Search

Acute myeloid leukemia (AML) is one of the most common malignancies of the hematopoietic progenitor cell in adults. Quercetin has gained recognition over the years because of its anti-cancer effect with minimal toxicity. Herein, we aim to investigate the anti-leukemia mechanism of quercetin and to decipher the signaling pathway of quercetin in HL-60 leukemic cells. We observed that quercetin induces apoptosis and autophagic cell death, in which both pathways play an important role in suppressing the viability of leukemia cells. Phosphorylated AMPK (p-AMPK) protein expressions are lower in primary AML cells, HL-60 cells, KG-1 and THP-1 cells than in peripheral blood monocular cells. After quercetin treatment, the expression of p-AMPK is increased while the expression of p-mTOR is decreased in a dose-dependent manner. Mechanistically, compound C, an AMPK phosphorylation inhibitor, upregulates the phosphorylation of mTOR and inhibits autophagy and apoptosis in quercetin-induced HL-60 cells, while silencing of CaMKKβ inhibits the quercetin-induced phosphorylation of AMPK, resulting in increased mTOR phosphorylation. Furthermore, silencing of CaMKKβ inhibits the autophagy in HL-60 cells. Taken together, our data delineate that quercetin plays its anti-leukemia role by inhibiting cell viability and inducing apoptosis and autophagy in leukemia cells. Quercetin inhibits the phosphorylation of mTOR by regulating the activity of AMPK, thus playing a role in the regulation of autophagy and apoptosis. CaMKKβ is a potential upstream molecule for AMPK/mTOR signaling pathway, through which quercetin induces autophagy in HL-60 cells.

Lymphoma relapse is very common in clinical work, but lineage switch at relapse is rare. Although some cases have reported acute lymphocytic leukemia (ALL) switch to acute myeloid leukemia (AML) or myeloid sarcoma upon relapse, phenotype switch seldom occurs in other types of lymphoma. Here we report six cases with lineage switch from lymphoma to myeloid neoplasms. In our cohort, three cases were mantle cell lymphoma (MCL), and the other three cases were T-cell lymphoblastic lymphoma (T-LBL), B-cell lymphoblastic lymphoma (B-LBL), and diffuse large B-cell lymphoma (DLBCL) at the initial diagnosis. When linage switch occurred, most cases were AML M5 phenotypes, and only one case was myelodysplastic syndrome (MDS) phenotype. 11q23/mixed-lineage leukemia (MLL) rearrangement was negative in all cases. Although intensive therapy and stem cell transplantation have been applied in most cases, the poor outcome cannot be reversed. Therefore, we found that lineage switch could occur not only from ALL to AML or vice versa, but also from MCL or DLBCL to AML. Moreover, the incidence of MLL rearrangement in lineage switch is lower in adult hematologic malignancies as compared with pediatric patients.

The exploitation of fatigue life prediction methods based on fatigue indicator parameters revealed the influence of the defect size, position, and morphology on the fatigue life and fatigue behavior of additively manufactured metals. Meanwhile, Data‐driven life prediction methods are time‐efficient but inexplainable. Current machine learning‐based fatigue life prediction methods call for not only the accuracy but also the interpretability and stability of prediction results. Thus, the fusion of physical methods and machine learning methods has been a prevailing research topic in fatigue life prediction. In this study, a novel physics‐informed neural network framework is proposed by integrating a fatigue indicator parameter based on defects into the physical constraints term of a loss function. This method outperforms conventional machine learning methods in high‐cycle and very high‐cycle regimes, exhibiting superior prediction performance and generalization ability. Furthermore, the prediction results can be explained from a physical standpoint, correlating with the applicability range of the introduced physical equation describing defect positions. Highlights: A novel machine learning framework integrating a fatigue index parameter is proposed.The physics‐informed neural network has the best fatigue life prediction results.The prediction can be partially interpreted by the introduced physical model. [ABSTRACT FROM AUTHOR]

The effect of depositing 8YSZ between serving as an intermediate layer of the P92/Al2O3 was analyzed via finite element analysis. The result shows that depositing an 8YSZ buffer coat beneath the Al2O3 will dramatically decrease the maximum principal stress in the coating system in thermal shock. The stress intensity factor, KI, and J-integral are also decreased which indicates the crack propagation resistance is improved. Inserting a 100 nm 8YSZ buffer layer could reduce the KI and J-integral by 2 orders of magnitude. Thus, cracks are less likely to initiate and propagate. Moreover, coating an 8YSZ layer between the P92/Al2O3 can significantly change the stress distribution pattern in the Al2O3 coating. The 8YSZ with a proper coefficient of thermal expansion between that of the Al2O3 and P92 and good deformability is an ideal buffer layer to improve the thermal cycle endurance and prolong the service life of the Al2O3 coating. [ABSTRACT FROM AUTHOR]

T cells' function and activation and the immunosuppressive effect of regulatory T cells (Tregs) play a pivotal role in the occurrence and progression of acute myeloid leukemia (AML). In this study, we investigate the expression of T cell activation markers and quantity of Tregs in bone marrow (BM) and peripheral blood (PB) from AML patients and further characterized their correlation with BM leukemic blasts. Expression of CD25, CD38, CD69, and HLA-DR on the surfaces of CD4+ and CD8+ T cells and the quantity of Tregs in BM and PB from new diagnosed (ND), relapsed-refractory (RR), complete remission (CR) AML patients were measured via flow cytometry. Compared to normal controls (NC), we found higher proportion of CD4+ CD69+ T cells, CD8+ CD69+ T cells and Tregs in PB. CD8+ CD38+ T cells and CD8+ HLA-DR+ T cells in RR were significantly higher than ND, CR and NC). Tregs were normalized when AML patients achieved CR. Moreover, there was a minor positive correlation between AML blasts and CD8+ CD25+ T cells or Tregs, while AML blasts had a minor negative correlation with CD4+ CD69+ T cells. Abnormal activation markers of T cells and Tregs may be involved in the pathological mechanism of ND and RR AML. Our results indicated that CD8+ CD38+ T cells and CD8+ HLA-DR+ T cells might be RR markers of AML patients. Furthermore, Tregs could be used as clinical indicators to evaluate prognosis for AML patients. [ABSTRACT FROM AUTHOR]

A deuterium permeation barrier is an essential part in the core component of nuclear reactors. It can protect the structure made of steel from being penetrated by deuterium in a fusion reactor. However, residual stress induced in the operation would dramatically influence the mechanical endurance of the coating, threatening the safety of the facilities. In this paper, finite element analysis was conducted to investigate the residual stress in nanoscale Al2O3 and Y2O3 coatings and their composites under thermal shock, from 700°C to 25°C. The max principal stress is assumed as the cause of crack initiation in the coating, because ceramics are brittle and fragile under tensile stress. Max shear stress and max Mises stress in the systems are also analyzed, and the effect of thickness in the range 100 nm to 1000 nm was investigated. The max principal stress in Al2O3 coating reaches its maximum value, 1.33 GPa, when the thickness of coating reaches 450 nm. And the max principal stress decreases at a very low rate as the thickness increases exceeding 450 nm. The max principal stress in Y2O3 coating increases rapidly as the thickness increases when the thickness of the coating is below 250 nm, and the max principal stress is at about 0.9 GPa when the thickness exceeds 500 nm. The max principal stress in the Y2O3/Al2O3 (150 nm) composite coating occurs in the Al2O3 layer and shows no difference from the single layer of 150 nm thick Al2O3 coating. The max principal stress site of all three kinds of coating is located at the edge of the coating 25 nm away from the interface. The result shows that residual thermal stress in the coating increases as the thickness increases when the thickness of the coating is below 200 nm due to the stress singularity of the interface. And as the thickness exceeds 500 nm, the increase in thickness has little impact on the residual thermal stress in the coating. Coating an Y2O3 top layer will not introduce any more residual thermal stress under the thermal shock condition. The Y2O3 coating causes much less residual stress under thermal shock compared with Al2O3 owing to its much lower Young's modulus. The max principal stress in the 300 nm thick Y2O3 coating is 0.85 GPa while that of the Al2O3 coating is 1.16 GPa. The max residual stress of the composite Y2O3/Al2O3 (150 nm) coating is determined by the Al2O3 layer. [ABSTRACT FROM AUTHOR]