Targeting unfolded protein response using albumin-encapsulated nanoparticles attenuates temozolomide resistance in glioblastoma.

BACKGROUND: Chemoresistant cancer cells frequently exhibit a state of chronically activated endoplasmic reticulum (ER) stress. Engaged with ER stress, the unfolded protein response (UPR) is an adaptive reaction initiated by the accumulation of misfolded proteins. Protein disulfide isomerase (PDI) is a molecular chaperone known to be highly expressed in glioblastomas with acquired resistance to temozolomide (TMZ). We investigate whether therapeutic targeting of PDI provides a rationale to overcome chemoresistance. METHODS: The activity of PDI was suppressed in glioblastoma cells using a small molecule inhibitor CCF642. Either single or combination treatment with TMZ was used. We prepared nanoformulation of CCF642 loaded in albumin as a drug carrier for orthotopic tumour model. RESULTS: Inhibition of PDI significantly enhances the cytotoxic effect of TMZ on glioblastoma cells. More importantly, inhibition of PDI is able to sensitise glioblastoma cells that are initially resistant to TMZ treatment. Nanoformulation of CCF642 is well-tolerated and effective in suppressing tumour growth. It activates cell death-triggering UPR beyond repair and induces ER perturbations through the downregulation of PERK signalling. Combination treatment of TMZ with CCF642 significantly reduces tumour growth compared with either modality alone. CONCLUSION: Our study demonstrates modulation of ER stress by targeting PDI as a promising therapeutic rationale to overcome chemoresistance.

NUV-pumped red-emitting Ca9MnK(PO4)7 phosphor: energy transfer and charge compensation.

The development of novel Mn-based phosphor hosts has received increasing interest in the search for highly efficient red emitting phosphors for white LED applications. In this study, Ca9MnK(PO4)7, a compound with the ß-Ca3(PO4)2-type structure, was successfully synthesized by a high-temperature solid-state reaction process. The Eu2+-doped Ca9MnK(PO4)7 phosphor exhibits a broadband red emission peaking at 650 nm. The optimal excitation wavelength is 395 nm, which matches that of commercial ultraviolet (NUV) chips. Codoping Ce3+ ions into the Ca9MnK(PO4)7:Eu2+ phosphor efficiently improves Mn2+ luminescence. Here, Ce3+ acts as a charge compensator rather than a sensitizer and substantially increases the effective number of Eu2+ and finally improves the red emission of Mn2+. The charge compensation mechanism is also verified by codoping some optically inert rare earth ions (Ln3+) including Y3+, La3+ and Gd3+. The results demonstrate that these developed Ca9MnK(PO4)7:Eu2+, Ln3+ phosphors have great potential for application in NUV-based white LEDs. The energy transfer approach combined with the charge compensation technique is valuable for improving the performance of the red-emitting Ca9MnK(PO4)7:Eu2+ phosphor, which can further be used in developing other Mn-based phosphors.

Investigation on flow field characteristics in an open-pit coal mine.

In this paper, the atmospheric flow field characteristics in a deep open-pit mine are investigated numerically and theoretically. A theoretical model on the recirculation length based on the energy equation is used, and a total variation diminishing (TVD) difference scheme with second-order accuracy is used to solve the NS equations with a standard two-equation k-ε turbulence model. The effects of elevated inner dump on the flow field characteristics of the open-pit mine are analyzed detailedly with the same inflow parameters. The results show that a recirculation zone exists in the open-pit mine due to the reflux from the high-pressure zone to the low-pressure zone. As the height of the inner dump increases, the flow becomes more complicated, and the low-pressure zone and the recirculation zone become bigger. The elevated inner dump makes it difficult for the internal fluid to flow to the outside, which results in the increase of the dust concentration. At last, the influences of key parameters on flow filed are conducted by normalizing the depth of the lowest direct current flow on the windward slope. The sensitivity analysis is done by study each influencing factor. This paper offers an effective way to study the flow field characteristics in an open-pit coal mine, which is essential to the dust pollution control of open-pit mine.

A new circulating accumulation emission model for assessing dust emission from open pit mine.

To reduce the inaccuracy of using the monitoring data outside the pit to evaluate the unorganized emission dust source of open pit mine, the circulating accumulation emission model is established. Based on the model, the monitoring data in the pit can be converted into the dust emission from the pit. The main conclusions include: (1) the circulating accumulation emission model is suitable for the dust diffusion process in open pit mine. The ratio of diffusion [Formula: see text] and the ratio of surplus [Formula: see text] were used to simulate the dust diffusion process in open pit mine, containing emission, retention and diffusion. (2) The initial value of the dust in the pit before the team operation has little influence on the final stable value. (3) When the external dust enters the pit, it will accumulate under the action of eddy current. The dust background value in the pit is different from that outside the pit. (4) The dust emission from the pit can be calculated from the monitoring data in the pit based on the circulating accumulation emission model. The model can deal with environmental changes such as the wind direction and speed, without arranging a lot of external monitoring equipment like the traditional external monitoring methods.

Integrated Analysis of RNA-Binding Proteins in Glioma.

RNA-binding proteins (RBPs) play important roles in many cancer types. However, RBPs have not been thoroughly and systematically studied in gliomas. Global analysis of the functional impact of RBPs will provide a better understanding of gliomagenesis and new insights into glioma therapy. In this study, we integrated a list of the human RBPs from six sources-Gerstberger, SONAR, Gene Ontology project, Poly(A) binding protein, CARIC, and XRNAX-which covered 4127 proteins with RNA-binding activity. The RNA sequencing data were downloaded from The Cancer Genome Atlas (TCGA) (n = 699) and Chinese Glioma Genome Atlas (CGGA) (n = 325 + 693). We examined the differentially expressed genes (DEGs) using the R package DESeq2, and constructed a weighted gene co-expression network analysis (WGCNA) of RBPs. Furthermore, survival analysis was also performed based on the univariate and multivariate Cox proportional hazards regression models. In the WGCNA analysis, we identified a key module involved in the overall survival (OS) of glioblastomas. Survival analysis revealed eight RBPs (PTRF, FNDC3B, SLC25A43, ZC3H12A, LRRFIP1, HSP90B1, HSPA5, and BNC2) are significantly associated with the survival of glioblastoma patients. Another 693 patients within the CGGA database were used to validate the findings. Additionally, 3564 RBPs were classified into canonical and non-canonical RBPs depending on the domains that they contain, and non-canonical RBPs account for the majority (72.95%). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that some non-canonical RBPs may have functions in glioma. Finally, we found that the knockdown of non-canonical RBPs, PTRF, or FNDC3B can alone significantly inhibit the proliferation of LN229 and U251 cells. Simultaneously, RNA Immunoprecipitation (RIP) analysis indicated that PTRF may regulate cell growth and death- related pathways to maintain tumor cell growth. In conclusion, our findings presented an integrated view to assess the potential death risks of glioblastoma at a molecular level, based on the expression of RBPs. More importantly, we identified non-canonical RNA-binding proteins PTRF and FNDC3B, showing them to be potential prognostic biomarkers for glioblastoma.

Optical properties and energy transfer of Eu2+/Ce3+ co-activated Na3Ca6(PO4)5 phosphor.

Ce(3+) /Eu(2+) co-doped Na3 Ca6 (PO4 )5 phosphors were prepared using a combustion-assisted synthesis method. X-Ray powder diffraction (XRD) analysis confirmed the formation of a Na3 Ca6 (PO4 )5 crystal phase. Na3 Ca6 (PO4 )5 :Eu(2+) phosphors have an efficient bluish-green emission band that peaks at 489 nm, whereas Ce(3+) -doped Na3 Ca6 (PO4 )5 showed a bright emission band at 391 nm. Analysis of the experimental results suggests that enhancement of the Eu(2+) emission intensity in co-doped Na3 Ca6 (PO4 )5 :Eu(2+) ,Ce(3+) phosphors is due to a resonance-type energy transfer from Ce(3+) to Eu(2+) ions, which is predominantly governed by an exchange interaction mechanism. These results indicate that Ce(3+) /Eu(2+) co-doped Na3 Ca6 (PO4 )5 is potentially useful as a highly efficient, bluish-green emitting, UV-convertible phosphor for white-light-emitting diodes.

Synthesis and luminescence properties of a novel blue emitting phosphor NaMgPO4:Eu(2+).

A novel blue-emitting phosphor of Eu(2+)-activated NaMgPO(4) was prepared by combustion-assisted synthesis. Sodium dihydrogen phosphate and magnesium nitrate were used as the source of Na, P and Mg, respectively. The ratios of magnesium and phosphorus components that were dissolved into the combustion solution were changed from 1:1 to 1:1.3. Their effect on the crystallinities and photoluminescence spectra of the phosphor particles were investigated. The post-heated phosphor particles had a broad excitation wavelength that ranged from 240 to 410 nm. The phosphor particles prepared from the combustion solution with a 1:1.2 ratio of magnesium to phosphorus had maximum emission intensity under ultraviolet excitation. The effect of doped Eu(2+) concentration on the emission intensity of PO4:Eu(2+) was also investigated.