Ferroptosis is implicated in various tumors, including glioblastoma. Artesunate (ART), an anti-malarial drug, exerted antitumor properties in several cancer types. However, the role of ferroptosis in ...the inhibiting effect of artesunate on glioblastoma remains unclear. The purpose of this study was to investigate the effects of ART on the ferroptosis of glioblastoma and to elucidate the underlying mechanisms. We found that ART inhibited the proliferation of glioblastoma cells in vitro and glioblastoma tumorigenesis in vivo. Characteristic changes of ferroptosis were observed in ART group, including GSH depletion, lipid peroxidation and iron overload. Meanwhile, the protein level of GPX4 were lower in ART group than that in control group. Ferrostatin-1, a ferroptosis inhibitor, could rescue the cell death induced by ART in U251 cells. Further examination of the mechanism revealed that the effect of ART on ferroptosis was partially governed by regulating iron homeostasis and p38 and ERK signaling pathway. These findings support that ART triggers ferroptosis in glioblastoma and might be a potential therapeutic agent for glioblastoma treatment.
A novel ultra-wideband (UWB) multiple-input multiple-output (MIMO) Vivaldi antenna with dual band-notched characteristics is presented and fabricated. The antenna is comprised of an improved ground ...plane and two microstrip feeding lines with a compact size of 26\times 26 mm 2 . The evolutionary process of the antenna is given. By etching the T-shaped slot on the ground plane, the port isolation between individual antenna elements can be greatly increased. Meanwhile, by adding two split ring resonator (SRR) of different sizes next to the microstrip feed lines, dual notches can be achieved to filter the interfere of WLAN and X-band communication satellites. The notched mechanism is analyzed from the surface current distributions. The experimental results show that the impedance bandwidth of the designed MIMO antenna is from 2.9 to 11.6 GHz, along with two notched bands covering 5.3-5.8 GHz and 7.85-8.55 GHz, and the mutual coupling is less than -16 dB in the whole working bandwidth. The MIMO antenna has good radiation characteristics, stable gain, and very low envelop correlation coefficient (ECC <;0.02), which is suitable for UWB MIMO system applications. The idea in this paper also has a certain guiding significance for the study of band-notched MIMO Vivaldi antenna.
We revisit the mechanism of high-harmonic generation (HHG) from solids by comparing HHG in laser fields with different ellipticities but a constant maximum amplitude. It is shown that the cutoff of ...HHG is strongly extended in a circularly polarized field. Moreover, the harmonic yield with large ellipticity is comparable to or even higher than that in the linearly polarized field. To understand the underlying physics, we develop a reciprocal-space-trajectory method, which explains HHG in solids by a trajectory ensemble from different ionization times and different initial states in the reciprocal space. We show that the cutoff extension is related to an additional preacceleration step prior to ionization, which has been overlooked in solids. By analyzing the trajectories and the time-frequency spectrogram, we show that the HHG in solids cannot be interpreted in terms of the classical recollision picture alone. Instead, the radiation should be described by the electron-hole interband polarization, which leads to the unusual ellipticity dependence. We propose a new four-step model to understand the mechanism of HHG in solids.
Purpose: Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is commonin glioma patients. In addition, mechanisms for the anti-tumor effects of ...temozolomide are largely unknown. Ferroptosis is a formof programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The presentstudy was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide.
Materials and Methods: We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde(MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detectthe production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecularmechanisms.
Results: Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, wefound that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied bya decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results alsoshowed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdownby siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells.
Conclusion: Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis bytargeting DMT1 expression in glioblastoma cells. KCI Citation Count: 0
Laser-induced electron tunneling ionization from atoms and molecules plays as the trigger for a broad class of interesting strong-field phenomena in attosecond community. Understanding the time of ...electron tunneling ionization is vital to achieving the ultimate accuracy in attosecond metrology. We propose a novel attosecond photoelectron interferometer, which is based on the interference of the direct and near-forward rescattering electron wave packets, to determine the time information characterizing the tunneling process. Adding a weak perturbation in orthogonal to the strong fundamental field, the phases of the direct and the near-forward rescattering electron wave packets are modified, leading to the shift of the interferogram in the photoelectron momentum distributions. By analyzing the response of the interferogram to the perturbation, the real part of the ionization time, which denotes the instant when the electron exits the potential barrier, and the associated rescattering time are precisely retrieved. Moreover, the imaginary part of the ionization time, which has been interpreted as a quantity related to electron motion under the potential barrier, is also unambiguously determined.
Abstract
Electron migration in molecules is the progenitor of chemical reactions and biological functions after light-matter interaction. Following this ultrafast dynamics, however, has been an ...enduring endeavor. Here we demonstrate that, by using machine learning algorithm to analyze high-order harmonics generated by two-color laser pulses, we are able to retrieve the complex amplitudes and phases of harmonics of single fixed-in-space molecules. These complex dipoles enable us to construct movies of laser-driven electron migration after tunnel ionization of N
2
and CO
2
molecules at time steps of 50 attoseconds. Moreover, the angular dependence of the migration dynamics is fully resolved. By examining the movies, we observe that electron holes do not just migrate along the laser polarization direction, but may swirl around the atom centers. Our result establishes a general scheme for studying ultrafast electron dynamics in molecules, paving a way for further advance in tracing and controlling photochemical reactions by femtosecond lasers.
Summary Background Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration. We therefore did a phase 1 ...trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis. Methods We assessed the retinal and visual function in 12 patients (aged 8–44 years) with RPE65 -associated Leber's congenital amaurosis given one subretinal injection of adeno-associated virus (AAV) containing a gene encoding a protein needed for the isomerohydrolase activity of the retinal pigment epithelium (AAV2-hRPE65v2) in the worst eye at low (1·5×1010 vector genomes), medium (4·8×1010 vector genomes), or high dose (1·5×1011 vector genomes) for up to 2 years. Findings AAV2-hRPE65v2 was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision (ie, dark adaptometry, pupillometry, electroretinography, nystagmus, and ambulatory behaviour). Patients had at least a 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision. The study is registered with ClinicalTrials.gov , number NCT00516477. Interpretation The safety, extent, and stability of improvement in vision in all patients support the use of AAV-mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain. Funding Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia, Foundation Fighting Blindness, Telethon, Research to Prevent Blindness, F M Kirby Foundation, Mackall Foundation Trust, Regione Campania Convenzione, European Union, Associazione Italiana Amaurosi Congenita di Leber, Fund for Scientific Research, Fund for Research in Ophthalmology, and National Center for Research Resources.
Molecules constituted by different isotopes are different in vibrational modes, making it possible to elucidate the mechanism of a chemical reaction via the kinetic isotope effect. However, the ...real-time observation of the vibrational motion of isotopic nuclei in molecules is still challenging due to its ultrashort time scale. Here we demonstrate a method to monitor the nuclear vibration of isotopic molecules with the frequency modulation of high-order harmonic generation (HHG) during the laser-molecule interaction. In the proof-of-principle experiment, we report a red shift in HHG from H
and D
. The red shift is ascribed to dominant HHG from the stretched isotopic molecules at the trailing edge of the laser pulse. By utilizing the observed frequency shift, the laser-driven nuclear vibrations of H
and D
are retrieved. These findings pave an accessible route toward monitoring the ultrafast nuclear dynamics and even tracing a chemical reaction in real time.
A multi-gas sensing system was developed based on the detection principle of the non-dispersive infrared (NDIR) method, which used a broad-spectra light source, a tunable Fabry–Pérot (FP) filter ...detector, and a flexible low-loss infrared waveguide as an absorption cell. CH4, C2H6, and CO2 gases were detected by the system. The concentration of CO2 could be detected directly, and the concentrations of CH4 and C2H6 were detected using a PCA-BP neural network algorithm because of the interference of CH4 and C2H6. The detection limits were achieved to be 2.59 ppm, 926 ppb, and 114 ppb for CH4, C2H6, and CO2 with an averaging time of 429 s, 462 s, and 297 s, respectively. The root mean square error of prediction (RMSEP) of CH4 and C2H6 were 10.97 ppm and 2.00 ppm, respectively. The proposed system and method take full advantage of the multi-component gas measurement capability of the mid-infrared broadband source and achieve a compromise between performance and system cost.
Cisplatin is a potent chemotherapeutic agent, but its clinical usage is limited by nephrotoxicity. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has ...antioxidant and anti-inflammatory properties and plays an important role in protecting cells from apoptosis. This study aims to examine the protective effects of SAMC on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection. Rats were treated with cisplatin with or without pre-treatment with SAMC. Renal function, histological change, oxidative stress markers and antioxidant enzyme activities were investigated. Apoptotic marker, nuclearfactor (NF)-κB activity, expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and inflammatory cytokines were also examined. The effect of SAMC on cell viability and apoptosis was examined in cultured human kidney (HK-2) cells. SAMC was confirmed to significantly attenuate cisplatin-induced renal damage by using histological pathology and molecular biological method. Pre-treatment with SAMC reduced NF-κB activity, up-regulated Nrf2 and NQO1 expression and down-regulated inflammatory cytokine levels after cisplatin administration. Cisplatin-induced apoptosis in HK-2 cells was significantly attenuated by SAMC. Thus our results suggest that SAMC could be a potential therapeutic agent in the treatment of the cisplatin-induced nephrotoxicity through its anti-apoptotic, anti-oxidant and anti-inflammatory effects.
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