Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases.

Fundus neovascularization diseases are a series of blinding eye diseases that seriously impair vision worldwide. Currently, the means of treating these diseases in clinical practice are continuously evolving and have rapidly revolutionized treatment opinions. However, key issues such as inadequate treatment effectiveness, high rates of recurrence, and poor patient compliance still need to be urgently addressed. Multifunctional nanomedicine can specifically respond to both endogenous and exogenous microenvironments, effectively deliver drugs to specific targets and participate in activities such as biological imaging and the detection of small molecules. Nano-in-micro (NIM) delivery systems such as metal, metal oxide and up-conversion nanoparticles (NPs), quantum dots, and carbon materials, have shown certain advantages in overcoming the presence of physiological barriers within the eyeball and are widely used in the treatment of ophthalmic diseases. Few studies, however, have evaluated the efficacy of NIM delivery systems in treating fundus neovascular diseases (FNDs). The present study describes the main clinical treatment strategies and the adverse events associated with the treatment of FNDs with NIM delivery systems and summarizes the anatomical obstacles that must be overcome. In this review, we wish to highlight the principle of intraocular microenvironment normalization, aiming to provide a more rational approach for designing new NIM delivery systems to treat specific FNDs.

Effects of arbuscular mycorrhizal fungi on the reduction of arsenic accumulation in plants: a meta-analysis.

Arsenic (As) accumulation in plants is a global concern. Although the application of arbuscular mycorrhizal fungi (AMF) has been suggested as a potential solution to decrease As concentration in plants, there is currently a gap in a comprehensive, quantitative assessment of the abiotic and biotic factors influencing As accumulation. A meta-analysis was performed to quantitatively investigate the findings of 76 publications on the impacts of AMF, plant properties, and soil on As accumulation in plants. Results showed a significant dose-dependent As reduction with higher mycorrhizal infection rates, leading to a 19.3% decrease in As concentration. AMF reduced As(V) by 19.4% but increased dimethylarsenic acid (DMA) by 50.8%. AMF significantly decreased grain As concentration by 34.1%. AMF also improved plant P concentration and dry biomass by 33.0% and 62.0%, respectively. The most significant reducing effects of As on AMF properties were seen in single inoculation and experiments with intermediate durations. Additionally, the benefits of AMF were significantly enhanced when soil texture, soil organic carbon (SOC), pH level, Olsen-P, and DTPA-As were sandy soil, 0.8%-1.5%, ≥7.5, ≥9.1 mg/kg, and 30-60 mg/kg, respectively. AMF increased easily extractable glomalin-related soil protein (EE-GRSP) and total glomalin-related soil protein (T-GRSP) by 23.0% and 28.0%, respectively. Overall, the investigated factors had significant implications in developing AMF-based methods for alleviating the negative effects of As stress on plants.

Selenium Removal from Wastewater by Microbial Transformation and Volatilization.

Selenium (Se) is a naturally occurring trace element that is nutritionally essential for humans and animals, but becomes toxic at high concentrations. This laboratory study explored the role of microbes in Se removal from contaminated wastewater via biological transformation and volatilization processes. Microbes could immobilize water-soluble selenate (SeO42-) and selenite (SeO32-) to water-insoluble elemental Se (Se0) and transform Se into volatile Se compounds found in the atmosphere. Results of this laboratory study showed that Bacillus cereus, a bacterial strain isolated from wheat straw and biosolid-WTR-sand substrates showed a significant biotransformation ability of reducing selenate and selenite to elemental Se and forming volatile Se organic compounds in wastewater. Overall, microbial Se chemical reduction, methylation, and volatilization are important processes in bioremediation of Se-contaminated wastewater.

Self-Charging Aqueous Zn//COF Battery with UltraHigh Self-Charging Efficiency and Rate.

Self-charging zinc batteries that combine energy harvesting technology with batteries are candidates for reliable self-charging power systems. However, the lack of rational materials design results in unsatisfactory self-charging performance. Here, a covalent organic framework containing pyrene-4,5,9,10-tetraone groups (COF-PTO) is reported as a cathode material for aqueous self-charging zinc batteries. The ordered channel structure of the COF-PTO provides excellent capacity retention of 98% after 18 000 cycles at 10 A g-1 and ultra-fast ion transfer. To visually assess the self-charging performance, two parameters, namely self-charging efficiency (self-charging discharge capacity/galvanostatic discharge capacity, η) and average self-charging rate (total discharge capacity after cyclic self-charging/total cyclic self-charging time, ν), are proposed for performance evaluation. COF-PTO achieves an impressive η of 96.9% and an ν of 30 mAh g-1 self-charge capacity per hour in 100 self-charging cycles, surpassing the previous reports. Mechanism studies reveal the co-insertion of Zn2+ and H+ double ions in COF-PTO of self-charging zinc batteries. In addition, the C═N and C═O (on the benzene) in COF-PTO are ortho structures to each other, which can easily form metal heterocycles with Zn ions, thereby driving the forward progress of the self-charging reaction and enhancing the self-charging performance.

Minimalist Design for Solar Energy Conversion: Revamping the π-Grid of an Organic Framework into Open-Shell Superabsorbers.

We apply a versatile reaction to a versatile solid: the former involves the electron-deficient alkene tetracyanoethylene (TCNE) as the guest reactant; the latter consists of stacked 2D honeycomb covalent networks based on the electron-rich ß-ketoenamine hinges that also activate the conjugated, connecting alkyne units. The TCNE/alkyne reaction is a [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) that forms strong push-pull units directly into the backbone of the framework-i.e., using only the minimalist "bare-bones" scaffold, without the need for additional side groups of alkynes or other functions. The ability of the stacked alkyne units (i.e., as part of the honeycomb mass) to undergo such extensive rearrangement highlights the structural flexibility of these covalent organic framework (COF) hosts. The COF solids remain porous, crystalline, and air-/water-stable after the CA-RE modification, while the resulting push-pull units feature distinct open-shell/free-radical character, are strongly light-absorbing, and shift the absorption ends from 590 nm to around 1900 nm (band gaps from 2.17-2.23 to 0.87-0.95 eV), so as to better capture sunlight (especially the infrared region which takes up 52% of the solar energy). As a result, the modified COF materials achieve the highest photothermal conversion performances, holding promise in thermoelectric power generation and solar steam generation (e.g., with solar-vapor conversion efficiencies >96%).

Palmitoyl transferases act as novel drug targets for pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is one of the most leading causes of cancer-related death across the world with the limited efficiency and response rate of immunotherapy. Protein S-palmitoylation, a powerful post-translational lipid modification, is well-known to regulate the stability and cellular distribution of cancer-related proteins, which is mediated by a family of 23 palmitoyl transferases, namely zinc finger Asp-His-His-Cys-type (ZDHHC). However, whether palmitoyl transferases can determine tumor progression and the efficacy of immunotherapy in PAAD remains unknown. METHODS: Bioinformatics methods were used to identify differential ZDHHCs expression in PAAD. A systematic pan-cancer analysis was conducted to assess the immunological role of ZDHHC3 using RNA sequencing data from The Cancer Genome Atlas database. In vivo Panc 02 subcutaneous tumor model validated the anti-tumor effect of knockdown of ZDHHC3 or intraperitoneal injection of 2-bromopalmitate (2-BP), a typical broad-spectrum palmitoyl transferases inhibitor. Furthermore, we explored therapeutic strategies with combinations of 2-BP with PD-1/PD-L1-targeted immunotherapy in C57BL/6 mice bearing syngeneic Panc 02 pancreatic tumors. RESULTS: ZDHHC enzymes were associated with distinct prognostic values of pancreatic cancer. We identified that ZDHHC3 expression promotes an immunosuppressive tumor microenvironment in PAAD. 2-BP suppressed pancreatic-tumor cell viability and tumor sphere-forming activities, as well as increased cell apoptosis in vitro, without affecting normal human pancreatic ductal epithelial cells. Furthermore, genetic inactivation of ZDHHC3 or intraperitoneal injection of 2-BP impeded tumor progression in Panc 02 pancreatic tumors with enhanced anti-tumor immunity. 2-BP treatment significantly enhanced the therapeutic efficacy of PD-1/PD-L1 inhibitors in Panc 02 pancreatic tumors. CONCLUSION: This study revealed some ZDHHC enzyme genes for predicting the prognosis of pancreatic cancer, and demonstrated that ZDHHC3 plays a critical oncogenic role in pancreatic cancer progression, highlighting its potential as an immunotherapeutic target of pancreatic cancer. In addition, combination therapy of 2-BP and PD-1/PD-L1 achieved synergic therapy effects in a mouse model of pancreatic cancer.

Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula.

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation.

Scale Effect of Surface Asperities on Stick-Slip Behavior of Zinc-Coated Steel.

Stick-slip behavior between friction pairs causes severe vibration problems such as abrasion and noise pollution, leading to material loss and deterioration in human health. This phenomenon is extremely complex because the surfaces of friction pairs have various asperities with different sizes. Therefore, it is of importance to understand the scale effect of asperities on the stick-slip behavior. Here, we selected four kinds of zinc-coated steels with multiscale surface asperities as a presentative example to reveal what types of asperities play the key role in affecting the stick-slip behavior. It is discovered that the stick-slip behavior is dominated by the density of small-scale asperities rather than large-scale asperities. High-density small-scale asperity increases the potential energy between asperities of the friction pairs, which leads to stick-slip behavior. It is suggested that decreasing the density of small-scale asperity on the surface significantly suppresses the stick-slip behavior. The present study reveals the scale effect of surface asperities on the stick-slip behavior and thus could offer a pathway to tailoring the surface topography of a wide range of materials for suppressing the stick-slip behavior.

The use of selenium for controlling plant fungal diseases and insect pests.

The selenium (Se) applications in biomedicine, agriculture, and environmental health have become great research interest in recent decades. As an essential nutrient for humans and animals, beneficial effects of Se on human health have been well documented. Although Se is not an essential element for plants, it does play important roles in improving plants' resistances to a broad of biotic and abiotic stresses. This review is focused on recent findings from studies on effects and mechanisms of Se on plant fungal diseases and insect pests. Se affects the plant resistance to fungal diseases by preventing the invasion of fungal pathogen through positively affecting plant defense to pathogens; and through negative effects on pathogen by destroying the cell membrane and cellular extensions of pathogen inside plant tissues after invasion; and changing the soil microbial community to safeguard plant cells against invading fungi. Plants, grown under Se enriched soils or treated with Se through foliar and soil applications, can metabolize Se into dimethyl selenide or dimethyl diselenide, which acts as an insect repellent compound to deter foraging and landing pests, thus providing plant mediated resistance to insect pests; moreover, Se can also lead to poisoning to some pests if toxic amounts of Se are fed, resulting in steady pest mortality, lower reproduction rate, negative effects on growth and development, thus shortening the life span of many insect pests. In present manuscript, reports are reviewed on Se-mediated plant resistance to fungal pathogens and insect pests. The future perspective of Se is also discussed on preventing the disease and pest control to protect plants from economic injuries and damages.

Targeting ZDHHC9 potentiates anti-programmed death-ligand 1 immunotherapy of pancreatic cancer by modifying the tumor microenvironment.

Immune checkpoint blockade (ICB) therapy targeting the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) axis has achieved considerable success in treating a wide range of cancers. However, most patients with pancreatic cancer remain resistant to ICB. Moreover, there is a lack of optimal biomarkers for the prediction of response to this therapy. Palmitoylation is mediated by a family of 23 S-acyltransferases, termed zinc finger Asp-His-His-Cys-type palmitoyltransferases (ZDHHC), which precisely control various cancer-related protein functions and represent promising drug targets for cancer therapy. Here, we revealed that tumor cell-intrinsic ZDHHC9 was overexpressed in pancreatic cancer tissues and associated with impaired anti-tumor immunity. In syngeneic pancreatic tumor models, the knockdown of ZDHHC9 expression suppressed tumor progression and prolonged survival time of mice by modifying the immunosuppressive ('cold') to proinflammatory ('hot') tumor microenvironment. Furthermore, ZDHHC9 deficiency sensitized anti-PD-L1 immunotherapy mainly in a CD8+ T cell dependent manner. Lastly, we employed the ZDHHC9-siRNA nanoparticle system to efficiently silence ZDHHC9 in pancreatic tumors. Collectively, our findings indicate that ZDHHC9 overexpression in pancreatic tumors is a mechanism involved in the inhibition of host anti-tumor immunity and highlight the importance of inactivating ZDHHC9 as an effective immunotherapeutic strategy and booster for anti-PD-L1 therapy against pancreatic cancer.

MMP9-Responsive Graphene Oxide Quantum Dot-Based Nano-in-Micro Drug Delivery System for Combinatorial Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD), especially wet AMD with choroidal neovascularization (CNV), commonly causes blindness in older patients and disruption of the choroid followed by second-wave injuries, including chronic inflammation, oxidative stress, and excessive matrix metalloproteinase 9 (MMP9) expression. Increased macrophage infiltrate in parallel with microglial activation and MMP9 overexpression on CNV lesions is shown to contribute to the inflammatory process and then enhance pathological ocular angiogenesis. Graphene oxide quantum dots (GOQDs), as natural antioxidants, exert anti-inflammatory effects and minocycline is a specific macrophage/microglial inhibitor that can suppress both macrophage/microglial activation and MMP9 activity. Herein, an MMP9-responsive GOQD-based minocycline-loaded nano-in-micro drug delivery system (C18PGM) is developed by chemically bonding GOQDs to an octadecyl-modified peptide sequence (C18-GVFHQTVS, C18P) that can be specifically cleaved by MMP9. Using a laser-induced CNV mouse model, the prepared C18PGM shows significant MMP9 inhibitory activity and anti-inflammatory action followed by antiangiogenic effects. Moreover, C18PGM combined with antivascular endothelial growth factor antibody bevacizumab markedly increases the antiangiogenesis effect by interfering with the "inflammation-MMP9-angiogenesis" cascade. The prepared C18PGM shows a good safety profile and no obvious ophthalmic or systemic side effects. The results taken together suggest that C18PGM is an effective and novel strategy for combinatorial therapy of CNV.

Topographic constraints on the distribution of selenium in the supergene environment: A case study at Yutangba, China.

The local topography and leaching conditions significantly affect the spatial distribution of selenium (Se) in the local environment. However, the driving factors controlling Se distribution have not been well addressed. In this paper, taking Yutangba, a village known for human selenosis in China, as an example, we demonstrate how topographic factors influence the spatial distribution of Se in soils and plants. In the scenarios of slope ≤25°, the correlations among slope and soil/extractable/plant Se are significantly negative (P < 0.05), whereas they become weak or unclear when the slope is > 25°, suggesting that 25° of slope is a critical transition boundary. Similar observations were further verified by the soil erosion modulus (SEM) and the surface runoff intensity index (SRI), indicating that Se transport via soil erosion is limited and accounts for 11.2-17% of the soil Se, while surface runoff plays a dominant role in the Se distribution, accounting for 83-88.1%. Soil extractable Se is negatively correlated with SRI (Pearson r = -0.87 at slope < 25°), showing that the migration capacity of Se is higher at steep terrain and controlled by topography through soil erosion and surface runoff. The positive relationship between plant Se and soil/extractable Se demonstrates that topography indirectly influences plant Se through soil Se bioavailability. Abnormally local Se enrichment observed at the elevated steep hillside (>25°) in northwestern Yutangba primarily was resulted from the weathering of Se-rich rocks. These observations confirm that the topographic slope gradient influences the transport and spatial distribution of soil Se, implying that topography should be considered when studying the spatial distribution of soil Se at a regional scale, especially for the Se-poor belt in China.

Coiling followed by staged flow diversion for large and giant intracranial aneurysms.

Objective: Delayed aneurysm rupture is a fatal complication after flow diversion treatment for large and giant intracranial aneurysms. This study aimed to investigate the feasibility and safety of coiling first and followed by planned flow diversion to prevent delayed aneurysm rupture. Methods: From January 2017 to December 2021 in two institutions, patients with unruptured intracranial aneurysms treated by coiling first and planned flow diversion were retrospectively collected. Data on demographic and aneurysmal characteristics, procedural details, and clinical and angiographic outcomes were reviewed. Results: Thirty patients were included (7 Males and 23 Females; Median age 57 years). Aneurysmal size ranged from 11.8 to 26.8 mm, with a median value of 18.5 mm. All aneurysms were located within the intradural segment of internal carotid arteries. Coiling and planned flow diversion were successfully performed in all patients. The time interval between coiling and flow diversion was 3.9-6.7 weeks, with a median value of 5.2 weeks. No hemorrhagic or ischemic complications occurred during the procedures and follow-up. Complete or subtotal occlusion was achieved in 86.7% (26/30) at the last angiographic follow-up (median 6.7 months). Conclusion: The preliminary data suggested that coiling unruptured intracranial aneurysms followed by planned flow diversion is both safe and effective. Further studies with larger cohorts are needed to verify the effect of this new strategy in preventing delayed rupture after flow diversion.

Chromatin remodeler Dmp18 regulates apoptosis by controlling H2Av incorporation in Drosophila imaginal disc development.

Programmed Cell Death (PCD) or apoptosis is a highly conserved biological process and plays essential roles both in the development and stress context. In Drosophila, expression of pro-apoptotic genes, including reaper (rpr), head involution defective (hid), grim, and sickle (skl), is sufficient to induce cell death. Here, we demonstrate that the chromatin remodeler Dmp18, the homolog of mammalian Znhit1, plays a crucial role in regulating apoptosis in eye and wing development. We showed that loss of Dmp18 disrupted eye and wing development, up-regulated transcription of pro-apoptotic genes, and induced apoptosis. Inhibition of apoptosis suppressed the eye defects caused by Dmp18 deletion. Furthermore, loss of Dmp18 disrupted H2Av incorporation into chromatin, promoted H3K4me3, but reduced H3K27me3 modifications on the TSS regions of pro-apoptotic genes. These results indicate that Dmp18 negatively regulates apoptosis by mediating H2Av incorporation and histone H3 modifications at pro-apoptotic gene loci for transcriptional regulation. Our study uncovers the role of Dmp18 in regulating apoptosis in Drosophila eye and wing development and provides insights into chromatin remodeling regulating apoptosis at the epigenetic levels.

Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions.

The adenosine A2A receptor (A2AR), a G protein-coupled receptor, is involved in numerous and varied physiological and pathological processes, including inflammation, immune responses, blood flow, and neurotransmission. Accordingly, it has become an important drug target for the treatment of neuropsychiatric disorders. However, the exact brain distribution of A2AR in regions outside the striatum that display relatively low levels of endogenous A2AR expression has hampered the exploration of A2AR functions under both physiological and pathological conditions. To further study the detailed distribution of the A2AR in low-expression regions, we have generated A2AR knock-in mice in which the 3xHA-2xMyc epitope tag sequence was fused to the C-terminus of A2AR (A2AR-tag mice) via CRISPR/Cas9 technology. Here, using CRISPR/Cas9 technology, we have generated A2AR knock-in mice in which the 3xHA-2xMyc epitope tag sequence was fused to the C-terminus of A2AR (A2AR-tag mice). The A2AR-tag mice exhibited normal locomotor activity and emotional state. Consistent with previous studies, A2AR fluorescence was widely detected in the striatum, nucleus accumbens, and olfactory tubercles, with numerous labeled cells being evident in these regions in the A2AR-tag mouse. Importantly, we also identified the presence of a few but clearly labeled cells in heterogeneous brain regions where A2AR expression has not previously been unambiguously detected, including the lateral septum, hippocampus, amygdala, cerebral cortex, and gigantocellular reticular nucleus. The A2AR-tag mouse represents a novel useful genetic tool for monitoring the expression of A2AR and dissecting its functions in brain regions other than the striatum.

Effect of Wear-Induced Surface Deformation on Stick-Slip Friction of Galvanized Automotive Steels.

This study examined the influence of worn surfaces on the stick-slip friction of galvanized automotive steel and revealed the intrinsic role of surface topography parameters in the stick-slip friction with wear. The results show that the surface deformation induced by wear significantly affects the stick-slip friction. The stick-slip friction can be suppressed by increasing the vertical area of the surface deformation because of reductions in the difference between the static and kinetic friction coefficients. The friction behavior changes from stick-slip friction to smooth sliding when the skewness exceeds a critical value, thus suggesting that this parameter can be used as an effective surface topography parameter to describe the stick-slip friction of galvanized automotive steel with worn surfaces. The findings can help improve the understanding of the mechanism of the stick-slip friction of materials with worn surfaces and provide an approach to suppress the noise and vibration caused by the stick-slip friction of galvanized automotive steel.

Immunomodulation of MiRNA-223-based nanoplatform for targeted therapy in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is characterized by pathological angiogenesis and associated inflammation in the retina and is the leading cause of childhood blindness. MiRNA-223 (miR-223) drives microglial polarization toward the anti-inflammatory phenotype and offers a therapeutic approach to suppress inflammation and consequently pathological neovascularization. However, miRNA-based therapy is hindered by the low stability and non-specific cell-targeting ability of delivery systems. In the present study, we developed folic acid-chitosan (FA-CS)-modified mesoporous silica nanoparticles (PMSN) loaded with miR-223 to regulate retinal microglial polarization. The FA-CS/PMSN/miR-223 nanoparticles exhibited high stability and loading efficiency, achieved targeted delivery, and successfully escaped from lysosomes. In cultured microglial cells, treatment with FA-CS/PMSN/miR-223 nanoparticles upregulated the anti-inflammatory gene YM1/2 and IL-4RA, and downregulated the proinflammatory genes iNOS, IL-1ß, and IL-6. Notably, in a mouse oxygen-induced retinopathy model of ROP, intravitreally injected FA-CS/PMSN/miR-223 nanoparticles (1 µg) decreased the retinal neovascular area by 52.6%. This protective effect was associated with the reduced and increased levels of pro-inflammatory (M1) and anti-inflammatory (M2) cytokines, respectively. Collectively, these findings demonstrate that FA-CS/PMSN/miR-223 nanoparticles provide an effective therapeutic strategy for the treatment of ROP by modulating the miR-223-mediated microglial polarization to the M2 phenotype.

The global change of gene expression pattern caused by PTEN mutation affects the prognosis of glioblastoma.

Glioblastoma (GBM), an aggressive primary tumor, is common in humans, accounting for 12-15% of all intracranial tumors, and has median survival of fewer than 15 months. Since a growing body of evidence suggests that conventional drugs are ineffective against GBM, our goal is to find emerging therapies that play a role in its treatment. This research constructs a risk model to predict the prognosis of GBM patients. A set of genes associated with GBM was taken from a GBM gene data bank, and clinical information on patients with GBM was retrieved from the Cancer Genome Atlas (TCGA) data bank. One-way Cox and Kaplan-Meier analyses were performed to identify genes in relation to prognosis. Groups were classified into high and low expression level of PTEN expression. Prognosis-related genes were further identified, and multi-factor Cox regression analysis was used to build risk score equations for the prognostic model to construct a survival prognostic model. The area under the ROC curve suggested that the pattern had high accuracy. When combined with nomogram analysis, GJB2 was considered an independent predictor of GBM prognosis. This study provides a potential prognostic predictive biological marker for GBM patients and confirms that GJB2 is a key gene for GBM progression.