Non-volatile 2D MoS2/black phosphorus heterojunction photodiodes in the near- to mid-infrared region.

Cutting-edge mid-wavelength infrared (MWIR) sensing technologies leverage infrared photodetectors, memory units, and computing units to enhance machine vision. Real-time processing and decision-making challenges emerge with the increasing number of intelligent pixels. However, current operations are limited to in-sensor computing capabilities for near-infrared technology, and high-performance MWIR detectors for multi-state switching functions are lacking. Here, we demonstrate a non-volatile MoS2/black phosphorus (BP) heterojunction MWIR photovoltaic detector featuring a semi-floating gate structure design, integrating near- to mid-infrared photodetection, memory and computing (PMC) functionalities. The PMC device exhibits the property of being able to store a stable responsivity, which varies linearly with the stored conductance state. Significantly, device weights (stable responsivity) can be programmed with power consumption as low as 1.8 fJ, and the blackbody peak responsivity can reach 1.68 A/W for the MWIR band. In the simulation of Faster Region with convolution neural network (CNN) based on the FLIR dataset, the PMC hardware responsivity weights can reach 89% mean Average Precision index of the feature extraction network software weights. This MWIR photovoltaic detector, with its versatile functionalities, holds significant promise for applications in advanced infrared object detection and recognition systems.

Non-volatile rippled-assisted optoelectronic array for all-day motion detection and recognition.

In-sensor processing has the potential to reduce the energy consumption and hardware complexity of motion detection and recognition. However, the state-of-the-art all-in-one array integration technologies with simultaneous broadband spectrum image capture (sensory), image memory (storage) and image processing (computation) functions are still insufficient. Here, macroscale (2 × 2 mm2) integration of a rippled-assisted optoelectronic array (18 × 18 pixels) for all-day motion detection and recognition. The rippled-assisted optoelectronic array exhibits remarkable uniformity in the memory window, optically stimulated non-volatile positive and negative photoconductance. Importantly, the array achieves an extensive optical storage dynamic range exceeding 106, and exceptionally high room-temperature mobility up to 406.7 cm2 V-1 s-1, four times higher than the International Roadmap for Device and Systems 2028 target. Additionally, the spectral range of each rippled-assisted optoelectronic processor covers visible to near-infrared (405 nm-940 nm), achieving function of motion detection and recognition.

LacNAc modification in bone marrow stromal cells enhances resistance of myelodysplastic syndrome cells to chemotherapeutic drugs.

Chemotherapeutic drugs are used routinely for treatment for myelodysplastic syndrome (MDS) patients but are ineffective in a substantial proportion of patients. Abnormal hematopoietic microenvironments, in addition to spontaneous characteristics of malignant clones, contribute to ineffective hematopoiesis. In our study, we found expression of enzyme ß1,4-galactosyltransferase 1 (ß4GalT1), which regulates N-acetyllactosamine (LacNAc) modification of proteins, is elevated in bone marrow stromal cells (BMSCs) of MDS patients, and also contributes to drug ineffectiveness through a protective effect on malignant cells. Our investigation of the underlying molecular mechanism revealed that ß4GalT1-overexpressing BMSCs promoted MDS clone cells resistant to chemotherapeutic drugs and also showed enhanced secretion of cytokine CXCL1 through degradation of tumor protein p53. Chemotherapeutic drug tolerance of myeloid cells was inhibited by application of exogenous LacNAc disaccharide and blocking of CXCL1. Our findings clarify the functional role of ß4GalT1-catalyzed LacNAc modification in BMSCs of MDS. Clinical alteration of this process is a potential new strategy that may substantially enhance effectiveness of therapies for MDS and other malignancies, by targeting a niche interaction.

Transfer of IGF2BP3 Through Ara-C-Induced Apoptotic Bodies Promotes Survival of Recipient Cells.

Cytosine arabinoside (Ara-C) has been the standard therapeutic agent for myelodysplastic syndromes (MDS) and adult acute myeloid leukemia (AML) patients for decades. Considerable progress has been made in development of new treatments for MDS/AML patients, but drug resistance remains a major clinical problem. Apoptotic bodies (ABs), produced by late apoptotic cells, can enclose bioactive components that affect cell-cell interactions and disease progression. We isolated and identified drug-induced ABs from Ara-C-tolerance cells. Treatment of sensitive cells with Ara-C-induced ABs resulted in Ara-C-resistant phenotype. We further investigated components and functions of Ara-C-induced ABs. Proteomics analysis in combination with mass spectrometry revealed that Ara-C-induced ABs carried numerous RNA-binding proteins, notably including insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). Delivery of AB-encapsulated IGF2BP3 promoted survival of recipient cells by activating PI3K-AKT and p42-44 MAPK pathways. High IGF2BP3 level in ABs from MDS/AML patient plasma was correlated with poor overall survival. Our findings demonstrate that AB-derived IGF2BP3 plays an essential role in acquired Ara-C resistance in MDS/AML patients, and is a potential therapeutic target for suppression of Ara-C resistance.

When Glycosylation Meets Blood Cells: A Glance of the Aberrant Glycosylation in Hematological Malignancies.

Among neoplasia-associated epigenetic alterations, changes in cellular glycosylation have recently received attention as a key component of hematological malignancy progression. Alterations in glycosylation appear to not only directly impact cell growth and survival, but also alter the adhesion of tumor cells and their interactions with the microenvironment, facilitating cancer-induced immunomodulation and eventual metastasis. Changes in glycosylation arise from altered expression of glycosyltransferases, enzymes that catalyze the transfer of saccharide moieties to a wide range of acceptor substrates, such as proteins, lipids, and other saccharides in the endoplasmic reticulum (ER) and Golgi apparatus. Novel glycan structures in hematological malignancies represent new targets for the diagnosis and treatment of blood diseases. This review summarizes studies of the aberrant expression of glycans commonly found in hematological malignancies and their potential mechanisms and defines the specific roles of glycans as drivers or passengers in the development of hematological malignancies.

Roles of ten-eleven translocation family proteins and their O-linked ß-N-acetylglucosaminylated forms in cancer development.

Members of the ten-eleven translocation (TET) protein family of which three mammalian TET proteins have been discovered so far, catalyze the sequential oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine which serve an important role in embryonic development and tumor progression. O-GlcNAcylation (O-linked ß-N-acetylglucosaminylation) is a reversible post-translational modification known to serve important roles in tumorigenesis and metastasis especially in hematopoietic malignancies such as myelodysplastic syndromes, chronic myelomonocytic leukemia and acute myeloid leukemia. O-GlcNAcylation activity requires only two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). OGT catalyzes attachment of GlcNAc sugar to serine, threonine and cytosine residues in proteins, while OGA hydrolyzes O-GlcNAc attached to proteins. Numerous recent studies have demonstrated that TETs can be O-GlcNAcylated by OGT, with consequent alteration of TET activity and stability. The present review focuses on the cellular, biological and biochemical functions of TET and its O-GlcNAcylated form and proposes a model of the role of TET/OGT complex in regulation of target proteins during cancer development. In addition, the present review provides directions for future research in this area.

[Effect of B4GALT1 on Proliferation of Its Co-cultured Human Acute Myeloid Leukemia Cell Line in Bone Marrow Stromal Cells].

OBJECTIVE: To investigate the effect of bone marrow stromal cell glycosyltransferase B4GALT1 expression on hematopoietic cell proliferation and its upstream regulation mechanism. METHODS: B4GALT1 was overexpressed in human bone marrow stromal cell line HS5, which was then co-cultured with acute myeloid leukemia cell line KG1a. And its effect on hematopoietic cell proliferation was detected by flow cytometry. Dual luciferase reporter assay, real-time PCR and Western blot were used to predict and validate upstream transcription factors that regulate stromal cell B4GALT1 expression. RESULTS: Overexpression of B4GALT1 in HS5 significantly promoted the proliferation of KG1a in the co-culture system. B4GALT1 expression in stromal cells positively correlated with upstream c-Jun expression, which was verified by JNK/c-Jun inhibitors. CONCLUSION: The differential expression of glycosyltransferases and their corresponding glycosylation in the hematopoietic microenvironment play an important role.

Multiple Roles of Glycans in Hematological Malignancies.

The three types of blood cells (red blood cells for carrying oxygen, white blood cells for immune protection, and platelets for wound clotting) arise from hematopoietic stem/progenitor cells in the adult bone marrow, and function in physiological regulation and communication with local microenvironments to maintain systemic homeostasis. Hematological malignancies are relatively uncommon malignant disorders derived from the two major blood cell lineages: myeloid (leukemia) and lymphoid (lymphoma). Malignant clones lose their regulatory mechanisms, resulting in production of a large number of dysfunctional cells and destruction of normal hematopoiesis. Glycans are one of the four major types of essential biological macromolecules, along with nucleic acids, proteins, and lipids. Major glycan subgroups are N-glycans, O-glycans, glycosaminoglycans, and glycosphingolipids. Aberrant expression of glycan structures, resulting from dysregulation of glycan-related genes, is associated with cancer development and progression in terms of cell signaling and communication, tumor cell dissociation and invasion, cell-matrix interactions, tumor angiogenesis, immune modulation, and metastasis formation. Aberrant glycan expression occurs in most hematological malignancies, notably acute myeloid leukemia, myeloproliferative neoplasms, and multiple myeloma, etc. Here, we review recent research advances regarding aberrant glycans, their related genes, and their roles in hematological malignancies. Our improved understanding of the mechanisms that underlie aberrant patterns of glycosylation will lead to development of novel, more effective therapeutic approaches targeted to hematological malignancies.

Altered susceptibility to apoptosis and N­glycan profiles of hematopoietic KG1a cells following co­culture with bone marrow­derived stromal cells under hypoxic conditions.

Mesenchymal stromal cells are an important component of the bone marrow microenvironment (niche), where they support hematopoiesis via direct cell­cell interactions with hematopoietic stem and progenitor cells, and by releasing soluble factors. Glycans, including N­glycans, are involved in numerous biological processes, including inflammation, cell­cell interactions, as well as cancer development and progression. Lectin­based microarray analysis has provided a powerful new tool in recent years, for the investigation of aberrantly expressed N­glycans and their functions in the bone marrow microenvironment. In the present study, we used an in vitro stromal/hematopoietic cell co­culture system to examine the effects of stromal­derived signals on apoptosis susceptibility of co­cultured KG1a hematopoietic cells under hypoxic (1% O2) conditions. MALDI­TOF/TOF­MS analysis was used for the comparative global profiling of N­glycans in KG1a cells and co­cultured KG1a cells under hypoxia. KG1a cells became more susceptible to p53­dependent apoptosis when co­cultured with HS27A human stromal cells (derived from normal bone marrow) under hypoxia. We observed enhanced levels of core­fucosylated N­glycans (catalyzed by FUT8), bisecting GlcNAc (catalyzed by MGAT3), and their corresponding genes in co­cultured cells. In addition we observed that overexpressing MGAT3 or FUT8 facilitated cell apoptosis in KG1a cells. Collectively, our data revealed the profiling of N­glycans in KG1a cells before and after stroma contact. Our findings and future functional studies of core­fucosylated N­glycans and bisecting GlcNAc, will improve our understanding of the bone marrow microenvironment.

A lectin-based isolation/enrichment strategy for improved coverage of N-glycan analysis.

Glycomics provides an increasingly useful research tool as the genomes and proteomes of more and more animal species are elucidated. In view of the general complexity and heterogeneity of glycans, improved depth-of-coverage and sensitivity are required for glycosylation analysis. In this study, we established the lectin-based isolation/enrichment strategy for total glycomic information. Specific lectins are added onto the filter to capture corresponding glycans prior to release of N-glycans by peptide N-glycosidase F (PNGase F). Non-bound glycans and bound glycans are released and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), respectively. Application of the strategy to chicken ovalbumin, normal mouse mammary epithelial cells (NMuMG), and human serum resulted in detection of 5, 6, and 11 additional N-glycan structures, respectively. The strategy facilitates identification of intact N-glycans in biological samples, and can be extended to detailed analysis of O-glycome or glycoproteome.

Quantitative analysis of glycans, related genes, and proteins in two human bone marrow stromal cell lines using an integrated strategy.

Altered expression of glycans is associated with cell-cell signal transduction and regulation of cell functions in the bone marrow micro-environment. Studies of this micro-environment often use two human bone marrow stromal cell lines, HS5 and HS27a, co-cultured with myeloid cells. We hypothesized that differential protein glycosylation between these two cell lines may contribute to functional differences in in vitro co-culture models. In this study, we applied an integrated strategy using genomic, proteomic, and functional glycomic techniques for global expression profiling of N-glycans and their related genes and enzymes in HS5 cells versus HS27a cells. HS5 cells had significantly enhanced levels of bisecting N-glycans (catalyzed by MGAT3 [ß-1,4-mannosyl-glycoprotein 4-ß-N-acetylglucosaminyltransferase]), whereas HS27a cells had enhanced levels of Galß1,4GlcNAc (catalyzed by ß4GalT1 [ß4-galactosyltransferase I]). This integrated strategy provides useful information regarding the functional roles of glycans and their related glycogenes and glycosyltransferases in the bone marrow microenvironment, and a basis for future studies of crosstalk among stromal cells and myeloma cells in co-culture.