Single-cell RNA-seq reveals novel immune-associated biomarkers for predicting prognosis in AML patients with RUNX1::RUNX1T1.

Acute myeloid leukemia (AML) with t(8;21)(q22;q22);(RUNX1::RUNX1T1) is highly heterogeneous and malignant. It has a relapse rate of nearly 40 %, resulting in clinical resistance or refractoriness to chemotherapy. Immune cells, particularly CD4(+) T and CD8(+) T lymphocytes, have been discovered to be dysfunctional in this condition, and functional recovery shows promising efficiency in preclinical trials. Here, with single-cell transcriptomic data from de novo AML patients with RUNX1::RUNX1T1 and at various stages following disease progression, we investigated the genes correlated with T-cell proliferation and activation. In leukemia cells, ADA, AHCY, GPN3 and LTBR were markedly highly expressed compared to those in T-cell at diagnosis, and they tended to increase with disease progression. Additionally, we discovered that AHCY was an effective biomarker to predict the overall survival as well as relapse-free survival of AML patients with RUNX1::RUNX1T1. The correlation of AHCY with infiltrated immune cells and immune checkpoints was also investigated. AML cohorts from two other independent studies, TCGA LAML (n = 145) and the GEO dataset (n = 104), also demonstrated an inferior outcome for AML patients with high AHCY expression. In conclusion, our research revealed that AHCY might function as a novel indicator to predict the prognosis and efficiency of T-cell proliferation and activation in AML patients with RUNX1::RUNX1T1.

Bimetallic Ions Functionalized Metal-Organic-Framework Nanozyme for Tumor Microenvironment Regulating and Enhanced Photodynamic Therapy for Hypoxic Tumor.

Photodynamic therapy (PDT), as a light irradiation inducing reactive oxygen species (ROS) generation for cancer treatment, offers facile and promising solutions with respect to spatiotemporal control of ROS generation, and minimizes the systemic toxicity and side effects for highly precise tumor therapy. However, the PDT efficiency is often severely compromised by the complex tumor microenvironment (TME), such as the hypoxic condition and overexpressed antioxidants. Here, for the first time, a bimetallic ion-modified metal-organic framework nanozyme (Zr4+ -MOF-Ru3+ /Pt4+ -Ce6@HA, ZMRPC@HA) is designed. ZMRPC@HA with catalase (CAT) and glutathione oxidase (GSHOx) mimetic activities, can efficiently regulate TME by generation of O2 and deplete the GSH synergistically for enhancing the long-term PDT efficacy toward the hypoxic tumor. The in vitro cell inhibition and in vivo on tumor xenograft evaluations demonstrate the PDT strategy by using ZMRPC@HA can successfully inhibit the differentiation and proliferation of tumor cells under a 660 nm laser irradiation in deep tissues. These findings open a new avenue for the design of multimetallic ions functionalized MOF-based nanozymes with multienzyme mimetic activities toward the antitumor and various other biological applications.

Comprehensive analysis of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2): A potential novel pan-cancer immune checkpoint.

Tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2) is encoded by TNFAIP8L2 and is a newly identified negative regulator of natural and acquired immunity that plays a critical function in maintaining immune homeostasis. Recently, CAR-NK immune cell therapy has been a focus of major research efforts as a novel cancer therapeutic strategy. TIPE2 is a potential checkpoint molecule for immune cell maturation and antitumor immunity that could be used as a novel NK cell-based immunotherapeutic approach. In this study, we explored the expression of TNFAIP8L2 across various tumor types and found that TNFAIP8L2 was highly expressed in most tumor types and correlated with prognosis. Survival analysis showed that TNFAIP8L2 expression was predictive of improved survival in cervical-squamous-cell-carcinoma (CESC), sarcoma (SARC) and skin-cutaneous-melanoma (SKCM). Conversely, TNFAIP8L2 expression predicted poorer survival in acute myeloid leukemia (LAML), lower-grade-glioma (LGG), kidney-renal-clear-cell-carcinoma (KIRC) and uveal-melanoma (UVM). Analysis of stemness features and immune cell infiltration indicated that TNFAIP8L2 was significantly associated with cancer stem cell index and increased macrophage and dendritic cell infiltration. Our data suggest that TNFAIP8L2 may be a novel immune checkpoint biomarker across different tumor types, particularly in LAML, LGG, KIRC and UVM, and may have further utility as a potential target for immunotherapy.

Beyond the fluorescence labelling of novel nitrogen-doped silicon quantum dots: the reducing agent and stabilizer for preparing hybrid nanoparticles and antibacterial applications.

Silicon quantum dots (SiQDs) have fully demonstrated their applicability in light of their fluorescence. The extension of their applications to other fields, especially considering their excellent biocompatibility, would be more appealing. Herein, a kind of versatile nitrogen-doped silicon quantum dot (N-SiQD) was facilely synthesized via a one-pot hydrothermal method with 3-aminopropyltrimethoxysilane and tetraethylpentylamine as sources. The N-SiQDs were used as a probe for bacterial imaging owing to their good fluorescence properties, stability and biocompatibility. Besides, owing to N doping rendering the N-SiQDs stronger reducibility and Au affinity, the N-SiQDs displayed unique reduction capability, and were attempted as a reducing agent and stabilizer for the synthesis of the nanocomposite, i.e. N-SiQDs stabilized Au nanoparticles (N-SiQDs-AuNPs), under mild conditions. The N-SiQDs-AuNPs showed superior catalytic performance to citric-AuNPs due to the synergistical catalytic effect. In addition, the N-SiQDs exhibited good antibacterial properties against Gram-positive (S. aureus) and Gram-negative bacteria (E. coli) without obvious negative influence on the cells, particularly avoiding the use of any other external stimulation. This study may open a new avenue to use SiQDs for the synthesis of nanocomposites and other biomedicine applications beyond as a fluorescent probe.

Au3+ -Functionalized UiO-67 Metal-Organic Framework Nanoparticles: O2•- and •OH Generating Nanozymes and Their Antibacterial Functions.

The synthesis and characterization of Au3+ -modified UiO-67 metal-organic framework nanoparticles, Au3+ -NMOFs, are described. The Au3+ -NMOFs reveal dual oxidase-like and peroxidase-like activities and act as an active catalyst for the catalyzed generation of O2•- under aerobic conditions or •OH in the presence of H2 O2 . The two reactive oxygen species (ROS) agents O2•- and •OH are cooperatively formed by Au3+ -NMOFs under aerobic conditions, and in the presence of H2 O2. The Au3+ -NMOFs are applied as an effective catalyst for the generation ROS agents for antibacterial and wound healing applications. Effective antibacterial cell death and inhibition of cell proliferation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacterial colonies are demonstrated in the presence of the Au3+ -NMOFs. In addition, in vivo experiments demonstrate effective wound healing of mice wounds infected by S. aureus, treated by the Au3+ -NMOFs.

Gata2-L359V impairs primitive and definitive hematopoiesis and blocks cell differentiation in murine chronic myelogenous leukemia model.

GATA2, a key transcription factor in hematopoiesis, is frequently mutated in hematopoietic malignancies. How the GATA2 mutants contribute to hematopoiesis and malignant transformation remains largely unexplored. Here, we report that Gata2-L359V mutation impeded hematopoietic differentiation in murine embryonic and adult hematopoiesis and blocked murine chronic myeloid leukemia (CML) cell differentiation. We established a Gata2-L359V knockin mouse model in which the homozygous Gata2-L359V mutation caused major defects in primitive erythropoiesis with an accumulation of erythroid precursors and severe anemia, leading to embryonic lethality around E11.5. During adult life, the Gata2-L359V heterozygous mice exhibited a notable decrease in bone marrow (BM) recovery under stress induction with cytotoxic drug 5-fluorouracil. Using RNA sequencing, it was revealed that homozygous Gata2-L359V suppressed genes related to embryonic hematopoiesis in yolk sac, while heterozygous Gata2-L359V dysregulated genes related to cell cycle and proliferation in BM Lin-Sca1+c-kit+ cells. Furthermore, through chromatin immunoprecipitation sequencing and transactivation experiments, we found that this mutation enhanced the DNA-binding capacity and transcriptional activities of Gata2, which was likely associated with the altered expression of some essential genes during embryonic and adult hematopoiesis. In mice model harboring BCR/ABL, single-cell RNA-sequencing demonstrated that Gata2-L359V induced additional gene expression profile abnormalities and partially affected cell differentiation at the early stage of myelomonocytic lineage, evidenced by the increase of granulocyte-monocyte progenitors and monocytosis. Taken together, our study unveiled that Gata2-L359V mutation induces defective hematopoietic development and blocks the differentiation of CML cells.

Recent advances in visual detection for cancer biomarkers and infectious pathogens.

It is an urgency to detect infectious pathogens or cancer biomarkers using rapid, simple, convenient and cost-effective methods in complex biological samples. Many existing approaches (traditional virus culture, ELISA or PCR) for the pathogen and biomarker assays face several challenges in the clinical applications that require lengthy time, sophisticated sample pre-treatment and expensive instruments. Due to the simple and rapid detection manner as well as no requirement of expensive equipment, many visual detection methods have been considered to resolve the aforementioned problems. Meanwhile, various new materials and colorimetric/fluorescent methods have been tried to construct new biosensors for infectious pathogens and biomarkers. However, the recent progress of these aspects is rarely reviewed, especially in terms of integration of new materials, microdevice and detection mechanism into the visual detection systems. Herein, we provide a broad field of view to discuss the recent progress in the visual detection of infectious pathogens and cancer biomarkers along with the detection mechanism, new materials, novel detection methods, special targets as well as multi-functional microdevices and systems. The novel visual approaches for the infectious pathogens and biomarkers, such as bioluminescence resonance energy transfer (BRET), metal-induced metallization and clustered regularly interspaced short palindromic repeats (CRISPR)-based biosensors, are discussed. Additionally, recent advancements in visual assays utilizing various new materials for proteins, nucleic acids, viruses, exosomes and small molecules are comprehensively reviewed. Future perspectives on the visual sensing systems for infectious pathogens and cancers are also proposed.

The Recent Advances of Fluorescent Sensors Based on Molecularly Imprinted Fluorescent Nanoparticles for Pharmaceutical Analysis.

Fluorescent nanoparticles have good chemical stability and photostability, controllable optical properties and larger stokes shift. In light of their designability and functionability, the fluorescent nanoparticles are widely used as the fluorescent probes for diverse applications. To enhance the sensitivity and selectivity, the combination of the fluorescent nanoparticles with the molecularly imprinted polymer, i.e. molecularly imprinted fluorescent nanoparticles (MIFN), was an effective way. The sensor based on MIFN (the MIFN sensor) could be more compatible with the complex sample matrix, which was especially widely adopted in medical and biological analysis. In this mini-review, the construction method, detective mechanism and types of MIFN sensors are elaborated. The current applications of MIFN sensors in pharmaceutical analysis, including pesticides/herbicide, veterinary drugs/drugs residues and human related proteins, are highlighted based on the literature in the recent three years. Finally, the research prospect and development trend of the MIFN sensor are forecasted.

Measuring spin Hall effect of light by cross-polarization intensity ratio.

We propose and realize a simple technique to measure the tiny spin Hall effect of light from the ratio of the minimum and the maximum intensities along two cross-polarization directions, without the requirement of a position-sensitive detector in the conventional weak measurement. Furthermore, the weak intensity ratio is dramatically amplified by purposely choosing the intensity along the direction close to that of the minimum instead of the maximum along the perpendicular polarization direction, which is verified by the experimental results. In principle, this method also can be modified for measurement of the high extinction ratio of a polarizer.