Transferrin, a Cell Pilot and Iron Provider Based on its Interaction with the Overexpressed Transferrin Receptors

Transferrin (Tf) is the serum protein responsible for delivering iron to the erythron and peripheral tissues. Transferrin receptor (TfR), a key receptor in the regulation of iron and is activated by the ferric ion loaded Tf, is overexpressed on the surface of various cancer cells due to their malignant transformation. Based on the Tf-TfR transport mechanism, Tf has been projected to be dually used as a pilot for nanoparticles to target the tumor cells with over expressed TfRs and an intracellular iron provider. Dihydroartemisinin (DHA) is believed a promising tumor therapeutic agent for its unique mechanism of cytotoxicity. When DHA chemically damaging cells, ferrous ions are required to react with the drug. In this research highlight, we discuss our latest published findings which demonstrate the enhanced cytotoxicity of DHA helped with a nanographene oxide carrier and the Tf-TfR transport system, and the potential for its anti-tumor application. This approach gives a further understanding on the role of ligand and receptor in tumor treatments

Biochemistry and Molecular Biology DNA Duplex-Based Photodynamic Molecular Beacon for Targeted Killing of Retinoblastoma Cell

PURPOSES. Retinoblastoma (RB) is the most common primary intraocular malignancy of infancy. An alternative RB treatment protocol is proposed and tested. It is based on a photodynamic therapy (PDT) with a designed molecular beacon that specifically targets the murine double minute x (MDMX) high-expressed RB cells. METHODS. A MDMX mRNA triggered photodynamic molecular beacon is designed by binding a photosensitizer molecule (pyropheophorbide-a, or PPa) and a black hole quencher-3 (BHQ3) through a complementary oligonucleotide sequence. Cells with and without MDMX highexpression are incubated with the beacon and then irradiated with a laser. The fluorescence and reactive oxygen species are detected in solution to verify the specific activation of PPa by the perfectly matched DNA targets. The cell viabilities are evaluated with CCK-8 and flow cytometry assay. RESULTS. The fluorescence and photo-cytoxicity of PPa is recovered and significantly higher in the MDMX high-expressed Y79 and WERI-Rb1 cells, compared to that with the MDMX lowexpressed cells. CONCLUSIONS. The synthesized beacon exhibits high PDT efficiency toward MDMX highexpressed RB cells. The data suggest that the designed beacon may provide a potential alternative for RB therapy and secures the ground for future investigation

Life Assessment of Railway Tunnel Lining Structure Based on Reliability Theory

The reliability of the tunnel lining during its service life has significance for tunnel safety management. To capture the performance of the lining under the effect of deterioration factors, the time-varying reliability theory was applied to predict the service life of the lining. The failure process of the lining structure under an erosion environment was analyzed. The limit state equations of the lining structure were established based on the durability criterion and the bearing capacity criterion, respectively. The time-varying reliability of the tunnel was calculated using the Monte-Carlo method with an engineering example, and the service life of the tunnel under different criteria was predicted based on the target reliability. The results show that the predicted service life of the tunnel is 77.5 years under the durability criterion and 95 years under the bearing capacity criterion, assuming that the tunnel structure is in an erosive environment at the beginning of construction and that no protective measures are taken under the most unfavourable conditions. The durability meets the structural applicability, and the bearing capacity meets the structural safety, which is in line with the actual needs of the project. The study results can provide a basis and reference for the future durability design, life prediction, and maintenance management of similar service tunnels

A Knowledge-Based Simulated Annealing Algorithm to Multiple Satellites Mission Planning Problems

The multiple satellites mission planning is a complex combination optimization problem. A knowledge-based simulated annealing algorithm is proposed to the multiple satellites mission planning problems. The experimental results suggest that the proposed algorithm is effective to the given problem. The knowledge-based simulated annealing method will provide a useful reference for the improvement of existing optimization approaches

A data analysis method for isochronous mass spectrometry using two time-of-flight detectors at CSRe

The concept of isochronous mass spectrometry (IMS) applying two time-of-flight (TOF) detectors originated many years ago at GSI. However, the corresponding method for data analysis has never been discussed in detail. Recently, two TOF detectors have been installed at CSRe and the new working mode of the ring is under test. In this paper, a data analysis method for this mode is introduced and tested with a series of simulations. The results show that the new IMS method can significantly improve mass resolving power via the additional velocity information of stored ions. This improvement is especially important for nuclides with Lorentz factor $\gamma$-value far away from the transition point $\gamma _t$ of the storage ring CSRe.Comment: published in Chinese Physics C Vol. 39, No. 10 (2015) 10620

(Z)3,4,5,4'-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level.

Calcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4′-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti-cancer activity by mediating calcium signaling pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi-targeting drug for treating G-R patients

Determination of heavy metals in chinese prickly ash from different production areas using inductively coupled plasma-mass spectrometry

Purpose: To determine the heavy metal content of Chinese prickly ash (CPA) produced in various areas of China.Methods: CPA samples collected from different production areas in China were subjected to microwave digestion, and the contents of copper (Cu), nickel (Ni), chromium (Cr), lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), tin (Sn), and antimony (Sb) were determined by inductively coupled plasma-mass spectrometry (ICP-MS).Results: Heavy metal levels in the CPA samples followed the order: Cu (3.29-24.17 mg/kg) > Cr (0.04-7.33 mg/kg) > Ni (0.88-6.86 mg/kg) > Pb (0.00-3.84 mg/kg) > As (0.0011-1.08 mg/kg) > Cd (0.029-0.211 mg/kg) > Sb (0.03-0.21 mg/kg) > Sn (0.00-0.15 mg/kg) > Hg (0.000-0.032 mg/kg). Metal-to-metal correlation studies showed that there were significant correlations between Cu-Cr (p = -4.02), Cu-Ni (p = 0.561), Cu-As (p = 0.554) and Ni-As (p = 0.428) at the 0.01 level. Also, some metal-to-metal correlations were observed in Pb-Cr (p = 0.351), Pb-Cu (p = -0.310), Sb-Cd (p = 0.322), Sb-Hg (p = 0.311) and Cd-Sn (p = 0.309) at the 0.05 level. The highest concentrations of Pb and As in CPA exceeded the maximum permissible limits in China. Based on current safety standards, the concentrations of heavy metals in these CPA samples mean they are safe for human consumption.Conclusions: The status of heavy metal concentrations of CPA should be further investigated in Sichuan, Shaanxi, Shanxi and Jiangsu. In addition, ICP-MS is a reliable and rapid technique for the determination of the heavy metals in CPA.Keywords: Chinese prickly ash, Heavy metals, Inductively-coupled plasma-mass spectrometry, Food safet

Identification and expression profile of a putative basement membrane protein gene in the midgut of Helicoverpa armigera

<p>Abstract</p> <p>Background</p> <p>The midgut undergoes histolysis and remodeling during the larval to adult transition in holometabolous insects, but the molecular mechanisms underlying this process are not well understood.</p> <p>Results</p> <p>Using Suppression Subtractive Hybridization (SSH), we identified a 531 bp cDNA predicted to encode a 176 amino acid protein, which we call <it>hmg176</it>. Northern and western blot analysis suggested that high levels of <it>hmg176 </it>are expressed in the midgut during molting, but not during metamorphosis. HMG176 protein was detected by immunofluorescence within the membrane of fat bodies and the basement membrane of the midgut of both molting and feeding larvae, but not in metamorphically committed larvae. <it>In situ </it>hybridization revealed that <it>hmg176 </it>transcripts mainly localized to the columnar cells of the midgut. Interestingly, a non-steroidal ecdysone agonist, RH-2485, significantly upregulated expression of <it>hmg176</it>.</p> <p>Conclusion</p> <p>These observations suggest that <it>hmg176 </it>encodes a larval-specific protein that may participate in sustaining larval midgut during larval development, possibly in response to ecdysteroid <it>in vivo</it>. This study will enlighten our understanding of the molecular mechanisms of tissue histolysis during metamorphosis.</p

NH3_{3} (1,1) hyperfine intensity anomalies in the Orion A molecular cloud

In LTE, the two inner satellite lines (ISLs) and the two outer satellite lines (OSLs) of the NH$_{3}$ (1,1) transition are each predicted to have equal intensities. However, hyperfine intensity anomalies (HIAs) are observed to be omnipresent in star formation regions, which is still not fully understood. In addressing this issue, we find that the computation method of the HIA by the ratio of the peak intensities may have defects, especially when being used to process the spectra with low velocity dispersions. Therefore we define the integrated HIAs of the ISLs (HIA$_{\rm IS}$) and OSLs (HIA$_{\rm OS}$) by the ratio of their redshifted to blueshifted integrated intensities and develop a procedure to calculate them. Based on this procedure, we present a systematic study of the integrated HIAs in the northern part of the Orion A MC. We find that integrated HIA$_{\rm IS}$ and HIA$_{\rm OS}$ are commonly present in the Orion A MC and no clear distinction is found at different locations of the MC. The medians of the integrated HIA$_{\rm IS}$ and HIA$_{\rm OS}$ are 0.921$\pm$0.003 and 1.422$\pm$0.009, respectively, which is consistent with the HIA core model and inconsistent with the CE model. Selecting those 170 positions where both integrated HIAs deviate by more than 3-$\sigma$ from unity, most (166) are characterized by HIA$_{\rm IS}$1, which suggests that the HIA core model plays a more significant role than the CE model. The remaining four positions are consistent with the CE model. We compare the integrated HIAs with the para-NH$_{3}$ column density ($N$(para-NH$_{3}$)), kinetic temperature ($T_{\rm K}$), total velocity dispersion ($\sigma_{\rm v}$), non-thermal velocity dispersion ($\sigma_{\rm NT}$), and the total opacity of the NH$_{3}$ (1,1) line ($\tau_{0}$). Their correlations can not be fully explained by neither the HIA core nor the CE model.Comment: 12 pages, 10 figures, accepted for publication in A&

Detection of Quasi-periodic Oscillations in SGR 150228213

The detection of quasi-periodic oscillations (QPOs) in magnetar giant flares (GFs) has brought a new perspective to study the mechanism of magnetar bursts. Due to the scarcity of GFs, searching QPOs from magnetar short bursts is reasonable. Here we report the detection of a high frequency QPO at approximately 110 Hz and a wide QPO at approximately 60 Hz in a short magnetar burst SGR 150228213, with a confidence level of 3.35$\sigma$. This burst was initially attributed to 4U 0142+61 by $Fermi$/GBM on location, but we haven't detected such QPOs in other bursts from this magnetar. We also found that there was a repeating fast radio burst associated with SGR 150228213 on location. Finally, we discuss the possible origins of SGR 150228213