Exploring causal effects and potential mediating mechanisms of genetically linked environmental senses with intracerebral hemorrhage.

The occurrence mechanism of intracerebral hemorrhage remains unclear. Several recent studies have highlighted the close relationship between environmental senses and intracerebral hemorrhage, but the mechanisms of causal mediation are inconclusive. We aimed to investigate the causal relationships and potential mechanisms between environmental senses and intracerebral hemorrhage. Multiple Mendelian randomization methods were used to identify a causal relationship between environmental senses and intracerebral hemorrhage. Gut microbiota and brain imaging phenotypes were used to find possible mediators. Enrichment and molecular interaction analyses were used to identify potential mediators and molecular targets. No causal relationship between temperature and visual perception with intracerebral hemorrhage was found, whereas long-term noise was identified as a risk factor for intracerebral hemorrhage (OR 2.95, 95% CI: 1.25 to 6.93, PIVW = 0.01). The gut microbiota belonging to the class Negativicutes and the order Selenomonadales and the brain image-derived phenotypes ICA100 node 54, edge 803, edge 1149, and edge 1323 played mediating roles. "Regulation of signaling and function in synaptic organization" is the primary biological pathway of noise-induced intracerebral hemorrhage, and ARHGAP22 may be the critical gene. This study emphasized the importance of environmental noise in the prevention, disease management, and underlying biological mechanisms of intracerebral hemorrhage.

Characterization of the m6A/m1A/m5C/m7G-related regulators on the prognosis and immune microenvironment of glioma by integrated analysis of scRNA-seq and bulk RNA-seq data.

BACKGROUND: Proliferation, metabolism, tumor occurrence and development in gliomas are greatly influenced by RNA modifications. However, no research has integrated the four RNA methylation regulators of m6A, m1A, m5C and m7G in gliomas to analyze their relationship with glioma prognosis and intratumoral heterogeneity. METHODS: Based on three in-house single-cell RNA-sequencing (scRNA-seq) data, the glioma heterogeneity and characteristics of m6A/m1A/m5C/m7G-related regulators were elucidated. Based on publicly available bulk RNA-sequencing (RNA-seq) data, a risk-score system for predicting the overall survival (OS) for gliomas was established by three machine learning methods and multivariate Cox regression analysis, and validated in an independent cohort. RESULTS: Seven cell types were identified in gliomas by three scRNA-seq data, and 22 m6A/m1A/m5C/m7G-related regulators among the marker genes of different cell subtypes were discovered. Three m6A/m1A/m5C/m7G-related regulators were selected to construct prognostic risk-score model, including EIFA, NSUN6 and TET1. The high-risk patients showed higher immune checkpoint expression, higher tumor microenvironment scores, as well as higher tumor mutation burden and poorer prognosis compared with low-risk patients. Additionally, the area under the curve values of the risk score and nomogram were 0.833 and 0.922 for 3 year survival and 0.759 and 0.885 for 5 year survival for gliomas. EIF3A was significantly highly expressed in glioma tissues in our in-house RNA-sequencing data (p < 0.05). CONCLUSION: These findings may contribute to further understanding of the role of m6A/m1A/m5C/m7G-related regulators in gliomas, and provide novel and reliable biomarkers for gliomas prognosis and treatment.

Linkage Effect Induced by Hierarchical Architecture in Magnetic MXene-based Microwave Absorber.

Hierarchical architecture engineering is desirable in integrating the physical-chemical behaviors and macroscopic properties of materials, which present great potential for developing multifunctional microwave absorption materials. However, the intrinsic mechanisms and correlation conditions among cellular units have not been revealed, which are insufficient to maximize the fusion of superior microwave absorption (MA) and derived multifunctionality. Herein, based on three models (disordered structure, porous structure, lamellar structure) of structural units, a range of MXene-aerogels with variable constructions are fabricated by a top-down ice template method. The aerogel with lamellar structure with a density of only 0.015 g cm-3 exhibits the best MA performance (minimum reflection loss: -53.87 dB, effective absorption bandwidth:6.84 GHz) at a 6 wt.% filling ratio, which is preferred over alternative aerogels with variable configurations. This work elucidates the relationship between the hierarchical architecture and the superior MA performance. Further, the MXene/CoNi Composite aerogel with lamellar structure exhibits >90% compression stretch after 1000 cycles, excellent compressive properties, and elasticity, as well as high hydrophobicity and thermal insulation properties, broadening the versatility of MXene-based aerogel applications. In short, through precise microstructure design, this work provides a conceptually novel strategy to realize the integration of electromagnetic stealth, thermal insulation, and load-bearing capability simultaneously.

Prediction model for poor short-term prognosis in patients with chronic subdural hematoma after burr hole drainage: a retrospective cohort study.

Chronic subdural hematoma (CSDH) is a common condition in neurosurgery. With an aging population, there is increasing attention on the prognosis of patients following surgical intervention. We developed a postoperative short-term prognostic prediction model using preoperative clinical indicators, aiming to assist in perioperative medical decision-making and management. The dataset was randomly divided into training and validation cohorts. An mRS score greater than 2 one month after discharge was considered indicative of a poor prognosis. In the training cohort, the least absolute shrinkage and selection operator (LASSO) regression analysis was used for multivariate analysis to identify independent risk factors and construct a prediction nomogram for poor prognosis one month after discharge. The performance of the nomogram was assessed using the Receiver Operating Characteristic (ROC) curve and calibration curve. A Decision Curve Analysis (DCA) was also conducted to determine the net benefit threshold of the prediction model. Among the 505 participants, 18.8% (95/505) had a poor prognosis one month after discharge. The baseline characteristics did not significantly differ between the training cohort and the validation cohort. LASSO regression analysis in the training cohort reduced the predictors to four potential factors. Further multivariate logistic analyses in the training cohort identified four independent predictors: age, admission Glasgow Coma Scale (GCS) score, hemiparesis, and hemoglobin count. These predictors were incorporated into the nomogram prediction model. Internal validation using ROC analysis, calibration curves, and other methods demonstrated a strong correlation between the observed and predicted likelihood of poor prognosis one month after discharge. The visualized nomogram prediction model we developed for short-term postoperative prognosis of chronic subdural hematoma after burr hole drainage aids in predicting short-term outcomes and guiding clinical treatment decisions. Further external validation is needed in the future to confirm its effectiveness.

Structural Electromagnetic Absorber Based on MoS2 /PyC-Al2 O3 Ceramic Metamaterials.

Limited by the types of suitable absorbents as well as the challenges in engineering the nanostructures (e.g., defects, dipoles, and hetero-interface) using state-of-the-art additive manufacturing (AM) techniques, the electromagnetic (EM) wave absorption performance of the current ceramic-based materials is still not satisfying. Moreover, because of the high residual porosity and the possible formation of cracks during sintering or pyrolysis, AM-formed ceramic components may in many cases exhibit low mechanical strength. In this work, semiconductive MoS2 and conductive PyC modified Al2 O3 (MoS2 /PyC-Al2 O3 ) ceramic-based structural EM metamaterials are developed by innovatively harnessing AM, precursor infiltration and pyrolysis (PIP), and hydrothermal methods. Three different meta-structures are successfully created, and the ceramic-based nanocomposite benefit from its optimization of EM parameters. Ultra-broad effective absorption bandwidth (EAB) of 35 GHz is achieved by establishment of multi-loss mechanism via nanostructure engineering and fabrication of meta-structures via AM. Due to the strengthening by the PyC phase, the bending strength of the resulting ceramics can reach ≈327 MPa, which is the highest value measured on 3D-printed ceramics of this type that has been reported so far. For the first time, the positive effect deriving from the engineering of the microscopic nano/microstructure and of the macroscopic meta-structure of the absorber on the permittivity and EM absorption performance is proposed. Integration of outstanding mechanical strength and ultra-broad EAB is innovatively realized through a multi-scale design route. This work provides new insights for the design of advanced ceramic-based metamaterials with outstanding performance under extreme environment.

Identification and validation of DNA methylation-driven gene PCDHB4 as a novel tumor suppressor for glioblastoma diagnosis and prognosis.

Aberrant DNA methylation is a critical regulator of gene expression in the development and progression of glioblastoma (GBM). However, the impact of methylation-driven gene PCDHB4 changes on GBM occurrence and progression remains unclear. Therefore, this study aimed to identify the PCDHB4 gene for early diagnosis and prognostic evaluation and clarify its functional role in GBM. Methylation-driven gene PCDHB4 was selected for GBM using the multi-omics integration method based on publicly available data sets. The diagnostic capabilities of PCDHB4 methylation and 5-hydroxymethylcytosines were validated in tissue and blood cell-free DNA (cfDNA) samples, respectively. Combined survival analysis of PCDHB4 methylation and immune infiltration cells evaluated the prognostic predictive performance of GBM patients. We identified that the PCDHB4 gene achieved high discriminative capabilities for GBM and normal tissues with an area under the curve value of 0.941. PCDHB4 hypermethylation was observed in cfDNA blood samples from GBM patients. Compared with GBM patients with PCDHB4 hypermethylation level, patients with PCDHB4 hypomethylation level had significantly poorer overall survival (p = 0.035). In addition, GBM patients with PCDHB4 hypermethylation and high infiltration of CD4+ T cell activation level had a favorable survival (p = 0.026). Moreover, we demonstrated that mRNA expression of PCDHB4 was downregulated in GBM tissues and upregulated in GBM cell lines with PCDHB4 demethylation, and PCDHB4 overexpression inhibited GBM cell proliferation and migration. In summary, we discovered a novel methylation-driven gene PCDHB4 for the diagnosis and prognosis of GBM and demonstrated that PCDHB4 is a tumor suppressor in vitro experiments.

Locally secreted BiTEs complement CAR T cells by enhancing killing of antigen heterogeneous solid tumors.

Bispecific T cell engagers (BiTEs) are bispecific antibodies that redirect T cells to target antigen-expressing tumors. We hypothesized that BiTE-secreting T cells could be a valuable therapy in solid tumors, with distinct properties in mono- or multi-valent strategies incorporating chimeric antigen receptor (CAR) T cells. Glioblastomas represent a good model for solid tumor heterogeneity, representing a significant therapeutic challenge. We detected expression of tumor-associated epidermal growth factor receptor (EGFR), EGFR variant III, and interleukin-13 receptor alpha 2 (IL13Rα2) on glioma tissues and cancer stem cells. These antigens formed the basis of a multivalent approach, using a conformation-specific tumor-related EGFR targeting antibody (806) and Hu08, an IL13Rα2-targeting antibody, as the single chain variable fragments to generate new BiTE molecules. Compared with CAR T cells, BiTE T cells demonstrated prominent activation, cytokine production, and cytotoxicity in response to target-positive gliomas. Superior response activity was also demonstrated in BiTE-secreting bivalent T cells compared with bivalent CAR T cells in a glioma mouse model at early phase, but not in the long term. In summary, BiTEs secreted by mono- or multi-valent T cells have potent anti-tumor activity in vitro and in vivo with significant sensitivity and specificity, demonstrating a promising strategy in solid tumor therapy.

Exploration of Twin-Modified Grain Boundary Engineering in Metallic Copper Predominated Electromagnetic Wave Absorber.

High density and skin effect restrict the research progress of metal predominated electromagnetic wave absorbing (EMA) materials. Although some works try to solve it, they do not focus on the metal itself and do not involve the optimization of the active site of the inherent defects of the metal. In this work, the modulation of morphology, composition, interface, defects, and conductivity is achieved by adjusting the ratio of copper salt to reducing agent chitosan. Uniquely, the appearance of twin boundaries (TBs) accelerates the ability of the homogeneous interfaces to transfer charges, resists the oxidation of metal Cu0 , keeps the high electric conductivity of Cu0 nanoparticles, and enhances the conduction loss, which provides a boost for electromagnetic wave dissipation. As a result, the metal Cu0 predominated absorber (Cu-NC (N-doped carbon)-10,) exhibits an ultra-width effective absorption band of 8.28 GHz (9.72-18.00 GHz) at a thickness of 2.47 mm and the minimum reflection loss (RL) value of -63.8 dB with a thickness of 2.01 mm. In short, this work explores the EM regulation mechanism of TBs compared with grain boundaries (GBs), which provides a new insight for the rational design of metal predominated EMA materials.

Synthesis of Single-Component Metal Oxides with Controllable Multi-Shelled Structure and their Morphology-Related Applications.

Multi-shelled hollow spheres metal oxides, namely materials with more than three shells, have attracted increasing attention due to their unique structure. The preparation methods of typical metal oxides including NiO, Co3 O4 and ZnO etc. have been summarized in this review. Simultaneously, the parameters that influence the ultimate morphologies, shell number as well as the compositions have also been discussed. The potential application fields in energy conversion and storage, electromagnetic wave absorption, photocatalysis that related to the unique structure are also highlighted. Finally, the future researches of multi-shelled hollow spheres metal oxides are further discussed.

Ivermectin inhibits the growth of glioma cells by inducing cell cycle arrest and apoptosis in vitro and in vivo.

Glioma, the most predominant primary malignant brain tumor, remains uncured due to the absence of effective treatments. Hence, it is imperative to develop successful therapeutic agents. This study aimed to explore the antitumor effects and mechanisms of ivermectin (IVM) in glioma cells in vitro and in vivo. The effects of IVM on cell viability, cell cycle arrest, apoptosis rate, and morphological characteristics were determined respectively by MTT assay/colony formation assay, flow cytometry, and transmission electron microscope. In addition, the expression levels of cycle-related and apoptosis-associated proteins were individually examined by Western blot analysis. Moreover, cell proliferation and apoptosis analyses were carried out by TUNEL, Ki-67, cleaved caspase-3, and cleaved caspase-9 immunostaining assay. Our results demonstrated that IVM has a potential dosage-dependent inhibition effect on the apoptosis rate of glioma cells. Meanwhile, the results also revealed that IVM induced apoptosis by increasing caspase-3 and caspase-9 activity, upregulating the expressions of p53 and Bax, downregulating Bcl-2, activating cleaved caspase-3 and cleaved caspase-9, and blocking cell cycle in G0/G1 phase by downregulating levels of CDK2, CDK4, CDK6, cyclin D1, and cyclin E. These findings suggest that IVM has an inhibition effect on the proliferation of glioma cells by triggering cell cycle arrest and inducing cell apoptosis in vitro and in vivo, and probably represents promising agent for treating glioma.

TUSC3 suppresses glioblastoma development by inhibiting Akt signaling.

Glioblastoma multiform is one of the most common and most aggressive brain tumors in humans. The molecular and cellular mechanisms responsible for the onset and progression of GBM are elusive and controversial. The function of tumor suppressor candidate 3 (TUSC3) has not been previously characterized in GBM. TUSC3 was originally identified as part of an enzyme complex involved in N-glycosylation of proteins, but was recently implicated as a potential tumor suppressor gene in a variety of cancer types. In this study, we demonstrated that the expression levels of TUSC3 were downregulated in both GBM tissues and cells, and also found that overexpression of TUSC3 inhibits GBM cell proliferation and invasion. In addition, the effects of increased levels of methylation on the TUSC3 promoter were responsible for decreased expression of TUSC3 in GBM. Finally, we determined that TUSC3 regulates proliferation and invasion of GBM cells by inhibiting the activity of the Akt signaling pathway.

Risk Factors for Infections Related to Lumbar Drainage in Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: A solid knowledge associated with lumbar drainage (LD)-related infections in spontaneous subarachnoid hemorrhage (SAH) patients is necessary and that would be useful in taking effective measures to cope with this complication. We aimed to describe incidence rates and risk factors associated with LD-related infections in SAH patients. METHODS: A retrospective review was performed on SAH patients who underwent LD between July 2010 and August 2015. Patient charts were reviewed to retrieve demographic, clinical, and laboratory data. LD-related infections were defined based on culture results of cerebrospinal fluid in combination with clinical symptoms. Infection rates were calculated, and a logistic regression model was developed to identify risk factors. RESULTS: A total of 629 SAH patients (25-82 years age range, 42.8 % male) were treated with LD in the period. LD-related infections were identified in 36 patients (5.7 %). Longer duration of LD (≥4 days: p = 0.0037) and puncture site leakage (p < 0.0001) appeared to be risk factors for infection. The infection rate increased with length of the hospital stay (16-20 days: p = 0.0032; ≥21 days: p = 0.0007). 84.6 % of the isolated bacteria were Gram-positive, and the most commonly associated pathogens were Methicillin-resistant coagulase-negative Staphylococcus (MRCNS, 61.5 %). CONCLUSIONS: The patients with LD for more than 4 days or with puncture site leakage had more risk of infection. Infected patients were more likely to stay longer in the hospital. MRCNS were identified as the most frequent causal pathogens. And the use of antibiotics during LD did not appear to reduce the risk of infection.

Human amniotic epithelial stem cells inhibit microglia activation through downregulation of tumor necrosis factor-α, interleukin-1ß and matrix metalloproteinase-12 in vitro and in a rat model of intracerebral hemorrhage.

BACKGROUND AIMS: The molecular mechanisms by which stem cell transplantation improves functional recovery after intracerebral hemorrhage (ICH) are not well understood. Accumulating evidence suggests that microglia cells are activated shortly after ICH and that this activation contributes to secondary ICH-induced brain injury. We studied the effect of human amniotic epithelial stem cells (HAESCs) on microglia activation. METHODS: To study the effect of HAESCs in vitro, we used thrombin to activate the microglia cells. Twenty-four hours after thrombin treatment, the levels of tumor necrosis factor-α and interleukin-1ß were measured by enzyme-linked immunosorbent assay. In vivo, the HAESCs were transplanted into the rat striatum 1 day after collagenase-induced ICH. The expression levels of matrix metalloproteinase (MMP)-12 and microglia infiltration in the peri-hematoma tissues were determined 7 days after ICH through the use of reverse transcriptase-polymerase chain reaction and immunohistochemical analysis, respectively. RESULTS: Thrombin-activated microglia expression of tumor necrosis factor-α, interleukin-1ß and MMP-12 was significantly reduced through contact-dependent and paracrine mechanisms when the HAESCs were co-cultured with microglia cells. After transplantation of HAESCs in rat brains, the expression levels of MMP-12 and microglia infiltration in the peri-hematoma tissues were significantly reduced. CONCLUSIONS: Our observations suggest that microglia activation could be inhibited by HAESCs both in vitro and in vivo, which may be an important mechanism by which the transplantation of HAESCs reduces brain edema and ameliorates the neurologic deficits after ICH. Therefore, we hypothesize that methods for suppressing the activation of microglia and reducing the inflammatory response can be used for designing effective treatment strategies for ICH.

Discovery of Deactivation Phenomenon in NiCo2 S4 /NiS2 Electromagnetic Wave Absorbent and Its Reactivation Mechanism.

Over the past century, extensive research has been carried out on various types of microwave absorption (MA) materials, primarily emphasizing mechanism, performance, and even toward smart device. However, the deactivation, a crucial concern for practical applications, has long been long-neglected. In this work, an in-depth exploration of the deactivation mechanism reveals a significant competition between metal and oxygen, leading to the replacement of the S-M (M = Ni and Co) bond by a new S─O bond on the surface of absorber. This substitution initiates a series of collapse effect that introduces additional defective sites and diminishes the potential for charge transport. Subsequently, passive and active anti-deactivation strategies are developed to target the deactivation. The passive strategy involved intentionally creating electron-deficient structures at the initial Ni and Co sites in the crystal through the Fe doping engineering, with the objective of preventing the generation of S─O bonds. Furthermore, the active anti-deactivation strategy allows for the precise control of absorber deactivation and reactivation by employing accelerated thermodynamic and kinetic methods, enabling a reversible transformation of S-M through competitive reactions with S─O bonds. Finally, a fast deactivation and reactivation method is first proposed promising to stimulate further innovations and breakthroughs in practical applications.

Risk Factors for Seizures After Titanium Cranioplasty: Five-Year Experience from a Single Institution.

OBJECTIVE: Seizures are one of the complications that can occur after cranioplasty (CP). In some regions, titanium mesh remains the material of choice for CP. However, risk factors for seizures after titanium CP have been less studied. The purpose of this study was to identify potential risk factors for early seizures (≤7 days) and late seizures (>8 days) after titanium CP in a single institution. METHODS: A retrospective review was conducted of 241 consecutive patients who received titanium CP at the First Affiliated Hospital of Harbin Medical University from January 2016 to December 2020. Univariate and multivariable logistic regression analyses were performed to determine the independent risk factors for new-onset seizures after titanium CP. RESULTS: Fifteen patients (6.22%) experienced early post-CP seizures, and late post-CP seizures were observed in 81 patients (33.61%). A flaccid concave cranial defect (P = 0.042) was associated with early post-CP seizures, whereas hypertension (P < 0.001) was the only significant predictor for late seizures after titanium CP. CONCLUSIONS: Seizure is a common complication after titanium CP, especially in patients who do not receive prophylactic antiepileptic drugs before the procedure. Risk factors for new-onset seizures at different periods after titanium CP were found to be different. In addition, radiologic factors before titanium CP may play a role in early new-onset seizures after titanium CP and should not be ignored.

Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke.

Background: Hemorrhagic stroke (HS), a leading cause of death and disability worldwide, has not been clarified in terms of the underlying biomolecular mechanisms of its development. Circulating metabolites have been closely associated with HS in recent years. Therefore, we explored the causal association between circulating metabolomes and HS using Mendelian randomization (MR) analysis and identified the molecular mechanisms of effects. Methods: We assessed the causal relationship between circulating serum metabolites (CSMs) and HS using a bidirectional two-sample MR method supplemented with five ways: weighted median, MR Egger, simple mode, weighted mode, and MR-PRESSO. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO served for the sensitivity analyses. The Steiger test and reverse MR were used to estimate reverse causality. Metabolic pathway analyses were performed using MetaboAnalyst 5.0, and genetic effects were assessed by linkage disequilibrium score regression. Significant metabolites were further synthesized using meta-analysis, and we used multivariate MR to correct for common confounders. Results: We finally recognized four metabolites, biliverdin (OR 0.62, 95% CI 0.40-0.96, PMVMR = 0.030), linoleate (18. 2n6) (OR 0.20, 95% CI 0.08-0.54, PMVMR = 0.001),1-eicosadienoylglycerophosphocholine* (OR 2.21, 95% CI 1.02-4.76, PMVMR = 0.044),7-alpha-hydroxy-3 -oxo-4-cholestenoate (7-Hoca) (OR 0.27, 95% CI 0.09-0.77, PMVMR = 0.015) with significant causal relation to HS. Conclusion: We demonstrated significant causal associations between circulating serum metabolites and hemorrhagic stroke. Monitoring, diagnosis, and treatment of hemorrhagic stroke by serum metabolites might be a valuable approach.

Alterations in Astrocyte Subpopulations in Glioma and Identification of Cuproptosis-Related Genes Using Single-Cell RNA Sequencing.

Purpose: Mitochondrial metabolism is essential for energy production and the survival of brain cells, particularly in astrocytes. Cuproptosis is a newly identified form of programmed cell death that occurs due to the disruption of mitochondrial metabolism caused by excessive copper toxicity. However, the relationship between cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) and the prognosis of gliomas remains unclear. Patients and Methods: In this study, we utilized 32,293 cells obtained from three in-house single-cell RNA sequencing (scRNA-seq) datasets, along with 6,148 cells acquired from the Chinese Glioma Genome Atlas (CGGA) involving 14 glioma patients, to identify and validate the TME of gliomas. Results: Based on an analysis of 32,293 single cells, we investigated intra-tumor heterogeneity, intercellular communication, and astrocyte differentiation trajectories in gliomas. Our findings revealed that the TGFß signaling pathway exhibited a higher relative strength in astrocyte subpopulations. Additionally, we identified a novel three-gene signature (CDKN2A, SOX2, and MPC1) was identified for prognostic prediction. Furthermore, glioma patients with a high-risk score demonstrated poorer overall survival (OS) compared to those with a low-risk score in both training and testing datasets (P training set < 0.001; P test set = 0.037). Conclusion: Our study revealed the prognostic value of the CRGs in astrocytes exhibiting tumor immunosuppressive characteristics in glioma. We established a novel three-gene prognostic model that offers new insights into the prognosis and treatment strategies for gliomas.

Gut microbiota linked to hydrocephalus through inflammatory factors: a Mendelian randomization study.

Background: The gut microbiota (GM) has been implicated in neurological disorders, but the relationship with hydrocephalus, especially the underlying mechanistic pathways, is unclear. Using Mendelian randomization (MR), we aim to discover the mediating role of inflammatory factors in the relationship between GM and hydrocephalus. Methods: After removing confounders, univariable and multivariable MR analyses were performed using summary statistics to assess the causal relationships between GM, inflammatory factors (IL-17A and IL-27), and types of hydrocephalus. Meta-analyses were used to reconcile the differences in MR results between different hydrocephalus sources. Finally, mediator MR analyses were applied to determine the mediating effect of inflammatory factors. Various sensitivity analysis methods were employed to ensure the reliability and stability of the results. Results: After correction for P-values, Firmicutes (phylum) (OR, 0.34; 95%CI, 0.17-0.69; P = 2.71E-03, P FDR = 2.44E-02) significantly reduced the risk of obstructive hydrocephalus. The remaining 18 different taxa of GM had potential causal relationships for different types of hydrocephalus. In addition, Firmicutes (phylum) decreased the risk of obstructive hydrocephalus by increasing levels of IL-17A (mediating effect = 21.01%), while Eubacterium ruminantium group (genus) increased the risk of normal-pressure hydrocephalus by decreasing levels of IL-27 (mediating effect = 7.48%). Conclusion: We reveal the connection between GM, inflammatory factors (IL-17A and IL-27), and hydrocephalus, which lays the foundation for unraveling the mechanism between GM and hydrocephalus.

Construction and validation of a TAMRGs prognostic signature for gliomas by integrated analysis of scRNA and bulk RNA sequencing data.

BACKGROUND: This study aimed to construct and validate a prognostic model based on tumor associated macrophage-related genes (TAMRGs) by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data. METHODS: The scRNA-seq data of three inhouse glioma tissues were used to identify the tumor-associated macrophages (TAMs) marker genes, the DEGs from the The Cancer Genome Atlas (TCGA) - Genotype-Tissue Expression (GTEx) dataset were used to further select TAMs marker genes. Subsequently, a TAMRG-score was constructed by Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis in the TCGA dataset and validated in the Chinese Glioma Genome Atlas (CGGA) dataset. RESULTS: We identified 186 TAMs marker genes, and a total of 6 optimal prognostic genes including CKS2, LITAF, CTSB, TWISTNB, PPIF and G0S2 were selected to construct a TAMRG-score. The high TAMRG-score was significantly associated with worse prognosis (log-rank test, P<0.001). Moreover, the TAMRG-score outperformed the other three models with AUC of 0.808. Immune cell infiltration, TME scores, immune checkpoints, TMB and drug susceptibility were significantly different between TAMRG-score groups. In addition, a nomogram were constructed by combing the TAMRG-score and clinical information (Age, Grade, IDH mutation and 1p19q codeletion) to predict the survival of glioma patients with AUC of 0.909 for 1-year survival. CONCLUSION: The high TAMRG-score group was associated with a poor prognosis. A nomogram by incorporating TMARG-score could precisely predict glioma survival, and provide evidence for personalized treatment of glioma.

OPN gene polymorphism and the serum OPN levels confer the susceptibility and prognosis of ischemic stroke in Chinese patients.

AIM: To investigate the association of Osteopontin (OPN) gene polymorphism and serum thrombin-cleaved OPN level with the susceptibility to ischemic stroke (IS) and its prognosis. METHODS: A total of 377 patients with IS and 551 healthy individuals were recruited. The OPN gene polymorphisms at -156 G>GG, -443 C>T and -66 T>G were genotyped. Serum full-length and the thrombin-cleaved OPN were determined. RESULTS: We found that only the -443 C>T polymorphism was significantly associated with the susceptibility to IS. The -443 CC represented a near 2 time higher risk for IS incidence than TT carriers. Also, the -443 CC genotype had significantly poorer outcome and they significantly had higher occurrence for bad recovery as determined by modified Rankin Scale (mRS) (OR=2.18, p=0.043) and Barthel Index (BI) (OR=2.12, p=0.05). The mean serum thrombin-cleaved OPN level in IS group were significantly higher than that in control group. ROC analysis showed that the thrombin-cleaved OPN level (cut-off value, 166.8 ng/ml) can discriminate IS patients from controls with a specificity of 86.3% and a sensitivity of 57.7%. The serum thrombin-cleaved OPN was significantly associated with the clinical outcome at 12 months after discharge from hospital. CONCLUSION: These results suggest that the -443 C>T polymorphism of OPN gene and serum thrombin-cleaved OPN can be used as a biomarker for the susceptibility and prognosis of IS patients.