Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ...ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.
We introduce the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) stellar parameter pipeline at Peking University – lsp3, developed and implemented for the determinations of radial ...velocity V
r and stellar atmospheric parameters (effective temperature T
eff, surface gravity log g, metallicity Fe/H) for the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC). We describe the algorithms of lsp3 and examine the accuracy of parameters yielded by it. The precision and accuracy of parameters yielded are investigated by comparing results of multi-epoch observations and of candidate members of open and globular clusters, with photometric calibration, as well as with independent determinations available from a number of external data bases, including the PASTEL archive, the APOGEE, SDSS and RAVE surveys, as well as those released in the LAMOST DR1. The uncertainties of lsp3 parameters are characterized and quantified as a function of the spectral signal-to-noise ratio (SNR) and stellar atmospheric parameters. We conclude that the current implementation of lsp3 has achieved an accuracy of 5.0 km s−1, 150 K, 0.25 dex, 0.15 dex for the radial velocity, effective temperature, surface gravity and metallicity, respectively, for LSS-GAC spectra of FGK stars of SNRs per pixel higher than 10. The lsp3 has been applied to over a million LSS-GAC spectra collected hitherto. Stellar parameters yielded by the lsp3 will be released to the general public following the data policy of LAMOST, together with estimates of the interstellar extinction E(B − V) and stellar distances, deduced by combining spectroscopic and multiband photometric measurements using a variety of techniques.
A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's ...Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.
Our goal in this work was to illustrate the Epstein-Barr virus (EBV)-modulated global biochemical profile and provide a novel metabolism-related target to improve the therapeutic regimen of ...nasopharyngeal carcinoma (NPC). We used a metabolomics approach to investigate EBV-modulated metabolic changes, and found that the exogenous overexpression of the EBV-encoded latent membrane protein 1 (LMP1) significantly increased glycolysis. The deregulation of several glycolytic genes, including hexokinase 2 (HK2), was determined to be responsible for the reprogramming of LMP1-mediated glucose metabolism in NPC cells. The upregulation of HK2 elevated aerobic glycolysis and facilitated proliferation by blocking apoptosis. More importantly, HK2 was positively correlated with LMP1 in NPC biopsies, and high HK2 levels were significantly associated with poor overall survival of NPC patients following radiation therapy. Knockdown of HK2 effectively enhanced the sensitivity of LMP1-overexpressing NPC cells to irradiation. Finally, c-Myc was demonstrated to be required for LMP1-induced upregulation of HK2. The LMP1-mediated attenuation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis resulted in the stabilization of c-Myc. These findings indicate a close relationship between EBV and glycolysis in NPC. Notably, LMP1 is the key regulator of the reprogramming of EBV-mediated glycolysis in NPC cells. Given the importance of EBV-mediated deregulation of glycolysis, anti-glycolytic therapy might represent a worthwhile avenue of exploration in the treatment of EBV-related cancers.
Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
Theoretical analysis has revealed a specific resonance that shares the same condition as Landau resonance, but instead involves wave electromagnetic fields rather than traditionally electrostatic ...fields. While this resonance, referred to as electromagnetic Landau resonance due to its properties, is considered significant for magnetospheric dynamics, rare reports or evaluations based on observations have been made thus far. Here, we present an event detected by the Magnetospheric Multiscale mission near the dayside magnetopause. During this event, ∼748‐eV protons are observed to be in resonance with a wave. Detailed data analysis demonstrates the resonant velocity closely matches the wave's parallel phase speed, which, combined with the significant work done by wave perpendicular electric field, confirms this interaction as electromagnetic Landau resonance. Further investigation indicates these protons are being secularly accelerated within this resonance. Consequently, our observations provide the first empirical evidence supporting the previously suggested theoretical importance of the electromagnetic Landau resonance.
Plain Language Summary
The electromagnetic Landau resonance shares the same resonance condition as the normal Landau resonance, but differs in that it involves the electromagnetic components of wave fields instead of the electrostatic components found in the case of the latter. Although it has been examined in theories and confirmed to occur in space plasmas experimentally, this resonance, especially the accompanying evolution of particle velocity distributions, has yet to be evaluated quantitatively through spacecraft observations. In this paper, we report the first observation of this resonance obtained by the Magnetospheric Multiscale mission near the dayside magnetosphere. In the reported case, protons of ∼400–1,000 eV are found to be in resonance with a wave. A more detailed examination of the observed fields and protons shows the corresponding resonant velocity is nearly identical to the wave's parallel phase speed. This observation, combined with the significant work done by wave perpendicular electric field, conclusively confirms the observed interaction as the electromagnetic Landau resonance. Further investigation indicates the protons are secularly accelerated by the wave via this resonance. Hence, our observations provide empirical evidence supporting the previously suggested theoretical significance of the electromagnetic Landau resonance.
Key Points
MMS observations of electromagnetic Landau resonance near the dayside magnetopause are presented
This resonance follows the same condition as the Landau resonance, but modulates particles via the electromagnetic components of wave fields
Analysis of the observed fields and protons provide conclusive evidence for this resonance accelerating protons
In superconductors, electrons are paired and condensed into the ground state. An impurity can break the electron pairs into quasiparticles with energy states inside the superconducting gap. The ...characteristics of such in-gap states reflect accordingly the properties of the superconducting ground state. A zero-energy in-gap state is particularly noteworthy, because it can be the consequence of non-trivial pairing symmetry or topology. Here we use scanning tunnelling microscopy/spectroscopy to demonstrate that an isotropic zero-energy bound state with a decay length of ∼10 Å emerges at each interstitial iron impurity in superconducting Fe(Te,Se). More noticeably, this zero-energy bound state is robust against a magnetic field up to 8 T, as well as perturbations by neighbouring impurities. Such a spectroscopic feature has no natural explanation in terms of impurity states in superconductors with s-wave symmetry, but bears all the characteristics of the Majorana bound state proposed for topological superconductors, indicating that the superconducting state and the scattering mechanism of the interstitial iron impurities in Fe(Te,Se) are highly unconventional.
A sub‐population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumor relapse and metastasis. In our ...study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin‐resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin‐resistant TSCC cells, which displayed CSC‐like properties and exhibited EMT. SOX8 was also overexpressed in chemoresistant patients with TSCC and was associated with higher lymph node metastasis, advanced tumor stage and shorter overall survival. Stable knockdown of SOX8 in cisplatin‐resistant TSCC cells inhibited chemoresistance, tumorsphere formation, and EMT. The Wnt/β‐catenin pathway mediated the cancer stem‐like properties in cisplatin‐resistant TSCC cells. Further studies showed that the transfection of active β‐catenin in SOX8 stable‐knockdown cells partly rescued the SOX8 silencing‐induced repression of stem‐like features and chemoresistance. Through chromatin immunoprecipitation and luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled‐7 (FZD7) and induced the FZD7‐mediated activation of the Wnt/β‐catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7‐mediated Wnt/β‐catenin pathway.
What's new?
Tongue cancer frequently spreads to the lymph nodes, and while chemotherapy with cisplatin has improved 5‐year survival rates, all too often the cancer becomes resistant to chemotherapy and returns. Here, the authors show that tongue squamous cell carcinoma (TSCC) cells that have acquired cisplatin resistance express more SOX‐8 mRNA than their parent TSCC cells. Getting rid of SOX‐8, they showed, hampered the cells' chemoresistance as well as the epithelial to mesenchymal transition. Adding active beta‐catenin to the cells lacking SOX‐8 partially restored these properties, showing that SOX‐8 acts through the Wnt/beta‐catenin pathway.
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