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Mechanically, HITTERS functions as RNA scaffold to promote MRE11-RAD50-NBS1 complex formation in the repair of ER stress-induced DNA damage. To sum up, this study presents a novel lncRNA, namely HITTERS, which links ER stress and DDR together in OSCC.Chromatin modifications, such as histone acetylation, ubiquitination, and methylation, play fundamental roles in maintaining chromatin architecture and regulating gene transcription. Although their crosstalk in chromatin remodeling has been gradually uncovered, the functional relationship between histone ubiquitination and methylation in regulating immunity and inflammation remains unclear. Here, it is reported that USP38 is a novel histone deubiquitinase that works together with the histone H3K4 modifier KDM5B to orchestrate inflammatory responses. USP38 specifically removes the monoubiquitin on H2B at lysine 120, which functions as a prerequisite for the subsequent recruitment of demethylase KDM5B to the promoters of proinflammatory cytokines Il6 and Il23a during LPS stimulation. KDM5B in turn inhibits the binding of NF-κB transcription factors to the Il6 and Il23a promoters by reducing H3K4 trimethylation. Furthermore, USP38 can bind to KDM5B and prevent it from proteasomal degradation, which further enhances the function of KDM5B in the regulation of inflammation-related genes. Loss of Usp38 in mice markedly enhances susceptibility to endotoxin shock and acute colitis, and these mice display a more severe inflammatory phenotype compared to wild-type mice. The studies identify USP38-KDM5B as a distinct chromatin modification complex that restrains inflammatory responses through manipulating the crosstalk of histone ubiquitination and methylation.Tumor cells present profound alterations in their composition, structural organization, and functional properties. A landmark of cancer cells is an overall altered mechanical phenotype, which so far are linked to changes in their cytoskeletal regulation and organization. Evidence exists that the plasma membrane (PM) of cancer cells also shows drastic changes in its composition and organization. However, biomechanical characterization of PM remains limited mainly due to the difficulties encountered to investigate it in a quantitative and label-free manner. Here, the biomechanical properties of PM of a series of MCF10 cell lines, used as a model of breast cancer progression, are investigated. Notably, a strong correlation between the cell PM elasticity and oncogenesis is observed. The altered membrane composition under cancer progression, as emphasized by the PM-associated cholesterol levels, leads to a stiffening of the PM that is uncoupled from the elastic cytoskeletal properties. Conversely, cholesterol depletion of metastatic cells leads to a softening of their PM, restoring biomechanical properties similar to benign cells. As novel therapies based on targeting membrane lipids in cancer cells represent a promising approach in the field of anticancer drug development, this method contributes to deciphering the functional link between PM lipid content and disease.Electrochemical nitrogen reduction reaction (NRR) provides a facile and sustainable strategy to produce ammonia (NH3) at ambient conditions. However, the low NH3 yield and Faradaic efficiency (FE) are still the main challenges due to the competitive hydrogen evolution reaction (HER). https://www.selleckchem.com/btk.html Herein, a three-phase electrocatalyst through in situ fabrication of Au nanoparticles (NPs) located on hydrophobic carbon fiber paper (Au/o-CFP) is designed. The hydrophobic CFP surface facilitates efficient three-phase contact points (TPCPs) for N2 (gas), electrolyte (liquid), and Au NPs (solid). Thus, concentrated N2 molecules can contact the electrocatalyst surface directly, inhibiting the HER since the lowered proton concentration and overall enhancing NRR. The three-phase Au/o-CFP electrocatalyst presents an excellent NRR performance with high NH3 yield rate of 40.6 µg h-1 mg-1 at -0.30 V and great FE of 31.3% at -0.10 V versus RHE (0.1 m Na2SO4). The N2-bubble contact angle result and cyclic voltammetry analysis confirm that the hydrophobic interface has a relatively strong interaction with N2 bubble for enhanced NRR and weak electrocatalytic activity for HER. Significantly, the three-phase Au/o-CFP exhibits excellent stability with a negligible fluctuation of NH3 yield and FE in seven-cycle test. This work provides a new strategy for improving NRR and simultaneously inhibiting HER.Despite the outstanding optoelectronic properties of MoS2 and its analogues, synthesis of such materials with desired features including fewer layers, arbitrary hollow structures, and particularly specifically customized morphologies, via inorganic reactions has always been challenging. Herein, using predesigned lanthanide-doped upconversion luminescent materials (e.g., NaYF4Ln) as templates, arbitrary MoS2 hollow structures with precisely defined morphologies, widely variable dimensions, and very small shell thickness (≈2.5 nm) are readily constructed. Most importantly, integration of the near-infrared-responsive template significantly improves the photoresponse of up to 600 fold in device made of NaYF4Yb/Er@MoS2 compared with that of MoS2 nanosheets under 980 nm laser illumination. Multichannel optoelectronic device is further fabricated by simply changing luminescent ions in the template, e.g., NaYF4Er@MoS2, operating at 1532 nm light excitation with a 276-fold photoresponse enhancement. The simple chemistry, easy operation, high reliability, variable morphologies, and wide universality represent the most important advantages of this novel strategy that has not been accessed before.The existing literature data shows that conventional aluminium alloys may not be suitable for use in stellar-radiation environments as their hardening phases are prone to dissolve upon exposure to energetic irradiation, resulting in alloy softening which may reduce the lifetime of such materials impairing future human-based space missions. The innovative methodology of crossover alloying is herein used to synthesize an aluminium alloy with a radiation resistant hardening phase. This alloy-a crossover of 5xxx and 7xxx series Al-alloys-is subjected to extreme heavy ion irradiations in situ within a TEM up to a dose of 1 dpa and major experimental observations are made the Mg32(Zn,Al)49 hardening precipitates (denoted as T-phase) for this alloy system surprisingly survive the extreme irradiation conditions, no cavities are found to nucleate and displacement damage is observed to develop in the form of black-spots. This discovery indicates that a high phase fraction of hardening precipitates is a crucial parameter for achieving superior radiation tolerance.
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