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.

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.

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.

Association of seizures with COVID-19 infection in underage during the pandemic: A systematic review and meta-analysis.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused worldwide transmission. The aim of this systematic review and meta-analysis was to investigate the morbidity and characteristics of seizures after SARS-CoV-2 infection in underage (≤18 y) and to provide valuable reference material for subsequent clinical treatment. METHODS: PubMed/MEDLINE, Cochrane, and EMBASE databases were searched up to 10th May 2023. We utilized the search strategy of medical subject headings combined with entry terms to search all related literatures. RESULTS: The meta-analysis was performed according to PRISMA reporting guidelines. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ). A total of 12 articles were selected, including 4153 subjects and 333 seizure-prone minor patients with COVID-19. The morbidity of seizures after SARS-CoV-2 infection in immature patients was approximately 8.2 (95 % CI, 4.7%-12.4 %). By subgroup analysis, we know that the morbidity of male, Americas, with fever and first occurrence of seizures were 4.2% (95 % CI, 0.4-10.5 %), 4.6 % (95 % CI, 0.4 %-11.7 %), 5.4 % (95 % CI, 2.6 %-9.1 %) and 3.7 % (95 % CI, 0.7 %-8.2 %), respectively. Generalized seizures are the main type of seizures (80.6 %). CONCLUSIONS: Seizures can be caused by SARS-CoV-2 infection in underage groups, with a pooled morbidity of 8.2% and a higher morbidity in females, in African regions, in febrile groups and during 2022-2023. In addition, generalized seizures being the predominant seizure type.

Effect of doramectin on programmed cell death pathway in glioma cells

Purpose Doramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells. Methods In this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting. Results We found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways. Conclusion Our research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy (AU)

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.

Ultrasonic Field Induces Better Crystallinity and Abundant Defects at Grain Boundaries to Develop CuS Electromagnetic Wave Absorber.

Ultrasonic field (USF) is widely used to regulate the intrinsic properties of materials that are not applied in electromagnetic wave (EMW) absorption. One reason is that the lack of a response mechanism for the materials to USF hinders the expansion of their EMW absorption performance. Therefore, to address this issue, a series of CuS nanoparticles with diverse anions are constructed in the presence or absence of USF. The ultrasonic-induced cavitation effect can significantly promote CuS crystallization and lead to the accumulation of S defects at the grain boundaries (GBs). Furthermore, the S defects at the GBs are easily oriented and arranged, allowing the polarization relaxation retention to be maintained at 10 wt%. Consequently, the CuS with a nitrate precursor under USF shows an optimum effective absorption bandwidth (EAB) of 10.24 GHz at a thickness of 3.5 mm, which is 228.6% more than that without the USF. CuS with a chloride precursor also achieves an EAB of 3.92 GHz, even at a considerably low filler ratio. Thus, this study demonstrates the response mechanism of diverse anions to the USF for the first time and provides a novel technique to optimize the EMW absorption performance of semiconductors.

Development and validation of cuproptosis molecular subtype-related signature for predicting immune prognostic characterization in gliomas.

PURPOSE: Cuproptosis, a novel programmed cell death, plays an important role in glioma growth, angiogenesis, and immune response. Nonetheless, the role of cuproptosis-related genes (CRGs) in the prognosis and tumor microenvironment (TME) of gliomas remains unknown. METHODS: By non-negative matrix factorization consensus clustering, 1286 glioma patients were classified based on the mRNA expression levels of 27 CRGs and investigated the association of immune infiltration and clinical characteristics with cuproptosis subtypes. A CRG-score system was constructed using LASSO and multivariate Cox regression methods and validated in independent cohorts to predict the prognosis of glioma patients. RESULTS: Glioma patients were divided into two cuproptosis subtypes. Cluster C2 was enriched in immune-related pathways, had higher macrophage M2, neutrophils, and CD8 + T cells, and poorer prognosis compared with cluster C1 which was enriched in metabolism-related pathways. We further constructed and validated the ten-gene CRG risk scores. Glioma patients in the high CRG-score group had higher tumor mutation burden, higher TME scores, and poorer prognoses compared with the low CRG-score group. Additionally, the AUC value of the CRG-score was 0.778 in predicting the prognosis of gliomas. WHO grading, IDH mutation, 1p/19q codeletion, and MGMT methylation were significant differences between high and low CRG-score groups. CONCLUSION: This study demonstrated that CRG-score was related to immune cell infiltration and could accurately predict gliomas' prognosis. Our findings may provide a novel understanding of the potential role of cuproptosis molecular pattern and TME in the immune response and prognosis of glioma patients.

Efficacy of single-pill combination in uncontrolled essential hypertension: A systematic review and network meta-analysis.

This study aimed to evaluate the efficacy of single-pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching Pubmed, EMBASE, the Cochrane Library, and Web of Science collected only randomized controlled trials on the efficacy of single-pill combination antihypertensive drugs in people with uncontrolled essential hypertension. The search period is from the establishment of the database to July 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias Assessment, and statistical analyses were performed using Review Manage 5.3 and Stata 15.1 software. This review ultimately included 32 references involving 16 273 patients with uncontrolled essential hypertension. The results of the network meta-analysis showed that a total of 11 single-pill combination antihypertensive drugs were included, namely: Amlodipine/valsartan, Telmisartan/amlodipine, Losartan/HCTZ, Candesartan/HCTZ, Amlodipine/benazepril, Telmisartan/HCTZ, Valsartan/HCTZ, Irbesartan/amlodipine, Amlodipine/losartan, Irbesartan/HCTZ, and Perindopril/amlodipine. According to SUCRA, Irbesartan/amlodipine may rank first in reducing systolic blood pressure (SUCRA: 92.2%); Amlodipine/losartan may rank first in reducing diastolic blood pressure (SUCRA: 95.1%); Telmisartan/amlodipine may rank first in blood pressure control rates (SUCRA: 83.5%); Amlodipine/losartan probably ranks first in diastolic response rate (SUCRA: 84.5%). Based on Ranking Plot of the Network, we can conclude that single-pill combination antihypertensive drugs are superior to monotherapy, and ARB/CCB combination has better advantages than other SPC in terms of systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate. However, due to the small number of some drug studies, the lack of relevant studies has led to not being included in this study, which may impact the results, and readers should interpret the results with caution.

Erratum: Moxidectin induces Cytostatic Autophagic Cell Death of Glioma Cells through inhibiting the AKT/mTOR Signalling Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.46697.].

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.

Effect of doramectin on programmed cell death pathway in glioma cells.

PURPOSE: Doramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells. METHODS: In this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting. RESULTS: We found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways. CONCLUSION: Our research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy.

The causal effects between gut microbiota and hemorrhagic stroke: a bidirectional two-sample Mendelian randomization study.

Background: Recent studies have suggested that the composition of gut microbiota (GM) may change after intracerebral hemorrhage. However, the causal inference of GM and hemorrhagic stroke is unknown. Mendelian Randomization (MR) is an effective research method that removes confounding factors and investigates the causal relationship between exposure and outcome. This study intends to explore the causal relationship between GM and hemorrhagic stroke with the help of MR. Methods: Univariable and multivariable MR analyses were performed using summary statistics of the GM (n = 18,340) in the MiBioGen consortium vs. the FinnGen consortium R9 summary statistics (intracerebral hemorrhage, subarachnoid hemorrhage, and nontraumatic intracranial hemorrhage). Causal associations between gut microbiota and hemorrhagic stroke were analyzed using inverse variance weighted, MR-Egger regression, weighted median, weighted mode, simple mode, and MR-PRESSO. Cochran's Q statistic, MR-Egger regression, and leave-one-out analysis were used to test for multiplicity and heterogeneity of instrumental variables. Separate reverse MR analyses were performed for microbiota found to be causally associated with hemorrhagic stroke in the forward MR analysis. Also, multivariate MR analyses were conducted after incorporating common confounders. Results: Based on the results of univariable and multivariate MR analyses, Actinobacteria (phylum) (OR, 0.80; 95%CI, 0.66-0.97; p = 0.025) had a protective effect against hemorrhagic stroke, while Rikenellaceae RC9 gut group (genus) (OR, 0.81; 95%CI, 0.67-0.99; p = 0.039) had a potential protective effect. Furthermore, Dorea (genus) (OR, 1.77; 95%CI, 1.27-2.46; p = 0.001), Eisenbergiella (genus) (OR, 1.24; 95%CI, 1.05-1.48; p = 0.013) and Lachnospiraceae UCG008 (genus) (OR, 1.28; 95%CI, 1.01-1.62; p = 0.041) acted as potential risk factors for hemorrhagic stroke. The abundance of Dorea (genus) (ß, 0.05; 95%CI, 0.002 ~ 0.101; p = 0.041) may increase, and that of Eisenbergiella (genus) (ß, -0.072; 95%CI, -0.137 ~ -0.007; p = 0.030) decreased after hemorrhagic stroke according to the results of reverse MR analysis. No significant pleiotropy or heterogeneity was detected in any of the MR analyses. Conclusion: There is a significant causal relationship between GM and hemorrhagic stroke. The prevention, monitoring, and treatment of hemorrhagic stroke through GM represent a promising avenue and contribute to a deeper understanding of the mechanisms underlying hemorrhagic stroke.

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.

The MAI score: A novel score to early predict shunt-dependent hydrocephalus in patients with aneurysmal subarachnoid hemorrhage after surgery.

OBJECTIVE: As a chronic complication of aneurysmal subarachnoid hemorrhage(aSAH), Shunt dependent hydrocephalus (SDHC) often leads to severe neurological deficits. At present, risk factors of SDHC after aSAH are being refined. So this study aims to investigate independent risk factors and develop a novel score to identify early the patients who require a permanent shunt. METHOD: Five hundred twenty-four patients treated in the first affiliated hospital of Harbin medical university from March 2019 to March 2021 were analyzed. We collected clinical and radiographic data of patients within 72 h after the ictus. The relevant factors were firstly analyzed by univariate analysis, and the significant factors (p < 0.05) were included in the multivariate logistic regression analysis to obtain the independent risk factors with statistical differences. The MAI score was established based on the contribution of different independent risk factors to the outcome. the new score was validated in another cohort (97 patients with aSAH from April and June 2021). RESULT: We enrolled 524 aneurysm patients and 41(7.82%) patients who underwent ventriculoperitoneal shunt (VPS) after aneurysm treatment. Based on univariate and multivariate analysis, Acute Hydrocephalus (OR 6.498,:95% confidence interval (CI) 1.98-21.33, p = 0.002), Intraventricular hemorrhage (OR 3.55,:95%CI 1.189-10.599, p = 0.023) and Modified Fisher score ≥ 3 (OR 5.846, 95%CI 2.649-12.900, p = 0.001) were independent risk factors. The novel score was assigned according to the contribution of different independent risk factors to the results. The MAI score: Modified Fisher grade ≥ 3 (1 point), Acute Hydrocephalus (1 point), Intraventricular hemorrhage (1 point). In the receiver operating characteristic curve analysis, the area under the curve (AUC) for the MAI score is 0.773 (p < 0.0001, 95%CI 0.686-0.861). Patients scoring 2-3 MAI points showed a 10-fold higher risk for shunt dependency than patients scoring 0-1 MAI points (p < 0.001). We performed internal validation of the MAI scoring system. The scoring system reliably predicted SDHC after aSAH. The AUC of the internal validation was 0.950 (p ＝ 0.002, 95%CI 0.863-1.000). CONCLUSION: We develop a novel score based on univariate and multivariate analysis. The effectiveness of the MAI score has been confirmed in this study, which can more accurately predict SDHC after aASH and can be widely used in clinical practice. Prospective studies are needed for validation in the future.

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.

Microstructure induced dielectric loss in lightweight Fe3O4 foam for electromagnetic wave absorption.

Fe3O4 has been extensively applied in electromagnetic wave absorption field profiting from its advantageous magnetic loss, low cost and environmental benignity. Nevertheless, the inherent drawbacks of high density, low permittivity and easily magnetic aggregation are still the obstacles for pristine Fe3O4 becoming ideal absorbents. To overcome such limitations, a design mentality of constructing 3D structure shaped by curled 2D porous surface is proposed in this study. 3D structure overcomes the easy-agglomeration issue of 2D materials and meanwhile maintains their conductivity. The complex permittivity of samples is regulated by adjusting the microstructure of Fe3O4 to achieve optimum impedance matching. Defect induced polarization and interfacial polarization are the main loss mechanisms. Impressively, the density of S0.5 is only 0.05078 g/cm3 and the effective absorption bandwidth is up to 6.24 GHz (11.76-18 GHz) at 1.8 mm. This work provided a new insight for structurally improving the EMW absorption performance of pure magnetic materials.

Doramectin inhibits glioblastoma cell survival via regulation of autophagy in vitro and in vivo.

Glioblastoma (GBM) is one of the most widespread and lethal types of cancer. However, there are currently no drugs or therapeutic strategies that can completely cure GBM. Doramectin (DRM) has a broad range of activities against endoparasites and ectoparasites, and is extensively used in livestock. In the present study, the effect of DRM on the induction of autophagy in U87 and C6 GBM and glioma cell lines, as well as the mechanism of autophagy, were examined. First, transmission electron microscopy, plasmid transfection and western blot analysis demonstrated that DRM could induce autophagy in U87 and C6 cells in vitro. Next, MTT and colony formation assays revealed that DRM­induced autophagy prevented U87 and C6 cell viability and colony formation ratio. In addition, DRM­induced autophagy promoted U87 and C6 cell apoptosis, as indicated by DAPI analysis and flow cytometry. Furthermore, transcriptome analysis demonstrated that DRM modulated a number of genes and pathways involved in autophagy. In a nude mouse xenograft model, immunohistochemical staining and the TUNEL assay demonstrated that the effect of DRM on the tumor was consistent with that in vivo. These data indicated that DRM induced autophagy mainly by blocking the PI3K/AKT/mTOR signaling pathway in GBM cells. DRM­induced autophagy promoted the inhibition of GBM cell proliferation and apoptosis in vitro and in vivo. The present study suggested that DRM may be an effective drug for the treatment of GBM.