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Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML. [ABSTRACT FROM AUTHOR]

Background: Acute lymphoblastic leukemia (ALL) is one of the most common pediatric cancers, characterized by the malignant proliferation of leukemic cells. Despite advancements in treatment, the prognosis for refractory and relapsed ALL remains poor, underscoring the need for novel therapeutic targets and approaches. Methods: To investigate the anti-leukemic properties of MG132, MTS assays were employed to assess cell viability, and flow cytometry was used to evaluate apoptosis. Mechanistic studies, including qRT-PCR, Western blotting, and lentivirus-mediated FOXO3a knockdown, were conducted to explore MG132's effects on the Akt/FOXO3a/Bim signaling pathway. A xenograft mouse model was utilized to validate the in vivo efficacy of MG132 in suppressing tumor growth. Results: MG132 inhibited cell proliferation and induced apoptosis in both ALL cell lines and primary cells in a concentration-dependent manner. Mechanistic studies revealed that MG132 promoted FOXO3a nuclear localization by suppressing Akt phosphorylation and preventing FOXO3a degradation, leading to increased Bim expression. Furthermore, FOXO3a knockdown significantly reduced MG132's anti-proliferative effects. In vivo, MG132 markedly inhibited tumor growth in the xenograft model. Conclusion: These findings suggest that MG132 exerts potent anti-leukemic effects through modulation of the Akt/FOXO3a/Bim axis, offering a promising therapeutic avenue for treating ALL. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common chronic joint inflammatory disease characterized by progressive destruction of the articular cartilage, bone remodeling, and excessive chronic pain. Most therapeutic approaches do not rescue the progression of OA effectively or provide relief of symptoms. Protaetia brevitarsis seulensis larva (PBSL), which is attracting attention, is an edible insect with very high nutritional value and herbal medicine for the treatment of blood stasis, hepatic disease, and various inflammatory diseases. However, the effect of PBSL on OA has not yet been investigated. This study aimed to demonstrate the effects of PBSL water extract on the progression of OA using monosodium iodoacetate (MIA)‐induced mice and SW1353 chondrocytes or murine macrophages. We injected MIA into the intraarticular area of mice following pretreatment with either saline or PBSL (200 mg/kg) for 2 weeks, and then locomotor activity, microcomputed tomography and histopathological analysis, quantitative reverse transcriptase–polymerase chain reaction analysis, and western blot analysis were performed. To determine the molecular effects of PBSL, we used interleukin‐1β (IL‐1β)‐induced SW1353 chondrosarcoma or lipopolysaccharide (LPS)‐stimulated macrophages. Pretreatment with PBSL diminished the symptoms of OA. Physical activity, articular cartilage damage, and the generation of microfractures were rescued by pretreatment with PBSL in the mouse model. Pretreatment with PBSL suppressed the progress of OA through the regulation of articular cartilage degradation genes and inflammation in both in vivo and in vitro models. Our results demonstrated that PBSL has value as edible insect that can be used in the development of functional foods for OA. [ABSTRACT FROM AUTHOR]

Highly selective etching of silicon nitride over silicon oxide is one of the most important processes especially for the fabrication of vertical semiconductor devices including 3D NAND (Not And) devices. In this study, isotropic dry etching characteristics of SiN x and SiO2 using ClF3/Cl2 remote plasmas have been investigated. The increase of Cl2 percent in ClF3/Cl2 gas mixture increased etch selectivity of SiN x over SiO2 while decreasing SiN x etch rate. By addition of 15% Cl to ClF3/Cl2, the etch selectivity higher than 500 could be obtained with the SiN x etch rate of ∼8 nm min−1, and the increase of Cl percent to 20% further increased the etch selectivity to higher than 1000. It was found that SiN x can be etched through the reaction from Si–N to Si–F and Si–Cl (also from Si–Cl to Si–F) while SiO2 can be etched only through the reaction from Si–O to Si–F, and which is also in extremely low reaction at room temperature. When SiN x /SiO2 layer stack was etched using ClF3/Cl2(15%), extremely selective removal of SiN x layer in the SiN x /SiO2 layer stack could be obtained without noticeable etching of SiO2 layer in the stack and without etch loading effect. [ABSTRACT FROM AUTHOR]