Oculocerebrorenal syndrome of Lowe (OCRL) controls leukemic T-cell survival by preventing excessive PI(4,5)P hydrolysis in the plasma membrane.

T-cell acute lymphoblastic leukemia (T-ALL) is one of the deadliest and most aggressive hematological malignancies, but its pathological mechanism in controlling cell survival is not fully understood. Oculocerebrorenal syndrome of Lowe is a rare X-linked recessive disorder characterized by cataracts, intellectual disability, and proteinuria. This disease has been shown to be caused by mutation of oculocerebrorenal syndrome of Lowe 1 (OCRL1; OCRL), encoding a phosphatidylinositol 4,5-bisphosphate [PI(4,5)P] 5-phosphatase involved in regulating membrane trafficking; however, its function in cancer cells is unclear.

An acquired phosphatidylinositol 4-phosphate transport initiates T-cell deterioration and leukemogenesis.

Lipid remodeling is crucial for malignant cell transformation and tumorigenesis, but the precise molecular processes involved and direct evidences for these in vivo remain elusive. Here, we report that oxysterol-binding protein (OSBP)-related protein 4 L (ORP4L) is expressed in adult T-cell leukemia (ATL) cells but not normal T-cells. In ORP4L knock-in T-cells, ORP4L dimerizes with OSBP to control the shuttling of OSBP between the Golgi apparatus and the plasma membrane (PM) as an exchanger of phosphatidylinositol 4-phosphate [PI(4)P]/cholesterol.

Loss of miR-31-5p drives hematopoietic stem cell malignant transformation and restoration eliminates leukemia stem cells in mice.

Leukemia stem cells (LSCs) propagate leukemia and are responsible for the high frequency of relapse of treated patients. The ability to target LSCs remains elusive, indicating a need to understand the underlying mechanism of LSC formation. Here, we report that miR-31-5p is reduced or undetectable in human LSCs compared to hematopoietic stem progenitor cells (HSPCs).

BF group chelated AIE fluorescent probe for polarity mapping of lipid droplets in cells and in vivo.

Lipid droplets (LDs), are multi-functional organelles with the storage of neutral lipids and proteins, participating in various of physiological processes. However, abnormal of LDs in morphology and numbers always lead to multiple diseases, including cancer, viral infection, obesity, inflammation. To better understand the physiological function of LDs in living cells, we designed two new fluorescent probes LDs-CA and LDs-BCA based on the triphenylamine and coumarin fluorophores to monitor LDs polarity and numbers variation in this work.

A non-peptide probe for detecting chymotrypsin activity based on protection-deprotection strategy in living systems.

Chymotrypsin (CHT) plays a vital role in the metabolism of organisms and affects cell proliferation and apoptosis. Abnormal levels of CHT will lead to a variety of diseases, such as inflammatory arthritis, diabetes, pharyngitis, indigestion, and pancreatic cancer. Therefore, it is significant to design an effective method for the detection of CHT in living systems.

A coumarin-based TICT fluorescent probe for real-time fluorescence lifetime imaging of mitochondrial viscosity and systemic inflammation .

Systemic inflammation, linked with abnormal mitochondrial viscosity, is reported to be associated with cerebro-cardiovascular disease and Alzheimer's disease. Therefore, it is of great significance to detect the mitochondrial viscosity to indicate the inflammatory signal . Considering the strategies of fluorescent molecular rotors (FMRs) and fluorescence lifetime imaging microscopy (FLIM), we have rationally designed a novel mitochondrial viscosity-specific fluorescent probe Mito-VCI, based on coumarin fluorophores with benzo[]indolium as the rotor group.

ORP4L Extracts and Presents PIP from Plasma Membrane for PLCβ3 Catalysis: Targeting It Eradicates Leukemia Stem Cells.

Leukemia stem cells (LSCs) are a rare subpopulation of abnormal hematopoietic stem cells (HSCs) that propagates leukemia and are responsible for the high frequency of relapse in therapies. Detailed insights into LSCs' survival will facilitate the identification of targets for therapeutic approaches. Here, we develop an inhibitor, LYZ-81, which targets ORP4L with high affinity and specificity and selectively eradicates LCSs in vitro and in vivo.

OSBP-related protein 4L promotes phospholipase Cβ3 translocation from the nucleus to the plasma membrane in Jurkat T-cells.

Phosphoinositide phospholipases C (PLCs) are a family of eukaryotic intracellular enzymes with important roles in signal transduction. In addition to their location at the plasma membrane, PLCs also exist within the cell nucleus where they are stored. We previously demonstrated that OSBP-related protein 4L (ORP4L) anchors cluster of differentiation 3ϵ (CD3ϵ) to the heterotrimeric G protein subunit (Gα) to control PLCβ3 relocation and activation.

Hierarchical Assembly of a {Co} Cluster from Two Vertex-Fused {Co} Clusters and Their Single-Molecule Magnetism.

We present the synthesis, structural characterization, and magnetic properties of two high-nuclearity cobalt clusters formulated as [Co(μ-OH)(μ-Cl)(dpbt)(ptd)Cl][Co(HO)Cl]·(CH)CHOH (1) and [Co(μ-OH)(μ-Cl)(dpbt)(ptd)Cl]·2CHCHOH (2), respectively (Hdpbt = 5,5'-bis(pyridin-2-yl)-3,3'-bis(1,2,4-triazole) and Hptd = 3-(pyridin-2-yl)-1,2,4-triazine-5,6-diol). Compound 1 is composed of an inner [Co(μ-OH)(μ-Cl)] cubane and an outer [Co(dpbt)(ptd)Cl] defective adamantane. Compound 2 reveals a giant {Co} cluster possessing a dual-[Co] skeleton from 1.

Oxysterol-binding protein-related protein 4L promotes cell proliferation by sustaining intracellular Ca2+ homeostasis in cervical carcinoma cell lines.

Oxsterol binding protein-related protein 4 (ORP4) is essential for cell proliferation, but the underlying mechanism is unclear. ORP4 is expressed as three variants, ORP4L, ORP4M and ORP4S. Here, we reported that silencing of ORP4L with specific small interfering RNA (siRNA) inhibited the proliferation of human cervical cancer cell lines C33A, HeLa and CaSki, the reverse effect being observed in ORP4L overexpressing cells.

Efficient production of l-lactic acid by an engineered Thermoanaerobacterium aotearoense with broad substrate specificity.

Background: Efficient conversion of lignocellulosic biomass to optically pure lactic acid is a key challenge for the economical production of biodegradable poly-lactic acid. A recently isolated strain, Thermoanaerobacterium aotearoense SCUT27, is promising as an efficient lactic acid production bacterium from biomass due to its broad substrate specificity. Additionally, its strictly anaerobic and thermophilic characteristics suppress contamination from other microoragnisms.

Disruption of lactate dehydrogenase through homologous recombination to improve bioethanol production in Thermoanaerobacterium aotearoense.

To enhance ethanol production in Thermoanaerobacterium aotearoense, the lactate dehydrogenase (ldh) gene, which is responsible for lactic acid production in a key branch pathway, was successfully disrupted via homologous recombination. ldh-up and ldh-down were designed and amplified based on JW/SL-YS485-AY 278026, and they were subsequently used as homologous fragments with an inserted erythromycin resistance gene to construct the targeted vector based on pBLUESCRIPT II SK(+). Southern hybridization and PCR-based assay definitely confirmed that the ldh gene in the Δldh mutant was disrupted by the insertion of the erythromycin resistance gene.

Increase of urinary concentrations of 8-hydroxy-2'-deoxyguanosine in diesel exhaust emission inspector exposed to polycyclic aromatic hydrocarbons.

Purpose: The objectives of this study were to explore the factors influencing urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in diesel engine exhaust emission inspectors (inspectors), the association between polycyclic aromatic hydrocarbons (PAHs) exposure and fine particulate matter (PM(2.5)) levels in diesel exhaust particles (DEPs), and the PAHs exposure levels in diesel vehicle emission inspection stations (inspection stations).

Methods: Twenty-eight inspectors and a control group of thirty-eight individuals matched by age and gender were recruited for this study.

High efficiency hydrogen production from glucose/xylose by the ldh-deleted Thermoanaerobacterium strain.

A strictly anaerobic, thermoacidophilic, H(2)-producing bacterium was isolated and designated as Thermoanaerobacterium aotearoense. The optimized cultivation conditions for H(2) production are 55 degrees C, pH 6.5 and 10gl(-1) of glucose or xylose.