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Arsenic trioxide (ATO) has exhibited remarkable efficacy in treating acute promyelocytic leukemia (APL), primarily through promoting the degradation of the PML-RARα fusion protein. However, ATO alone fails to confer any survival benefit to non-APL acute myeloid leukemia (AML) patients and exhibits limited efficacy when used in combination with other agents. Here, we explored the general toxicity mechanisms of ATO in APL and potential drugs that could be combined with ATO to exhibit synergistic lethal effects on other AML. We demonstrated that PML-RARα degradation and ROS upregulation were insufficient to cause APL cell death. Based on the protein synthesis of different AML cells and their sensitivity to ATO, we established a correlation between ATO-induced cell death and protein synthesis. Our findings indicated that ATO induced cell death by damaging nascent polypeptides and causing ribosome stalling, accompanied by the activation of the ZAKα-JNK pathway. Furthermore, ATO-induced stress activated the GCN2–ATF4 pathway, and ribosome-associated quality control cleared damaged proteins with the assistance of p97. Importantly, our data revealed that inhibiting p97 enhanced the effectiveness of ATO in killing AML cells. These explorations paved the way for identifying optimal synthetic lethal drugs to enhance ATO treatment on non-APL AML.

CD19‐chimeric antigen receptor (CAR)‐based T‐cell therapy has produced promising clinical responses in patients with relapsed or refractory B‐cell malignancies. However, a significant portion of patients with mature B cell‐derived malignancies, including chronic lymphocytic leukemia (CLL) and non‐Hodgkin's lymphoma (NHL), do not respond to CD19‐CAR‐T cell therapy. Whether any characteristics and biomarkers intrinsic to cancer cells themselves can predict the CD19‐CAR‐T cell therapeutic response remains largely unknown. Surprisingly, by using experimental models, we show here that malignant B cells bearing CD21, a mature B cell marker, could not be efficiently killed by CD19‐CAR‐T cells. CD19, CD21, and CD81, together with CD225, form the B cell coreceptor complex that enhances B cell‐mediated signaling. Our results indicated that CD21 affected the recognition of CD19‐positive tumor cells by CD19‐CAR‐T cells and impaired the antitumor capacities of these effector cells. We have not only uncovered a mechanism underlying the impairment of CD19‐CAR‐T cells in mature B cell‐derived CLL and NHL, but also proposed a pretreatment biomarker that may predict CD19‐CAR‐T cell therapeutic response, thus preventing foreseeable therapy failure and suggesting optimal personized therapies. Tumor‐intrinsic CD21 impairs the target cell recognition and the cytotoxicity of the CD19‐CAR‐T cells.

Gd2O2S:Pr3+, Ce3+scintillation phosphors (GOS) were successfully synthesized via a homogeneous precipitation followed by solid-state reaction method with Gd2O3, Pr(NO3)3·6H2O, Ce(NO3)3·6H2O, HNO3, NH3·H2O, CO(NH2)2, Na2CO3, and sublimated sulfur (S) as the starting materials. Fourier transform infrared spectrometer (FT-IR), differential scanning calorimetry-thermogravimetry (DSC-TG), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and photoluminescence (PL) were used to characterize the obtained products. FT-IR and DSC-TG results reveal that the precursor is mostly composed of gadolinium and carbonate groups with some crystal water and can be transformed into Gd2O3phase at 1000 °C for 2 h in air. XRD analysis shows that pure Gd2O2S phase can be synthesized with the molar ratio of Gd2O3:Na2CO3:S=1:5:20 when the reaction temperature is 1000 °C and the reaction time is 2 h. FE-SEM analysis shows that the morphology of the obtained Gd2O2S product has a block and irregular polyhedron structure with a significant increase in size of about 4 μm. PL spectrum analysis shows that the strongest green emission of Gd2O2S:0.20% Pr3+, 0.0025% Ce3+scintillation phosphor is observed around 513 nm, which is attributed to the 3P0→3H4transition of Pr3+ions. The average lifetime τ is calculated to be 1.43 μs for Gd2O2S:0.20% Pr3+, 0.0025% Ce3+scintillation phosphor. The above results meet the wavelength and lifetime requirements of GOS fluorescent screen used in medical radiotherapy linear accelerator.

Glass ceramics composed of Na2O–BaO–Bi2O3–Nb2O5–Al2O3–SiO2(NBBN-AS) were modified by rare-earth doping and prepared via the melt-quenching process accompanied by controlled crystallization. High-resolution transmission electron microscopy displayed the glassy matrix closely encompassing the nanosized NaNbO3, Ba2NaNb5O15, BaAl2Si2O8, and AlNbO4crystalline grains. With rare-earth doping, the NBBN-AS glass ceramics’ theoretical energy storage density can reach 22.48 J/cm3. This excellent energy storage property is credited with increasing breakdown strength, and numerical simulation was applied to reveal the intrinsic mechanism for increased breakdown strength by rare-earth doping. The charge–discharge results indicated a giant power density of 220 MW/cm3as well as an ultrafast discharge speed of 11 ns. The results indicate that the glass ceramic can be used in advanced capacitor applications.

For glass-ceramics, how to realize the collaborative optimization of BDS and permittivity is the key to improve the energy storage density. In this work, ZrO2is introduced into BPKNAS glass-ceramics as nucleating agent to promote crystal development of glass-ceramics and then achieve high permittivity. When 1.5 mol% ZrO2is added, the glass-ceramics have the highest permittivity (∼128.59) and meanwhile possess high BDS (1948.90 kV/cm) due to the dense microstructure. Therefore, BPKNAS-1.5ZrO2glass-ceramics has the highest theoretical energy storage density (21.62 J/cm3). Moreover, the permittivity variation of BPKNAS-1.5ZrO2glass-ceramics is less than 6 % in the wide temperature range from −80 to 300 °C, showing excellent temperature stability. In addition, BPKNAS-1.5ZrO2glass-ceramics possesses ultrahigh power density, which reaches up to 382.40 MW/cm3in overdamped circuit. The above evidence shows that BPKNAS-1.5ZrO2glass-ceramics with ultrahigh energy storage density and power density is very competitive in the field of energy storage applications.