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The application of controlled-release fertilizer was an effective measure to improve the fertilizers utilization, increase yield, and reduce environmental pollution. This study aimed to explore the effects of application times and frequency and fertilization ratio of controlled-release compound fertilizer with different nutrient release periods on apple production. The experimental design consisted of controlled-release compound fertilizers with nutrient release period of 3 months (C3), controlled-release compound fertilizers with nutrient release period of 6 months (C6), and common compound fertilizer (CCF). The treatments included (1) one-time application of C6 in March (B-C6); (2) one-time application of C6 in October (H-C6); (3) one-time application of 50% C3 and 50% C6 in March (B-(50C3 + 50C6)); (4) one-time application of 70% C3 and 30% C6 in March (B-(70C3 + 30C6)); (5) common compound fertilizer (CCF) with one-time application of CCF in March (B-CCF); and (6) common compound fertilizer with three-time application of CCF in March, June, and October (CT). The index of apple yield, apple tree growth index, fruit quality, and soil nutrient status were evaluated in 2-year filed production system. The results indicated that the treatment of B-(50C3 + 50C6) significantly improved the growth of apple trees on trunk diameter, plant height, new shoot growth and chlorophyll content, and the apple yield increased by 8.82%. By comprehensive comparison of yield, soil nutrients, and fruit tree growth indexes, the treatment with (B-(50C3 + 50C6)) was considered to be the best controlled-release fertilizer application method.

Background：Glioblastoma multiforme (GBM) is one of the most common malignancies in the world and many studies have used traditional high-throughput RNA sequencing (bulk RNA-seq) data to explore its potential prognostic markers. However, it is unable to detect specific cellular and molecular changes in tumour cells. The aim of this study was to use single cell RNA-seq (scRNA-seq) to discover marker genes in endothelial cells and to construct a prognostic model for GBM patients in combination with traditional RNA-seq data.Methods：Bulk RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and The China Glioma Genome Atlas (CGGA) databases. 10x scRNA-seq data for GBM were obtained from the Gene Expression Omnibus (GEO) database. The uniform manifold approximation and projection (UMAP) was used for downscaling and cluster identification. Key modules and differentially expressed genes (DEGs) were identified by weighted gene correlation network analysis (WGCNA). Non-negative matrix decomposition (NMF) algorithm was used to identify different subtypes based on DEGS. And Cox regression analysis was used to build prognostic models. Finally, differences in mutational landscape, immune cell abundance, immune checkpoint inhibitors (ICIs)-associated genes, immunotherapy effects and enriched pathways were also investigated between different risk groups.RESULT：The analysis of scRNA-seq data from eight samples revealed 13 clusters and four cell types. After applying differential analysis, endothelial cells were identified as the most important significant cell type. In addition, we explored potential neoangiogenic pathways in GBM after controlling for phenotypic differences between GBM and normal brain tissue ECs at the single cell level. Overall, through differential analysis, WGCNA and screening of endothelial cell marker genes, we identified 157 DEGs for the construction of prognostic models. In addition, based on DEGs,the NMF algorithm identified two clusters with different prognostic and immunological features observed. We finally built a prognostic model based on the expression levels of four of these key genes. Higher risk scores were significantly associated with poorer survival outcomes and were associated with low mutation rates in IDH genes and upregulation of immune checkpoints such as PD-L1 and CD276. The CGGA cohort served as an external validation cohort for our findings.Conclusion：We built and validated a 4-gene signature for GBM using 10 scRNA-seq and bulk RNA-seq data in this work. We believe our findings will provide greater insight into the characteristics of ECs in GBM and provide potential prognostic biomarkers to design rational treatment plans.

BackgroundThe epidermal growth factor receptor (EGFR) family belongs to the transmembrane protein receptor of the tyrosine kinase I subfamily and has 4 members: EGFR/ERBB1, ERBB2, ERBB3, and ERBB4. The EGFR family is closely related to the occurrence and development of a variety of cancers.Materials/methodsIn this study, we used multiple online bioinformatics websites, including ONCOMINE, TCGA, CGGA, TIMER, cBioPortal, GeneMANIA and DAVID, to study the expression profiles, prognostic values and immune infiltration correlations of the EGFR family in glioma.ResultsWe found that EGFR and ERBB2 mRNA expression levels were higher in glioblastoma (GBM, WHO IV) than in other grades (WHO grade II & III), while the ERBB3 and ERBB4 mRNA expression levels were the opposite. EGFR and ERBB2 were notably downregulated in IDH mutant gliomas, while ERBB3 and ERBB4 were upregulated, which was associated with a poor prognosis. In addition, correlation analysis between EGFR family expression levels and immune infiltrating levels in glioma showed that EGFR family expression and immune infiltrating levels were significantly correlated. The PPI network of the EGFR family in glioma and enrichment analysis showed that the EGFR family and its interactors mainly participated in the regulation of cell motility, involving integrin receptors and Rho family GTPases.ConclusionsIn summary, the results of this study indicate that the EGFR family members may become potential therapeutic targets and new prognostic markers for glioma.

The main aim of this study was to investigate the therapeutic effect of endovascular interventional therapy on cerebral venous sinus thrombosis (CVST). 137 patients with CVST were included, 92 patients were treated with interventional therapy, and 45 patients were treated with conventional anticoagulant therapy. Through endovascular therapy (EVT) combined with therapy, the patients were treated with EVT in combination with conventional anticoagulant therapy, and the prognosis of the two groups of patients was evaluated. The results showed that 26 patients were complicated with female-specific infections in the combined EVT group, and 7 patients had female-specific infections in the simple anticoagulant therapy (LMWH) group. In terms of central nervous system infections, the EVT group was significantly lower than the LMWH group, P < 0.001 , and the difference was statistically significant. There were 2 cases of EVT involving the inferior sagittal sinus and 12 cases of LMWH involving the inferior sagittal sinus, P < 0.001 , and the difference had statistical significance. Through the RANKIN scale (mRS) score, it was classified as complete recovery and good prognosis (dependent variable). The patients receiving EVT with good prognosis (96.7%) were more than those receiving simple anticoagulant therapy (84.4%), and 78.3% were completely recovered after EVT, and 77.5% were completely recovered after anticoagulant therapy. Therefore, it can be concluded that gender, malignant tumors, thrombosis, and sinuses are all risk factors affecting the prognosis of patients; both endovascular interventional therapy and anticoagulant therapy can significantly improve the prognosis of patients.

Glioma is the most common malignant primary brain tumour in adults. Despite improvements in neurosurgery and radiotherapy, the prognosis of glioma patients remains poor. One of the main limitations is that there are no proper clinical therapeutic targets for glioma. Therefore, it is crucial to find one or more effective targets. Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT family of genes. Abnormal expression of STAT3 is involved in the process of cell proliferation, migration, invasion, immunosuppression, angiogenesis, dryness maintenance, and resistance to radiotherapy and chemotherapy in glioma. Therefore, STAT3 has been considered an ideal therapeutic target in glioma. Noncoding RNAs (ncRNAs) are a group of genes with limited or no protein-coding capacity that can regulate gene expression at the epigenetic, transcriptional and posttranscriptional level. In this review, we summarized the ncRNAs that are correlated with the ectopic expression of STAT3 in glioma.

High-concentration glutamic acid (Glu) induced by ischemic stroke can be inhibited by glutamate transporter-1 (GLT-1), which is the main mechanism for preventing excessive extracellular glutamate accumulation in the central nervous system. Upregulation of miR-124 could reduce the infarct area and promote the recovery of neurological function after ischemic stroke. A previous study investigated whether miR-124 could regulate GLT-1 expression in normal culture conditions. However, the role of miR-124 in the regulation of GLT-1 expression and further mechanisms after ischemic stroke remain unclear. In this study, the effects of miR-124 on GLT-1 expression in astrocytes after ischemic stroke were explored using an in vitro model of ischemic stroke (oxygen-glucose deprivation/reperfusion, OGD/reperfusion). The expression of GLT-1 was significantly decreased with lower expression of miR-124 in astrocytes injured by OGD/reperfusion. When miR-124 expression was improved, the expression of GLT-1 was notably increased in astrocytes injured by OGD/reperfusion. The results revealed that GLT-1 expression in astrocytes had a relationship with miR-124 after OGD/reperfusion. However, a direct interaction could not be confirmed with a luciferase reporter assay. Further results demonstrated that an inhibitor of Akt could decrease the increased protein expression of GLT-1 induced by miR-124 mimics, and an inhibitor of mTOR could increase the reduced protein expression of GLT-1 caused by a miR-124 inhibitor in astrocytes injured by different OGD/reperfusion conditions. These results indicated that miR-124 could regulate GLT-1 expression in astrocytes after OGD/reperfusion through the Akt and mTOR pathway.

According to the requirement of the on-line fault diagnosis of the servo DC motors used in TT&C antenna, which is applicated in aerospace exploration, noise reduction and power spectrum analysis with wavelet packet are studied in this paper. The ability of feature extraction and pattern recognition are the characteristics of wavelet packet noise reduction, which are applied to analyze the motor's current signals in different branches, thus the characteristic parameters of the fault motors can be shown clearly. We proposed a servo DC motor fault diagnosis model based on informatization theory, which improves the reliability of fault diagnosis result, and the accuracy of data screening increases from 70.5% to 92%. The result shows that the fault diagnosis model can trigger alarm accurately, it is also effective and superior in fault location.

Long non-coding RNAs (lncRNAs) have been implicated in the development and progression of tumors. However, the roles and underlying mechanisms of long intergenic non-protein coding RNA 1116 (LINC01116), a member of the lncRNA family, in glioma progression are largely unclear. The expression of LINC01116 and microRNA (miR)-744-5p in glioma tissues and cells was detected by reverse transcription-quantitative PCR. The influences of LINC01116 or miR-744-5p on cell proliferation and invasion were evaluated by Cell Counting Kit-8, colony formation and Transwell assays, and western blotting was used to detect the expression of p53 pathway proteins. A dual-luciferase reporter system was used to locate common binding sites between miR-744-5p and LINC01116 or the 3′ untranslated region of E3 ubiquitin-protein ligase Mdm2 (MDM2). RNA immunoprecipitation was used to determine the interactions between RNAs and proteins. Moreover, a xenograft mouse model was constructed to investigate the effects of LINC01116 in vivo, followed by a TdT-mediated dUTP nick end labeling assay to determine the degree of apoptosis in nude mouse tumors. LINC01116 was found to be highly expressed in glioma tissues, which was associated with a malignant phenotype. LINC01116 promoted the proliferation and invasiveness of glioma cells, and inhibited the p53 pathway by preserving the expression of MDM2 mRNA via miR-744-5p sponging. Furthermore, a low degree of miR-744-5p expression was observed in glioma tissues, which was negatively associated with the expression of LINC01116. Overexpression of miR-744-5p inhibited the proliferation and invasiveness of glioma cells, which was rescued by LINC01116. Finally, LINC01116 knockdown inhibited tumor growth in nude mice. In conclusion, LINC01116 is aberrantly expressed and promotes the progression of glioma by regulating the miR-744-5p-MDM2-p53 pathway. In future, targeting LINC01116 may therefore be a potential therapeutic approach for patients with glioma.

Background: Epidermal growth factor receptor (EGFR) family belongs to the transmembrane protein receptor of tyrosine kinase I subfamily, including 4 members, they are EGFR/ERBB1, ERBB2, ERBB3, ERBB4. The EGFR family is closely related to the occurrence and development of a variety of cancers.Material/Methods: In this research, we used multiple online bioinformatics websites including ONCOMINE, TCGA, CGGA, TIMER, cBioPortal, GeneMANIA and DAVID to study the expression profiles, prognostic values and immune infiltration correlations of EGFR family in glioma.Results: We found that EGFR and ERBB2 mRNA expression levels were the higher in glioblastoma (GBM, WHO IV) than other grades (WHO grade II&III), While ERBB3 and ERBB4 mRNA expression levels were opposite. EGFR and ERBB2 were notably downregulated in IDH mutant gliomas, while ERBB3 and ERBB4 were the opposite. Besides, ERBB2 and ERBB4 in glioma patients were associated with poor prognosis. In addition, correlation analysis between EGFR family expression and immune infiltrating levels in glioma showed that EGFR family expression and immune infiltrating levels were significantly correlated. PPI network of EGFR family in glioma and enrichment analysis showed that EGFR family and their interactors mainly participated in regulation of cell motility involved integrin receptors and Rho family GTPases.Conclusions: In summary, this study indicates that EGFR family may become potential targets and new prognostic markers for glioma.

Background: Long noncoding RNAs( lncRNAs) have been reported to be associated with tumorigenesis and development of glioma. LINC00662 has been implicated in pathogenesis of various human cancers. However, role of LINC00662 in glioma remains unknown.Methods: Bioinformatics methods were used to analysis the expression of LINC00662 in glioma. RT-qPCR was performed to examine the expression levels of LINC00662 in glioma tissues and cell lines. The effect of LINC00662 in cell proliferation and invasion was evaluated by Cell Counting Kit-8(CCK-8), clone colony formation and transwell assay. Luciferase reporter assays were performed to investigate the interaction between miR-340-5p and LINC00662, 3’UTR of STAT3. CHIP-qPCR and Luciferase reporter assays were used to demonstrate the interaction between STAT3 and the promoter region of LINC00662. Rescue assays and Tumor xenografts in nude mice were applied to verify the effect of LINC00662 in modulating miR-340-5p/ STAT3 signal pathway.Results: LINC00662 was frequently high expressed and associated with malignant phenotype of glioma. LINC00662 knockdown inhibited proliferation, invasion and glioma-genesis of glioma. Moreover, LINC00662 knockdown repressed development of glioma by inhibiting the expression and activation of STAT3 pathway. Mechanically, LINC00662 acted as a ceRNA sponging miR-340-5p to protect the expression of STAT3. More importantly, LINC00662 was one of direct target genes of STAT3.Conclusions: There was a positive regulation loop between LINC00662 and STAT3. LINC00662 might be an oncogene in glioma. Targeting LINC00662 was a potential strategy in glioma therapy.

Long non-coding RNAs (lncRNAs) have been demonstrated to serve important roles in a variety of human tumor types. The lncRNA small nucleolar RNA host gene 7 (SNHG7) is associated with a variety of cancer types, such as esophageal cancer, breast cancer and gastric neoplasia. Based on previous studies that examined SNHG7 expression in tumors, it has become clear that SNHG7 modulates tumorigenesis and cancer progression by acting as a competing endogenous RNA. SNHG7 can sponge tumor-suppressive microRNAs and regulate downstream signaling pathways. In addition, overexpression of SNHG7 is associated with the clinical characteristics of patients with cancer by regulating cellular proliferation, invasion and metastasis and by inhibiting apoptosis via a variety of mechanisms of action. The function of SNHG7 in tumorigenesis and cancer progression indicates that it can potentially act as a novel therapeutic target or a diagnostic biomarker for cancer therapy or detection, respectively.

Long noncoding RNAs (lncRNAs) are composed of > 200 nucleotides; they lack the ability to encode proteins but play important roles in a variety of human tumors. A large number of studies have shown that dysregulated expression of lncRNAs is related to tumor oncogenesis and progression. Emerging evidence shows that SNHG3 is a novel oncogenic lncRNA that is abnormally expressed in various tumors, including osteosarcoma, liver cancer, lung cancer, etc. SNHG3 primarily competes as a competitive endogenous RNA (ceRNA) that targets tumor suppressor microRNAs (miRNAs) and ceRNA mechanisms that regulate biological processes of tumors. In addition, abnormal expression of SNHG3 is significantly correlated with patient clinical features. Upregulation of SNHG3 contributes to biological functions, including tumor cell proliferation, migration, invasion and EMT. Therefore, SNHG3 may represent a potential diagnostic and prognostic biomarker, as well as a novel therapeutic target.

Objective: This study aimed to explore the effect of astaxanthin (ATX) on neuron damage, inflammatory factor expression and oxidative stress in mice with subarachnoid hemorrhage (SAH). Methods: Specific-pathogen-free, ‘Institute of Cancer Research’, male mice were randomly divided into four groups: SAH group, sham group, SAH + placebo group (SAH + Vehicle group) and SAH + ATX group. Neurological function was scored in each group. Brain water content, reactive oxygen species (ROS) content and inflammatory factor levels in the brain were detected by wet-dry weighting method, DCFH-DA fluorescent probe staining method and ELISA, respectively. Expression of NADPH oxidase 2 (NOX2), glial fibrillary acidic protein (GFAP) and apoptosis-related proteins Bax and Bcl-2 were detected by Western blot and quantitative real-time polymerase chain reaction. Neuronal apoptosis was detected by TUNEL staining. Results: Compared with sham group, neurological score, brain water content and ROS content in the other three groups increased significantly (all P0.05). Conclusion: Astaxanthin can decrease neuron damage, inhibit inflammatory response, and improve oxidative stress in SAH mice. Thus, astaxanthin is a method for treating SAH.

To date, the molecular mechanism underlying constitutive signal transducer and activator of transcription 3 (STAT3) activation in gliomas is largely unclear. In this study, we report that Smad6 is overexpressed in nuclei of glioma cells, which correlates with poor patient survival and regulates STAT3 activity via negatively regulating the Protein Inhibitors of Activated STAT3 (PIAS3). Mechanically, Smad6 interacts directly with PIAS3, and this interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and the Ring domain of PIAS3. Smad6 recruits Smurf1 to facilitate PIAS3 ubiquitination and degradation, which also depends on the MH2 domain and the PY motif of Smad6. Consequently, Smad6 reduces PIAS3-mediated STAT3 inhibition and promotes glioma cell growth and stem-like cell initiation. Moreover, the Smad6 MH2 transducible protein restores PIAS3 expression and subsequently reduces gliomagenesis. Collectively, we conclude that nuclear-Smad6 enhances glioma development by inducing PIAS3 degradation and subsequent STAT3 activity upregulation., In glioma STAT3 signaling contributes to gliomagenesis. Here, the authors show that Smad6 expression correlates with poor survival and is overexpressed in glioma cells, and regulates STAT3 activity via negatively regulating PIAS3.

Background Long noncoding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and development of glioma. LINC00662 has been involved in the pathogenesis of various human cancers. However, the mechanism underlying which LINC00662 exerts its role in glioma needs further exploration. In addition, regulation mechanism of LINC00662 expression in glioma remains unknown. Methods and materials RT-qPCR was performed to evaluate the expression levels of LINC00662, miR-340-5p in glioma tissues and cell lines. The effect of LINC00662 and miR-340-5p in cell proliferation and invasion was assessed by Cell Counting Kit-8(CCK-8), clone colony formation and Transwell assay. Luciferase reporter assays and RNA immunoprecipitation assay validated the miR-340-5p-target relationships with LINC00662 or STAT3. CHIP-qPCR and Luciferase reporter assays were used to demonstrate the interaction between STAT3 and the promoter region of LINC00662. A tumor xenografts model was implemented to verify the effect of LINC00662 on glioma development in vivo. Results We found that LINC00662 was frequently highly expressed and related to the malignant phenotype of glioma. LINC00662 knockdown inhibited the proliferation, invasion and glioma genesis of glioma. LINC00662 acted as a ceRNA sponging miR-340-5p to protect the expression of STAT3. In addition, STAT3 was forced to the promoter region of LINC00662 and promoted its transcription. In vivo experiments demonstrated that targeting LINC00662 may be a potential strategy in glioma therapy. Conclusion There was a positive regulation loop between LINC00662 and STAT3 in glioma. LINC00662 might be an oncogene in glioma. Targeting LINC00662 was a potential strategy in glioma therapy.

Background miR-129-5p has been reported to be abnormally expressed and plays an important role in the progression of various malignancies. However, its role in gliomas and its exact molecular mechanism need further research. Methods and materials RT-qPCR was performed to evaluate miR-129-5p and HOXC10 mRNA expression levels in tissues and cell lines. Cell proliferation was detected via Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU) and clone formation assays. Luciferase assays were used to validate the binding of seeds between miR-129-5p and HOXC10. A tumor xenograft model was developed to study the effect of miR‐129-5p on glioma growth in vivo. Results miR-129-5p was expressed at low levels in glioma tissues and cell lines. miR-129-5p overexpression inhibited glioma proliferation, migration and invasion. miR-129-5p negatively and directly targeted HOXC10. At the same time, HOXC10 was upregulated in glioma cancer, and HOXC10 knockdown inhibited cell proliferation, migration and invasion. Conclusion miR-129-5p inhibits glioma development by altering HOXC10 expression and may therefore serve as a new diagnostic marker and therapeutic target for glioma in the future.

A novel water- and fertilizer-management strategy has been developed in the study, which was called nutrient-water carrier. The nutrient-water carrier (NC) was prepared from N, O-carboxymethyl chitosan (NOCMC), acrylic acid (AA) and polyphosphate urea (PDUP) by solution polymerization. The nutrients content of NC was more than 70%, and it showed excellent water-retention and slow-released capacity properties. The optimal superabsorbent sample with excellent water absorbency (791.26 g/g) was obtained under the condition: 75% of AA neutralized, 10 wt% NOCMC, 5 wt% PDUP, 0.6 wt% APS, 0.05% MBA to AA weight, reaction at 70 °C for 2.0 h. After loading 25 wt% PDUP to AA weight into the polymer network, the swelling degree (SD) of optimal NC arrived 482.59 g/g. FTIR, SEM, EDS and TG were used to characterize the structure and performance of optimal NC. Results illustrated that the semi-interpenetrate structure (semi-IPN) was constructed by the incorporation of linear PUDUP into the superabsorbent network, and the NC could dramatically enhance the water holding capacity of sandy loam, six-folders than without NC. In addition, the application of NC in sandy loam soil had a positive synergistic effect on the root length and seedling height of maize. Furthermore, the slow-released behavior for N, P and K was investigated. All the facts indicated that the NC could improve nutrients-efficiency, prolong the period of fertilizer release, decrease irrigation frequency and address environmental pollution, which was expected to be widely used in semi-arid and arid areas.

Glioblastoma (GBM) is the most common primary malignant tumor in adults, and its morbidity and mortality are very high. Although progress has been achieved in the treatment of GBM, such as surgery, chemotherapy and radiotherapy, in recent years, the prognosis of patients with GBM has not improved significantly. MicroRNAs (miRNAs) are endogenous noncoding single-stranded RNAs consisting of approximately 20-22 nucleotides that regulate gene expression at the posttranscriptional level by binding to target protein-encoding mRNAs. Notably, miRNAs regulate various carcinogenic pathways, one of which is the epidermal growth factor receptor (EGFR) signaling pathway, which controls cell proliferation, invasion, migration, angiogenesis and apoptosis. In this review, we summarize the novel discoveries of roles for miRNAs targeting the factors in the EGFR signaling pathway in the occurrence and development of GBM. In addition, we describe their potential roles as biomarkers for the diagnosis and prognosis of GBM and for determining the treatment resistance of GBM and the efficacy of therapeutic drugs.

Widespread invasiveness, represented by the invasion and migration, is the most important characteristic of glioblastoma multiforme (GBM) and is the main reason for therapeutic failure and recurrence of the tumor. Hypoxia is one of the main microenvironment in determining tumor invasiveness. Therefore, intense efforts aimed at improved therapeutics are ongoing to demonstrate the molecular mechanisms governing GBM migration and invasion. This study aims to explore the role of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and its relationship with hypoxia inducible factor-1α (HIF-1α) in the migration and invasion of human glioblastoma U87 cells under hypoxia. In the study, we found that hypoxia could activate the PI3K/Akt/mTOR pathway associated with the enhancements of the migration and invasion of human glioblastoma U87 cells. When the PI3K/Akt/mTOR pathway and HIF-1α were inhibited by the siRNAs or inhibitors, the migration and invasion of human glioblastoma U87 cells were suppressed. Meanwhile, the expression of HIF-1α could be inhibited by the siRNA or inhibitors of PI3K/Akt/mTOR pathway. The aforementioned results demonstrate that hypoxia could induce enhancements of migration and invasion by activating PI3K/Akt/mTOR pathway by targeting HIF-1α in human glioblastoma U87 cells, which provide a theoretical basis for the treatments of GBM by targeting the PI3K/Akt/mTOR/HIF-1α pathway.

To date, the anti-tumor mechanism of the deleted in liver cancer 2 (DLC2) in gliomas is still unclear. The study shows that TAp73α expression and TAp73α/TAp73β ratio are frequently high in gliomas and that TAp73α and TAp73β have opposite roles in regulating proliferation and apoptosis of glioma cells. Moreover, DLC2 is low-expressed in gliomas, which negatively correlates with TAp73α expression and TAp73α/TAp73β ratio. More importantly, DLC2 inhibits development of glioma by decreasing expression of TAp73α, which changes the expression ratio of TAp73α/TAp73β in glioma cells. Mechanically, DLC2 interacts directly with TAp73α and induces TAp73α ubiquitination and degradation, which is mediated through SAM domain of DLC2 and TAp73α. In detail, DLC2 with SAM domain deletion fails to interact with TAp73α and induce TAp73α ubiquitination and degradation, and SAM deletion decreased tumorigenesis-inhibition effect of DLC2. In conclusion, DLC2 inhibits glioma development by inducing TAp73α degradation and subsequent change of TAp73α/TAp73β expression ratio.

Resveratrol (Res) has been reported to elicit many cellular responses including cell cycle arrest, differentiation, and apoptosis. This makes it a novel and potential anticancer agent. Moreover, the lipophilicity of Res raises the possibility of its application as a potential model drug in nanoparticle based delivery systems. Resveratrol is incorporated into mPEG-PCL based nanoparticles with high encapsulation efficiency due to its lipophilicity. The significant finding of the current study is that Res-loaded nanoparticles at lower concentration could lead to significantly higher cell death compared to equivalent dose of free Res and this difference of cytotoxicity could not be abrogated by the antioxidant Vitamin E. Furthermore, free Res shows significant less cytotoxicity than the equivalent dose of Res-loaded nanoparticles with the preconditioning of Vitamin E. Meanwhile, reactive oxygen species (ROS) determination revealed the significantly lower intracellular ROS levels in Res-treated cells compared to nanoparticle-treated cells. Therefore, the differential cytotoxicity between Res and Res-loaded nanoparticles may be mediated by the discrepancy of intracellular ROS levels. The present results suggest that Res-loaded nanoparticles could be a potential useful chemotherapeutic formulation for malignant glioma therapy and the development of traditional Chinese medicine with nanoscale drug formation warrants more intensive research in order to evaluate its clinical feasibility.

Temozolomide (TMZ), a DNA alkylating agent, represents the most important chemotherapeutic option for the treatment of glioblastoma in the clinic. Despite its frequent use, the therapeutic efficacy of TMZ remains very limited due to its frequent resistance in glioblastoma. Previous evidence suggested that curcumin (CUM), an ingredient of the Indian spice turmeric, is able to sensitize glioblastoma to TMZ treatment. However, the underlying molecular mechanism remains elusive. In the present study, we performed in vitro and in vivo experiments to evaluate the interaction of CUM and TMZ on the inhibition of glioblastoma and to investigate its potential mechanisms of action using U87MG cell lines and xenograft mouse models. We demonstrated that CUM enhanced the therapeutic response to TMZ in U87MG glioblastoma by enhancing apoptosis. We then proceeded to investigate the potential apoptotic signaling pathways that are involved. We observed a synergistic effect of the combination of CUM and TMZ in generating reactive oxygen species (ROS) production, suggesting that ROS may contribute to the impact of CUM on sensitizing TMZ treatment. We also showed that CUM and TMZ treatment alone significantly suppressed phosphorylated AKT and mTOR, whereas their combination achieved a more pronounced inhibitory effect. These data indicated that blockage of AKT/mTOR signaling appeared to contribute to the elevated apoptosis caused by the combination treatment with CUM and TMZ. In conclusion, this study provided molecular insights into the effects of CUM on the therapeutic response of glioblastoma to TMZ and opened new avenues for optimizing the therapeutic effects of TMZ-based therapies.

As a potential anticancer agent, curcumin (Cum) has been reported for its chemopreventive and chemotherapeutic activity in a series of cancers through influencing cell cycle arrest, differentiation, apoptosis, etc. Therefore, the potential activity against various cancers of Cum raises the possibility of its application as a novel model drug in nanoparticle-based delivery systems. The current study reported a spherical core-shell structure curcumin-loaded nanoparticle (Cum-np) formed by amphilic methoxy polyethylene glycol-poly(caprolactone) (mPEG-PCL) block copolymers. Characterization tests indicated that Cum was incorporated into mPEG-PCL-based nanoparticles with high encapsulation efficiency due to its lipophilicity. The incorporated Cum could be released from Cum-np in a sustained manner. Cum was effectively transported into the cells by nanoparticles through endocytosis and localized around the nuclei in the cytoplasms. In vitro studies proved that the cytotoxicity of Cum-np would be pro-apoptosis effect against rat C6 glioma cell line in a dose-dependent manner. The present results suggest that Cum-np could be a potential useful chemotherapeutic formulation for malignant glioma therapy. Moreover, the development of traditional Chinese medicine with nanoscale drug formation warrants more intensive research for its clinical applications.