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Background Cuproptosis is a newly discovered form of cell death. It's regulated by a string of genes. The genes are identified to influence the tumor progression, but in glioma, the cuproptosis-related genes are little studied.Method The Cancer Genome Atlas and The Genotype-Tissue Expression were used to screen for SLC31A1 gene expression in glioma and healthy tissue samples. The results were validated using the Gene Expression Omnibus and real-time quantitative PCR. The Human Protein Atlas and The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium were used to validate our results at the protein level. Multivariable analysis and Kaplan-Meier survival curves were used to examine the relationship between SLC31A1 gene expression, clinical parameters, and survival rates. The online Search Tool for the Retrieval of Interacting Genes/Proteins was used to find the genes and proteins that correlate to SLC31A1. The immune infiltration analysis was performed using the Tumor Immune Estimation Resource databases.Results The glioma patients have higher SLC31A1 expression levels, which increase as the WHO grade escalates. The survival analysis illustrates that the SLC31A1 gene expression negatively correlates with OS, PFS, and DSS. The immune infiltration analysis shows the SLC31A1 gene positively correlates with Th2 cells, Macrophages, and M2 type macrophages and negatively correlates with pDC cells, NK CD56bright cells, and CD8 T cells.Conclusion The SLC31A1 gene expression can shorten the survival time of glioma patients. It also can promote the formation of a tumor-suppressive microenvironment.

Glioma is the most common malignant tumor in brain and it has abundant long non-coding RNAs (lncRNAs), However, the specific role of lncRNAs and its mechanism in glioma remain unclear. LncRNA is a valuable cancer biomarker and they have been reported to be involved in genomic instability. Moreover, lncRNAs related to genomic instability has not been reported in glioma. In this study, we performed a prognostic model constructed with genomic instability-associated lncRNAs and further validated it with mutation correlation analysis, model comparison, independent prognostic value analysis, clinical stratification, examination of the external data set and cell line validation. This model provides us with a new kit for evaluating the prognosis of glioma.

Glioblastoma (GBM) generally has a dismal prognosis, and it is associated with a poor quality of life as the disease progresses. However, the development of effective therapies for GBM has been deficient. Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family in the ubiquitin-proteasome pathway and a vital regulator of tumour progression, but its role in GBM is unclear. In this study, we aimed to clarify the role of UBE2T in GBM. Bioinformatics analysis identified UBE2T as an independent risk factor for gliomas. Immunohistochemistry was used to measure UBE2T expression in GBM and normal tissue samples obtained from patients with GBM. The effects of UBE2T on GBM cell invasion and migration were analysed using the Transwell assay. BALB/c nude mice were used for the in vivo assays. Immunoblotting and immunoprecipitation were performed to determine the molecular mechanisms. UBE2T was highly expressed in GBM tissues, and its expression was linked to a poor prognosis. In vitro, depletion of UBE2T significantly suppressed cell invasion and migration. Moreover, UBE2T depletion suppressed the growth of GBM subcutaneous tumours in vivo. Further experiments revealed that UBE2T suppressed invasion and migration by regulating epithelial- mesenchymal transition (EMT) via stabilising GRP78 in GBM cells. We uncovered a novel UBE2T/GRP78/EMT regulatory axis that modulates the malignant progression and recurrence of GBM, indicating that the axis might be a valuable therapeutic target.

Thedemo raw data for the code of"An integrated imaging sensor for aberration-corrected 3D photography", which is published in Nature, 2022.If you use this data,please cite the companion paper where the original method appeared: Wu, J., Guo, Y., Deng, C. et al. "An integrated imaging sensor for aberration-corrected 3D photography". Nature (2022).&nbsp

Light-field microscopy has achieved success in various applications of life sciences that require high-speed volumetric imaging. However, existing light-field reconstruction algorithms degrade severely in low-light conditions, and the deconvolution process is time-consuming.This study aims to develop a noise robustness phase-space deconvolution method with low computational costs.We reformulate the light-field phase-space deconvolution model into the Fourier domain with random-subset ordering and total-variation (TV) regularization. Additionally, we build a time-division-based multicolor light-field microscopy and conduct the three-dimensional (3D) imaging of the heart beating in zebrafish larva at over 95 Hz with a low light dose.We demonstrate that this approach reduces computational resources, brings a tenfold speedup, and achieves a tenfold improvement for the noise robustness in terms of SSIM over the state-of-the-art approach.We proposed a phase-space deconvolution algorithm for 3D reconstructions in fluorescence imaging. Compared with the state-of-the-art method, we show significant improvement in both computational effectiveness and noise robustness; we further demonstrated practical application on zebrafish larva with low exposure and low light dose.

Glioblastoma (GBM) is one of the most aggressive primary malignant brain tumors. The major challenge is the lack of effective therapeutic drugs due to the blood-brain barrier (BBB) and tumor heterogeneity. Remdesivir (RDV), a new member of the nucleotide analog family, has previously been shown to have excellent antiviral effects and BBB penetration, and was predicted here to have anti-GBM effects. In vitro experiments, RDV significantly inhibited the growth of GBM cells, with IC

Glioblastoma multiforme (GBM) is one of the most devastating brain malignancies worldwide and is considered to be incurable. However, the mechanisms underlying its aggressiveness remain unclear. The expression of ADAM17 in tissue samples was detected by immunohistochemistry. Knockdown and rescue experiments were used to demonstrate the regulatory effect of ADAM17 on the invasion ability of GBM cells. Western Blot and qPCR were used to detect the expression of related proteins and RNAs. Moreover, a luciferase reporter assay was performed to verify whether miR-145 directly binds to the 3′-UTR of ADAM17. We revealed that ADAM17 was overexpressed in GBM tissues and correlated positively with poor prognosis. The knockdown of ADAM17 obviously suppressed the invasiveness of GBM cell lines. Furthermore, we found that knockdown of ADAM17 decreased activation of EGFR/Akt/C/EBP-β signaling, and consequently upregulated miR-145 expression in GBM cell lines. Notably, miR-145 directly targeted the ADAM17 3′-UTR and suppressed expression levels of ADAM17. Our findings define an ADAM17/EGFR/miR-145 feedback loop that drives the GBM invasion. Reciprocal regulation between ADAM17 and miR-145 results in aberrant activation of EGFR signaling, suggesting that inhibition of ADAM17 expression can be an ideal therapeutic strategy for the treatment of GBM.

Medulloblastoma (MB) is one of the most common central nervous system tumors in children. At present, the vital role of immune abnormalities has been proved in tumorigenesis and progression. However, the immune mechanism in MB is still poorly understood. In the present study, 51 differentially expressed immune-related genes (DE-IRGs) and 226 survival associated immune-related genes (Sur-IRGs) were screened by an integrated analysis of multi-array. Moreover, the potential pathways were enriched by functional analysis, such as ‘cytokine–cytokine receptor interaction’, ‘Ras signaling pathway’, ‘PI3K-Akt signaling pathway’ and ‘pathways in cancer’. Furthermore, 10 core IRGs were identified from DE-IRGs and Sur-IRGs. And the potential regulatory mechanisms of core IRGs were also explored. Additionally, a new prognostic model, including 7 genes (HDGF, CSK, PNOC, S100A13, RORB, FPR1, and ICAM2) based on IRGs, was established by multivariable COX analysis. In summary, our study revealed the underlying immune mechanism of MB. Moreover, we developed a prognostic model associated with clinical characteristics and could reflect the infiltration of immune cells.

Glioblastoma (GBM) is one of the most common malignancies of the central nervous system, and the Isocitrate Dehydrogenase (IDH) mutation status of GBM has been recognized as a critical prognostic indicator. However, the molecular mechanism underlying the GBM with different IDH mutation status is still not unclear. In this study, a total of 353 DEGs including 207 up-regulated and 146 down-regulated were screened from multiple GBM data sets. Moreover, the biological processes and pathways enriched by DEGs were mainly associated with tumor progression, especially invasion and migration. Then, eight hub genes, including SDC4, SERPINE1, TNC, THBS1, COL1A1, CXCL8, TIMP1 and VEGFA, were selected from a PPI network. Finally, core genes, SERPINE1 and TIMP1, were identified from hub genes by survival analysis and sample validation. Overall, in this study, we revealed underlying molecular mechanisms in GBMs with different IDH mutation status and identified core genes that could be potential markers and targets for diagnosis and treatment of GBMs.

Medulloblastoma (MB) is one of the most common intracranial malignancies in children. The present study applied integrated bioinformatics to identify potential core genes associated with the pathogenesis of MB and reveal potential molecular mechanisms. Through the integrated analysis of multiple data sets from the Gene Expression Omnibus (GEO), 414 differentially expressed genes (DEGs) were identified. Combining the protein-protein interaction (PPI) network analysis with gene set enrichment analysis (GSEA), eight core genes, including CCNA2, CCNB1, CCNB2, AURKA, CDK1, MAD2L1, BUB1B, and RRM2, as well as four core pathways, including "cell cycle", "oocyte meiosis", "p53 pathway" and "DNA replication" were selected. In independent data sets, the core genes showed superior diagnostic values and significant prognostic correlations. Moreover, in the pan-caner data of the cancer genome atlas (TCGA), the core genes were also widely abnormally expressed. In conclusion, this study identified core genes and pathways of MB through integrated analysis to deepen the understanding of the molecular mechanisms underlying the MB and provide potential targets and pathways for diagnosis and treatment of MB.

// Hailong Liu 1, 2 , Qianwen Sun 3 , Mingshan Zhang 1 , Zhihua Zhang 1, 2 , Xinyi Fan 2 , Hongyu Yuan 2 , Cheng Li 1 , Yuduo Guo 1 , Weihai Ning 1 , Youliang Sun 4 , Yongmei Song 2 , Chunjiang Yu 1 1 Department of Neurosurgery, Sanbo Brain Hospital Capital Medical University, Beijing, P.R. China 2 State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China 3 Department of Neurology, Qilu Hospital Shandong University, Jinan, P.R. China 4 School of Basic Medical Science, Capital Medical University, Beijing, P.R. China Correspondence to: Chunjiang Yu, email: neurosurgery2@163.com Yongmei Song, email: symlh2006@163.com Keywords: medulloblastoma, folate receptor 1, prognosis, biomarker, therapeutic target Received: November 22, 2016 Accepted: February 07, 2017 Published: February 18, 2017 ABSTRACT Medulloblastoma is the most common malignant brain tumor in children. Folate receptor 1 (Folr1) was abundantly expressed in some epithelial malignancies. However the expression profile and the role of clinicopathological significance and therapeutic target potential in medulloblastoma still remain elusive. Currently we detected the expression of Folr1 in medulloblastoma and identified the diagnostic application by evaluating the clinical, pathological and neuroimaging values. Then we developed a target therapeutic compound with Folr1, which exhibited promising efficiency in treatment of medulloblastoma. Folr1 expression was up-regulated in medulloblastoma and positively correlated with percentage of Ki-67 and MMP9 labeling, pathological subtypes, serum Folr1 levels and CSF spreading on MRI. The level of serum Folr1 showed rational sensitivity and specificity in predicting histological subgroups. Strong Folr1 expression was recommended as the independent value regarding the prognosis of patients with medulloblastoma. Folr1 targeted therapy attenuated the tumor growth and metastasis with down-regulation of MMPs proteins and activation of apoptosis. Immunostaining analysis in the xenograft samples showed the decreased Ki-67 and MMP9 index providing the strong evidences that Folr1 targeted application can suppress the proliferation and invasion. Our findings uncovered in Folr1 a predictive candidate and therapeutic target for medulloblastoma.

Blood-brain barrier (BBB) obstruction and the drug resistance of tumor cells severely reduce the efficiency of most chemotherapeutic drugs in the treatment of glioblastoma (GBM). Here, a thiolated oligo (p-phenylenevinylene) (Ang-OPV-PTX) bearing Angiopep-2 and paclitaxel (PTX) with BBB penetration capacity and increased drug efficiency is developed for GBM treatment. Ang-OPV-PTX can effectively penetrate the BBB through LRP1-mediated endocytosis with the help of Angiopep-2. In addition, the high level of reactive oxygen species (ROS) in GBM cells induces the crosslinking of sulfhydryl groups on Ang-OPV-PTX, leading to the formation of bulk aggregates, which prevents the efflux of the drug from tumor cells and improves drug efficacy. Moreover, Ang-OPV-PTX can specifically target and locate in GBM for a long-term therapeutic effect in vivo rather than normal tissues. Based on these characteristics, Ang-OPV-PTX has great potential in the clinical application of GBM chemotherapy.

For military and civilian applications, the ultra-wideband Radio Frequency (RF) receiver is in great demand. As the development and requirement in near future, a very receiver which can handle frequency carrier ranging tens of GHz is urgently desired [1]. Also considering that the electronic circuit receiver combined a mixer and analog to digital converter(ADC) has to filtering the extra signal at the back end [2], it is essential to provide a means to channelize the broadband signal spectrum into frequency channels of which bandwidths are compatible with digital electronics [3].

Medulloblastoma is the most common malignant CNS tumor of childhood. High expression of folate receptor 1 (Folr1) was observed in some malignant epithelial tumors. However its expression and the role for clinicopathological significance and targeted therapeutic potential in MB still remain unclear. Currently we have detected the expression of Folr1 in MB and identified its clinical, pathological and radiological values to be considered as a biomarker for diagnosis of MB. Then we studied the targeted treatment of MB with Folr1 targeted cytarabine (Folr1-Ara-C) both in vitro and in vivo. Folr1 were overexpressed in MB, while the level correlated with pathological subtypes. Folr1 expression was positively correlated with CSF spreading, Ki-67, MMP9, pathological subtypes and serum Folr1. Factors of age, CSF spreading, Ki-67, MMP9, strong Folr1 expression and pathological subtypes were found to be the independent prognostic values for patients with MB. Serum Folr1 showed rational sensitivity and specificity in demonstrating histological types. Folr1-Ara-C led to changes in cellular proliferation and invasion with down-regulation of MMPs proteins and activation of apoptosis in vitro. Using mouse xenografts, Folr1-Ara-C suppressed tumor growth and improved survival by MRI and PET/CT. Immunohistochemical analysis showed decreased Ki-67 and MMP9 index suggesting the effects on proliferation and invasion in vivo. Folr1 may be considered as a predictive candidate for histological types and serum Folr1 may be a novel non-invasive biomarker. The application of Folr1-Ara-C contributed to be one kind of targeted therapies for MB.

BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor in children. Although accumulated research suggests that cancer stem-like cells may play a key role in medulloblastoma tumorigenesis, the molecular mechanisms of proliferation still remain elusive and further investigation can provide a novel application for therapeutic target in MB patients. METHODS: The expression of MELK and EZH2 was detected by tissue microarray analysis with 88 MBs and its association with prognosis was identified. Co-location of MELK and EZH2 in MB CSCs and tissues was studied by using confocal and immunostaining. Immunoblotting analysis following co-immunoprecipitation was performed to check the interaction between MELK and EZH2. Through the loss-of-function study by siRNA, CSCs-drived tumor growth was detected. Then we studied the targeted treatment of MB with MELK and EZH2 inhibitor in vivo to confirm the molecular basis of MELK and EZH2. RESULTS: MELK and EZH2 co-located in the nuclei of MB CSCs and MB with extensive nodularity and large cell/anaplastic differed the staining levels as measured using microarray analysis when compared with the other two subgroups. The proportion of MELK positive staining cells was the potential indicator for the survival. MELK bound and phosphorylated EZH2 and its methylation was induced by EZH2 in MB, which regulated the proliferation of CSCs. MELK and EZH2 depletion by siRNA or treatment of inhibitors attenuated the MB CSCs-derived tumor growth in vivo. CONCLUSION: Interaction between MELK and EZH2 is essential for MB CSCs-drived tumor proliferation, thereby identifying a potential therapeutic strategy for MB patients.