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Resourceful beyond-graphene two-dimensional (2D) carbon crystals have been proposed/synthesized; however, the fundamental knowledge of their melting thermodynamics remains lacking. Here, the structural and thermodynamic properties of nine contemporary 2D carbon crystals upon heating are investigated using first-principle-based ReaxFF molecular dynamics simulations. Those 2D carbon crystals show distinct evolution of energetic and Lindemann index that distinguish their thermal stabilities. There are two or three critical temperatures at which structural transformation occurs for non-hexagon-contained 2D carbon allotropes. Analysis of polygons reveals that non-hexagon-contained 2D carbon crystals show thermally induced hex-graphene transitions via mechanisms such as bond rotations, dissociation, and reformation of bonds. The study provides new insights into the thermodynamics and pyrolysis chemistry of 2D carbon materials, as well as structural transitions, which is of great importance in the synthesis and application of 2D materials in high-temperature processing and environment.

Purpose Our previous study has shown that PTPRZ1-MET (ZM) fusion is a viable target for MET inhibitors in gliomas. However, the diversity and prevalence of somatic MET alterations in diffuse gliomas are still elusive and need to be extensively characterized for identifying novel therapeutic targets. Methods Totally, 1,350 glioma patients and 31 patient-derived cells were collected from the Chinese Glioma Genome Atlas (CGGA) and published data. All kinds of MET fusions and/or splicing variants (MET F/SVs) were identified by bioinformatical methods. Single-cell RNA sequencing (scRNA-seq) were used for validation. In vitro experiments of drug resistance were conducted for the possibility of MET-targeted treatment. Results MET F/SVs but not genomic amplification, were highly enriched in the secondary glioblastomas (sGBM) and marked worse prognosis. Further molecular and scRNA-seq analysis revealed that MET F/SVs were induced in the course of glioma evolution and highly associated with MET overexpression. Subsequent in vitro and the clinical study showed that cells and patients harboring MET F/SVs have better response to MET inhibitors. Conclusion Our findings expanded the percentage of gliomas with abnormal MET alterations and suggested that a subgroup of gliomas harboring MET F/SVs may benefit from MET-targeted therapy.

Microemulsions have been attracting great attention for their importance in various fields including nanomaterials fabrication, food industry, drug delivery, and enhanced oil recovery. Atomistic insights into the self-microemulsifying process and the underlying mechanisms are crucial for the design and tuning of the size of microemulsion droplets towards applications. In this work, coarse-grained models were used to investigate the role of droplet sizes played in the preliminary self-microemulsifying process. Time evolution of liquid mixtures consisting of several hundreds of water/surfactant/oil droplets was resolved in large-scale simulations. By monitoring the size variation of the microemulsion droplets in the self-microemulsifying process, the dynamics of diameter distribution of water/surfactant/oil droplets were studied. The underlying mass transport mechanisms responsible for droplet size evolution and stability were elucidated. Specifically, temperature effects on the droplet size were clarified. This work supplies the knowledge of the self-microemulsifying of the water-in-oil microemulsions at the nanoscale. The results are expected to serve as guidelines for practical strategies for preparing a microemulsion system with desirable droplet sizes and properties.

Aims We aimed to create a tumor recurrent‐based prediction model to predict recurrence and survival in patients with low‐grade glioma. Methods This study enrolled 291 patients (188 in the training group and 103 in the validation group) with clinicopathological information and transcriptome sequencing data. LASSO‐COX algorithm was applied to shrink predictive factor size and build a predictive recurrent signature. GO, KEGG, and GSVA analyses were performed for function annotations of the recurrent signature. The calibration curves and C‐Index were assessed to evaluate the nomogram's performance. Results This study found that DNA repair functions of tumor cells were significantly enriched in recurrent low‐grade gliomas. A predictive recurrent signature, built by the LASSO‐COX algorithm, was significantly associated with overall survival and progression‐free survival in low‐grade gliomas. Moreover, function annotations analysis of the predictive recurrent signature exhibited that the signature was associated with DNA repair functions. The nomogram, combining the predictive recurrent signature and clinical prognostic predictors, showed powerful prognostic ability in the training and validation groups. Conclusion An individualized prediction model was created to predict 1‐, 2‐, 3‐, 5‐, and 10‐year survival and recurrent rate of patients with low‐grade glioma, which may serve as a potential tool to guide postoperative individualized care., Based on large sample of clinical and sequencing data, we constructed an individualized prediction model for recurrence time predicting. The prediction model is accurate and simple enough to be widely applied for postoperative individualized care guidance of low‐grade gliomas.

Background: Old age has been demonstrated to be a risk factor for GBM, but the underlying biological mechanism behind this association is still unclear. We designed this study with the goal of determining a mechanistic explanation for the link between age and pathogenesis in GBM. Methods: In total, we enrolled transcriptome data from 616 primary GBM samples and 41 non-tumor brain samples in this study. Transcriptome data and clinical information were obtained from the CGGA, TCGA, and GSE53890 databases. Gene Set Variation Analysis and Gene Ontology analyses were the primary analytical methods used in this study. All statistical analyses were performed using R. Findings: We found that the expression of RPP30, an independent prognostic factor in GBM, was negatively correlated with age in both tumor and non-tumor brain samples. However, the post-transcriptional modifications carried out by RPP30 were different in primary GBM and non-tumor brain samples. RPP30 affected protein expression of cancer pathways by performing RNA modifications. Further, we found that RPP30 was related to drug metabolism pathways important in GBM. Interpretation: The decreased expression of RPP30 in older patients might be a pathogenic factor for GBM. Funding Statement: This work was supported by grants from National Natural Science Foundation of China (No. 81672479, 81802994), National Natural Science Foundation of China (NSFC)/Research Grants Council (RGC) Joint Research Scheme (81761168038), Beijing Municipal Administration of Hospitals’ Mission Plan (SML20180501). Declaration of Interests: No potential conflicts of interest were disclosed. Ethics Approval Statement: This study was approved by Beijing Tiantan Hospital institutional review board (IRB). All patients provided written informed consent for the publication of all associated data in this study.

Immune response mediated by macrophages is critical in tumor progression and implicates new targets in potential efficient immunotherapies. Tumor associated macrophages (TAM) are divided into either polarized M1 or M2 phenotype depending on different regulators of polarization and pro- or anti-oncogenic roles they play. Glioma-infiltrated TAMs have been newly reported contrary to the current polarization dogma. Instead, macrophages in glioma exhibit a continuum phenotype between the M1- and M2-like TAM that resembling M0 macrophage. Here we proposed an OS (overall survival)-correlated gene EFEMP2 (EGF containing fibulin-like extracellular matrix protein 2) via screening with transcriptional expression levels and methylation data in two glioma databases. EFEMP2 was found highly expressed in glioma of higher WHO grade and Mesenchymal subtype glioma, and its transcriptional level could predict OS efficiently in validation datasets. EFEMP2 exhibited a remarkable preference of intercellular expression. In vitro assay showed that EFEMP2’s level in medium was closely related to glioma cells’ growth. Moreover, EFEMP2 expression level was remarkably correlated with immunological responses. M0-like macrophage as a feature of malignancy of glioblastoma revealed distinct assembly in glioma with high level of EFEMP2. These results revealed EFEMP2’s role as a potential characteristic marker of malignant glioma, which are enriched of M0 macrophage.

Background Glioblastoma is the most malignant tumor of the central nervous system. Several prediction models have been produced to aid in prognosis assessment. Age, a primary decision factor for prognosis, is associated with increased genomic alterations, however the exact link between increased age and poor prognosis is unknown. Objective In this study, we aimed to reveal the underlying cause of poor prognosis in elderly patients. Methods This study included data on 616 primary GBM tumor samples from the CGGA and TCGA databases and 41 nontumor brain tissue samples obtained from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53890. Hallmarks and clinicopathological characteristics were evaluated in both tumor and nontumor brain tissues. The association between choice of treatment regimen and age was measured using ANOVA and Student's t test. Results Age was a robust predictor of poor prognosis in glioma. No age‐related hallmarks of cancer were detected, including pathological characteristics or mutations. However, treatment choice was strongly significantly different between old and young patients. Combined chemo‐radiation therapy could benefit old and young GBM patients, however, old patients are currently less likely to choose it. Conclusion The vast divergence in prognosis between young and old GBM patients is largely caused by choice of treatment rather than age‐related tumor genomic characteristics. Postoperative standard radio‐ and chemotherapy provide strong benefits to primary glioblastoma patients of all ages., The main reason of poorer prognosis in elder patients was conservative treatment choosing, while standard radio‐ and chemotherapy should be generalized in all age grade of patients.

Unwanted gas hydrates blockage is a threat to the safety of oil-gas pipeline systems. Deploying passive anti-hydrate surfaces is a promising approach to circumventing the long-lasting hydrate problem, and a precise understanding of the interactions between hydrate and solid surfaces is a prerequisite for the creation of such surfaces. In this work, the underlying mechanisms and the key influencing factors of hydrate adhesion are explored by large-scale molecular dynamics simulations. Hydrates with an intermediate layer (IML) containing varied gas content are brought to contact with solid surfaces having different levels of wettability and roughness. It is found that the final IML structure is dictated by the gas concentration. Enriching gas content in the vicinity of solid surfaces is crucial for lowering hydrate adhesion strength. The results indicate that forming a molecular gas layer or gas bubbles on solid surfaces can enable the automatic detachment of the eventually formed hydrate on a pipeline wall surface under the action of shear flow. This study manifests our approach of utilizing an interfacial gas-enrichment strategy (IGES) for weakening hydrate adhesion as a novel passive anti-hydrate surface design. An interfacial gas-enrichment strategy for mitigating hydrate adhesion and blockage

Janus nanoparticles (NPs) hold great potential in enhanced oil recovery (EOR), although the mechanism remains unclear. In the study, the displacement dynamics of trapped oil in the rough channel by Janus NPs are unraveled through atomistic modeling. The results indicate that Janus NPs with large polar faces significantly recover more oil from the nano-pocket (nano groove of the surface). The structure of adsorbed NPs on the wall of oil-trapping nano-pockets strongly causes the local wettability alteration, which ultimately determines the oil recovery. The crucial events in oil recovery by Janus NPs, termed ‘adsorption invasion process’, are identified, which comprise of anchoring onto the surface, pinning at the edge, and entering inside the pocket. The controlling factors are further detailed, including identification of the residual oil, displacement pressure, and the geometry of the oil-water interface inside nano-pockets. With the proposed analysis, the “huff-n-puff” mode is verified as the optimized application method for Janus NPs. For the first time, our results bring to light the dynamic wettability alteration on the rough surface by Janus NPs from atomistic insights. The findings reveal the intrinsic EOR mechanism of Janus NPs, which could guide the design and application of Janus NPs in EOR.

Natural gas hydrate is a promising future energy source, but it also poses a huge threat to oil and gas production due to its ability to deposit within and block pipelines. Understanding the atomistic mechanisms of adhesion between the hydrate and solid surfaces and elucidating its underlying key determining factors can shed light on the fundamentals of novel antihydrate materials design. In this study, large-scale molecular simulations are employed to investigate the hydrate adhesion on solid surfaces, especially with focuses on the atomistic structures of intermediate layer and their influences on the adhesion. The results show that the structure of the intermediate layer formed between hydrate and solid surface is a competitive equilibrium of induced growth from both sides, and is regulated by the content of guest molecules. By comparing the fracture behaviors of the hydrate–solid surface system with different intermediate structures, it is found that both the lattice areal density of water structure and the adsorption of guest molecules on the interface together determine the adhesion strength. Based on the analysis of the adhesion strength distribution, we have also revealed the origins of the drastic difference in adhesion among different water structures such as ice and hydrate. Our simulation indicates that ice-adhesion strength is approximately five times that of lowest hydrate adhesion strength. This finding is surprisingly consistent with the available experimental results.

Glioblastoma is a paradigm of cancer-associated immunosuppression, limiting the effects of immunotherapeutic strategies. Thus, identifying the molecular mechanisms underlying immune surveillance evasion is critical. Recently, the preferential expression of inhibitory natural killer (NK) cell receptor CD161 on glioma-infiltrating cytotoxic T cells was identified. Focusing on the molecularly annotated, large-scale clinical samples from different ethnic origins, the data presented here provide evidence of this immune modulator's essential roles in brain tumor biology.Retrospective RNA-seq data analysis was conducted in a cohort of 313 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 603 patients in The Cancer Genome Atlas (TCGA) database. In addition, single-cell sequencing data from seven surgical specimens of glioblastoma patients and a model in which patient-derived glioma stem cells were cocultured with peripheral lymphocytes, were used to analyze the molecular evolution process during gliomagenesis.CD161 was enriched in high-grade gliomas and isocitrate dehydrogenase (IDH)-wildtype glioma. CD161 acted as a potential biomarker for the mesenchymal subtype of glioma and an independent prognostic factor for the overall survival (OS) of patients with glioma. In addition, CD161 played an essential role in inhibiting the cytotoxicity of T cells in glioma patients. During the process of gliomagenesis, the expression of CD161 on different lymphocytes dynamically evolved.The expression of CD161 was closely related to the pathology and molecular pathology of glioma. Meanwhile, CD161 promoted the progression and evolution of gliomas through its unique effect on T cell dysfunction. Thus, CD161 is a promising novel target for immunotherapeutic strategies in glioma treatment.

Background The prognosis for diffuse gliomas is very poor and the mechanism underlying their malignant progression remains unclear. Here, we aimed to elucidate the role and mechanism of the RNA N6,2′-O-dimethyladenosine (m6A) reader, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), in regulating the malignant progression of gliomas. Methods YTHDF2 mRNA levels and functions were assessed using several independent datasets. Western blotting, quantitative polymerase chain reaction, and immunohistochemistry were used to evaluate the expression levels of YTHDF2 and other molecules in human and mouse tumor tissues and cells. Knockdown and overexpression were used to evaluate the effects of YTHDF2, methyltransferase-like 3 (METTL3), and UBX domain protein 1 (UBXN1) on glioma malignancy in cell and orthotopic xenograft models. RNA immunoprecipitation (RIP), methylated RIP, and RNA stability experiments were performed to study the mechanisms underlying the oncogenic role of YTHDF2. Results YTHDF2 expression was positively associated with a higher malignant grade and molecular subtype of glioma and poorer prognosis. YTHDF2 promoted the malignant progression of gliomas in both in vitro and in vivo models. Mechanistically, YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-κB activation. We further revealed that UBXN1 overexpression attenuated the oncogenic effect of YTHDF2 overexpression and was associated with better survival in patients with elevated YTHDF2 expression. Conclusions Our findings confirmed that YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-κB activation via UBXN1 with a primary focus on m6A modification.

Background Inhibitors of immune checkpoints have shown little effect in clinical trials involving glioma patients. Here, we explored novel targets for use in future treatments. Previous studies showed the sialic acid-binding Ig-like lectin (Siglec) family to have a specific role in immunosuppression. We aimed to study the characteristics and immune function of Siglec family members. Methods Transcriptome data from 1024 glioma samples and 1551 glioma single cells were used in our study. Clinical and molecular pathology information was also included. Statistical, bioinformatical methods, and single-cell sequencing analysis were applied to investigate the role of Siglec family members. Results Siglecs-5, -7, -9, and -16 showed a significant correlation with immunosuppression in glioma. They are typically expressed in higher grade, IDH-wildtype, and mesenchymal subtype gliomas. Siglec-5, -7, and -9 had a similar immune function to TIM-3, while Siglec-16 was similar to PD-L1, suppressing tumor immunity via different mechanisms. Joint use of Siglec-inhibitors and immune checkpoint inhibitors could prolong the survival of glioma patients. Conclusion Siglec-5, -7, -9, and -16 suppressed tumor immunity in different ways. Joint usage of inhibitors may be an effective means to improve the efficacy of glioma immunotherapy.

Background PTPRZ1‐MET (ZM) is a critical genetic alteration driving the progression of lower‐grade glioma. Glioma patients harboring ZM could benefit from MET inhibitors. According to the remarkable role of ZM as a driver of glioma progression and indicator of MET inhibitor sensitivity, it is necessary to detect this alteration even when it presents in glioma with relatively fewer copies. Methods Herein, we proposed that ZM could be detected with a high‐sensitive method of reverse transcriptase PCR with 50 amplification cycles. Via this newly proposed detection method, we depicted the incidence preference of ZM fusion in a cohort of 485 glioma patients. To further explore the oncogenic nature of ZM, we predicated the protein structure alteration of MET kinase brought by its fusion partner. Results The incidence of ZM fusions was much higher than previous report. ZM fusions exhibited a striking preference in lower‐grade glioma and secondary glioblastoma. By contrast, none of patients with primary glioblastoma was detected harboring ZM fusion. In each of the four variants of ZM, the fusion partner segment of MET contained a remarkable coiled‐coil motif. In glioma cells expressing ZM, MET kinase could be activated in a ligand‐independent manner, which might be contributed by the special coiled‐coil structure brought by the fusion partner. Corresponding to the 3D structural analysis and cell line experiment, the ZM positive clinical specimens showed hyperactivations of MET signaling. Conclusions ZM fusions are critical drivers of glioma progression and effective target of MET inhibitor. Early detection could be performed with a high‐sensitive method of reverse transcriptase PCR. The hyperactivations of MET signaling driving glioma progression might be contributed by a ligand‐independent activation enabled by the protein structure modification of extracellular domain of MET in ZM fusions., Glioma tissue RNA was abstracted after surgery. RT‐PCR of 50 amplification cycles then was performed with the primers designed based on the PTPRZ1 and MET segments that are common to all the four ZM fusion variants. The PCR products of different ZM variants were of different sizes. All the PCR product bands on agarose gel were purified and sequenced via Sanger sequencing. The sequencing reads were aligned to the known ZM fusion sequences. The existence and the variant of ZM fusions then was confirmed and clinically reported.

Nanoparticles (NPs) possess great potentials in applications to enhanced oil recovery (EOR), the underlying mechanisms of which however remain to be explored. In this study, the motion of NPs and the local pressure distribution in a trapped oil droplet/nanofluid system in confined nanochannels are scrutinized by molecular dynamic simulations. Depending on the particle wettability, three different motion patterns have been observed: hydrophilic NPs are more likely to be adsorbed on the solid surface of the channel and stay close to the three-phase contact areas, hydrophobic NPs tend to move inside the oil droplet as clusters, and NPs with mixed hydrophobicity are prone to be trapped at the oil-water interface. It is shown that the existence of NPs introduces high local pressure in the nanochannels, especially at locations where NPs aggregate. Significantly, in the three-phase contact area for hydrophilic NPs, the local pressure distribution features the postulated structural disjoining pressure reported in the literature. For the first time, our molecular dynamics simulation results elucidate nanoparticle-induced structural disjoining pressure at the atomistic scale. The results thus provide a better understanding on the fundamentals of nanofluids in confined channels and serve as guidelines for the design of NPs for EOR applications.

Glioma is the most common and malignant cancer of the central nervous system, and the prognosis is poor. Metabolic reprogramming is a common phenomenon that plays an important role in tumor progression including gliomas. Searching the representative process among numerous metabolic processes to evaluate the prognosis aside from the glycolytic pathway may be of great significance. A novel prediction signature was constructed in the present study based on gene expression. A total of 1027 glioma samples with clinical and RNA-seq data were used in the present study. Lasso-Cox, gene set variation analysis, Kaplan–Meier survival curve analysis, Cox regression, receiver operating characteristic curve, and elastic net were performed for constructing and verifying predictive models. The R programming language was used as the main tool for statistical analysis and graphical work. This signature was found to be stable in prognostic prediction in the Chinese Glioma Genome Atlas Network and the Cancer Genome Atlas databases. The possible mechanism was also explored, revealing that the aforementioned signature was closely related to DNA replication and ATP binding. In summary, a prognosis prediction signature for patients with glioma based on five genes was constructed and showed great potential for clinical application.

It is well accepted that nanofluids have great potential in enhanced oil recovery (EOR). However, the EOR mechanisms by nanofluids largely remain elusive. In the study, the displacement dynamics of residual oil trapped in rough channels by different nanofluids under varied injection pumping forces are investigated by atomistic modeling. Our results indicate that both hydrophilic nanoparticles (NPs) and Janus NPs have highly obvious oil displacement effects. Specifically, hydrophilic NPs increase the viscosity and enlarge the sweeping scope of injected fluid, while Janus NPs favor either staying at the oil-water interface to reduce the interfacial tension or adsorbing onto the convex surface. Under the drag of the injecting flux, Janus NPs displace trapped oil molecules and alter the local surface wettability by sliding along the surface. In contrast, hydrophobic NPs are prone to migrate into the oil phase, which not only reinforces the trapping effect of the oil molecules by the rough surface but also poses a risk of channel blockage. Despite that the oil displacement effect of all the injection fluids is found to be less significant with low pumping force, the Janus NPs are able to maintain a stable oil displacement performance under low pumping force thanks to their sufficiently long contact time with oil phase. Furthermore, analysis on capillary number indicate that Janus NPs have outstanding application potentials in reservoirs under realistic flooding conditions. Our findings provide atomistic insights into the mechanism of nanofluids in EOR and shed light on the selection and optimization of NPs.

Activating alterations of the MET gene are well-characterized oncogenic drivers, and MET inhibitors could successfully treat several tumor types with MET alterations, including gliomas with PTPRZ1-MET fusion. However, the full diversity and prevalence of MET alterations in gliomas are still lacking to accurately identify a subset of patients likely to benefit from MET inhibitor treatment. Here, we interrogated genomic profiles of 1,351 gliomas, and further identify 60 cases harboring MET alterations, including MET fusions and various MET exon skipping events. MET RNA alterations, but not MET amplification, are highly enriched in the secondary glioblastomas (sGBM) with significantly worse prognosis. Further molecular analysis has shown that MET RNA alterations acting an additive effects of MET overexpression are induced in the course of glioma evolution. In vitro and clinical studies indicate cells and patients harboring MET alterations have better response to MET inhibitors. Collectively, these data suggest that a subgroup of gliomas harboring MET alterations likely to have benefit from MET-targeted therapy.

Glutaredoxin is central to cellular redox chemistry and regulates redox homeostasis and malignant progression of many cancers. In glioma, the role of its coding gene (GLRX) remains unclear. We aimed to elucidate the role of glutaredoxin at the transcriptome level and its clinical prognostic value in glioma. In total, we evaluated 1,717 glioma samples with transcriptome data and corresponding clinical data as well as single-cell sequencing data from 6 glioma patients from publicly available databases. Gene set variation analysis and gene ontology analysis were performed to reveal the biological function of GLRX. The immune cell enrichment score was calculated by GSVA analysis. Single-cell sequencing data was visualized by t-distributed stochastic neighbor embedding analysis. The prognostic value of GLRX in glioma was verified by the Kaplan-Meier curve and multivariate COX analysis. GLRX was found to be highly enriched in gliomas of higher grades with wild-type IDH, without 1p/19q co-deletion, and with a methylated MGMT promoter. Moreover, GLRX could be a potential marker for the mesenchymal molecular subtype of gliomas. The expression of GLRX was closely related to the tumor immune process, immune checkpoints, and inflammatory factors with GLRX being specifically expressed in M0 macrophages. GLRX is also shown to be an independent prognostic factor in glioma. Altogether, our study outcomes show that GLRX is highly enriched in malignant gliomas and is closely related to the tumor immune microenvironment. Therefore, GLRX-targeted cell redox regulatory therapy may enhance the efficacy of glioma immunotherapy.

1p/19q codeletion, which leads to the abnormal expression of 1p19q genes in oligodendroglioma, is associated with chemosensitivity and favorable prognosis. Here, we aimed to explore the clinical implications of 1p19q gene expression in 1p/19q non-codel gliomas. We analyzed expression of 1p19q genes in 668 1p/19q non-codel gliomas obtained from The Cancer Genome Atlas (n = 447) and the Chinese Glioma Genome Atlas (n = 221) for training and validation, respectively. The expression of 1p19q genes was significantly correlated with the clinicopathological features and overall survival of 1p/19q non-codel gliomas. Then, we derived a risk signature of 25 selected 1p19q genes that not only had prognosis value in total 1p/19q non-codel gliomas but also had prognosis value in stratified gliomas. The prognosis value of the risk signature was superior than known clinicopathological features in 1p/19q non-codel gliomas and was also highly associated with the following features: loss of CDKN2A/B copy number in mutant-IDH-astrocytoma; telomerase reverse transcriptase (TERT) promoter mutation, combined chromosome 7 gain/chromosome 10 loss and epidermal growth factor receptor amplification in wild-type-IDH-astrocytoma; classical and mesenchymal subtypes in glioblastoma. Furthermore, genes enriched in the biological processes of cell division, extracellular matrix, angiogenesis significantly correlated to the signature risk score, and this is also supported by the immunohistochemistry and cell biology experiments. In conclusion, the expression profile of 1p19q genes is highly associated with the malignancy and prognosis of 1p/19q non-codel gliomas. A 25-1p19q-gene signature has powerfully predictive value for both malignant molecular pathological features and prognosis across distinct subgroups of 1p/19q non-codel gliomas.

Background: Glioblastoma (GBM) is the most common and malignant cancer in the central nervous system, and radiotherapy is wildly applied in GBM treatment. However, the sensitivity of radiotherapy varies in different patients. In order to solve this clinical dilemma, a radiosensitivity prediction signature was constructed based on genomic methylation. Methods: In this study, a total of 1044 primary GBM samples with clinical and methylation microarray data were involved. LASSO-COX, GSVA, Kaplan-Meier survive curve and COX regression were performed in construction and verification of predictive models. R language was used as the main tool for statistical analysis and graphical work. Findings: Through the integration analysis of methylation and survival data in primary GBM, a novel prognostic and radio-sensitivity prediction signature was constructed. Interpretation: This signature was stable in prognosis prediction in TCGA and CGGA databases. The possible mechanism was also explored, this signature was closely related to DNA repair functions. Importantly, this signature could predict whether GBM patients could benefit from radiotherapy. In conclusion, our study built a radiosensitivity prediction signature for GBM patients based on five methylated probes with great potential for clinical application. Funding: National Natural Science Foundation of China (No. 81672479). Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: This study was approved by Beijing Tiantan Hospital institutional review board (IRB).

Background Treatment insensitivity is the main cause of glioma. This study was designed to screen out effective drugs for recurrent gliomas based on the transcriptomics data. Methods A total of 1,018 glioma patients with transcriptome sequencing data and clinical data were included in this study. There were 325 patients in the discovery cohort, including 229 primary patients and 92 recurrent patients. There were 693 patients in the validation cohort, including 422 primary patients and 271 relapsed patients. Drug Resistant Scores (DRS) of 4,865 drugs of each patient were used for screening. The analysis and drawing in this study were mainly based on R language. Results After high-throughput drug screening, we found that recurrent glioma patients were most sensitive to sermorelin. Further analysis revealed that sermorelin was suitable for recurrent patients with high grade, IDH-wildtype and 1p/19q non-codeletion status. GO and KEGG analyses found that sermorelin may inhibit tumor cell proliferation by cell cycle blocking. Moreover, sermorelin was also related to the immune system process and negatively regulated immune checkpoints and M0 macrophages. Lastly, the Kaplan-Meier method showed the patient's benefit from sermorelin was independent of postoperative adjuvant treatment. Conclusions Recurrent glioma patients are sensitive to sermorelin and it makes effect through glioma cells proliferation inhibiting and immune response enhancing.

Background: Co-deletion of chromosome arms 1p and 19q in oligodendroglial tumors is associated with chemosensitivity and favorable prognosis. Here, we explored the prognostic value of the expression of a panel of 1p19q genes in 1p/19q non-codeletion gliomas. Methods: We analyzed expression of 1p19q genes in 668 1p/19q non-codel gliomas obtained from The Cancer Genome Atlas (TCGA) (n = 447) and the Chinese Glioma Genome Atlas (CGGA) (n = 221) for training and validation, respectively. Least Absolute Shrinkage and Selection Operator Cox regression analysis was applied to build a gene risk signature. Results: Expression of 1p19q genes was significantly associated with the overall survival of patients with 1p/19q non-codel gliomas. We derived a risk signature of 25 selected 1p19q genes that successfully stratified the overall survival of 1p/19q non-codel glioma patients in both the TCGA and CGGA datasets into high- and low-risk groups (both P < 0.0001). Bioinformatics analysis revealed that the signature genes were significantly enriched in cell division, extracellular matrix, angiogenesis, DNA damage repair, and immune or inflammatory response processes, and these were supported by the immunohistochemistry. The risk signature not only predicted the chemoradiotherapeutic outcomes of glioblastoma and WHO grade III glioma patients but was also an independent prognostic marker for patients with 2016 WHO integrated diagnosis glioma subtypes. Conclusion: A risk signature consisting of 25 1p19q genes identified high-risk and low-risk categories of 1p/19q non-codel gliomas. This signature may be helpful for developing potential treatments strategies for these patients. Funding Statement: This work was supported by the National Natural Science Foundation of China (81773208, 81402052); the Beijing Nova Program (Z16110004916082); the National Key Research and Development Plan (2016YFC0902500). Declaration of Interests: The authors declare: "none." Ethics Approval Statement: This study was approved by the institutional review board of Beijing Tiantan Hospital.