Thymocyte selection-associated high mobility group box protein (TOX) is regarded as a crucial transcription factor involved in T cell exhaustion in acute myeloid leukemia (AML). Previous studies have identified aberrant TOX expression as a major oncogenic driver in hematologic malignancies, indicating that TOX may potentially be both an immune biomarker and an immunotherapy target. However, due to heterogeneity in the distribution patterns of TOX and its correlation with clinical prognosis, the mechanism underlying TOX-mediated tumor immune responses remains unclear.
View Article and Find Full Text PDFLack of biopsies after treatment, especially in solid tumors, restricts the understanding of chimeric antigen receptor (CAR)-T cells -related characteristic in vivo, thus hindering the development of strategies to improve CAR-T cells efficacy. Here, we applied nineteen individual single-cell RNA sequencing (scRNA-seq) data from clinical samples of digestive cancers to explore the characteristics of tumor-infiltrating T cells (TILs) to identify effective targets which might be benefit for enhancing the function of CAR-T cells. The data showed that natural killer cell granule protein 7 (NKG7) was overexpressed in TILs and positively associated with anti-PD1 or anti-CTLA4 therapy in digestive cancers.
View Article and Find Full Text PDFAs urbanization speeds up, the concept of healthy cities is receiving more focus. This article compares Chongzuo and Nanning in Guangxi with Beijing to assess the development gaps in cities in Guangxi. An indicator system for healthy cities was designed from six dimensions-healthy economy, healthy population, healthy healthcare, healthy environment, healthy facilities, and healthy transportation-and 26 secondary indicators, which were selected from 2005 to 2022, and an improved factor analysis was used to synthesize a healthy city index (HCI).
View Article and Find Full Text PDFGlyphosate as an effective broad-spectrum herbicide is frequently detected in various water and soil resources. Given the ubiquity of β-MnO and δ-MnO colloids in groundwater and soil, the abiotic removal of glyphosate by MnO colloids was investigated. β-MnO colloids exhibited superior glyphosate removal efficiency, up to 37%, compared to 21% for δ-MnO colloids at a pH of 4.
View Article and Find Full Text PDFPolyketides are natural products synthesized by polyketide synthases (PKSs), where acyltransferase (AT) domains play a crucial role in selection of extender units. Engineering of AT domains enables the site-specific incorporation of non-natural extender units, leading to generation of novel derivatives. Here, we determined the crystal structures of AT domains from the fifth module of tylosin PKS (TylAT5) derived from Streptomyces fradiae and the eighth module of spinosad PKS (SpnAT8) derived from Saccharopolyspora spinosa, and combined them with molecular dynamics simulations and enzyme kinetic studies to elucidate the molecular basis of substrate selection.
View Article and Find Full Text PDFThe recombination of charges and thermal excitation of carriers at the interface between methylammonium lead iodide perovskite (PVK) and the carbon electrode are crucial factors that affect the optoelectronic performance of carbon-based hole transport layer (HTL)-free perovskite photodetectors. In this work, a method was employed to introduce SnS quantum dots (QDs) on the back surface of perovskite, which passivated the defect states on the back surface of perovskite and addressed the energy-level mismatch issue between perovskite and carbon electrode. Performance testing of the QDs and the photodetector revealed that SnS QDs possess energy-level structures that are well matched with perovskite and have high absorption coefficients.
View Article and Find Full Text PDFBasic research shows that flavonoids have anti-inflammatory effects that influence rheumatoid arthritis (RA) in rats. Investigating potential dietary interventions for RA helps prevent the onset and progression of the disease. Clinical evidence on the association of flavonoid and subclass intake with RA is lacking.
View Article and Find Full Text PDFModulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed.
View Article and Find Full Text PDFObjective: This study explored the dynamic functional connective (DFC) alterations in patients with rheumatoid arthritis (RA) and investigated the correlation between the neuropsychiatric symptoms, peripheral inflammation and DFC alterations.
Method: Using resting-state functional MRI, we investigated the DFC based on spatial independent component analysis and sliding window method for 30 patients with RA and 30 healthy controls (HCs). The Spearman correlation was calculated between aberrant DFC alterations, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HAD), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR).
Background: Cognitive deficits are common in rheumatoid arthritis (RA) patients, but the mechanisms remain unclear. We investigated the effective connectivity and structural alterations of the core brain regions in RA patients with cognitive impairment.
Methods: Twenty-four female patients with RA and twenty-four healthy controls were enrolled.
Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation (VISTA), programmed cell death 1 (PD-1), T cell immunoglobulin and mucin-domain-containing-3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis.
View Article and Find Full Text PDFWith the success of immune checkpoint inhibitors (ICI), such as anti- programmed death-1 (PD-1) antibody for solid tumors and lymphoma immunotherapy, a number of clinical trials with ICIs have been attempted for acute myeloid leukemia (AML) immunotherapy; however, limited clinical efficacy has been reported. This may be due to the heterogeneity of immune microenvironments and various degrees of T cell exhaustion in patients and may be involved in the IFN-γ pathway. In this study, we first characterized the percentage of PD-1+ and T cell immunoglobulin mucin-domain-containing-3 (Tim-3) +IFN-γ+ T cells in peripheral blood (PB) in AML compared with healthy individuals (HIs) by flow cytometry and further discussed the possibility of the reversal of T cell exhaustion to restore the secretion capacity of cytokines in T cells in AML based on blockade of PD-1 or Tim-3 (anti-PD-1 and anti-Tim-3 antibody) in vitro using a cytokine protein chip.
View Article and Find Full Text PDFRhamnose methylation of spinosyn critical for insecticidal activity is orchestrated by substrate specificity of three S-adenosyl-L-methionine (SAM) dependent methyltransferases (MTs). Previous in vitro enzymatic assays indicate that 3'-O-MT SpnK accepts the rhamnosylated aglycone (RAGL) and 2'-O-methylated RAGL as substrates, but does not tolerate the presence of a methoxy moiety at the O-4' position of the rhamnose unit. Here we solved the crystal structures of apo and ligand-bound SpnK, and used molecular dynamic (MD) simulations to decipher the molecular basis of substrate specificity.
View Article and Find Full Text PDFObjective: To identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and assess the relation between visuospatial dysfunction and disease activity in RA patients using mental rotation task (MRT)-based functional magnetic resonance imaging (fMRI).
Methods: A total of 27 RA patients (11 in remission, 16 in active) and 27 well-matched controls were enrolled. The visuospatial function of the subjects was measured by MRT.
Antimony (Sb) is a toxic and carcinogenic element that often enters soil in the form of antimony trioxide (SbO) and coexists with manganese (Mn) in weakly alkaline conditions. Mn oxides such as birnessite have been found to promote the oxidative dissolution of SbO, but few researches concerned the co-transformations of SbO and Mn(II) in environment. This study investigated the mutual effect of abiotic oxidation of Mn(II) and the coupled oxidative dissolution of SbO.
View Article and Find Full Text PDFThe reliable viscoelastic characterization and prediction of micellar solution is still required in industrial applications of the solution, e.g., in surfactant flooding and pharmaceuticals.
View Article and Find Full Text PDFV-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is considered as an immunosuppressive factor and potential therapeutic target for anticancer therapy. However, little is known about VISTA expression and its role in immunosuppression in multiple myeloma (MM). In this study, VISTA expression and co-expression with programmed cell death receptor-1 (PD-1), T cell immunoglobulin mucin-domain-containing-3 (Tim-3), and T cell immunoglobulin and ITIM domain (TIGIT) in CD3+, CD4+, CD8+, and regulatory T (Treg) cells were analyzed in patients with MM by multi-color fluorescent flow cytometry of peripheral blood (PB) and bone marrow (BM) samples from 36 patients with MM and compared to 36 PB samples and 10 BM samples from healthy individuals (HIs), which served as controls.
View Article and Find Full Text PDFExperimental viscoelastic data and the corresponding theoretical analysis of corn starch paste in the past 30 years indicate an evident deficiency of the viscoelastic characterization of the paste. The purposes of the study are to check the capability of a recent model on describing the viscoelasticity of the paste and to improve the viscoelastic analysis. The linear viscoelastic property; the steady shear viscosity and the first normal stress difference () of a cross-linked waxy corn starch paste mixed with sucrose experimentally reported in 2003 were characterized with a structuralized viscoelastic constitutive equation in the present paper.
View Article and Find Full Text PDFMany studies have confirmed groundwater phosphorus (P) enrichment by anthropogenic and geogenic sources. However, the effects of colloidal iron (Fe) and manganese (Mn) on the groundwater P distribution remain poorly-understood. This study investigated the spatial distribution of three forms of Fe, Mn, and P (particulate, colloidal, and truly soluble) in aquifers based on groundwater monitoring data and sediment core samples for the Jianghan Plain.
View Article and Find Full Text PDFThe error caused by pseudo-midpoint effect in the use of the Moody chart was analyzed. The pseudo-midpoint effect appears in the linear interpolation method usually used to read the Moody chart. The maximum of the error is about 4%, which is significantly lower than the 15% accuracy of the chart in the literature.
View Article and Find Full Text PDFA new species of Dalyelliidae, Wang and You, is described based on material collected in southern China through an integrative approach combining morphological, histological, and molecular (18S and 28S rDNA) data. sp. nov.
View Article and Find Full Text PDFPrevious studies have shown increased aberrant expression of immune checkpoint (IC) proteins, such as programmed cell death receptor-1 (PD-1) and T cell immunoglobulin mucin-domain-containing-3 (Tim-3) on T cells from patients with multiple myeloma (MM), which result in T cell exhaustion and dysfunction. However, little is known about the mechanism regulating aberrant IC protein expression. In this study, we analyzed the expression of TOX (thymocyte selection-associated HMG BOX), a crucial transcription factor involved in T cell exhaustion, and its co-expression with PD-1, Tim-3, and CD244 in T cell subsets by multi-color fluorescent flow cytometry in peripheral blood (PB) and bone marrow (BM) samples from patients with MM.
View Article and Find Full Text PDFThe release of residual ammonium (RA) leaching agent from weathered crust elution-deposited rare earth tailings would cause serious environmental pollution, and it was necessary to efficiently remove it from the ore body before the mine closure. In this study, occurrence states of the RA were determined and dynamic elution of RA from rare earth tailings by using magnesium chloride as eluent was investigated. Effects of initial concentration, pH, flow rate, and particle size on the ammonium removal efficiency were investigated, and variations of ammonium occurrence states before and after elution were determined.
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