Autocrine VEGF-B signaling maintains lipid synthesis and mitochondrial fitness to support T cell immune responses.

T cells rewire their metabolic activities to meet the demand of immune responses, but how to coordinate the immune response by metabolic regulators in activated T cells is unknown. Here, we identified autocrine VEGF-B as a metabolic regulator to control lipid synthesis and maintain the integrity of the mitochondrial inner membrane for the survival of activated T cells. Disruption of autocrine VEGF-B signaling in T cells reduced cardiolipin mass, resulting in mitochondrial damage, with increased apoptosis and reduced memory development.

Glutamine deprivation in glioblastoma stem cells triggers autophagic SIRT3 degradation to epigenetically restrict CD133 expression and stemness.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor, and glioblastoma stem cells (GSCs) are the primary cause of GBM heterogeneity, invasiveness, and resistance to therapy. Sirtuin 3 (SIRT3) is mainly localized in the mitochondrial matrix and plays an important role in maintaining GSC stemness through cooperative interaction with the chaperone protein tumor necrosis factor receptor-associated protein 1 (TRAP1) to modulate mitochondrial respiration and oxidative stress. The present study aimed to further elucidate the specific mechanisms by which SIRT3 influences GSC stemness, including whether SIRT3 serves as an autophagy substrate and the mechanism of SIRT3 degradation.

Rapid Prediction of Adulteration Content in Based on Data and Image Features Fusions from Near-Infrared Spectroscopy and Hyperspectral Imaging Techniques.

(AR) is an herb and food source with great economic, medicinal, and ecological value. (DC.) Koidz.

The value of deep learning-based computer aided diagnostic system in improving diagnostic performance of rib fractures in acute blunt trauma.

Background: To evaluate the value of a deep learning-based computer-aided diagnostic system (DL-CAD) in improving the diagnostic performance of acute rib fractures in patients with chest trauma.

Materials And Methods: CT images of 214 patients with acute blunt chest trauma were retrospectively analyzed by two interns and two attending radiologists independently firstly and then with the assistance of a DL-CAD one month later, in a blinded and randomized manner. The consensusdiagnosis of fib fracture by another two senior thoracic radiologists was regarded as reference standard.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging Findings of Infrapatellar Fat Pad Signal Abnormalities: Comparison Between Symptomatic and Asymptomatic Knee Osteoarthritis.

Rationale And Objectives: Infrapatellar fat pad (IPFP) proton density-weighted images (PdWI) hyperintense regions on MRI are an important imaging feature of knee osteoarthritis (KOA) and are thought to represent inflammation which may induce knee pain. The aim of the study was to compare the intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) findings of PdWI hyperintense regions of IPFP between symptomatic and asymptomatic KOA and to determine whether IVIM-DWI parameters can be used as an objective biomarker for symptomatic KOA.

Materials And Methods: In total, 84 patients with symptomatic KOA, 43 asymptomatic KOA persons, and 30 healthy controls with MRI were retrospectively reviewed.

The RSL3 Induction of Lung Adenocarcinoma Cell Ferroptosis by Inhibition of USP11 Activity and the NRF2-GSH Axis.

Antioxidant transcription factor NRF2 plays a pivotal role in cell ferroptosis. lung adenocarcinoma (LUAD) is a specific molecular subtype of -mutant LUAD. The activation of mutant in combination with the inactivation of and abnormally increases NRF2 expression, while high NRF2 confers LUAD cell resistance to ferroptosis.

Dysregulation of SIRT3 SUMOylation Confers AML Chemoresistance via Controlling HES1-Dependent Fatty Acid Oxidation.

Sirtuin 3 (SIRT3) deacetylase is a key regulator for chemoresistance in acute myeloid leukemia (AML) cells due to its capability of modulating mitochondrial metabolism and reactive oxygen species (ROS). SIRT3 is de-SUMOylated by SUMO-specific peptidase 1 (SENP1), which enhances its deacetylase activity. Therefore, dysregulation of SIRT3 SUMOylation may lead to fortified chemoresistance in AML.

Mitotic SENP3 activation couples with cGAS signaling in tumor cells to stimulate anti-tumor immunity.

Our previous studies show that the mitotic phosphorylation of SUMO-specific protease 3 (SENP3) can inhibit its de-SUMOylation activity in G2/M phase of the cell cycle. Inhibition of SENP3 plays a critical role in the correct separation of sister chromatids in mitosis. The mutation of mitotic SENP3 phosphorylation causes chromosome instability and promotes tumorigenesis.

SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization.

The metabolic program is altered during macrophage activation and influences macrophage polarization. Glutaminolysis promotes accumulation of α-ketoglutarate (αKG), leading to Jumonji domain-containing protein D3 (Jmjd3)-dependent demethylation at H3K27me3 during M2 polarization of macrophages. However, it remains unclear how αKG accumulation is regulated during M2 polarization of macrophages.

Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas.

Although oncogenicity of the stem cell regulator SOX9 has been implicated in many solid tumors, its role in lymphomagenesis remains largely unknown. In this study, SOX9 was overexpressed preferentially in a subset of diffuse large B-cell lymphomas (DLBCLs) that harbor IGH-BCL2 translocations. SOX9 positivity in DLBCL correlated with an advanced stage of disease.

Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development.

Metabolic programming and mitochondrial dynamics along with T cell differentiation affect T cell fate and memory development; however, how to control metabolic reprogramming and mitochondrial dynamics in T cell memory development is unclear. Here, we provide evidence that the SUMO protease SENP1 promotes T cell memory development via Sirt3 deSUMOylation. SENP1-Sirt3 signalling augments the deacetylase activity of Sirt3, promoting both OXPHOS and mitochondrial fusion.

P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint.

In response to DNA damage, p53-mediated signaling is regulated by protein phosphorylation and ubiquitination to precisely control G2 checkpoint. Here we demonstrated that protein SUMOylation also engaged in regulation of p53-mediated G2 checkpoint. We found that G2 DNA damage suppressed SENP3 phosphorylation at G2/M phases in p53-dependent manner.

NRF2 SUMOylation promotes de novo serine synthesis and maintains HCC tumorigenesis.

Nuclear factor erythroid-2 related factor 2 (NRF2) is a pivotal transcription factor that maintains cellular redox homeostasis and facilitates the development of malignant tumor phenotypes. At the molecular level, NRF2 promotes de novo serine synthesis and SUMOylation affects its function. Our results indicated that the SUMO1 acceptor site of NRF2 is the conserved lysine residue 110 (K110), and that NRF2 SUMOylation deficiency inhibited tumorigenesis in hepatocellular carcinoma (HCC).

Combined intravoxel incoherent motion diffusion-weighted MR imaging and magnetic resonance spectroscopy in differentiation between osteoporotic and metastatic vertebral compression fractures.

Purpose: Our purpose was to combine intravoxel incoherent motion diffusion-weighted MR imaging (IVIM-DWI) and magnetic resonance spectroscopy (MRS) to differentiate osteoporotic fractures from osteolytic metastatic vertebral compression fractures (VCFs).

Methods: A total of 70 patients with VCFs were included and divided into two groups, according to their causes of fractures based on pathological findings or clinical follow-up. All patients underwent conventional sagittal T1WI, T2WI, STIR, IVIM-DWI, and single-voxel MRS.

SENP1-Sirt3 Signaling Controls Mitochondrial Protein Acetylation and Metabolism.

Sirt3, as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolic adaption to various stresses. However, how to regulate Sirt3 activity responding to metabolic stress remains largely unknown. Here, we report Sirt3 as a SUMOylated protein in mitochondria.

SUMO-Specific Protease 1 Is Critical for Myeloid-Derived Suppressor Cell Development and Function.

Myeloid-derived suppressor cells (MDSC) can suppress immunity and promote tumorigenesis, and their abundance is associated with poor prognosis. In this study, we show that SUMO1/sentrin-specific peptidase 1 (SENP1) regulates the development and function of MDSC. SENP1 deficiency in myeloid cells promoted MDSC expansion in bone marrow, spleen, and other organs.

Synthesis of Oridonin Derivatives via Mizoroki-Heck Reaction and Click Chemistry for Cytotoxic Activity.

Background: Natural products (NPs) are evolutionarily chosen "privileged structures" that have a profound impact upon the anticancer drug discovery and development progress. However, the search for new drugs based on structure modification of NPs has often been hindered due to the tedious and complicated synthetic pathways. Fortunately, Mizoroki-Heck reaction and copper-catalyzed alkyne-azide cycloaddition (CuAAC) could provide perfect strategies for selective modification on NPs even in the presence of liable functionalities.

A retrospective study of SPECT/CT scans using SUV measurement of the normal pelvis with Tc-99m methylene diphosphonate.

Objective: To perform quantitative measurement based on the standardized uptake value (SUV) of Tc-99m methylene diphosphonate (MDP) in the normal pelvis using a single-photon emission tomography (SPECT)/computed tomography (CT) scanner.

Material And Methods: This retrospective study was performed on 31 patients with cancer undergoing bone SPECT/CT scans with 99mTc-MDP. SUVmax and SUVmean of the normal pelvis were calculated based on the body weight.

Mitotic Phosphorylation of SENP3 Regulates DeSUMOylation of Chromosome-Associated Proteins and Chromosome Stability.

Progression of mitotic cell cycle and chromosome condensation and segregation are controlled by posttranslational protein modifications such as phosphorylation and SUMOylation. However, how SUMO isopeptidases (SENP) regulate cell mitotic procession is largely unknown. Here, we demonstrate that precise phosphorylation of SENP3 during mitosis suppresses SENP3 deSUMOylation activity towards chromosome-associated proteins, including topoisomerase IIα (TopoIIα).

Senp2 regulates adipose lipid storage by de-SUMOylation of Setdb1.

One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is associated with many pathological conditions including hyperlipidemia, insulin resistance, and type 2 diabetes. In this study, we observed the overexpression of SUMO-specific protease 2 (Senp2) in adipose tissues during obesity.

SENP1 deficiency promotes ER stress-induced apoptosis by increasing XBP1 SUMOylation.

The transcription factor X box-binding protein 1 (XBP1) is a key component of the endoplasmic reticulum (ER) stress response. Recently, it has been reported that the spliced XBP1 (XBP1s), an activated XBP1 during ER stress, can be SUMOylated. Here, we identify Sentrin/SUMO-specific protease 1 (SENP1) as a specific de-SUMOylation protease for XBP1.