MUC1 promotes glioblastoma progression and TMZ resistance by stabilizing EGFRvIII.

Epidermal growth factor receptor variant III (EGFRvIII) is a mutant isoform of EGFR with a deletion of exons 2-7 making it insensitive to EGF stimulation and downstream signal constitutive activation. However, the mechanism underlying the stability of EGFRvIII remains unclear. Based on CRISPR-Cas9 library screening, we found that mucin1 (MUC1) is essential for EGFRvIII glioma cell survival and temozolomide (TMZ) resistance. We revealed that MUC1-C was upregulated in EGFRvIII-positive cells, where it enhanced the stability of EGFRvIII. Knockdown of MUC1-C increased the colocalization of EGFRvIII and lysosomes. Upregulation of MUC1 occurred in an NF-κB dependent manner, and inhibition of the NF-κB pathway could interrupt the EGFRvIII-MUC1 feedback loop by inhibiting MUC1-C. In a previous report, we identified AC1Q3QWB (AQB), a small molecule that could inhibit the phosphorylation of NF-κB. By screening the structural analogs of AQB, we obtained EPIC-1027, which could inhibit the NF-κB pathway more effectively. EPIC-1027 disrupted the EGFRvIII-MUC1-C positive feedback loop in vitro and in vivo, inhibited glioma progression, and promoted sensitization to TMZ. In conclusion, we revealed the pivotal role of MUC1-C in stabilizing EGFRvIII in glioblastoma (GBM) and identified a small molecule, EPIC-1027, with great potential in GBM treatment.

Identification of long non-coding RNA HERC2P2 as a tumor suppressor in glioma.

Long non-coding RNAs (lncRNAs) have been reported to play important roles in glioma; however, most of them promote glioma progression. We constructed a competing endogenous (ceRNA) network based on the Chinese Glioma Genome Atlas dataset, and lncRNA hect domain and RLD 2 pseudogene 2 (HERC2P2) is the core of this network. Highly connected genes in the ceRNA network classified the glioma patients into three clusters with significantly different survival rates. The expression of HERC2P2 is positively correlated with survival and negatively correlated with clinical grade. Cell colony formation, Transwell and cell scratch tests were performed to evaluate the role of HERC2P2 in glioblastoma growth. Furthermore, we overexpressed HERC2P2 in U87 cells and established a mouse intracranial glioma model to examine the function of HERC2P2 in vivo. In conclusion, we identified a lncRNA with tumor suppressor functions in glioma that could be a potential biomarker for glioma patients.

Adsorption Behaviour of Tween 85 on Nano-Aluminium Particles in Aluminium/JP-10 Suspensions.

A stability analyser and a rheometer were used to study the effects of Tween 85 (polyoxyethylene sorbitan trioleate) on the dispersion properties of nano-aluminium/JP-10 (exo-tetrahydrodicyclopentadiene) suspensions. Results show that the addition of Tween 85 can effectively improve the stability of two-phase suspensions by hindering particle aggregation and reduce the viscosity of a system. The surface characteristics of the zeta potential and the contact angle were measured. The dispersion of the suspensions was improved by Tween 85 mainly by enhancing the steric hindrance of particles. The adsorbed particles obtained in JP-10 with different Tween 85 concentrations were analysed via scanning electron microscopy and Fourier transform infrared spectroscopy to explore the adsorption behaviour of Tween 85 molecules on the surface of aluminium particles and to confirm that Tween 85 formed an adsorption layer on the particle surface. Thermogravimetric analysis indicated that the adsorption amount of Tween 85 increased with its concentration in JP-10. The roughness analysis of the surface of adsorbed particles was measured via atomic force microscopy to characterise the thickness of the adsorption layer. The results showed that Tween 85 molecules formed an irregular adsorption layer on the particle surface, and an increase in the concentration of Tween 85 in JP-10 increased the thickness of the adsorption layer.

EGFR/EGFRvIII remodels the cytoskeleton via epigenetic silencing of AJAP1 in glioma cells.

EGFR amplification and mutations are the most common oncogenic events in GBM. EGFR overexpression correlates with GBM invasion, but the underlying mechanisms are poorly understood. In a previous study, we showed that AJAP1 is involved in regulating F-actin to inhibit the invasive ability of GBM. In addition, in a GBM cell line, the AJAP1 promoter was highly bound by H3K27me3 and, through bioinformatics analysis, we found that AJAP1 expression was negatively correlated with EGFR. In this study, we found that the pathway downstream of EGFR had a higher activation level in GBM cell lines, which led to excessive tumor suppressor silencing. Therefore, we deduced that in glioma cells, the pathway downstream of EGFR remodels the cytoskeleton via AJAP1 epigenetic silencing to enhance invasion. Furthermore, MK2206 reversed AJAP1 downregulation by inhibiting the EGFR pathway. In vivo, MK2206 also inhibited the proliferation and local invasion of 87-EGFRvIII. These data suggest that activation of the EGFR signal transduction pathway genetically silences anti-oncogenes to enhance GBM malignancy. MK2206 might be a promising therapeutic for EGFR/EGFRvIII-positive GBMs.

The CRISPR/Cas9 system targeting EGFR exon 17 abrogates NF-κB activation via epigenetic modulation of UBXN1 in EGFRwt/vIII glioma cells.

Worldwide, glioblastoma (GBM) is the most lethal and frequent intracranial tumor. Despite decades of study, the overall survival of GBM patients remains unchanged. epidermal growth factor receptor (EGFR) amplification and gene mutation are thought to be negatively correlated with prognosis. In this study, we used proteomics to determine that UBXN1 is a negative downstream regulator of the EGFR mutation vIII (EGFRvIII). Via bioinformatics analysis, we found that UBXN1 is a factor that can improve glioma patients' overall survival time. We also determined that the down-regulation of UBXN1 is mediated by the upregulation of H3K27me3 in the presence of EGFRvIII. Because NF-κB can be negatively regulated by UBXN1, we believe that EGFRwt/vIII activates NF-κB by suppressing UBXN1 expression. Importantly, we used the latest genomic editing tool, CRISPR/Cas9, to knockout EGFRwt/vIII on exon 17 and further proved that UBXN1 is negatively regulated by EGFRwt/vIII. Furthermore, knockout of EGFR/EGFRvIII could benefit GBM in vitro and in vivo, indicating that CRISPR/Cas9 is a promising therapeutic strategy for both EGFR amplification and EGFR mutation-bearing patients.

Experiment and mechanism investigation on advanced reburning for NO(x) reduction: influence of CO and temperature.

Pulverized coal reburning, ammonia injection and advanced reburning in a pilot scale drop tube furnace were investigated. Premix of petroleum gas, air and NH3 were burned in a porous gas burner to generate the needed flue gas. Four kinds of pulverized coal were fed as reburning fuel at constant rate of 1g/min. The coal reburning process parameters including 15% approximately 25% reburn heat input, temperature range from 1100 degrees C to 1400 degrees C and also the carbon in fly ash, coal fineness, reburn zone stoichiometric ratio, etc. were investigated. On the condition of 25% reburn heat input, maximum of 47% NO reduction with Yanzhou coal was obtained by pure coal reburning. Optimal temperature for reburning is about 1300 degrees C and fuel-rich stoichiometric ratio is essential; coal fineness can slightly enhance the reburning ability. The temperature window for ammonia injection is about 700 degrees C approximately 1100 degrees C. CO can improve the NH3 ability at lower temperature. During advanced reburning, 72.9% NO reduction was measured. To achieve more than 70% NO reduction, Selective Non-catalytic NO(x) Reduction (SNCR) should need NH3/NO stoichiometric ratio larger than 5, while advanced reburning only uses common dose of ammonia as in conventional SNCR technology. Mechanism study shows the oxidization of CO can improve the decomposition of H2O, which will rich the radical pools igniting the whole reactions at lower temperatures.

[Pore structure and desulfurization characteristics of organic calcium].

Calcination of oganic calcium was carried out in fixed bed, pore structure of tested sample was analyzed with auto-adsorption analyzer, and desulfurization experiment was studied by intelligent sulfur determination analyzer. Specific surface area of calcium magnesium acetate (CMA) was 46.6 m2/g after calcination at 900 degrees C, almost four times of that of limestone. Specific surface area of calcium acetate (CA) were mainly made up of pore of diameter less than 5 nm, and those of CMA was chiefly contributed by middle pore of diameter about 5 nm. Agglomeration of CA occurred in pore of diameter less than 5 nm, while CMA was sintered in whole range of pore size distribution. Agglomeration of organic calcium were slighter. Desulfurization efficiency of organic calcium ranged from 62.28% to 75.55% at 1000 degrees C as calcium/sulfur ratio being one, which was one time more than that of limestone. Perfect pore structure of organic calcium contributes to higher desulfurization efficiency.

[Influence factors of hydrogen production in straw fermentation].

Biohydrogen production from straw by anaerobic fermentation of digested sludge was studied. The influence of the main parameters such as particle size, the ratio of substrate to cellulase, pretreatment method and pH on the straw fermentation was investigated. With NaOH pretreatment, the rice straw with average particle size of 170 tm was fermented after hydrolyzed by cellulase with the ratio of substrate to cellulase as 1:1. And its maximal velocity and the total volume of hydrogen are respectively 0.58 mL/(h x g) and 90.5 m/g.

[Desulfurization characteristic of organic calcium at high temperature].

Aim to control the emission of SO2 during coal combustion, desulfurization characteristic of organic calcium was studied by intelligent sulfur determination analyzer. Sulfur releasing curve changed from two "peak value" to one for addition of organic calcium, with velocity of SO2 release decreasing. Efficiency of sulfur reduction was double when organic calcium was used under 1 000 degrees C compared to limestone, and reduction efficiency of calcium magnesium acetate was 73.84%. Sulfur content, furnace temperature, calcium/sulfur ratio and paticle's diameter were important factors as for desulfurizing rate. Sulfur removal efficiency was improved with coal's sulfur content increasing or particle's diameter decreasing. Decreasing degree of reduction efficiency lowered with sulfur content increasing as temperature improved. Efficiency remained high level as 59.08% by calcium magnesium acetate at 1 200 degrees C. Perfect efficiency could be reached as calcium/sulfur ratio being one and augmentation degree was inapparent with more calcium addition. Therefore organic calciums are excellent absorbent for desulfurization and calcium magnesium acetate has best sulfur removal efficiency.

[Fluorine removal efficiency of organic-calcium during coal combustion].

Effectiveness of calcium magnesium acetate (CMA) and calcium acetate(CA) as feasible HF capture were studied by means of fixed bed tube furnaces. The effects of temperature, particle diameter and Ca/S molar ratio on the fluorine removal efficiency were studied. By contract with CaCO3 at the same condition, we find that the HF capture effectiveness of those sorbents is superior to CaCO3, especially at high temperature. At 1 000 - 1 100 degrees C, the efficiency of fluorine removal during coal combustion of CMA is 1.68 - 1.74 times as that of CaCO3; the efficiency of fluorine removal during coal combustion of CA is 1.28 - 1.37 times as that of CaCO3.

[Emission of fluorine from black liquor coal-water slurry combustion].

The paper is about the emission of fluorine from an experimental boiler of 0.25 MW when burning black liquor coal-water slurry (CWS). The result is compared with CWS. And the analysis of effect factors is also carried out. Experimental research show that, the content of fluorine in CWS, which was less than 30 mg/kg, was relatively low. The emission ratio and concentration of fluorine were 70% - 90% and 2.0 - 2.6 mg/m3 respectively when burning common CWS; while the data of those when combusting black liquor CWS were 45% - 80% and 1.7 - 3.0 mg/m3 respectively. The hearth temperature and the element of CWS were two factors of emission fluorine when burning CWS.

[Study on the calcium-based sorbent for removal fluorine during coal combustion].

In the paper, the reaction of CaO-HF and fluorine removal mechanics at high temperature by blending calcium-based sorbents with coal during coal combustion were discussed, and test results about fluorine retention during coal combustion in fluidized bed and chain-grate furnace were reported. The results identified that lime and calcium-based sorbets developed can restratin the emission of fluorine during coal combustion. The efficiency of fluorine removal can reach 66.7%-70.0% at Ca/F 60-70 by blending lime with coal in fluidized bed combustion, and the efficiency of fluorine removal are between 57.32% and 75.19% by blending calcium-based sorbets with coal in chain-grate furnace combustion. Blending CaO or lime with coal during coal combustion can remove SO2 and HF simultaneously.

One family investigation and pathogeny research on ectrodactyly, absence of radius side part palm and split foot malformation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>The paper is a study on the clinical symptoms and pathogeny of ectrodactyly and absence of radius side part palm and split foot malformation of some patients in one family.</p><p><b>METHODS</b>Based on the patient family investigation,a normal control group and a patient group were established. Then, polymerase chain reaction technique was used for DNA sequencing and analysis of the two groups for their exons 5-8 gene group DNA of P63 gene.</p><p><b>RESULTS</b>The medical examination found that the patients' upper bilateral limbs are short of thumbs, forefingers and middle fingers, and have radius side part palm and double lower limbs foot clefts malformation. The pathogeny research revealed that the PCR expansion pieces of the exons 5-8 of P63 are 284 bp, 259 bp, 245 bp and 259 bp respectively, and the size of the expansion piece of the patients was the same as that of the normal people group. However, a respective comparison between the DNA serial of the expansion piece of the patient and that of the normal people group and that of the P63 gene in the human gene bank showed that mutation occurs at the number 665 base pair of exon 5 of P63, namely a mutation from G to A.</p><p><b>CONCLUSION</b>The ectrodactyly, absence of radius side part palm and split foot malformation are caused by the mutation of base pair at number 665 of the exon 5 of P63.</p>