Interfacial adsorption behavior of the Aspergillus oryzae lipase-chitosan complex and stability evaluation of the resultant Pickering emulsion.

To prompt the application of the chitosan (CS)-Aspergillus oryzae lipase (AOL) complex in the construction of novel biphasic catalysis medium, its Pickering emulsion stabilization ability as well as adsorption behavior in the oil-water interface were investigated and the stability of resultant emulsion was evaluated. The results indicated that the CS-AOL complex assembled in mass ratio 1:5 was an effective Pickering stabilizer and up to 90 % AOL could be retained in the emulsion interface. Quartz crystal microbalance with dissipation monitoring suggested that the CS-AOL complex spontaneously absorbed to oil-water interface; absorption dynamics analysis revealed that the adsorption was driven by diffusion accompanied by rapid structural rearrangement; while interfacial dilatational rheology demonstrated the formation of an elastic film in the oil-water interface. The Pickering emulsions were pseudoplastic and that in oil fraction 0.6 exhibited the elastic behavior in contrast to the viscous behavior in oil fractions 0.2 and 0.4. The Pickering emulsion exhibited excellent stability against storage for up to 28 d, pHs 2.0-12.0, heating at 25-90 °C, and up to 500 mmol/L NaCl, and the corresponding interfacial AOL retentions exceeded 80 % during exposure to these conditions. Hence, the CS-AOL complex could be used as a stabilizer to construct Pickering emulsion-based biphasic catalysis systems.

Fabrication of lipase-loaded particles by coacervation with chitosan.

Coacervation of the lipase from Aspergillus oryzae (AOL) with chitosan was a feasible way to fabricate lipase-loaded particles and the optimum conditions were phase separation pH 5.5, chitosan to AOL mass ratio 1:5, and temperature 25 °C in the absence of NaCl, which conferred an AOL loading efficiency of up to 95.48% and activity recovery of 69.60%. The AOL-chitosan coacervates were highly porous and more susceptible to weight loss upon heating. Coacervation with chitosan increased the activity of AOL and shifted its optimum pH from 7.0 to 6.0, but exerted no effect on its optimum temperature (45 °C). Thermal deactivation kinetics analysis revealed that the coacervated AOL was more thermal stable, while the Michaelis-Menten kinetics analysis indicated that coacervation with chitosan increased the Vmax of AOL by 2.4 folds, but decreased its substrate affinity by 3.6 folds. Hence, the AOL-chitosan coacervates are potential in the construction of Pickering emulsion-based lipase catalysis systems.

Metabolic expression profiling stratifies diffuse lower-grade glioma into three distinct tumour subtypes.

BACKGROUND: Lower-grade gliomas (LGGs) show highly metabolic heterogeneity and adaptability. To develop effective therapeutic strategies targeting metabolic processes, it is necessary to identify metabolic differences and define metabolic subtypes. Here, we aimed to develop a classification system based on metabolic gene expression profile in LGGs. METHODS: The metabolic gene profile of 402 diffuse LGGs from the Cancer Genome Atlas (TCGA) was used for consensus clustering to determine robust clusters of patients, and the reproducibility of the classification system was evaluated in three Chinese Glioma Genome Atlas (CGGA) cohorts. Then, the metadata set for clinical characteristics, immune infiltration, metabolic signatures and somatic alterations was integrated to characterise the features of each subtype. RESULTS: We successfully identified and validated three highly distinct metabolic subtypes in LGGs. M2 subtype with upregulated carbohydrate, nucleotide and vitamin metabolism correlated with worse prognosis, whereas M1 subtype with upregulated lipid metabolism and immune infiltration showed better outcome. M3 subtype was associated with low metabolic activities and displayed good prognosis. Three metabolic subtypes correlated with diverse somatic alterations. Finally, we developed and validated a metabolic signature with better performance of prognosis prediction. CONCLUSIONS: Our study provides a new classification based on metabolic gene profile and highlights the metabolic heterogeneity within LGGs.

Popliteal artery transection associated with a minimally displaced tibial plateau fracture: a case report and review of the literature.

BACKGROUND: Poplital artery transection injury is potentially catastrophic, or even life-threatening. Severe traumas, including open fracture, gunshot, stabs, and knee dislocation and complex fracture of proximal tibia or distal femur, are the common causes of high rate of amputation due to popliteal artery trauma. No report mentions vascular injury associated with minimally displaced tibial plateau fracture in adult. CASE PRESENTATION: A 30-year-old male presented with popliteal artery transection injury associated with minimally displaced tibial plateau fracture. He presented to emergency department, 6 h after fall from ground into a 1-m height hole. Physical examination suggested acute ischemia, with signs of paleness, coldness, anesthesia, hemorrhagic bullae below the right knee level. There was severe swelling and ecchymosis in popliteal fossa and around the leg with significant calf tenderness and pedal edema. Tibialis posterior, dorsalis pedis, and popliteal arterial pulses were not palpable. Radiograph suggested minimally displaced tibial plateau fracture with no evidence of knee dislocation. The patient was taken up for emergency surgery after consultation with vascular surgeon. During the closed reduction external fixation and compartment decompression, popliteal artery trunk was found transected and end-to-end repair was performed. During the post-operational period, no complication was developed and the patient was followed-up for 1 year. At the one-year follow-up, he acquired good stability of his right knee with full range of motion. CONCLUSION: Significant swelling and ecchymosis should alert the surgeons to the possibility of vascular injury in knee joint injury, even if there is no fracture or dislocation, or fracture is minimally displaced.

Promising hen egg-derived proteins/peptides (EDPs) for food engineering, natural products and precision medicines.

Hen eggs (HEs) provide valuable nutrients for humans, including proteins, carbohydrates, lipids and vitamins. Recent studies revealed a number of novel egg-derived proteins/peptides (EDPs), and EDPs may play a crucial role in food industry and medical therapy. First, these EDPs were purified from the enzyme-catalyzed hydrolysates of egg proteins and were characterized by biochemical assays such as gel electrophoresis, HPLC, mass spectrometry, proteomic and peptideomic analysis, etc. Second, some EDPs can be used as nontoxic bio-preservatives and functional nutraceuticals for replacing harmful sodium nitrite, inhibiting foodborne pathogens, promoting metal-ion absorption and improving meat-product quality, and these new features will be widely used in the field of food production. Third, novel medical properties of EDPs comprise anti-oxidative, anti-microbial, anti-inflammatory and anti-nociceptive activities, which will benefit prevention of cardiovascular diseases, cancers, diabetic mellitus, immune disorders, etc. In summary, this review gives a real insight into the novel nutritional, biological and medical functions of EDPs, predictably facilitating the applications of EDPs in production of nutritive supplements, functional nutraceuticals and therapeutic medicines.

Emergency irradiation with 3.4 Gy/2f in sellar/suprasellar germinoma patients with rapid visual acuity decline.

BACKGROUND: Rapid visual acuity (VA) decline was a common complaint in patients with sellar/suprasellar germinoma. In our hospital, 3.4 Gy/2f of emergency irradiation was applied to save patient VA and enable subsequent chemoradiotherapy. This study aimed to investigate the efficacy of emergency irradiation with 3.4 Gy/2f in patients with sellar/suprasellar germinoma who had rapid VA decline. METHODS: From January 2014 to December 2017, 33 patients with sellar/suprasellar germinoma who complained of VA decline within 3 months received 3.4 Gy/2f of emergency irradiation in Beijing Tiantan Hospital. The best-corrected VA (BCVA) and mean deviation (MD) were measured. Correlations between visual function change and clinical factors, including age at diagnosis, duration of VA decline, extent of tumor regression, serum level of tumor markers, were analyzed. RESULTS: Among 33 patients with sellar/suprasellar germinoma, the median diameter and volume of sellar/suprasellar lesions were 32 mm (range: 5-55 mm) and 12.9 cm (range 0.6-58.5 cm), respectively. Data on pre- and post-emergency-irradiation BCVA were obtained in 32 patients. For the right eyes, BCVA was improved in 23 patients (71.9%), unchanged in 7 (21.9%), and worsened in 2 (6.2%); and for the left eyes, these numbers were 27 (84.4%), 4 (12.5%), and 1 (3.1%), respectively. In terms of the logarithm of the minimum angle of resolution (logarithm of the minimum angle of resolution = Log (1/BCVA) score, the improvement was significant in both eyes (P < 0.001). In terms of MD, six patients had paired data and the improvement was marginal in the right eyes (P = 0.068) and significant in the left eyes (P = 0.043). However, no clinical factor was found to have correlation with visual function improvement. CONCLUSION: In sellar/suprasellar germinoma patients with VA decline, 3.4 Gy/2f of emergency irradiation was effective in improving visual function.

Molecular and clinical characterization of TMEM71 expression at the transcriptional level in glioma.

BACKGROUND: Glioma is the most common and aggressive type of primary brain tumor in adults. Although radiotherapy and chemotherapy are used in the treatment of glioma, survival remains unsatisfactory. Chemoresistance is one of the primary reasons for the poor prognosis of glioma. Several studies have demonstrated that glioma stem cells (GSC) may be one of the reasons for chemoresistance. In this article, we attempt to search for a new biomarker related to GSC and chemoresistance in glioma. METHODS: We used three datasets (GSE23806, COSMIC, and CGGA) to search for the genes related to GSC, temozolomide (TMZ) resistance, and overall survival. The selected gene was investigated with respect to the relationship between mRNA levels and clinical characteristics in the CGGA and TCGA dataset. Gene ontology (GO) analysis was used for bioinformatics analysis. Kaplan-Meier survival analysis and Cox regression analysis were used for survival analysis. RESULTS: The transmembrane protein 71 (TMEM71) gene was selected for further research. TMEM71 was highly expressed in GSCs and TMZ-resistant cells. The TMEM71 mRNA levels increased with increasing grades of glioma. In IDH-wild-type and MGMT-unmethylated samples, TMEM71 was overexpressed. The TMEM71 transcript levels were also increased significantly in mesenchymal subtype gliomas. GO analysis demonstrated that TMEM71 was related to the immune and inflammatory responses, cell proliferation, cell migration, chemotaxis, and the response to drugs. Specifically, PD-1, PD-L1, TIM-3, and B7-H3 were tightly associated with TMEM71 expression. This result indicates that TMEM71 may play an important role in the immune response. More importantly, high expression of TMEM71 was correlated with short survival time in both glioma and glioblastoma patients. CONCLUSION: In summary, TMEM71 expression was increased in GBM and associated with immune response. Our study suggests that TMEM71 may function as an oncogene and serve as a new effective therapeutic target for the treatment of glioma.

The complete mitochondrial genome of Yao silkworm (Bombyx mori).

Here, we describe the first complete mitochondrial genome of Yao silkworm, a unique silkworm resource native at Guangxi, China. This circular molecule is 15,656 bp long and contains the typical set of 37 genes (13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes) and one non-coding A + T-rich region of 494 bp long. The genome organization and gene arrangement are identical to those observed in all available Bombyx mori strains. The phylogenetic tree inferred from Bayesian inference provides a molecular evidence that Yao silkworm belongs to the domestic silkworm (B. mori), rather than a novel silkworm species.

PIN1, a perspective on genetic biomarker for nonalcoholic fatty liver disease (NAFLD).

OBJECTIVE: A novel genetic and molecular basis of nonalcoholic fatty liver disease (NAFLD) was explored. STUDY DESIGN: A 38-year-old male, who has no bad living and dietary habits, was diagnosed as NAFLD. The potential pathogenic role of Pin1 was evaluated by enzyme-linked immunosorbent (ELISA) assay and single nucleotide polymorphism (SNP) sequencing. RESULTS: ELISA determined a six-time higher concentration of plasma Pin1 compared to our previous data. Nine PIN1 SNPs were sequenced and classified according to their NAFLD-pathogenic risks, suggesting that rs2233678 and rs2287839 may be the most important genotypes that result in Pin1 overexpression and NAFLD development. CONCLUSION: In summary, this work explores a novel basis for early-onset NAFLD and highlights that elevated plasma Pin1 may predict NAFLD risk at early stage. Hypothetically, inhibiting Pin1 may benefit NAFLD prevention in the future.

Role of Recursive Partitioning Analysis and Graded Prognostic Assessment on Identifying Non-Small Cell Lung Cancer Patients with Brain Metastases Who May Benefit from Postradiation Systemic Therapy.

BACKGROUND: The role of postradiation systemic therapy in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) was controversial. Thus, we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) and graded prognostic assessment (GPA) in identifying population who may benefit from postradiation systemic therapy. METHODS: The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively. Cox regression was used for multivariate analysis. Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA. RESULTS: Of 216 included patients, 67.1% received stereotactic radiosurgery (SRS), 24.1% received whole-brain radiation therapy (WBRT), and 8.8% received both. After radiotherapy, systemic therapy was administered in 58.3% of patients. Multivariate analysis found that postradiation systemic therapy (yes vs. no) (hazard ratio [HR] = 0.361, 95% confidence interval [CI] = 0.202-0.648, P = 0.001), radiation technique (SRS vs. WBRT) (HR = 0.462, 95% CI = 0.238-0.849, P = 0.022), extracranial metastasis (yes vs. no) (HR = 3.970, 95% CI = 1.757-8.970, P = 0.001), and Karnofsky performance status (<70 vs. ≥70) (HR = 5.338, 95% CI = 2.829-10.072, P < 0.001) were independent factors for survival. Further analysis found that subsequent tyrosine kinase inhibitor (TKI) therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class II (HR = 0.411, 95% CI = 0.183-0.923, P = 0.031) or with a GPA score of 1.5-2.5 (HR = 0.420, 95% CI = 0.182-0.968, P = 0.042). However, none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy. CONCLUSION: RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM if TKIs were chosen as postradiation systemic therapy.

[Coupling mode of irrigation and shading for good quality and proper yield of Coffea arabica in dry-hot region]. / 干热区小粒咖啡提质增产的灌水和遮荫耦合模式.

In a field experiment with three levels of irrigation, i.e., CI, DI75 and DI50(100%, 75% and 50% full irrigation) and four levels of shade, i.e., T100, T70, T55 and T40(100%, 70%, 55% and 40% natural radiation), the effects of irrigation and shading levels on growth, yield and quality of Coffea arabica were examined. The comprehensive benefit evaluation model was established under different irrigation and shading levels. The results showed that DI75 treatment increased the contents of fat and chlorogenic acid in dry bean by 6.0% and 10.2%, DI50 treatment significantly increased the content of caffeine of dry bean, but reduced water use efficiency. Compared with T100, T70 treatment increased the yield of dry bean and water use efficiency by 27.2% and 26.8%, respectively, and increased total sugar and chlorogenic acid content in dry bean by 6.3% and 5.5%. T55 and T40 treatments significantly reduced the yield of dry bean, water use efficiency, and the contents of caffeine and chlorogenic acid of dry bean. Compared with CIT100, DI75T70 treatment increased dry bean yield and water use efficiency by 28.0% and 44.5%, and increased the contents of total sugar, protein, fat and chlorogenic acid of dry bean by 12.2%, 14.7%, 6.6% and 10.0%, respectively, but reduced the concentration of caffeine by 8.3%. The comprehensive benefit of yield and quality of DI75T70 treatment (75% full irrigation, 70% natural radiation) was the best, which could implement good quality and proper yield of C. arabica.

Systemic Therapy after Radiotherapy Significantly Reduces the Risk of Mortality of Patients with 1-3 Brain Metastases: A Retrospective Study of 250 Patients.

BACKGROUND: For patients with a brain metastasis (BM), systemic therapy is usually administered after the completion of radiotherapy, especially in cases of multiple BMs. However, the role of systemic therapy in patients with a limited number of BMs is not clear. Therefore, we conducted a retrospective study to explore this question. METHODS: Consecutive patients with a pathologically confirmed malignancy and 1-3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China. RESULTS: A total of 250 patients were enrolled; of them, 135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy. In patients receiving whole-brain radiation therapy (WBRT) as radiotherapy, 28 received WBRT alone and 35 patients received WBRT plus systemic therapy. Of the patients treated with stereotactic radiosurgery (SRS), 107 received SRS alone and 80 received SRS plus systemic therapy. Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone (hazard ratio [HR] = 0.294, 95% confidence interval [CI] = 0.158-0.548). Further, when the analysis was conducted in subgroups of WBRT (HR = 0.230, 95% CI = 0.081-0.653) or SRS (HR = 0.305, 95% CI = 0.127-0.731), systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs. CONCLUSION: Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1-3 BMs.

Prognostic value of ion channel genes in Chinese patients with gliomas based on mRNA expression profiling.

Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of human cancer. However, the roles of ion channels in glioma remain controversial. We systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using whole-genome mRNA expression profiling. First, a molecular signature comprising 47 ion channel genes (IC47) was identified using Spearman's rank correlation test conducted between tumor grade and gene expression. We assigned a risk score based on IC47 to each glioma patient. We demonstrated that the risk score effectively predicted overall survival in glioma patients. Next, we screened IC47 in different molecular glioma subtypes. IC47 showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis and gene set variation analysis (GSVA) for the functional annotation of IC47 showed that patients with high-risk scores tended to exhibit the decreased expression of proteins associated with the apoptosis and cell adhesion, and higher expression of proteins associated with the cell cycle and cell proliferation. These results suggest that ion channel gene expression could improve the subtype classification in gliomas at the molecular level. The findings in the present study have been validated in two independent cohorts.

Asiatic acid ameliorates pulmonary fibrosis induced by bleomycin (BLM) via suppressing pro-fibrotic and inflammatory signaling pathways.

Idiopathic pulmonary fibrosis is known as a life-threatening disease with high mortality and limited therapeutic strategies. In addition, the molecular mechanism by which pulmonary fibrosis developed is not fully understood. Asiatic acid (AA) is a triterpenoid, isolated from Centella asiatica, exhibiting efficient anti-inflammatory and anti-oxidative activities. In our study, we attempted to explore the effect of Asiatic acid on bleomycin (BLM)-induced pulmonary fibrosis in mice. The findings indicated that pre-treatment with Asiatic acid inhibited BLM-induced lung injury and fibrosis progression in mice. Further, Asiatic acid down-regulates inflammatory cells infiltration in bronchoalveolar lavage fluid (BALF) and pro-inflammatory cytokines expression in lung tissue specimens induced by BLM. Also, Asiatic acid apparently suppressed transforming growth factor-beta 1 (TGF-ß1) expression in tissues of lung, accompanied with Collagen I, Collagen III, α-SMA and matrix metalloproteinase (TIMP)-1 decreasing, as well as Smads and ERK1/2 inactivation. Of note, Asiatic acid reduces NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome. The findings indicated that Asiatic acid might be an effective candidate for pulmonary fibrosis and inflammation treatment.

Role of KCNB1 in the prognosis of gliomas and autophagy modulation.

Increasing evidence suggests that ion channel genes play an important role in the progression of gliomas. However, the mechanisms by which ion channel genes influence the progression of glioma are not fully understood. We identified KCNB1 as a novel ion gene, associated with malignant progression and favorable overall survival (OS) and progression-free survival (PFS) in glioma patients from three datasets (CGGA, GSE16011 and REMBRANDT). Moreover, we characterized a novel function of autophagy induction accompanied by increased apoptosis and reduced proliferation and invasion of glioma cells for KCNB1. KEGG pathway analysis and in vitro studies suggested that the ERK pathway is involved in KCNB1-mediated regulation of autophagy, which was confirmed by inhibition of KCNB1-induced autophagy by using a selective ERK1/2 inhibitor (U0126) or siERK1/2. In vivo studies showed that KCNB1 induced autophagy while inhibiting tumor growth and increasing survival. Overall, our studies define KCNB1 as a novel prognostic factor for gliomas that exerts its tumor suppressive function through autophagy induction.

[Coupling effects of periodic rewatering after drought stress and nitrogen fertilizer on growth and water and nitrogen productivity of Coffea arabica]. / 干旱胁迫-复水与氮肥耦合对小粒咖啡生长和水氮生产力的影响.

The effects of periodic rewatering after drought stress and nitrogen fertilizer on growth, yield, photosynthetic characteristics of leaves and water and nitrogen productivity of Coffea arabica (Katim P7963) were studied under different nitrogen application levels in 2.5 consecutive years. Irrigation (periodic rewatering after drought stress) and nitrogen were designed as two factors, with four modes of irrigation, namely, full irrigation (IF-F: 100%ET0+100%ET0, ET0 was reference crop evapotranspiration), rewatering after light drought stress (IL-F: 80%ET0+100%ET0), rewatering after moderate drought stress (IM-F: 60%ET0+100%ET0) and rewatering after severe drought stress (IS-F: 40%ET0+100%ET0), and three levels of nitrogen, namely, high nitrogen (NH: 750 kg N·hm-2 each time), middle nitrogen (NM: 500 kg N·hm-2 each time), low nitrogen (NL: 250 kg N·hm-2 each time), and nitrogen was equally applied for 4 times. The results showed that irrigation and nitrogen had significant effect on plant height, stem diameter, yield and water and nitrogen productivity of C. arabica, and plant height and stem diameter showed S-curve with the day ordinal number, and leaf photosynthesis decreased significantly under drought stress but most photosynthesis index recovered somewhat after rewatering. Compared with IF-F, IL-F increased dry bean yield by 6.9%, while IM-F and IS-F decreased dry bean yield by 15.2% and 38.5%, respectively; IL-F and IM-F increased water use efficiency by 18.8% and 6.0%, respectively, while IS-F decreased water use efficiency by 12.1%; IL-F increased nitrogen partial productivity by 6.1%, while IM-F and IS-F decreased nitrogen partial productivity by 14.0% and 36.0%, respectively. Compared with NH, NM increased dry bean yield and water use efficiency by 20.9% and 19.3%, while NL decreased dry bean yield and water use efficiency by 42.4% and 41.9%, respectively; NM and NL increased nitrogen partial productivity by 81.4% and 72.9%, respectively. Compared with IF-FNH, IL-FNM increased dry bean yield, water use efficiency and nitrogen partial productivity by 37.6%, 52.9% and 106.4%, respectively. Regression analysis showed that the yield of dry bean was the maximum (2362 kg·hm-2) when the irrigation amount was 318 mm and the nitrogen application amount was 583 kg·hm-2; the water use efficiency was the maximum (0.78 kg·m-3) when the irrigationamount was 295 mm and the nitrogen application amount was 584 kg·hm-2, that's to say when yield of dry bean and water use efficiency reach the maximum value at the same time, the combination was the closest to IL-FNM. Therefore, the best combination of water and nitrogen model for C. arabica was IL-FNM.

A three ion channel genes-based signature predicts prognosis of primary glioblastoma patients and reveals a chemotherapy sensitive subtype.

Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of brain tumor. However, the roles of ion channels in glioma remain controversial. In the present study, we systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using RNAseq expression profiling. First, a molecular signature comprising three ion channel genes (KCNN4, KCNB1 and KCNJ10) was identified using Univariate Cox regression and two-tailed student's t test conducted in overall survival (OS) and gene expression. We assigned a risk score based on three ion channel genes to each primary Glioblastoma multiforme (pGBM) patient. We demonstrated that pGBM patients who had a high risk of unfavorable outcome were sensitive to chemotherapy. Next, we screened the three ion genes-based signature in different molecular glioma subtypes. The signature showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis for the functional annotation of the signature showed that patients with high-risk scores tended to exhibit the increased expression of proteins associated with apoptosis, immune response, cell adhesion and motion and vasculature development. Gene Set Enrichment Analysis (GSEA) results showed that pathways associated with negative regulation of programmed cell death, cell proliferation and locomotory behavior were highly expressed in the high-risk group. These results suggest that ion channel gene expression could improve the subtype classification in gliomas at the molecular level. The findings in the present study have been validated in two independent cohorts.

The comparison of clinical and biological characteristics between IDH1 and IDH2 mutations in gliomas.

BACKGROUND: Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are frequent in low-grade gliomas and secondary glioblastomas (sGBM). Because they yield the same oncometabolite, D-2-hydroxyglutarate, they are often treated as equivalent and pooled. The objective of this study was to provide insight into the differences between IDH1 and IDH2 mutant gliomas. METHODS: To investigate the different clinical and molecular characterization between IDH1 mutant and IDH2 mutant gliomas, we studied 811 patients with IDH1 mutations, IDH2 mutations and IDH1/2 wild-type. In addition, whole-transcriptome sequencing and DNA methylation data were used to assess the distribution of genetic changes in IDH1 and IDH2 mutant gliomas in a Chinese population-based cohort. RESULTS: Among 811 gliomas in our cohort, 448 cases (55.2%) harbored an IDH1 mutation, 18 cases (2.2%) harbored an IDH2 mutation and 345 cases (42.6%) harbored an IDH1/2 wild-type. We found that IDH1 and IDH2 are mutually exclusive in gliomas, and IDH2 mutations are mutually exclusive with PTEN, P53 and ATRX mutations. Patients with IDH2 mutations had a higher frequency of 1p/19q co-deletion (p < 0.05) than IDH1 mutant patients. In addition, a Gene Set Enrichment Analysis (GSEA) showed that IDH2 mutant gliomas were associated with the oxidative phosphorylation gene set, and the four most representative biological processes for genes commonly altered by hypermethylation in IDH2 mutant gliomas were the regulation of cell proliferation, cell motion, cell migration and response to hypoxia. Patients with IDH2 mutant gliomas exhibited longer Overall survival (OS) (p < 0.05) and longer Progression-free survival (PFS) (p < 0.05) than patients with IDH1/2 wild-type gliomas. However, their OS and PFS did not differ from that of IDH1 mutant patients. CONCLUSIONS: Our study revealed an intrinsic distinction between IDH1 and IDH2 mutant gliomas, and these mutations should be considered separately because their differences could have implications for the diagnosis and treatment of IDH1/2 mutant gliomas.

Tetrabromobisphenol-A/S and Nine Novel Analogs in Biological Samples from the Chinese Bohai Sea: Implications for Trophic Transfer.

Tetrabromobisphenol-A/S (TBBPA/S) analogs have raised substantial concern because of their adverse effects and potential bioaccumulative properties, such as TBBPA bis(allyl ether) (TBBPA-BAE) and TBBPA bis(2,3-dibromopropyl ether) (TBBPA-BDBPE). In this study, a comprehensive method for simultaneous determination of TBBPA/S and nine novel analogs, including TBBPA-BAE, TBBPA-BDBPE, TBBPS-BDBPE, TBBPA mono(allyl ether) (TBBPA-MAE), TBBPA mono(2-bromoallyl ether) (TBBPA-MBAE), TBBPA mono(2,3-dibromopropyl ether) (TBBPA-MDBPE), TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE in biological samples was developed. The distribution patterns and trophic transfer properties of TBBPA/S and analogs in various biological samples collected from the Chinese Bohai Sea were then studied in detail. For the first time, TBBPA-MBAE and TBBPS-BDBPE were detected in biological samples and TBBPA-MBAE was identified as a byproduct. The concentrations of TBBPA and analogs ranged from ND (not detected or below the method detection limit) to 2782.8 ng/g lipid weight (lw), and for TBBPS and analogs ranged from ND to 927.8 ng/g lw. High detection frequencies (>86%) for TBBPA, TBBPS and TBBPA-MAE, TBBPA-MDBPE, TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE were obtained. Meanwhile, TBBPA, TBBPS, and these five analogs displayed trophic dilution tendencies due to significantly negative correlations between trophic levels and lipid-corrected concentrations together with the trophic magnification factors (from 0.31 to 0.55). The results also indicated the novel TBBPA-MAE, TBBPA-MBAE, TBBPA-MDBPE, TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE could be generated not only as byproducts, but also as the probable transformation products of commercial TBBPA/S derivatives.

Low c-Met expression levels are prognostic for and predict the benefits of temozolomide chemotherapy in malignant gliomas.

Aberrant c-Met has been implicated in the development of many cancers. The objective of this study was to identify an unfavorable prognostic marker that might guide decisions regarding clinical treatment strategies for high-grade gliomas. C-Met expression was measured using immunohistochemistry in 783 gliomas, and we further analyzed c-Met mRNA levels using the Agilent Whole Genome mRNA Microarray in 286 frozen samples. In vitro, we performed cell migration and invasion assays. Cell sensitivity to temozolomide (TMZ) chemotherapy was determined using MTT assays. Both mRNA and protein levels of c-Met were significantly associated with tumor grade progression and inversely correlated with overall and progression-free survival in high-grade gliomas (all P < 0.0001). These findings were nearly consistent at the mRNA level across 3 independent cohorts. Multivariable analysis indicated that c-Met was an independent prognostic marker after adjusting for age, preoperative Karnofsky Performance Status (KPS) score, the extent of resection, radiotherapy, TMZ chemotherapy, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Further analysis in vitro revealed that downregulating the expression of c-Met dramatically inhibited cell migration and invasion capacities, enhanced sensitivity to TMZ chemotherapy in H4 and U87 glioma cells. Our results suggest that c-Met may serve as a potential predictive maker for clinical decision making.