High-Throughput Study of Amorphous Stability and Optical Properties of Superlattice-Like Ge-Sb-Te Thin Films.

A high-throughput ion beam sputtering system is used to synthesize compositional gradient superlattice-like (SLL) thin film libraries of Ge-Sb-Te alloys over the entire phase diagram. The optical properties and structural evolution of the Ge-Sb-Te combinatorial SLL thin film are investigated. A systematic screening over the annealing temperature, annealing time, and modulation period has elucidated the critical factors that affect the stability of the metastable phase and optical properties. It is found that amorphous stability and optical constant are highly dependent on the modulation period and chemical composition of the thin film. This data-driven approach offers new perspectives for accelerating the development of new materials with excellent optical and amorphous stability and for exploring their mechanisms, by greatly expanding the dataset of Ge-Sb-Te alloys with SLL structures through high-throughput experiments.

SETDB1 induces lenalidomide resistance in multiple myeloma cells via epithelial­mesenchymal transition and PI3K/AKT pathway activation.

SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is a histone H3K9 methyltransferase that stimulates cell proliferation by methylating AKT, which contributes to drug resistance in multiple myeloma (MM). Lenalidomide is an immunomodulatory agent widely used in the treatment of MM. However, lenalidomide resistance occurs in patients with MM. Currently, the role of SETDB1 in lenalidomide resistance in MM remains unclear. Thus, the present study aimed to explore the functional association between SETDB1 and lenalidomide resistance in MM. The analysis of GEO datasets revealed that SETDB1 was upregulated in lenalidomide-resistant MM cells and that its expression was associated with poor prognosis of patients with MM. Apoptosis analysis revealed that overexpression of SETDB1 in MM cells significantly decreased apoptosis, while knockdown of SETDB1 increased apoptosis. Furthermore, the IC50 value of lenalidomide in MM cells increased following SETDB1 overexpression and decreased following SETDB1 silencing. Additionally, SETDB1 mediated epithelial-mesenchymal transition (EMT) and activated the PI3K/AKT pathway. Mechanistic analysis revealed that inhibition of PI3K/AKT signaling in MM cells increased apoptosis, sensitized the cells to lenalidomide and inhibited EMT, whereas SETDB1 overexpression inhibited the effects of PI3K/AKT cascade inhibition. In conclusion, the findings of the present study indicated that SETDB1 promoted lenalidomide resistance in MM cells by promoting EMT and the PI3K/AKT signaling pathway. Thus, SETDB1 may be a potential therapeutic target for MM.

A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

[Apoptosis of in vitro cultured BMMNC from MDS patients induced by arsenic sulfide].

The aim of this study was to investigate the inhibition effect of arsenic sulfide (As2S2) on the growth of in vitro cultured BMMNC from MDS patients and to explore its possible cellular and molecular mechanisms. The apoptosis of MDS cells induced by As2S2 solution of different concentrations were studied with MTT, flow cytometry, and RT-PCR. The results showed that (1) low concentration of As2S2 (0-0.6 mg/L) had no marked inhibition effect on proliferation of MDS cells; (2) after treatment with 1.5-50 mg/L of As2S2, both low risk MDS cells and high risk MDS cells presented typical features of apoptosis with a dose-dependent manner, the expression of bcl-2 mRNA and the ratio of bcl-2/bax obviously decreased after As2S2 treatment (P < 0.05); (3) BMMNC from MDS patients had higher apoptosis ratio than that of BMMNC from control. It is concluded that BMMNC excessive apoptosis exists in MDS patients; low concentration of As2S2 (0-0.6 mg/L) shows no inhibition effect on proliferation of MDS cells; high concentration of As2S2 (1.5-50 mg/L) induces apoptosis of MDS cells.