Search

Purpose: To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT).Methods and Materials: Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed. The form of cell death, the number and area of colonies, and the regulatory proteins of necroptosis were characterized after radiation therapy in vitro. Finally, NSCLC xenografts and patient specimens were used to examine involvement of necroptosis after ablative HFRT in vivo.Results: Radiation therapy induced expected DNA damage and repair of NSCLC cell lines, but ablative HFRT at ≥10 Gy per fraction preferentially stimulated necroptosis in NSCLC cells and xenografts with high RIP3 expression, as characterized by induction and activation of RIP3 and mixed-lineage kinase domain-like protein and release of immune-activating chemokine high-mobility group box 1. In contrast, RNA interference of RIP3 attenuated ablative HFRT-induced necroptosis and activation of its regulatory proteins. Among central early-stage NSCLC patients receiving stereotactic body radiation therapy, high expression of RIP3 was associated with improved local control and progression-free survival (all P < .05).Conclusions: Ablative HFRT at ≥10 Gy per fraction enhances killing of NSCLC with high RIP3 expression via preferential stimulation of necroptosis. RIP3 may serve as a useful biomarker to predict favorable response to stereotactic body radiation therapy. [ABSTRACT FROM AUTHOR]

Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 (LRP16) is correlated with the progression of estrogen-related tumors, but the regulatory mechanism between LRP16 and prolactinoma remain unclear. This study demonstrates a variation in LRP16 with estrogen receptor α (ERα) in prolactinoma models and the up and downregulation effects of LRP16 on prolactin secretion of pituitary adenomas cells (GH 3 cells). In our study, 50 male SD rats (30-day-old) were randomly divided into five groups of 10 rats each. After 120 days of treatment, the rats were sacrificed, and the expression of LRP16 and ERα were examined by Western blot and immunohistochemistry to explore the changes in ERα, LRP16, and prolactin. After siRNA transfection of the respective genes, the GH3 cells were cultured, and their secretory function as well as the expression of ERα mRNA and prolactin were analyzed by enzyme-linked immunosorbent assay and real-time-polymerase chain reaction analysis. The results show that secretion of prolactin by GH 3 cells can be affected by up and downregulating LRP16 expression, which may provide a novel medical therapy in clinical trials. [ABSTRACT FROM AUTHOR]

In order to reduce the dependence of pedestrian navigation on satellite navigation system and wireless communication, a new method is proposed to construct pedestrian navigation system (PNS) based on micro inertial technology. In this paper, the distributed system structure is arranged on human feet and trunk, and the key technologies, namely the system initial alignment, the error correction, the precise gait-phase detection, the effect and the inhibition of environmental magnetic field, have been studied. Besides, theories and applications of the key technologies are also discussed, and the performance of the PNS has been analyzed in the environment of electromagnetic interference. Experimental results show that the positioning error of the route with electromagnetic interference accounts for 2% of the travel distance. The key technologies proposed in the study can effectively improve the positioning accuracy of PNS, and independently achieve longer time personal navigation in the attenuate or even invalid global navigation satellite system (GNSS) and wireless communication signal environment. [ABSTRACT FROM AUTHOR]

Highlights: [•] TDP-43 colocalizes and interacts with AICD. [•] TDP-43 enhances the transactivation of AICD. [•] TDP-43 enhances AICD-mediated TP53 transcription and apoptosis. [ABSTRACT FROM AUTHOR]

Schmid factors (m) for typical slip modes (basal 〈a〉, prismatic 〈a〉, pyramidal 〈a〉 and 〈c + a〉 slips) and twinning patterns ( and twins) were systematically calculated in hexagonal close-packed Cd, Zn, Mg, Zr, Ti and Be. A monotonic effect on m-values was presented for pyramidal 〈a〉 and 〈c + a〉 slips, and and twinning patterns with decreasing c/a ratio. The results calculated herein were used to characterize deformation behaviors and provide essential data for anisotropic feature analysis. [ABSTRACT FROM AUTHOR]

Abstract: Hexahistidine-tagged protein functionalized multi-walled carbon nanotubes (MWCNTs/6His-tagged protein) were prepared and characterized by ultraviolet–visible spectrophotometry and atomic force microscopy. Both static and dynamical adsorption experiments showed that the MWCNTs/6His-tagged protein served as good sorbent for the solid-phase extraction of Cu2+ and Ni2+. Effective on-line sorption of Cu2+ and Ni2+ on the MWCNTs/6His-tagged protein packed microcolumn was achieved in a pH range of 3.0–4.5 and 4.5–6.0, respectively. The retained Cu2+ and Ni2+ were efficiently eluted with 0.2molL−1 imidazole–HCl solution for on-line flame atomic absorption spectrometric determination. The MWCNTs/6His-tagged protein exhibited fairly fast kinetics for the sorption of Cu2+ and Ni2+, and offered up to 20,000 and 1800 times improvement in the tolerable concentrations of co-existing ions over the MWCNTs for solid-phase extraction of Cu2+ and Ni2+, respectively. On-line solid-phase extraction at a flow rate of 5.0mLmin−1 for 60s gave an enhancement factor of 29 for Cu2+ and 28 for Ni2+, a sample throughput of 45h−1, and a detection limit (3s) of 0.31μgL−1 for Cu2+ and 0.63μgL−1 for Ni2+. The precision for 11 replicate measurements was 2.4% for 10μgL−1 Cu2+, and 2.5% for 15μgL−1 Ni2+. [Copyright &y& Elsevier]

A anhydrous orthoborate Na 3 Tb(PO 4 ) 2 has been prepared and its crystal structure was determined by X-Ray diffraction of a non-merohedral twinned single crystal. The results show that the compound crystallizes in monoclinic space group C 2/ c and the structure features a 3D framework containing PO 4 , NaO 6 , NaO 7 , NaO 8 and TbO 8 polyhedra. Under near-UV excitation (370 nm), Na 3 Tb(PO 4 ) 2 shows intense characteristic emission bands of Tb 3+ (490 nm, 543 nm, 585 nm and 620 nm) with the CIE coordinate of (0.3062, 0.5901), corresponding to greenish color. The excitation spectrum covers a wide range from 340 nm to 390 nm, which indicates that phosphor Na 3 Tb(PO 4 ) 2 can be efficiently activated by near-UV LED ship. [ABSTRACT FROM AUTHOR]

Aerobic glycolysis, a metabolic hallmark of cancer, is associated with radioresistance in non-small cell lung cancer (NSCLC). Pyruvate kinase M2 isoform (PKM2), a key regulator of glycolysis, is expressed exclusively in cancers. However, the impact of PKM2 silencing on the radiosensitivity of NSCLC has not been explored. Here, we show a plasmid of shRNA-PKM2 for expressing a short hairpin RNA targeting PKM2 (pshRNA-PKM2) and demonstrate that treatment with pshRNA-PKM2 effectively inhibits PKM2 expression in NSCLC cell lines and xenografts. Silencing of PKM2 expression enhanced ionizing radiation (IR)-induced apoptosis and autophagy in vitro and in vivo , accompanied by inhibiting AKT and PDK1 phosphorylation, but enhanced ERK and GSK3β phosphorylation. These results demonstrated that knockdown of PKM2 expression enhances the radiosensitivity of NSCLC cell lines and xenografts as well as may aid in the design of new therapies for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: LRP16 gene has been characterized as an estrogen-responsive gene. One 1/2ERE/GC-rich site was previously identified to be indispensable for −676/−214 (region A) fragment within LRP16 regulatory region to confer E2 action. Here, we report that −213/−24 fragment (region B) has higher E2-responsiveness than that of region A in MCF-7 cells, but not in HeLa cells. Deletion and mutation analyses of region B showed that multiple GC-sites are involved in the E2-stimulated response and one 30-bp fragment (−213 to −184bp) is essential for conferring maximum E2-responsiveness. Results from the cotransfection assays containing Sp1-siRNA revealed that Sp1 is required for the basal transcription activity and E2-responsiveness of both regions A and B. Northern blot analysis demonstrated that inhibition of Sp1 in MCF-7 cells not only decreased the basal expression of LRP16, but markedly impaired its upregulation by E2. Results from gel mobility shift assays exhibited the direct binding of Sp1 protein to the 28-bp fragment (−211 to −184bp), which was enhanced by the ERα titer. Moreover, the functional interaction of ERα and Sp1 proteins in the presence of E2 at the GC-rich sites in region B was confirmed by chromatin immunoprecipitation (ChIP) assays. In general, these results demonstrate that GC-rich sites in the proximal promoter of LRP16 gene are sufficient for E2 activation of LRP16 and the −213/−184 fragment containing only one GC site is essential for the maximal induction in MCF-7 cells. We also provide a model for Sp1-dependent regulation of genes by E2 through GC-rich motifs. [Copyright &y& Elsevier]