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Heteroepitaxial growth of high Al-content AlGaN often results in a high density of threading dislocations and surface hexagonal hillocks, which degrade the performance and reliability of AlGaN-based UVC light emitting diodes (LEDs). In this study, the degradation mechanism and impurity/defect behavior of UVC LEDs in relation to the hexagonal hillocks have been studied in detail. It was found that the early degradation of UVC LEDs is primarily caused by electron leakage. The prominent contribution of the hillock edges to the electron leakage is unambiguously evidenced by the transmission electron microscopy measurements, time-of-flight secondary ion mass spectrometry, and conductive atomic force microscopy. Dislocations bunching and segregation of impurities, including C, O, and Si, at the hillock edges are clearly observed, which facilitate the trap-assisted carrier tunneling in the multiple quantum wells and subsequent recombination in the p-AlGaN. This work sheds light on one possible degradation mechanism of AlGaN-based UVC LEDs. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis plays a key role in human cancer, but its function and mechanism in glioma is not clear. P62/SQSTM1 was reported to inhibit ferroptosis via the activation of NRF2 signaling pathway. In this study we reveal a dual role of p62 in ferroptosis of glioblastoma (GBM) according to p53 status. Method: Lipid peroxidation analysis, transmission electron microscopy (TEM), GSH assay were performed to determine the level of ferroptosis. Western blot and qPCR were obtained to detect the expression of ferroptosis markers. Construction of mutant plasmids, immunoprecipitation, luciferase assay and rescue-experiments were performed to explore the regulatory mechanism. Results: P62 overexpression facilitates ferroptosis and inhibits SLC7A11 expression in p53 mutant GBM, while attenuates ferroptosis and promotes SLC7A11 expression in p53 wild-type GBM. P62 associates with p53 and inhibits its ubiquitination. The p53-NRF2 association and p53-mediated suppression of NRF2 antioxidant activity are diversely regulated by p62 according to p53 status. P53 mutation status is required for the dual regulation of p62 on ferroptosis. In wild-type p53 GBM, the classical p62-mediated NRF2 activation pathway plays a major regulatory role of ferroptosis, leading to increased SLC7A11 expression, resulting in a anti-ferroptosis role. In mutant p53 GBM, stronger interaction of mutant-p53/NRF2 by p62 enhance the inhibitory effect of mutant p53 on NRF2 signaling, which reversing the classical p62-mediated NRF2 activation pathway, together with increased p53's transcriptional suppression on SLC7A11 by p62, leading to a decrease of SLC7A11, resulting in a pro-ferroptosis role. Conclusion: Together, this study shows novel molecular mechanisms of ferroptosis regulated by p62; the mutation status of p53 is an important factor that determines the therapeutic response to p62-mediated ferroptosis-targeted therapies in GBM. [ABSTRACT FROM AUTHOR]

[Display omitted] • ICT ameliorates liver injury and excessive inflammatory response induced by hepatic IR in mice. • ICT activates PI3K/AKT/mTOR signaling pathway to inhibit hepatic IR-induced autophagy. • ICT attenuates oxidative stress and hepatocyte apoptosis after hepatic IR. Hepatic ischemia–reperfusion (IR) injury is a major complication of liver transplantation and gravely affects patient prognosis. Icaritin (ICT), the primary plasma metabolite of icariin (ICA), plays a critical role in anti-inflammatory and immunomodulatory processes. However, the role of ICT in hepatic IR injury remains largely undefined. In this study, we aimed to elucidate the role of ICT in hepatic IR injury. We established hepatic IR injury models in animals, as well as an oxygen-glucose deprivation/reperfusion (OGD/R) cell model. Liver injury in vivo was assessed by measuring serum alanine aminotransferase (ALT) levels, necrotic areas by liver histology and local hepatic inflammatory responses. For in vitro analyses, we implemented flow-cytometric and western blot analyses, transmission electron microscopy, and an mRFP-GFP-LC3 adenovirus reporter assay to assess the effects of ICT on OGD/R injury in AML12 and THLE-2 cell lines. Signaling pathways were explored in vitro and in vivo to identify possible mechanisms underlying ICT action in hepatic IR injury. Compared to the mouse model group, ICT preconditioning considerably protected the liver against IR stress, and diminished the levels of necrosis/apoptosis and inflammation-related cytokines. In additional studies, ICT treatment dramatically boosted the expression ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR proteins in hepatic cells following OGD/R damage. We also applied LY294002 (a PI3K inhibitor) and RAPA (rapamycin, an mTOR inhibitor), which blocked the protective effects of ICT in hepatocytes subjected to OGD/R. This study indicates that ICT attenuates ischemia–reperfusion injury by exerting anti-inflammation, anti-oxidative stress, and anti-autophagy effects, as demonstrated in mouse livers. We thus posit that ICT could have therapeutic potential for the treatment of hepatic IR injury. [ABSTRACT FROM AUTHOR]

Aims: Circular RNAs have been reported to play key roles in the progression of various cancers, including gliomas. The present study was designed to investigate the role of hsa_circ_0072309 in autophagy and temozolomide (TMZ) sensitivity in glioblastoma (GBM). Methods: The effect of hsa_circ_0072309 on autophagy and TMZ sensitivity were examined by GFP‐RFP‐LC3, transmission electron microscopy(TEM), flow cytometry, Western blot, and immunofluorescence. The mechanism of hsa_circ_0072309 regulating p53 signaling pathway was analyzed using Western blot, IP, and rescue experiments. Results: Low hsa_circ_0072309 expression predicts poor prognosis for glioma patients. The regulation of hsa_circ_0072309 on autophagy and TMZ sensitivity depends on the status of p53. Hsa_circ_0072309 promoted autophagy by p53 signaling pathway and enhanced sensitivity of glioblastoma to temozolomide (TMZ) in p53 wild‐type GBM, but not in p53 mutant GBM. Hsa_circ_0072309 inhibits p53 ubiquitination and increases the stability of p53 protein in the context of p53 wild‐type. MiR‐100 mediates hsa_circ_0072309 regulating p53. P53 inhibitor or autophagy inhibitor could reverse the effect of hsa_circ_0072309 on TMZ sensitivity in p53 wild‐type GBM. Conclusions: This study revealed a function of hsa_circ_0072309 promoting autophagy by p53 signaling pathway and enhancing TMZ sensitivity. These findings demonstrated that hsa_circ_0072309 may be a potential and promising target in designing the treatment strategy for GBM. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is an iron dependent cell death closely associated with p53 signaling pathway and is aberrantly regulated in glioblastoma (GBM), yet the underlying mechanism needs more exploration. Identifying new factors which regulate p53 and ferroptosis in GBM is essential for treatment. Methods: Glioma cell growth was evaluated by cell viability assays and colony formation assays. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays, and transmission electron microscopy were used to assess the degree of cellular lipid peroxidation of GBM. The mechanisms of RND1 in regulation of p53 signaling were analyzed by RT-PCR, western blot, immunostaining, co-immunoprecipitation, ubiquitination assays and luciferase reporter assays. The GBM‐xenografted animal model was constructed and the tumor was captured by an In Vivo Imaging System (IVIS). Results: From the The Cancer Genome Atlas (TCGA) database, we summarized that Rho family GTPase 1 (RND1) expression was downregulated in GBM and predicted a better prognosis of patients with GBM. We observed that RND1 influenced the glioma cell growth in a ferroptosis-dependent manner when GBM cell lines U87 and A172 were treated with Ferrostatin-1 or Erastin. Mechanistically, we found that RND1 interacted with p53 and led to the de-ubiquitination of p53 protein. Furthermore, the overexpression of RND1 promoted the activity of p53-SLC7A11 signaling pathway, therefore inducing the lipid peroxidation and ferroptosis of GBM. Conclusions: We found that RND1, a novel controller of p53 protein and a positive regulator of p53 signaling pathway, enhanced the ferroptosis in GBM. This study may shed light on the understanding of ferroptosis in GBM cells and provide new therapeutic ideas for GBM. [ABSTRACT FROM AUTHOR]

The conventional forging process for 6082 aluminum alloy entails the following steps: preheating, hot forging, solution heat treatment (SHT), and artificial aging. In this study, 6082 aluminum alloy automobile parts were successfully manufactured under industrialized conditions using a novel forging process that integrated SHT and hot forging into one operation, resulting in the cost savings compared with the conventional forging process. Mechanical properties were determined using tensile tests, while microstructural evolutions were revealed using optical microscopy (OM), scanning electron microscope (SEM), electron backscatter diffraction (EBSD), high-resolution transmission electron microscopy (HRTEM), and finite element method (FEM) simulation. It is found that the abnormal grain growth (AGG) induced by post-forging SHT occurred in the surface layer of conventionally processed parts, resulting in a decrease in the strengthening effects of grain boundary and dislocation, as well as a decrease in tensile strength, yield strength, and elongation. However, benefiting from the SHT before forging and the immediate quenching after forging, the AGG triggered by secondary recrystallization was suppressed by using the novel forging process. Along with achieving mechanical properties comparable to those obtained through conventional forging in the interior, the novelly processed parts' surface layer exhibits relatively consistent properties due to their homogeneous grain structure. The results above demonstrate the efficacy of the novel solution-forging integrated process, which is well-suited for industrial production, application, and promotion. [Display omitted] • 6082 aluminum alloy parts were manufactured using an integrated forging process. • Abnormal grain growth was suppressed by using the integrated forging process. • The integrally processed parts obtained uniform mechanical properties. [ABSTRACT FROM AUTHOR]

• High and very high cycle fatigue tests were performed on Inconel 718. • Dislocation accumulation and discontinuous slip induce crack initiation. • Microcracks initiate near non-metallic inclusions or band-grain boundary site. • Transformation from slip bands to HCF/VHCF microcracks was directly observed. • A life prediction model related to micro-defect size was developed. High and very high cycle fatigue (HCF and VHCF) behaviours and failure mechanism of Inconel 718 were investigated via ultrasonic fatigue tests and microscopic characterization techniques. It is shown that the S-N curve continuously decreases in the HCF regime, while forming a plateau for VHCF. Cracks initiate from a single site on the surface or subsurface. Site-specific focused ion beam sampling and transmission electron microscopy characterization reveal that the crack initiation is governed by slip-induced localized plastic deformation. Microcracks initiate near non-metallic inclusions or slip band-grain boundary site. Plus, a life correlation model considering the size of micro-defect was proposed to better correlate the fatigue life. [ABSTRACT FROM AUTHOR]

The strength and aging efficiency of precipitation-hardened aluminum alloys are always difficult to be obtained simultaneously. To address this issue, a novel fast-aging process, that is, a two-step aging coupled deformation process, was proposed. The influence of fast-aging parameters on the mechanical behavior of Al–Zn–Mg–Cu alloy was studied, and it was found that secondary aging, pre-aging, and deformation have a major effect, an auxiliary effect, and a coordinating effect, respectively, on the strength of aluminum alloys. Compared to traditional peak strength aging process of the T6 condition, the tensile strengths of the material are improved by 10 MPa (∼1.99%), and the aging time reduced by 89.58%. The continuous growth conditions of the precipitates throughout fast aging were analyzed in detail, and a competitive mechanism for the nucleation and growth of the precipitates in the matrix and on dislocations during secondary aging was proposed. Subsequently, the mechanisms were verified using differential scanning calorimetry (DSC) testing and transmission electron microscopy (TEM) observations. [ABSTRACT FROM AUTHOR]