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At least 469 records · Page 26

Nrf2 suppresses the function of dendritic cells to facilitate the immune escape of glioma cells

Nrf2 is presented in dendritic cells (DCs) and contributes to the maintenance of redox homeostasis. However, the expression pattern and function of Nrf2 in the maturation of DCs in the glioma-infiltrated microenvironment remain unrevealed. Our study aims to investigate the roles of Nrf2 in glioma cell-tamed DCs and their impact on the downstream T cell proliferation and cytotoxicity to glioma cells. It was showed that the inducible maturation of DCs was significantly suppressed after stimulation with tumor-conditioned medium (TCM) prepared from glioma cells (LN-18 and U118MG), as suggested by the decreased CD80, CD86 and IL-12 p70 expression and higher levels of IL-10 than the normal astrocyte medium treated DCs. Moreover, the TCM-exposed DCs had significantly increased expression and transcriptional activity of Nrf2 compared to the negative control. Nrf2 inhibition in DC cells substantially antagonized the inhibitory effects of TCM on the maturation and activation of DC cells, reflected by the elevated maturation markers and IL-12 p70. We further confirmed that Nrf2 inhibition in TCM-exposed DC cells promoted the proliferation of T cells as evaluated by the CFSE-labeled assay and Th1 response shown by the elevated production of IFN-γ. The cytotoxic T lymphocyte assay revealed that Nrf2 genetic suppression in DC cells greatly enhanced the capacity of T cells in the cytotoxicity to glioma cells dependent on the E:T ratio. Collectively, our study demonstrated that Nrf2 inhibition in DCs in glioma-exposed microenvironment could enhance the maturation of DCs and the subsequent activation of T cells and their cytotoxicity on glioma cells. - Highlights: • Glioma cells stimulated Nrf2 expression and maturation of dendritic cells. • Nrf2 restoration in DC antagonized glioma-mediated inhibitory effects on DC functions. • Nrf2 inhibition in DCs promoted T cell proliferation and Th1 response. • Nrf2 inhibition in DC cells promoted the killing of glioma cells by T lymphocytes.

60 APPLIED LIFE SCIENCES↗

YAP/STAT3 promotes the immune escape of larynx carcinoma by activating VEGFR1-TGFβ signaling to facilitate PD-L1 expression in M2-like TAMs

Larynx carcinoma (LC) is the most prevalent head and neck cancer among adults. LC xenograft mouse model was generated to verify the effect of VEGF on macrophage polarization and tumor growth in vivo. EdU assay was performed to measure the cell proliferation. Transwell assay was applied to assess cell migration. The expression of YAP and STAT3 was also significantly increased in LC tumor tissues. Moreover, both YAP and STAT3 overexpression in LC cells promoted the proliferation, migration, as well as the secretion of PD-L1 in M2-like TAMs. Mechanistically, the interaction between YAP and STAT3 facilitated the transcription of VEGF. Moreover, with a co-culture system, VEGF secretion in LC cells enhanced PD-L1 expression in M2-like TAMs via activating VEGFR1-TGFβ signaling pathway. Furthermore, VEGF secreted from LC cells also promoted the tumor growth of LC in vivo. We revealed that dysregulated YAP/STAT3 activity in LC cells could enhance the secretion of VEGF, which then functioned on M2-like TAMs via activating VEGFR1-TGFββ pathway to promote the expression of PD-L1 and immunosuppressive function of M2-like TAMs. Therefore, VEGF and PD-L1 might have a pivotal crosstalk between M2-like TAMs and LC cells, which provided a novel therapeutic target in regulating the metastasis of LC in future.

60 APPLIED LIFE SCIENCES↗

Restoring Escaped Zincate in Rechargeable Alkaline Zinc Batteries with a Seed-in-Nanoshell Design

Rechargeable alkaline zinc batteries are promising candidates for safe and low-cost energy storage, but suffer from ZnO dissolution that causes irreversible active material loss and rapid capacity decay. Here, we report a seed-in-nanoshell ZnO anode architecture that mitigates dissolution by combining physical confinement with electrochemical restoration of dissolved zincate species. ZnO particles are encapsulated within an ion-sieving carbon nanoshell that restricts zincate diffusion, maintains electrical conductivity, and stabilizes repeated solid–solution–solid transformations. Silver (Ag) nanoparticles incorporated into the nanoshell act as zincophilic nucleation seeds, lowering the Zn deposition barrier and directing the redeposition of dissolved zincate back to metallic Zn during charging. This confinement-enabled restoration mechanism converts zincate dissolution from an irreversible loss pathway into a recoverable process, enabling improved performance under harsh test conditions. The anode also delivers 227.9 mAh g −1 at −40 °C. Finally, a scalable tens-of-gram synthesis of ZnO@Ag is demonstrated, underscoring the practical potential of this strategy for advanced aqueous zinc batteries.

25 ENERGY STORAGE↗

Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair

De novo point mutations and chromosomal structural aberrations (CSA) detected in offspring of unaffected parents show a preferential paternal origin with higher risk for older fathers. Studies in rodents suggest that heritable mutations transmitted from the father can arise from either paternal or maternal misrepair of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk after mutagenic exposure. Understanding the susceptibility and mechanisms of transmission of paternal mutations is important in family planning after chemotherapy and donor selection for assisted reproduction. We report that treatment of male mice with melphalan (MLP), a bifunctional alkylating agent widely used in chemotherapy, induces DNA lesions during male mouse meiosis that persist unrepaired as germ cells progress through DNA repair-competent phases of spermatogenic development. After fertilization, unrepaired sperm DNA lesions are mis-repaired into CSA by the egg's DNA repair machinery producing chromosomally abnormal offspring. In conclusion, these findings highlight the importance of both pre- and post-fertilization DNA repair in assuring the genomic integrity of the conceptus.

59 BASIC BIOLOGICAL SCIENCES↗

Bowl breakout: Escaping the positive region when searching for saddle points

We present a scheme improving the minimum-mode following method for finding first order saddle points by confining the displacements of atoms to the subset of those subject to the largest force. By doing so it is ensured that the displacement remains of a local character within regions where all eigenvalues of the Hessian matrix are positive. However, as soon as a region is entered where an eigenvalue turns negative all atoms are released to maintain the ability of determining concerted moves. Applying the proposed scheme reduces the required number of force calls for the determination of connected saddle points by a factor two or more compared to a free search. Furthermore, a wider distribution of the relevant low barrier saddle points is obtained. Finally, the dependency on the initial distortion and the applied maximal step size is reduced making minimum-mode guided searches both more robust and applicable.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Ion-induced gamma-ray detection of fast ions escaping from fusion plasmas

A 12 × 12 pixel detector has been developed and used in a laboratory experiment for lost fast-ion diagnostics. With gamma rays in the MeV range originating from nuclear reactions {sup 9}Be(α, nγ){sup 12}C, {sup 9}Be(d, nγ){sup 12}C, and {sup 12}C(d, pγ){sup 13}C, a high purity germanium (HPGe) detector measured a fine-energy-resolved spectrum of gamma rays. The HPGe detector enables the survey of background-gamma rays and Doppler-shifted photo peak shapes. In the experiments, the pixel detector produces a gamma-ray image reconstructed from the energy spectrum obtained from total photon counts of irradiation passing through the detector's lead collimator. From gamma-ray image, diagnostics are able to produce an analysis of the fast ion loss onto the first wall in principle.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Existence of a return direction for plasma escaping from a pinched column in a plasma focus discharge

The use of multi-frame interferometry used on the PF-1000 device with the deuterium filling showed the existence of a return motion of the top of several lobules of the pinched column formed at the pinched plasma column. This phenomenon was observed in the presence of an over-optimal mass in front of the anode, which depressed the intensity of the implosion and the smooth surface of the pinched plasma column. The observed evolution was explored through the use of closed poloidal currents transmitted outside the pinched plasma. This interpretation complements the scenario of the closed currents flowing within the structures inside the pinched column, which has been published recently on the basis of observations from interferometry, neutron, and magnetic probe diagnostics on this device.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Atmospheric escape by magnetically driven wind from gaseous planets

We calculate the mass loss driven by magnetohydrodynamic (MHD) waves from hot Jupiters by using MHD simulations in one-dimensional flux tubes. If a gaseous planet has a magnetic field, MHD waves are excited by turbulence at the surface, dissipate in the upper atmosphere, and drive gas outflows. Our calculation shows that mass-loss rates are comparable to the observed mass-loss rates of hot Jupiters; therefore, it is suggested that gas flow driven by MHD waves can play an important role in the mass loss from gaseous planets. The mass-loss rate varies dramatically with the radius and mass of a planet: a gaseous planet with a small mass but an inflated radius produces a very large mass-loss rate. We also derive an analytical expression for the dependence of mass-loss rate on planet radius and mass that is in good agreement with the numerical calculation. The mass-loss rate also depends on the amplitude of the velocity dispersion at the surface of a planet. Thus, we expect to infer the condition of the surface and the internal structure of a gaseous planet from future observations of mass-loss rate from various exoplanets.

79 ASTRONOMY AND ASTROPHYSICS↗

The spectroscopic properties of Lyα-emitters at z ∼ 2.7: Escaping gas and photons from faint galaxies

We present a spectroscopic survey of 318 faint (R∼27, L∼0.1L{sub ∗}), Lyα-emission-selected galaxies (LAEs) in regions centered on the positions of hyperluminous QSOs (HLQSOs) at 2.5 v{sub esc}. Further observations, including deep spectroscopy in the observed near-IR, will further probe the evolution and enrichment of these galaxies in the context of their gaseous environments.

79 ASTRONOMY AND ASTROPHYSICS↗

Atmospheric escape by magnetically driven wind from gaseous planets. II. Effects of magnetic diffusion

We investigate roles of Alfvénic waves in the weakly ionized atmosphere of hot Jupiters by carrying out non-ideal MHD simulations with ohmic diffusion in one-dimensional magnetic flux tubes. Turbulence at the surface excites Alfvén waves, and they propagate upward to drive hot (≈10{sup 4} K) outflows. The magnetic diffusion plays an important role in the dissipation of the Alfvénic waves in the weakly ionized atmosphere of hot Jupiters. The mass-loss rate of the spontaneously driven planetary wind is considerably reduced, in comparison with that obtained from ideal MHD simulations because the Alfvénic waves are severely damped at low altitudes in the atmosphere, whereas the wave heating is still important in the heating of the upper atmosphere. Dependence on the surface temperature, planetary radius, and velocity dispersion at the surface is also investigated. We find an inversion phenomenon of the transmitted wave energy flux; the energy flux carried by Alfvén waves in the upper atmosphere has a nonmonotonic correlation with the input energy flux from the surface in a certain range of the surface temperature because the resistivity is determined by the global physical properties of the atmosphere in a complicated manner. We also point out that the heating and mass loss are expected only in limited zones if the open magnetic field is confined in the limited regions.

79 ASTRONOMY AND ASTROPHYSICS↗

Irreversible reactions and diffusive escape: Stationary properties

We study three basic diffusion-controlled reaction processes—annihilation, coalescence, and aggregation. We examine the evolution starting with the most natural inhomogeneous initial configuration where a half-line is uniformly filled by particles, while the complementary half-line is empty. We show that the total number of particles that infiltrate the initially empty half-line is finite and has a stationary distribution. We determine the evolution of the average density from which we derive the average total number N of particles in the initially empty half-line; e.g. for annihilation $\langle N\rangle = \frac{3}{16}+\frac{1}{4\π}$ . For the coalescence process, we devise a procedure that in principle allows one to compute P(N), the probability to find exactly N particles in the initially empty half-line; we complete the calculations in the first non-trivial case (N = 1). As a by-product we derive the distance distribution between the two leading particles.

97 MATHEMATICS AND COMPUTING↗

AMBIPOLAR ELECTRIC FIELD, PHOTOELECTRONS, AND THEIR ROLE IN ATMOSPHERIC ESCAPE FROM HOT JUPITERS

Atmospheric mass loss from Hot Jupiters can be large due to the close proximity of these planets to their host star and the strong radiation the planetary atmosphere receives. On Earth, a major contribution to the acceleration of atmospheric ions comes from the vertical separation of ions and electrons, and the generation of the ambipolar electric field. This process, known as the 'polar wind', is responsible for the transport of ionospheric constituents to Earth's magnetosphere, where they are well observed. The polar wind can also be enhanced by a relatively small fraction of super-thermal electrons (photoelectrons) generated by photoionization. We formulate a simplified calculation of the effect of the ambipolar electric field and the photoelectrons on the ion scale height in a generalized manner. We find that the ion scale height can be increased by a factor of 2-15 due to the polar wind effects. We also estimate a lower limit of an order of magnitude increase of the ion density and the atmospheric mass-loss rate when polar wind effects are included.

79 ASTRONOMY AND ASTROPHYSICS↗