ETV6::ACSL6 translocation-driven super-enhancer activation leads to eosinophilia in acute lymphoblastic leukemia through IL-3 overexpression.

ETV6::ACSL6 represents a rare genetic aberration in hematopoietic neoplasms and is often associated with severe eosinophilia, which confers an unfavorable prognosis requiring additional anti-inflammatory treatment. However, since the translocation is unlikely to produce a fusion protein, the mechanism of ETV6::ACSL6 action remains unclear. Here, we performed multi-omics analyses of primary leukemia cells and patient-derived xenografts from an acute lymphoblastic leukemia (ALL) patient with ETV6::ACSL6 translocation. We identified a super-enhancer located within the ETV6 gene locus and revealed translocation and activation of the super-enhancer associated with the ETV6::ACSL6 fusion. The translocated super-enhancer exhibited intense interactions with genomic regions adjacent to and distal from the breakpoint at chromosomes 5 and 12, including genes coding inflammatory factors such as IL-3. This led to modulations in DNA methylation, histone modifications, and chromatin structures, triggering transcription of inflammatory factors leading to eosinophilia. Furthermore, the bromodomain and extraterminal domain (BET) inhibitor synergized with standard-of-care drugs for ALL, effectively reducing IL-3 expression and inhibiting ETV6::ACSL6 ALL growth in vitro and in vivo. Overall, our study revealed for the first time a cis-regulatory mechanism of super-enhancer translocation in ETV6::ACSL6 ALL, leading to ALL-accompanying clinical syndrome. These findings may stimulate novel treatment approaches for this challenging ALL subtype.

OER catalytic performance of a composite catalyst comprising multi-layer thin flake Co3O4 and PPy nanofibers.

The oxygen evolution reaction (OER) plays a crucial role in energy conversion and storage processes, highlighting the significance of searching for efficient and stable OER catalysts. In this study, we have developed a composite catalyst, PPy@Co3O4, with outstanding catalytic performance for the OER. The catalyst was constructed by integrating multi-layer thin flake Co3O4 with attached PPy nanofibers, utilizing the rich active sites of Co3O4 and the flexibility and tunability of PPy nanofibers to optimize the catalyst structure. Through comprehensive characterization and performance evaluation, our results demonstrate that the PPy@Co3O4 (0.1 : 1) catalyst exhibits remarkable OER catalytic activity and stability. This research provides new strategies and insights for the development of efficient and stable OER catalysts, holding promising prospects for energy conversion and storage applications in relevant fields.

Case Report: Molecular and microenvironment change upon midostaurin treatment in mast cell leukemia at single-cell level.

Mast cell leukemia is a rare and aggressive disease, predominantly with KIT D816V mutation. With poor response to conventional poly-chemotherapy, mast cell leukemia responded to the midostaurin treatment with a 50% overall response rate (ORR), but complete remission rate is approximately 0%. Therefore, the potential mechanisms of midostaurin resistance and the exact impacts of midostaurin on both gene expression profile and mast cell leukemia microenvironment in vivo are essential for design tailored combination therapy targeting both the tumor cells and the tumor microenvironment. Here we report a 59-year-old male mast cell leukemia patient with KIT F522C mutation treated with midostaurin. Single-cell sequencing of peripheral blood and whole exome sequencing (WES) of bone marrow were performed before and 10 months after midostaurin treatment. In accordance with the clinical response, compared to the pretreatment aberration, the decline of mast cells and increase of T-, NK, B-cells in peripheral blood, and the decrease of the KIT F522C mutation burden in bone marrow were observed. Meanwhile, the emergence of RUNX1 mutation, upregulations of genes expression (RPS27A, RPS6, UBA52, RACK1) on tumor cells, and increased frequencies of T and NK cells with TIGIT, CTLA4, and LAG3 expression were observed after midostaurin treatment, predicting the disease progression of this patient. As far as we know, this is the first case reporting the clinical, immunological, and molecular changes in mast cell leukemia patients before and after midostaurin treatment, illustrating the in vivo mechanisms of midostaurin resistance in mast cell leukemia, providing important clues to develop a sequential option to circumvent tumor progression after targeting oncogene addiction and prolong patients' survival.

An AI-Aided Diagnostic Framework for Hematologic Neoplasms Based on Morphologic Features and Medical Expertise.

A morphologic examination is essential for the diagnosis of hematological diseases. However, its conventional manual operation is time-consuming and laborious. Herein, we attempt to establish an artificial intelligence (AI)-aided diagnostic framework integrating medical expertise. This framework acts as a virtual hematological morphologist (VHM) for diagnosing hematological neoplasms. Two datasets were established as follows: An image dataset was used to train the Faster Region-based Convolutional Neural Network to develop an image-based morphologic feature extraction model. A case dataset containing retrospective morphologic diagnostic data was used to train a support vector machine algorithm to develop a feature-based case identification model based on diagnostic criteria. Integrating these 2 models established a whole-process AI-aided diagnostic framework, namely, VHM, and a 2-stage strategy was applied to practice case diagnosis. The recall and precision of VHM in bone marrow cell classification were 94.65% and 93.95%, respectively. The balanced accuracy, sensitivity, and specificity of VHM were 97.16%, 99.09%, and 92%, respectively, in the differential diagnosis of normal and abnormal cases, and 99.23%, 97.96%, and 100%, respectively, in the precise diagnosis of chronic myelogenous leukemia in chronic phase. This work represents the first attempt, to our knowledge, to extract multimodal morphologic features and to integrate a feature-based case diagnosis model for designing a comprehensive AI-aided morphologic diagnostic framework. The performance of our knowledge-based framework was superior to that of the widely used end-to-end AI-based diagnostic framework in terms of testing accuracy (96.88% vs 68.75%) or generalization ability (97.11% vs 68.75%) in differentiating normal and abnormal cases. The remarkable advantage of VHM is that it follows the logic of clinical diagnostic procedures, making it a reliable and interpretable hematological diagnostic tool.

B-Doped g-C3N4/Black TiO2 Z-Scheme Nanocomposites for Enhanced Visible-Light-Driven Photocatalytic Performance.

Black TiO2 with abundant oxygen vacancies (OVs)/B-doped graphitic carbon nitride (g-C3N4) Z-scheme heterojunction nanocomposites are successfully prepared by the one-pot strategy. The OVs can improve not only photogenerated carrier separation, but also the sorption and activation of antibiotic compounds (tetracycline hydrochloride, TC). The prepared heterojunction photocatalysts with a narrow bandgap of ∼2.13 eV exhibit excellent photocatalytic activity for the degradation of tetracycline hydrochloride (65%) under visible light irradiation within 30 min, which is several times higher than that of the pristine one. The outstanding photocatalytic property can be ascribed to abundant OVs and B element-dope reducing the bandgap and extending the photo-response to the visible light region, the Z-scheme formation of heterojunctions preventing the recombination of photogenerated electrons and holes, and promoting their effective separation.

Sm0.5Sr0.5Co1-xNixO3-δ-A Novel Bifunctional Electrocatalyst for Oxygen Reduction/Evolution Reactions.

The development of non-precious metal catalysts with excellent bifunctional activities is significant for air-metal batteries. ABO3-type perovskite oxides can improve their catalytic activity and electronic conductivity by doping transition metal elements at B sites. Here, we develop a novel Sm0.5Sr0.5Co1-xNixO3-δ (SSCN) nanofiber-structured electrocatalyst. In 0.1 M KOH electrolyte solution, Sm0.5Sr0.5Co0.8Ni0.2O3-δ (SSCN82) with the optimal Co: Ni molar ratio exhibits good electrocatalytic activity for OER/ORR, affording a low onset potential of 1.39 V, a slight Tafel slope of 123.8 mV dec-1, and a current density of 6.01 mA cm-2 at 1.8 V, and the ORR reaction process was four-electron reaction pathway. Combining the morphological characteristic of SSCN nanofibers with the synergistic effect of cobalt and nickel with a suitable molar ratio is beneficial to improving the catalytic activity of SSCN perovskite oxides. SSCN82 exhibits good bi-functional catalytic performance and electrochemical double-layer capacitance.

Analysis of nanofiber-based La0.2Sr0.8TiO3-Gd0.2Ce0.8O1.9 electrode kinetics.

For the sake of comparison, a single cell with nanofiber-based LST-GDC composite anode (Cell-1) and a single cell with nanoparticle-based LST-GDC composite anode (Cell-2) are fabricated, respectively. The electrolyte ohmic resistances of the LST-GDC composite anode side half-cells are determined by an AC resistance measurement. Current interrupt is applied to measure the ohmic resistance of the half-cells. Combined with V-I characteristics, the influences of the potential drops caused by electrolyte ohmic resistance, electrode ohmic resistance and electrode electrochemical reaction on the cell kinetics are investigated. Under a current density of 0.6 A cm-2 at 850 °C, for the nanofiber-based LST-GDC composite anode (NF-LST-GDC), the electrode ohmic potential drop is 0.007 V and the potential drop caused by the electrode electrochemical reaction is 0.080 V. While for the nanoparticle-based LST-GDC composite anode (NP-LST-GDC), the corresponding potential drops are 0.159 V and 0.246 V, respectively. Both the potential drops of the former are lower than those of the latter. The kinetics of Cell-1 is greater than Cell-2, i.e., the kinetics of NF-LST-GDC is greater than that of NP-LST-GDC.