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In this work, the effects of proton-induced trap evolution on the electrical performances of AlGaN/GaN metal–insulator–semiconductor (MIS) high-electron-mobility-transistors (HEMTs) have been investigated in detail. Contrary to observed proton-induced degradation in sheet electron density (ns), carrier mobility (μn), and sheet resistance (RSH), a significant improvement in gate leakage current (IG) and off-state drain–source breakdown voltage (BVDS) is found in irradiated devices. The low-frequency noise (LFN) results show that the density of traps in the AlGaN layer and AlGaN/GaN interface increases after irradiation, which leads to a degradation in ns, μn, and RSH and an improvement in BVDS due to enhanced electron trapping and depletion. Furthermore, the measurement results obtained from the frequency-dependent conductance technique show that irradiated devices exhibit decreased trap density (DT) at the insulator/semiconductor interface with hardly changed trap energy level (ET), which confirms the observed proton-induced decrease in IG. An increase in DT at the AlGaN/GaN interface is also found after irradiation, which is consistent with LFN results. These traps with deeper ET induce a serious Coulomb scattering effect. This work provides valuable information for the systematic understanding of the proton irradiation effect of AlGaN/GaN MIS-HEMTs. [ABSTRACT FROM AUTHOR]

Acid‐induced cellular senescence is a critical underlying mechanism of intervertebral disc (IVD) degeneration (IDD). Acid stimulation activates a variety of biological changes including autophagy, endoplasmic reticulum stress, and related unfolded protein response (UPR), which are important regulators of cellular senescence. However, the precise mechanism of acid‐mediated UPR and autophagy in nucleus pulposus cell (NPC) senescence has not been fully elucidated. In this study, we used acid to mimic the acidic microenvironment of IVD, and rat NPCs were cultured with or without autophagy or UPR signaling small‐interfering RNAs. The related proteins and genes were assessed by immunofluorescence staining assay, Western blot analyses, and quantitative real‐time polymerase chain reaction to monitor the activation of these signals and classify the molecular mechanisms underlying the correlation between autophagy and UPR pathway. Cell cycle analyses, senescence‐associated β‐galactosidase staining, gene expression, and immunoblotting analyses were performed to observe NPC senescence. Results showed that acid stimulation not only induced NPC senescence, but also initiated UPR and autophagy. Silencing the binding immunoglobulin protein signaling of UPR or autophagy signaling promoted rat NPC senescence. Knock‐down of the UPR also blocked NPC autophagy. Taken together, UPR inhibits NPC senescence under acidic condition by activating autophagy. Hence, UPR‐dependent autophagy could be an effective biologic target for the treatment of IDD in the future. [ABSTRACT FROM AUTHOR]

Targeting cellular senescence and senescence associated secretory phenotype (SASP) through autophagy has emerged as a promising intervertebral disc (IVD) degeneration (IDD) treatment strategy in recent years. This study aimed to clarify the role and mechanism of autophagy in preventing IVD SASP. Methods involved in vitro experiments with nucleus pulposus (NP) tissues from normal and IDD patients, as well as an in vivo IDD animal model. GATA4's regulatory role in SASP was validated both in vitro and in vivo, while autophagy modulators were employed to assess their impact on GATA4 and SASP. Transcriptomic sequencing identified oxidized low-density lipoprotein receptor 1 (OLR1) as a key regulator of autophagy and GATA4. A series of experiments manipulated OLR1 expression to investigate associated effects. Results demonstrated significantly increased senescent NP cells (NPCs) and compromised autophagy in IDD patients and animal models, with SASP closely linked to IDD progression. The aged disc milieu impeded autophagic GATA4 degradation, leading to elevated SASP expression in senescent NPCs. Restoring autophagy reversed senescence by degrading GATA4, hence disrupting the SASP cascade. Moreover, OLR1 was identified for its regulation of autophagy and GATA4 in senescent NPCs. Silencing OLR1 enhanced autophagic activity, suppressing GATA4-induced senescence, and SASP expression in senescent NPCs. In conclusion, OLR1 was found to control autophagy-GATA4 and SASP, with targeted OLR1 inhibition holding promise in alleviating GATA4-induced senescence and SASP expression while delaying extracellular matrix degradation, offering a novel therapeutic approach for IDD management., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)