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Glioma, especially glioblastoma patients, present highly heterogeneous and immunosuppressive microenvironment, leading to their poor response to treatment and survival. Targeting the tumor microenvironment is considered a promising therapeutic strategy. M2 macrophages are highly infiltrated in glioma tissue, even up to 50% of the total number of bulk tissue cells. Here, we identified GPR65 as the hub gene of the M2 macrophage-related module in glioma through WGCNA analysis. The expression and prognosis analysis suggested that GPR65 was positively correlated with the malignancy and poor prognosis of glioma, and the heterogeneity analysis found that GPR65 was highly expressed in the vascular proliferation area of glioma, which matched the spatial expression characteristics of M2 macrophages. We further verified that GPR65 was highly expressed in macrophages but not tumor cells in the glioma microenvironment by single-cell data analysis and immunofluorescence. Most importantly, we found that inhibition of GPR65 was sufficient to reduce macrophages' polarization response to glioma cell and break the malignant cooperation with glioma cells. Our study reports the expression characteristics and malignant behavior of GPR65 in the glioma microenvironment, which provides a new alternative target of treatment to glioma microenvironment.
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Neoplasias Encefálicas , Glioma , Macrófagos , Receptores Acoplados a Proteínas G , Microambiente Tumoral , Microambiente Tumoral/fisiologia , Humanos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Glioma/patologia , Glioma/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Linhagem Celular TumoralRESUMO
Resulting from the solubility reduction of elemental sulfur during the development of high sulfur gas formations, sulfur deposition often occurs to reduce the gas production and threaten the safety of gas wells. Understanding the dissolution mechanism of elemental sulfur in natural gas is essential to reduce the risk caused by sulfur deposition. Because of the harsh conditions in the high-sulfur formations, it remains challenging to in situ characterize the dissolution-precipitation processes, making deficient the knowledge of sulfur dissolution mechanism. The dissolution of sulfur allotropes (SN, N = 2, 4, 6 and 8) in H2S, the main solvent of sulfur in natural gas, is studied in this work by means of first-principles calculations and molecular dynamics simulations. While S6 and S8 undergo physical interaction with H2S under the conditions corresponding to those at 1-6 km stratigraphic depths, S2 and S4 react with H2S and form stable polysulfides. Unravelling the mechanism would be helpful for understanding and controlling the sulfur deposition in high-sulfur gas development.
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Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) has been shown to facilitate progression and predict adverse prognostic outcome in many cancer types. However, the function of NCAPH in gliomas is still unclear. Series of experiments were taken to uncover the function of NCAPH in glioma. The expression of NCAPH and potential mechanism regulating progression of glioma was verified by bioinformatics analysis. Lentiviral transfection was used for establishment of loss-of-function and gain-of-function cell lines. CCK-8 assay and Colony-formation assay were used to evaluate proliferation. Transwell assay and Cell wound healing assay were used to assess migration and invasion. Cell cycle and apoptosis were measured by flow cytometry. Protein and RNA were quantified by WB and RT-PCR, respectively. The nude mice model of glioma was used to evaluate the effect of NCAPH in vivo. The expression of NCAPH increased significantly in glioma tissues and correlated with WHO grade, IDH wild-type and non-1p/19q codeletion. Glioma patients with high expression of NCAPH had an undesirable prognosis. Functionally, upregulated NCAPH promotes the malignant hallmarks of glioma cells in vivo and in vitro. NCAPH correlated with DNA damage repair ability of glioma cells and facilitated the proliferation, invasion, and migration of glioma cells by promoting the PI3K/AKT signaling pathway. This study identifies the important pro-tumor role of NCAPH in glioma and suggests that NCAPH is a potential therapeutic target.
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Bacteria contribute to many physiological functions of coral holobionts, including responses to bleaching. The bacterial genus, Endozoicomonas, dominates the microbial flora of many coral species and its abundance appears to be correlated with coral bleaching. However, evidences for decoupling of bleaching and Endozoicomonas abundance changes have also been reported. In 2020, a severe bleaching event was recorded at reefs in Taiwan, providing a unique opportunity to re-examine bleaching-Endozoicomonas association using multiple stony corals in natural environments. In this study, we monitored tissue color and microbiome changes in three coral species (Montipora sp., Porites sp., and Stylophora pistillata) in Kenting National Park, following the bleaching event. All tagged Montipora sp. and Porites sp. recovered from bleaching within 1 year, while high mortality occurred in S. pistillata. Microbiome analysis found no correlation of Endozoicomonas relative abundance and bleaching severity during the sampling period, but found a stronger correlation when the month in which bleaching occurred was excluded. Moreover, Endozoicomonas abundance increased during recovery months in Montipora sp. and Porites sp., whereas in S. pistillata it was nearly depleted. These results suggest that Endozoicomonas abundance may represent a gauge of coral health and reflect recovery of some corals from stress. Interestingly, even though different Endozoicomonas strains predominated in the three corals, these Endozoicomonas strains were also shared among coral taxa. Meanwhile, several Endozoicomonas strains showed secondary emergence during coral recovery, suggesting possible symbiont switching in Endozoicomonas. These findings indicate that it may be possible to introduce Endozoicomonas to non-native coral hosts as a coral probiotic.
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Endozoicomonas are often predominant bacteria and prominently important in coral health. Their role in dimethylsulfoniopropionate (DMSP) degradation has been a subject of discussion for over a decade. A previous study found that Endozoicomonas degraded DMSP through the dddD pathway. This process releases dimethyl sulfide, which is vital for corals coping with thermal stress. However, little is known about the related gene regulation and metabolic abilities of DMSP metabolism in Endozoicomonadaceae. In this study, we isolated a novel Endozoicomonas DMSP degrader and observed a distinct DMSP metabolic trend in two phylogenetically close dddD-harboring Endozoicomonas species, confirmed genetically by comparative transcriptomic profiling and visualization of the change of DMSP stable isotopes in bacterial cells using nanoscale secondary ion spectrometry. Furthermore, we found that DMSP cleavage enzymes are ubiquitous in coral Endozoicomonas with a preference for having DddD lyase. We speculate that harboring DMSP degrading genes enables Endozoicomonas to successfully colonize various coral species across the globe.
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Antozoários , Compostos de Sulfônio , Animais , Antozoários/metabolismo , Bactérias/metabolismo , Compostos de Sulfônio/metabolismoRESUMO
Glioma is an intracranial tumor characterized by high mortality and recurrence rates. In the present study, the association of TRPM8 channel-associated factor 2 (TCAF2) in glioma was investigated using bioinformatics, showing significant relationships with age, WHO grade, IDH, and 1p/19q status, as well as being an independent predictor of prognosis. Immunohistochemistry of a glioma sample microarray showed markedly increased TCAF2 expression in glioblastoma relative to lower-grade glioma, with elevated expression predominating in the tumor center. Raised TCAF2 levels promote glioma cell migratory/invasion properties through the epithelial-to-mesenchymal transition-like (EMT-like) process, shown by Transwell and scratch assays and western blotting. It was further found that the effects of TCAF2 were mediated by the activation of STAT3. These results suggest that TCAF2 promotes glioma cell migration and invasion, rendering it a potential drug target in glioma therapy.
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PURPOSE: Accurate preoperative radiological staging of adult-type diffuse glioma is crucial for effective prognostic stratification and selection of appropriate therapeutic interventions. The purpose of this study was to compare the effectiveness of apparent diffusion coefficient (ADC) maps generated from ultrahigh b-value diffusion-weighted imaging (DWI) for molecular grading with that for histological grading of adult-type diffuse glioma, and to evaluate the correlation between these ADC maps and molecular and histological biomarkers. METHODS: This study retrospectively enrolled forty adult-type diffuse glioma patients, diagnosed using the 2021 WHO classification criteria. Preoperative imaging data, including multiple b-value DWI and conventional magnetic resonance imaging, were collected. Tumors were graded using both histological and molecular criteria. Histogram analysis was conducted to generate 14 parameters for each tumor. Receiver operating characteristic curves and the area under the curve (AUC) were used to evaluate tumor grading and molecular status differentiation. Analysis of histological biomarkers was performed by calculating the Pearson and Spearman correlation coefficients of continuous and hierarchical variables, respectively. RESULTS: The intensity-related parameters for molecular grading were found to be superior to those for histological grading for the identification of WHO grade 4 (WHO4) adult-type diffuse glioma. The AUC of both grading systems increased with increasing b-values, with ADC8000-based histogram parameters showing the best results (molecular grading, square root: AUC = 0.897; histological grading, median: AUC = 0.737). The intensity-related parameters could also differentiate molecular WHO4 gliomas from histologically lower-grade gliomas (ADC8000-based square root: AUC = 0.919), and different ADC8000-based kurtosis was observed between molecular and histological WHO4 gliomas (AUC = 0.833). Significant correlations between the Ki-67 index and molecular status prediction for IDH, CDKN2A, and EGFR were also demonstrated. CONCLUSION: The histogram parameters derived from high b-value ADC maps were found to be more effective for differentiating molecular grades of WHO4 adult-type diffuse glioma than for differentiating histological grades.
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Neoplasias Encefálicas , Glioma , Humanos , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Estudos Retrospectivos , Glioma/diagnóstico por imagem , Glioma/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Gradação de Tumores , BiomarcadoresRESUMO
Recent studies have documented a rich phenomenology in twisted bilayer graphene (TBG), which is significantly relevant to interlayer electronic coupling, in particular to the cases under an applied electric field. While polarizability measures the response of electrons against applied fields, this work adopts a unique strategy of decomposing global polarizability into distributional contributions to access the interlayer polarization in TBG, as a function of varying twisting angles (θ). Through the construction of a model of twisted graphene quantum dots, we assess distributional polarizability at the first-principles level. Our findings demonstrate that the polarizability perpendicular to the graphene plates can be decomposed into intralayer dipoles and interlayer charge-transfer (CT) components, the latter of which provides an explicit measurement of the interlayer coupling strength and charge transfer potential. Our analysis further reveals that interlayer polarizability dominates the polarizability variation during twisting. Intriguingly, the largest interlayer polarizability and CT driven by an external field occur in the misaligned structures with a size-dependent small angle corresponding to the first appearance of AB stacking, rather than the well-recognized Bernal structures. A derived equation is then employed to address the size dependence on the angle corresponding to the largest values in interlayer polarizability and CT. Our investigation not only characterizes the CT features in the interlayer polarizability of TBG quantum dots, but also sheds light on the existence of the strongest interlayer coupling and charge transfer at small twist angles in the presence of an external electric field, thereby providing a comprehensive understanding of the novel properties of graphene-based nanomaterials.
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In this paper, we have thoroughly investigated the ORR mechanism of non-pyrolytic mono-1,10-phenanthroline-coordinated Cu2+ (Cu-N2 type) complexes and polymers by molecular dynamics and quantum mechanics calculation. In contrast to the complex-catalyzed ORR, which follows a direct four-electron pathway along intermediates of Cu(I)-Phen, the polymer-catalyzed ORR follows an indirect four-electron pathway by intermediates of Cu(II)-Phen. By analyzing the structure, spin population, electrostatic potential (ESP), and density of states, we confirmed that the higher ORR catalytic activity of the polymer is due to the conjugation effect of coplanar phenanthroline and Cu(II) in the planar reactants or at the base of the square-pyramidal intermediates. The conjugation effect allows the highest ESP to be located near the active center Cu(II), while the lower ESPs are distributed on the phenanthroline, which is very favorable for the reduction current. This will serve as a theoretical foundation for the development of new highly efficient ORR non-pyrolytic CuN2 polymer catalysts.
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Maintaining the integrity of crucial fiber tracts allows functional preservation and improved recovery in patients with glioma resection. Diffusion tensor imaging (DTI) and intraoperative subcortical mapping (ISM) are commonly required for pre- and intraoperative assessment of white matter fibers. This study investigated differences of clinical outcomes in glioma resection aided by DTI or ISM. A comprehensive literature retrieval of the PubMed and Embase databases identified several DTI or ISM studies in 2000-2022. Clinical data, including extent of resection (EOR) and postoperative neurological deficits, was collected and statistically analyzed. Heterogeneity was regressed by a random effect model and the Mann-Whitney U test was used to test statistical significance. Publication bias was assessed by Egger test. A total of 14 studies with a pooled cohort of 1837 patients were included. Patients undergoing DTI-navigated glioma surgery showed a higher rate of gross total resection (GTR) than ISM-assisted surgical resection (67.88%, [95% CI 0.55-0.79] vs. 45.73%, [95% CI 0.29-0.63], P = 0.032). The occurrence of early postoperative functional deficit (35.45%, [95% CI 0.13-0.61] vs. 35.60% [95% CI 0.20-0.53], P = 1.000), late postoperative functional deficit (6.00%, [95% CI 0.02-0.11] vs. 4.91% [95% CI 0.03-0.08], P = 1.000) and severe postoperative functional deficit (2.21%, [95% CI 0-0.08] vs. 5.93% [95% CI 0.01-0.16], P = 0.393) were similar between the DTI and ISM group, respectively. While DTI-navigation resulted in a higher rate of GTR, the occurrence of postoperative neurological deficits between DTI and ISM groups was comparable. Together, these data indicate that both techniques could safely facilitate glioma resection.
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Glioma , Substância Branca , Humanos , Imagem de Tensor de Difusão , Bases de Dados Factuais , Glioma/diagnóstico por imagem , Glioma/cirurgia , Período Pós-OperatórioRESUMO
The tumor immunosuppressive microenvironment (IME) significantly affects tumor occurrence, progression, and prognosis, but the underlying molecular mechanisms remain to make known. We investigated the prognostic significance of PDPN and its role in IME in glioma. Weighted gene co-expression network analysis (WGCNA) found PDPN closely related to IDH wildtype status and higher immune score. Correlation analysis suggested PDPN was highly positively relevant to immune checkpoints expression and immune checkpoints block responding status. Correlation analysis together with verification in vitro suggested PDPN highly positively relevant tumor-associated neutrophils (TANs) and tumor-associated macrophages (TAMs). Least absolute shrinkage and selection operator (LASSO) regression employed to develop the prediction model with TANs and TAMs markers showed that high risk scores predicted worse prognosis. We highlight that PDPN overexpression is an independent prognostic indicator, and promotes macrophage M2 polarization and neutrophil degranulation, ultimately devotes to the formation of an immunosuppressive tumor microenvironment. Our findings contribute to re-recognizing the role of PDPN in IDH wildtype gliomas and implicate promising target therapy combined with immunotherapy for this highly malignant tumor.
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Glioma , Humanos , Glioma/metabolismo , Prognóstico , Perfilação da Expressão Gênica , Microambiente Tumoral/genética , Glicoproteínas de Membrana/genéticaRESUMO
Mitosis and meiosis are crucial life activities that transmit eukaryotic genetic information to progeny in a stable and orderly manner. The formation and appearance of chromosomes, which are derived from chromatin, are the preconditions and signs of mitosis. When entering mitosis, interphase loose chromatin is highly spiralized and folded to form compact chromosomes. In recent years, it has been found that in addition to the well-known DNA, histones, and topoisomerase, a large protein complex called condensin plays an important role in the process of chromosome formation. Numerous studies have shown that the abnormal function of condensin can lead to incomplete or excessive concentration of chromatin, as well as disorder of genome organization process, abnormal transmission of genetic information, and ultimately lead to various diseases of individual, especially in nervous system diseases. In this review, the biological function of condensin and the potential pathogenic mechanism of condensin in nervous system diseases are briefly summarized. Therefore, the investigation of these mechanisms makes a significant contribution to the understanding of those related diseases and provides new ideas for clinical treatments.
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An efficient potassium persulfate-mediated radical addition of allenamides with diselenides was developed to create a workable route to 1,2-diselenide products. The reaction tolerates a wide spectrum of functional groups to deliver the products in good to excellent yields. Mechanistic investigations including a calculation study indicated that the radical cascade proceeds through a vinyl radical intermediate, which is formed via a selenium radical added to the terminal CîC double bond of allenamides.
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Compostos Organosselênicos , Peroxidação de Lipídeos , Compostos Organosselênicos/química , Compostos de Potássio , SulfatosRESUMO
Bacteria commonly form aggregates in a range of coral species [termed coral-associated microbial aggregates (CAMAs)], although these structures remain poorly characterized despite extensive efforts studying the coral microbiome. Here, we comprehensively characterize CAMAs associated with Stylophora pistillata and quantify their cell abundance. Our analysis reveals that multiple Endozoicomonas phylotypes coexist inside a single CAMA. Nanoscale secondary ion mass spectrometry imaging revealed that the Endozoicomonas cells were enriched with phosphorus, with the elemental compositions of CAMAs different from coral tissues and endosymbiotic Symbiodiniaceae, highlighting a role in sequestering and cycling phosphate between coral holobiont partners. Consensus metagenome-assembled genomes of the two dominant Endozoicomonas phylotypes confirmed their metabolic potential for polyphosphate accumulation along with genomic signatures including type VI secretion systems allowing host association. Our findings provide unprecedented insights into Endozoicomonas-dominated CAMAs and the first direct physiological and genomic linked evidence of their biological role in the coral holobiont.
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Gliomas are the most common primary brain cancer. While it has been known that calcium-related genes correlate with gliomagenesis, the relationship between calcium-related genes and glioma prognosis remains unclear. We assessed TCGA datasets of mRNA expressions with differentially expressed genes (DEGs) and enrichment analysis to specifically screen for genes that regulate or are affected by calcium levels. We then correlated the identified calcium-related genes with unsupervised/supervised learning to classify glioma patients into 2 risk groups. We also correlated our identified genes with immune signatures. As a result, we discovered 460 calcium genes and 35 calcium key genes that were associated with OS. There were 13 DEGs between Clusters 1 and 2 with different OS. At the same time, 10 calcium hub genes (CHGs) signature model were constructed using supervised learning, and the prognostic risk scores of the 3 cohorts of samples were calculated. The risk score was confirmed as an independent predictor of prognosis. Immune enrichment analysis revealed an immunosuppressive tumor microenvironment with upregulation of checkpoint markers in the high-risk group. Finally, a nomogram was generated with risk scores and other clinical prognostic independent indicators to quantify prognosis. Our findings suggest that calcium-related gene expression patterns could be applicable to predict prognosis and predict levels of immunosuppression.
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Bacteria in the coral microbiome play a crucial role in determining coral health and fitness, and the coral host often restructures its microbiome composition in response to external factors. An important but often neglected factor determining this microbiome restructuring is the ability of microbiome members to respond to changes in the environment. To address this issue, we examined how the microbiome structure of Acropora muricata corals changed over 9 months following a reciprocal transplant experiment. Using a combination of metabarcoding, genomics, and comparative genomics approaches, we found that coral colonies separated by a small distance harbored different dominant Endozoicomonas-related phylotypes belonging to two different species, including a novel species, "Candidatus Endozoicomonas penghunesis" 4G, whose chromosome-level (complete) genome was also sequenced in this study. Furthermore, the two dominant Endozoicomonas species had different potentials to scavenge reactive oxygen species, suggesting potential differences in responding to the environment. Differential capabilities of dominant members of the microbiome to respond to environmental change can (i) provide distinct advantages or disadvantages to coral hosts when subjected to changing environmental conditions and (ii) have positive or negative implications for future reefs. IMPORTANCE The coral microbiome has been known to play a crucial role in host health. In recent years, we have known that the coral microbiome changes in response to external stressors and that coral hosts structure their microbiome in a host-specific manner. However, an important internal factor, the ability of microbiome members to respond to change, has been often neglected. In this study, we combine metabarcoding, culturing, and genomics to delineate the differential ability of two dominant Endozoicomonas species, including a novel "Ca. Endozoicomonas penghunesis" 4G, to respond to change in the environment following a reciprocal transplant experiment.
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Antozoários , Gammaproteobacteria , Microbiota , Animais , Antozoários/genética , Bactérias/genética , Microbiota/genética , Genômica , Gammaproteobacteria/genéticaRESUMO
Background: Ferroptosis is a form of programmed cell death (PCD) that has been implicated in cancer progression, although the specific mechanism is not known. Here, we used the latest DepMap release CRISPR data to identify the essential ferroptosis-related genes (FRGs) in glioma and their role in patient outcomes. Methods: RNA-seq and clinical information on glioma cases were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). FRGs were obtained from the FerrDb database. CRISPR-screened essential genes (CSEGs) in glioma cell lines were downloaded from the DepMap portal. A series of bioinformatic and machine learning approaches were combined to establish FRG signatures to predict overall survival (OS) in glioma patients. In addition, pathways analysis was used to identify the functional roles of FRGs. Somatic mutation, immune cell infiltration, and immune checkpoint gene expression were analyzed within the risk subgroups. Finally, compounds for reversing high-risk gene signatures were predicted using the GDSC and L1000 datasets. Results: Seven FRGs (ISCU, NFS1, MTOR, EIF2S1, HSPA5, AURKA, RPL8) were included in the model and the model was found to have good prognostic value (p < 0.001) in both training and validation groups. The risk score was found to be an independent prognostic factor and the model had good efficacy. Subgroup analysis using clinical parameters demonstrated the general applicability of the model. The nomogram indicated that the model could effectively predict 12-, 36-, and 60-months OS and progression-free interval (PFI). The results showed the presence of more aggressive phenotypes (lower numbers of IDH mutations, higher numbers of EGFR and PTEN mutations, greater infiltration of immune suppressive cells, and higher expression of immune checkpoint inhibitors) in the high-risk group. The signaling pathways enriched closely related to the cell cycle and DNA damage repair. Drug predictions showed that patients with higher risk scores may benefit from treatment with RTK pathway inhibitors, including compounds that inhibit RTKs directly or indirectly by targeting downstream PI3K or MAPK pathways. Conclusion: In summary, the proposed cancer essential FRG signature predicts survival and treatment response in glioma.
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BACKGROUND: Intracranial aneurysm (IA) is a serious disease. Analyze and review the cases of anterior circulation ruptured IA by supraorbital lateral keyhole approach, and summarize the experiences of this approach. METHODS: Retrospective analysis of 16 cases of ruptured anterior circulation IA in our department from January 2019 to June 2020, CT angiography (CTA) was performed before operation. Analyzing the IA's parameters by 3D-CT reconstruction. The IA was clipped by supraorbital lateral keyhole approach combined with the 3D-skull reconstruction. Extraventricular drainage was performed before craniotomy. Intraoperative neurophysiological monitoring was performed during the operation. After operation, fluorescein angiography and vascular ultrasound were performed to check the clipping effect. Intracranial pressure monitor was performed postoperatively. CTA was reexamined one week after operation. The modified Rankin Scale (MRS) was performed 6 months after operation. RESULTS: There were 7 males (43.8%) and 9 females (56.2%), and the average age is 52.31 ± 11.12 years old. Among them, 11 patients (68.8%) were anterior communicating artery aneurysms and 5 (31.2%) were middle cerebral artery aneurysms. All patients were out of hospital within 10 days without any death, without cerebral infarction, cerebrospinal fluid leakage and neurological impairments. About mRS score, after 6 months follow-up, 8 cases (50%) had 0 point, 4 cases (25%) had 1 point, and 4 cases (25%) had 2 points. CONCLUSIONS: For ruptured anterior circulation IA, the supraorbital lateral keyhole approach combined with ventricular drainage, intraoperative electrophysiological monitoring, and intraoperative vascular ultrasound is a safe and minimally invasive treatment. The application of reconstruction clipping can reconstruct the diameter of parent vessel and reduce the recurrence rate of IA.
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Glioblastoma is the most common primary intracranial malignant tumor in adults and has high morbidity and high mortality. TMEM158 has been reported to promote the progression of solid tumors. However, its potential role in glioma is still unclear. Here, we found that TMEM158 expression in human glioma cells in the tumor core was significantly higher than that in noncancerous cells at the tumor edge using bioinformatics analysis. Cancer cells in patients with primary GBMs harbored significantly higher expression of TMEM158 than those in patients with WHO grade II or III gliomas. Interestingly, regardless of tumor grading, human glioma samples that were IDH1-wild-type (IDH1-WT) exhibited higher expression of TMEM158 than those with IDH1-mutant (IDH1-Mut). We also illustrated that TMEM158 mRNA expression was correlated with poor overall survival in glioma patients. Furthermore, we demonstrated that silencing TMEM158 inhibited the proliferation of glioma cells and that TMEM158 overexpression promoted the migration and invasion of glioma cells by stimulating the EMT process. We found that the underlying mechanism involves STAT3 activation mediating TMEM158-driven glioma progression. In vivo results further confirmed the inhibitory effect of the TMEM158 downregulation on glioma growth. Collectively, these findings further our understanding of the oncogenic function of TMEM158 in gliomas, which represents a potential therapeutic target, especially for GBMs.