No abstract

During metabolic reprogramming, glioma cells and their initiating cells efficiently utilized carbohydrates, lipids and amino acids in the hypoxic lesions, which not only ensured sufficient energy for rapid growth and improved the migration to normal brain tissues, but also altered the role of immune cells in tumor microenvironment. Glioma cells secreted interferential metabolites or depriving nutrients to injure the tumor recognition, phagocytosis and lysis of glioma-associated microglia/macrophages (GAMs), cytotoxic T lymphocytes, natural killer cells and dendritic cells, promoted the expansion and infiltration of immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and conferred immune silencing phenotypes on GAMs and dendritic cells. The overexpressed metabolic enzymes also increased the secretion of chemokines to attract neutrophils, regulatory T cells, GAMs, and dendritic cells, while weakening the recruitment of cytotoxic T lymphocytes and natural killer cells, which activated anti-inflammatory and tolerant mechanisms and hindered anti-tumor responses. Therefore, brain-targeted metabolic therapy may improve glioma immunity. This review will clarify the metabolic properties of glioma cells and their interactions with tumor microenvironment immunity, and discuss the application strategies of metabolic therapy in glioma immune silence and escape.

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Soil microbial community composition and litter quality are important drivers of litter decomposition, but how litter quality influences the soil microbial composition largely remains unknown. We conducted a microcosm experiment to examine the effects of changes in litter quality induced by long-term N deposition on soil microbial community composition. Mixed-species litter and single-species litter were collected from a field experiment with replicate plots exposed to long-term N-addition in a semiarid grassland in northern China. The litters were decomposed in a standard live soil after which the composition of the microbial community was determined by Illumina MiSeq Sequencing. Changes in litter stoichiometry induced by N-addition increased the diversity of the fungal community. The alpha-diversity of the fungal community was more sensitive to the type of litter (mixed-or single-species) than to the N-addition effects, with higher abundance of fungal OTUs and Shannon-diversity observed in soil with mixed-species litter. Moreover, the relative abundance of saprophytic fungi increased with increasing N-addition rates, which suggests that fungi play an important role in the initial stages of the decomposition process. Litter type and N addition did not significantly change the diversity of bacterial community. The relative abundance of ammonia-oxidizing bacteria was lower in high N-addition treatments than in those with lower N input, indicating that changes in litter stoichiometry could change ecosystem functioning via its effects on bacteria. Our results presented robust evidence for the plant-mediated pathways through which N-42 deposition affects the soil microbial community and biogeochemical cycling.

The precise control of the domain structure, layer thickness, and stacking order of graphene has attracted intense interest because of its great potential for nanoelectronics applications. Much effort has been devoted to synthesize semiconducting Bernal (AB)-stacked bilayer graphene because of its tunable band structure and electronic properties that are unavailable to single-layer graphene. However, fast growth of large-scale bilayer graphene sheets with a high AB-stacking ratio and high mobility on copper poses a tremendous challenge, which has to overcome the self-limiting effect. This study reports a low-cost but facile method to rapidly synthesize bilayer Bernal graphene by atmospheric pressure chemical vapor deposition using polystyrene as the feedstock. The bilayer graphene grains and continuous film obtained are of high quality and exhibit field-effect hole mobilities as high as 5700 and 2200 cm 2 V −1 s −1 at room temperature, respectively. In addition, a synchronous growth mechanism of bilayer graphene is revealed by monitoring the growth process, resulting in a high surface coverage of nearly 100% for a near-perfect AB-stacking order. This new synthesis route is significant for industrial application of bilayer graphene and investigation of the growth mechanism of graphene by the chemical vapor deposition process.

Objectives: Glioblastoma is the most common malignant glioma of all brain tumours.It is difficult to treat because of its poor response to chemotherapy and radiotherapy and high recurrence rate after treatment. The aetiology of glioblastoma is a result of disorders of multiple factors. Depending on cell signal transduction, these glioblastoma-associated factors lead to cell proliferation, differentiation and apoptosis.Therefore, investigation of the potential factors which involved in the development of glioblastoma could provide a new target for the treatment of glioblastoma. Materials and methods:We analysed the transcript expression of CLEC5A in glioblastoma by accessing The Cancer Genome Atlas (TCGA). qRT-PCR was performed to detect the RNA expression of genes in cells and tissues, and Western blot was used to measure the protein levels (Cyclin D1, Bcl-2, BAX, PCNA, MMP2, MMP9, Akt and Akt phosphorylation) in tissues and cells. Cell proliferation, migration, invasion, cycle and apoptosis were measured by CCK-8, transwell and flow cytometry assays, respectively. Ki67 level and lung metastasis were determined by immunochemistry and H&E staining. Results:In this study, we found that CLEC5A was highly upregulated in glioblastoma compared to normal brain tissues, which had an opposite relation with the overall patient survival. Downregulation of CLEC5A could inhibit cell proliferation, migration and invasion via promoting apoptosis and G1 arrest. In contrast, overexpression of CLEC5A stimulated cell proliferation, migration and invasion. In addition, we found that CLEC5A level was positively correlated with Akt phosphorylation level. Akt inhibitor or agonist could reverse the modulation effects of CLEC5A in glioblastoma.Moreover, In vivo results suggested that inhibition of CLEC5A significantly reduced tumour size, weight, cell proliferation ability and lung metastasis via inhibition of phosphorylation Akt. Conclusion:Both in vitro and in vivo evidences supported that CLEC5A was involved in glioblastoma pathogenesis via regulation of PI3K/Akt pathway. Thus, CLEC5A might serve as a potential therapeutic target in the treatment of glioblastoma in the future.

Temozolomide (TMZ) is currently the first-line drug used for clinical postoperative or non-surgical chemotherapy for glioma, but acquired and intrinsic resistance to TMZ limits its application. The anti-proliferative effect of formononetin on human glioma cells had been confirmed. To improve therapeutic effects of TMZ, we studied the effect of formononetin in combination with TMZ on C6 glioma cells. The anti-proliferative effect of C6 cells was tested by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The synergy was evaluated by Chou-Talalay method. Morphological changes were observed by hematoxylin-eosin (HE) staining. The effect of formononetin in combination with TMZ on apoptosis of C6 cells was investigated by flow cytometry. The effect of formononetin in combination with TMZ on migration of cells was investigated by wound healing assay and transwell assay. The expression of proteins related to apoptosis and migration were detected by Western blot. These results showed that formononetin or TMZ alone could inhibit the growth of C6 cells in dose-dependent manner and formononetin in combination with TMZ had synergy effect on C6 cells. Further changes in cell morphology could be observed in drug combination by HE staining. Drug combination enhanced the expression of Bax, Cleaved Caspase-3, Cleaved Caspase-9, decreased the expression of Bcl-2, and promoted tumor cells apoptosis. In addition, the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were down-regulated via drug combination which resulted into inhibiting migration of C6 cell. In conclusion, formononetin in combination with TMZ can play a synergistic role in anti-C6 cells, the mechanisms of synergy depended on multiple pathways.

The cultivation of Panax notoginseng is often seriously hindered by root rot disease caused by the accumulation of soil-borne pathogens. Here, the inhibitory activity of Brassica juncea volatiles on P. notoginseng root rot pathogens was assessed and compounds in volatiles were identified. Furthermore, the antimicrobial activity and mechanism of allyl isothiocyanate (AITC) were deciphered by integrated transcriptome and metabolome analyses. The volatiles of B. juncea showed dose-dependent antimicrobial activity against root rot pathogens. AITC, identified as the main volatile compound, not only significantly inhibited pathogen growth in vitro but also suppressed root rot disease in the field. Integrated transcriptomic and metabolomics analysis revealed that AITC inhibited Fusarium solani by interfering with energy production and induced the accumulation of ROS by decreasing the content of glutathione (GSH). In summary, B. juncea releases AITC to inhibit soil-borne pathogens and could be used as a rotation crop or soil fumigant to alleviate root rot disease.