GARNL3 identified as a crucial target for overcoming temozolomide resistance in EGFRvIII-positive glioblastoma.

OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.

Facile Synthesis of the Magnetic Metal Organic Framework Fe3O4@UiO-66-NH2 for Separation of Strontium.

A magnetic metal organic framework (MMOF) was synthesized and used to separate Sr2+ in aqueous solution. The shape and structure of prepared Fe3O4@UiO-66-NH2 were characterized, and the absorbed concentration of strontium was determined through inductively coupled plasma mass spectrometry. The results indicated that Fe3O4 and UiO-66-NH2 combined through chemical bonding. The experimental adsorption results for separation of Sr2+ in aqueous solution indicated that the adsorption of Sr2+ to Fe3O4@UiO-66-NH2 increased drastically from pH 11 to pH 13. The adsorption isotherm model indicated that the adsorption of Sr2+ conformed to the Freundlich isotherm model (R2 = 0.9919). The MMOF thus inherited the superior qualities of magnetic composites and metal organic frameworks, and can easily be separated under an external magnetic field. This MMOF thus has potential applications as a magnetic adsorbent for low level radionuclide 90Sr.

Determination of Trace Elements in Edible Nuts in the Beijing Market by ICP-M.

Nuts have received increased attention from the public in recent years as important sources of some essential elements, and information on the levels of elements in edible nuts is useful to consumers. Determination of the elemental distributions in nuts is not only necessary in evaluating the total dietary intake of the essential elements, but also useful in detecting heavy metal contamination in food. The aim of this study was to determine the mineral contents in edible nuts, and to assess the food safety of nuts in the Beijing market. Levels of Li, Cr, Mn, Co, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Cs, Ba, Pb, Th, and U in 11 types of edible nuts and seeds (macadamia nuts, lotus nuts, pistachios, sunflower seeds, pine nuts, almonds, walnuts, chestnuts, hazelnuts, cashews, and ginkgo nuts) as well as raisins were determined by inductively coupled plasma mass spectrometry (ICP-MS). The accuracy of the method was validated using standard reference materials GBW10014 (cabbage) and GBW10016 (tea). Our results provide useful information for evaluating the levels of trace elements in edible nuts in the Beijing market, will be helpful for improving food safety, and will aid in better protecting consumer interests.

New three-fold interpenetrated uranyl organic framework constructed by terephthalic acid and imidazole derivative.

A new 3-fold interpenetrated uranyl organic framework, UO2(bdc)(dmpi), was hydrothermally synthesized using 1,4-benzenedicarboxylic acid (H2bdc) and 1-(4-(1H-imidazol-1-yl)-2,5-dimethylphenyl)-1H-imidazole (dmpi). This framework, which was determined by synchrotron radiation X-ray, exhibited a new 3-fold interpenetrated (2,4)-connected topology with the Schläfli symbol of (12(6))(12)2. Additionally, large incurvation happened to the bond angle of [O=U=O](2+), which was always arranged in a rigorous line. Computational results based on density functional theory (DFT) indicated that the bent geometry of uranyl in UO2(bdc)(dmpi) was mainly due to the higher charge populations in the valence 6d shells of uranium, rendered by the electronegative imidazoles.

Determination of total tritium in urine from residents living in the vicinity of nuclear power plants in Qinshan, China.

To estimate the tritium doses of the residents living in the vicinity of a nuclear power plant, urine samples of 34 adults were collected from residents living near the Qinshan nuclear power plant. The tritium-in-urine (HTO plus OBT) was measured by liquid scintillation counting. The doses of tritium-in-urine from participants living at 2, 10 and 22 km were in a range of 1.26-6.73 Bq/L, 1.31-3.09 Bq/L and 2.21-3.81 Bq/L, respectively, while the average activity concentrations of participants from the three groups were 3.53 ± 1.62, 2.09 ± 0.62 and 2.97 ± 0.78 Bq/L, respectively. The personal committed effective doses for males were 2.5 ± 1.7 nSv and for females they were 2.9 ± 1.3 nSv. These results indicate that tritium concentrations in urine samples from residents living at 2 km from a nuclear power plant are significantly higher than those at 10 km. It may be the downwind direction that caused a higher dose in participants living at 22 km. All the measured doses of tritium-in-urine are in a background level range.

Radioactivity of drinking-water in the vicinity of nuclear power plants in China based on a large-scale monitoring study.

The public concern for radioactivity of drinking-water has been increasing in recent years after the rapid development of nuclear power plants, and especially after the Fukushima nuclear accident. In this study, the radioactivity of water samples collected in the vicinity of nuclear facilities from seven provinces in China was measured and an average annual equivalent effective dose derived from drinking-water ingestion was calculated. The results showed that, in winter and spring, the activities of gross α and ß ranged from 0.009 Bq/L to 0.200 Bq/L and from 0.067 Bq/L to 0.320 Bq/L, respectively. While, in summer and autumn, the activities of gross a and ß varied from 0.002 Bq/L to 0.175 Bq/L and from 0.060 Bq/L to 0.334 Bq/L. Our results indicated that the gross a and ß activities in these measured water samples were below the WHO recommended values (0.5 Bq/L for gross α and 1.0 Bq/L for gross ß) and the annual equivalent effective dose derived from drinking-water ingestion was at a safe level.

Determination of the metals by ICP-MS in wild mushrooms from Yunnan, China.

UNLABELLED: The elemental contents of Li, Cs, U, Co, As, Sr, Cd, Ba, Pb, Sb in 157 wild-grown mushrooms were determined by inductively coupled plasma mass spectrometry (ICP-MS). The mushrooms including 9 species were collected from 5 counties in Yunnan province, China. Based on the findings for the results from the certified reference materials GBW10014 (cabbage) and GBW10016 (tea), the data from the sample mushrooms were corrected. The contents of investigated trace elements in mushroom samples were determined as µg/g dry weight (dw) in the range of 0.030 to 13 for Li, 0.070 to 8.1 for Cs, 0.0010 to 0.28 for U, 0.040 to 5.4 for Co, 0.070 to 44 for As, 0.28 to 86 for Sr, and 0.15 to 23 for Cd. The maximum contents were 58, 11, and 0.11 for Ba, Pb, and Sb, respectively. The minimum contents of Ba, Pb, and Sb were below the detection limit of the method used. PRACTICAL APPLICATION: The analysis of 9 species wild-grown edible mushrooms in different regions provides the useful information to evaluate the levels of elements or of the toxic heavy metals, such as Cd, As in wild-grown edible mushrooms which grew in different regions of China for consumers and other interested groups, especially for the regulators.

Preparation of nanostructured materials by heterocoagulation-interaction of montmorillonite with synthetic hematite particles.

A nanostructured, porous material was prepared by heterocoagulation of negatively charged montmorillonite with positively charged synthetic spherical hematite particles. The process of heterocoagulation of such particles was monitored by turbidimetric titrations over the pH range 2.5-7.5. On the basis of the results of turbidimetric measurements, a series of solid materials were prepared for further characterization using ESEM, BET, XRD, and FTIR techniques. Environmental scanning electron microscopy detected isolated hematite particles or small hematite aggregates on montmorillonite surfaces (mass ratios 8:1 and 4:1). At a mass ratio of 1:1, exfoliated montmorillonite layers, covering the hematite particles as semi-transparent blankets were seen. A low mass ratio led to compact hematite particle aggregates covering the montmorillonite surfaces. Nitrogen-gas-adsorption isotherms revealed the sorption properties to be gradually dependent upon mass ratios. Pore volume distributions showed that mesopores with diameter of about 10-20 nm were produced in the heterocoagulates with mass ratios of 4:1, 1:1, and 1:8. The sample prepared with a 4:1 mass ratio showed the greatest BET surface area, which decreased slightly upon sample calcination at 500 degrees C. X-ray diffraction measurements were used to investigate layer stacking, by comparing the integral intensities of d(001) reflection. For this purpose, samples with 4:1 mass ratios, prepared both by heterocoagulation and mechanical grinding, were used. It was found that heterocoagulation effectively diminished the stacking of the layers to about 85%; hence, a significant amount of fundamental, 1 nm thick montmorillonite layers was achieved in this sample.