the relationship between USP7 and its substrate. In an in vivo experiment using an intracranial xenograft model in nude mice was constructed to assess the therapeutic effect of target USP7. Results Immunohistochemistry and western blotting confirmed that USP7 was significantly upregulated in glioblastoma samples. In in vitro experiments, inhibition of USP7 in GBM induced significant apoptosis. Co-IP and TMT proteomics identified a key anti-apoptotic substrate of USP7, ADP-ribosylation factor 4 (ARF4). Western blotting and IP confirmed that USP7 interacted directly with ARF4 and catalyzed the removal of the K48-linked polyubiquitinated chain that binded to ARF4. In addition, in vivo experiments revealed that USP7 inhibition significantly suppressed tumor growth and promoted the expression of apoptotic genes. Conclusions Targeted inhibition of USP7 enhances the ubiquitination of ARF4 and ultimately mediates the apoptosis of GBM cells. In a clinical sense, P5091 as a novel specific inhibitor of USP7 may be an effective approach for the treatment of GBM.

Inhibitors of programmed cell death ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) are commonly used in the clinic, but they are beneficial for only a minority of glioblastoma multiforme (GBM) patients. GBM has significant immunosuppressive properties, and there are many immunosuppressive cells and dysfunctional effector T cells in the tumor microenvironment (TME), which is one of the important reasons for the failure of clinical treatment of GBM. Here, we have identified P21 activated kinase 4 (PAK4) as a pivotal immune suppressor in the TME. PAK4 is a threonine protein kinase, and PAK4 knockdown attenuates vascular abnormalities and promotes T-cell infiltration. In this study, our results showed that the expression of PAK4 was significantly downregulated after VEGFR2 knockdown. Next, we constructed a coculture system of CD8+ T cells and GBM cells. Our findings showed that combined anti-PD-L1 and anti-VEGFR2 therapy can regulate the TME and inhibit GBM cells' immune escape; overexpression of PAK4 can reverse this effect. Finally, we tested the combination therapy in mouse intracranial graft tumor models and found that combination therapy can prolong mouse survival. These findings suggest that anti-VEGFR2 therapy can downregulate PAK4, reprogram the TME by increasing cytotoxic CD8+ T cells infiltration and activation, and enhance the therapeutic effect of anti-PD-L1 therapy on GBM cells.

Background: Glioblastoma (GBM) is the most aggressive primary malignant brain tumor and is associated with limited treatment options and poor prognosis. Conventional GBM cell lines undergo genetic drift and progressive divergence from patient-relevant molecular features over long-term culture, limiting their translational relevance. This study aimed to establish and characterize a novel isocitrate dehydrogenase 1 (IDH1)-wildtype GBM cell line, SHG142, along with its associated glioma stem-like cells (GSCs) and organoid models, to advance GBM biology and therapeutic research. Methods: Primary tumor tissue from a 70-year-old female patient was cultured under standard conditions to generate the SHG142 cell line, which was authenticated by short tandem repeat (STR) profiling. Phenotypic and genetic features were evaluated using immunofluorescence (IF), karyotyping, and whole-exome sequencing (WES) including a concordance analysis between an early bulk primary culture (P2) and late-passage SHG142 (P50). GSCs were isolated via serum-free culture and magnetic-activated cell sorting (MACS). Tumorigenicity and invasiveness were assessed through intracranial xenografts in nude mice (n = 6/group) and coculture with brain organoids derived from human embryonic stem cells (n = 4 independent organoids). Results: SHG142 cells exhibited stable morphology and proliferation over more than 50 passages, retained key GBM markers (e.g., Nestin, Glial Fibrillary Acidic Protein (GFAP), O6-methylguanine-DNA methyltransferase (MGMT), Ki-67, P53, S-100, CD34), and exhibited chromosomal instability (+7, –10, and t(9;13)). WES revealed mutations in the TERT promoter, TP53 and NF1 and supported lineage continuity from P2 to P50 through shared SNVs and conserved driver events. CD133+ SHG142 GSCs demonstrated stem-like properties and invasive behavior in vivo and in organoid coculture. Compared with xenografts derived from SHG142 cells, GSC-derived xenografts were associated with increased malignancy and shorter survival (median survival 25 vs. 31.5 days, p = 0.025). The organoid coculture model confirmed deep infiltration by proliferative, stem-like tumor cells. Conclusions: SHG142 and its GSCs represent a phenotypically stable, genetically defined GBM model with evidence of lineage continuity and retention of key driver events during in vitro propagation. Their tumorigenic and invasive properties make them valuable tools for mechanistic studies and preclinical therapeutic screening, supported by initial two-dimensional and three-dimensional drug response readouts that enable first-pass evaluation of therapeutic response.