Mitochondrial DNA release via the mitochondrial permeability transition pore activates the cGAS-STING pathway, exacerbating inflammation in acute Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear. METHODS: We measured mtDNA and 2'3'-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining. RESULTS: KD patient serum exhibited increased mtDNA and 2'3'-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation. CONCLUSION: These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.

Modifying Cotton Fabric Properties by Controlling HPMC Viscosity Grade to Limit Ink Spreading and Penetration.

In cotton fabric inkjet printing, the spreading and penetration of the ink seriously damage printing resolution and color strength. In this study, hydroxypropyl methyl cellulose (HPMC) with varying viscosity grades (6, 30, 100, 400, and 4000 mPa·s) were used for fabric pretreatment to reduce the ink spreading and penetration. The results indicated that HPMC with a high viscosity grade enhanced the ability of pretreatment paste to form a continuous HPMC film on the fiber surface. A continuous film could greatly increase the hydrophobicity of the fabric, thereby restricting the spreading and penetration of ink. Meanwhile, ink migration was also limited by the paste connected to the fibers and the swelling of the film, which was more significant at higher HPMC viscosity grades. However, the increase of the HPMC viscosity grade was not conducive to dye fixation. Additionally, HPMC with a viscosity grade of 100 mPa·s was considered a reasonable choice, which could improve printing resolution and color strength in industrial applications. This research provides a new approach for optimizing pretreatment paste to achieve high-quality printed products.

CircBIRC6 facilitates the malignant progression via miR-488/GRIN2D-mediated CAV1-autophagy signal axis in gastric cancer.

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.

Investigation on improvement of enantioseparation based on clindamycin phosphate by chiral deep eutectic solvents in capillary electrophoresis.

In this work, the potential synergetic effect between deep eutectic solvents and an antibiotic chiral selector (clindamycin phosphate) for enantioseparation was investigated in capillary electrophoresis. We synthesized a series of deep eutectic solvents with choline chloride as hydrogen bond acceptor and three α-hydroxyl acids (l-lactic acid, l-malic acid, and l-tartaric acid) as hydrogen bond donors. Compared to the single clindamycin phosphate separation system, significantly improved separations of model drugs were observed in several synergetic systems. Compared to deep eutectic solvents with a single hydrogen bond donor, deep eutectic solvents with mixed-type hydrogen bond donors were superior. The influences of several key parameters including the type and proportion of organic modifier, clindamycin phosphate concentrations, deep eutectic solvents concentrations, and buffer pH were investigated in detail. The mechanism of the enhanced separations in deep eutectic solvents systems was investigated by means of electroosmotic flow analysis, nuclear magnetic resonance analysis, and molecular modeling. It was the first time that the synergetic systems between deep eutectic solvents and antibiotic chiral selector were established in capillary electrophoresis, and these deep eutectic solvents were demonstrated to have a good synergetic effect with clindamycin phosphate for enantioseparation.

Acute invasive fungal sinusitis with orbital tip syndrome in patients on long-term use of ruxolitinib: a case report.

INTRODUCTION: A long-term ruxolitinib-treated patient with primary myelofibrosis, who was co-infected with aspergillosis infection during a short period, developed acute invasive fungal sinusitis with consequent orbit apex syndrome. This may be the first reported case in the world. This is a 75-year-old Chinese man; the patient was admitted with 2-month history of headache accompanied by numbness and 8-day history of vision loss. The preliminary clinical diagnoses were suspected acute invasive fungal sinusitis or adenoid cystic carcinoma. We performed endoscopic debridement and antifungal therapy. About 90 days after surgery, magnetic resonance imaging revealed no recurrence of pathological tissue. CONCLUSION: One of the bases for the occurrence of invasive fungal sinusitis may be the patient's long-term use of ruxolitinib for essential thrombocythemia. Some patients with invasive fungal sinuses have atypical nasal symptoms and are referred to the corresponding departments with eye and headache as the first symptoms. It is suggested that enhanced magnetic resonance imaging should be performed at an early stage. Surgical treatment in combination with antifungal and enhanced immunotherapy can effectively prevent the spread of infection and reduce the risk of death.

Alternating projection combined with fast gradient projection (FGP-AP) method for intensity-only measurement optical diffraction tomography in LED array microscopy.

Optical diffraction tomography (ODT) is a powerful label-free measurement tool that can quantitatively image the three-dimensional (3D) refractive index (RI) distribution of samples. However, the inherent "missing cone problem," limited illumination angles, and dependence on intensity-only measurements in a simplified imaging setup can all lead to insufficient information mapping in the Fourier domain, affecting 3D reconstruction results. In this paper, we propose the alternating projection combined with the fast gradient projection (FGP-AP) method to compensate for the above problem, which effectively reconstructs the 3D RI distribution of samples using intensity-only images captured from LED array microscopy. The FGP-AP method employs the alternating projection (AP) algorithm for gradient descent and the fast gradient projection (FGP) algorithm for regularization constraints. This approach is equivalent to incorporating prior knowledge of sample non-negativity and smoothness into the 3D reconstruction process. Simulations demonstrate that the FGP-AP method improves reconstruction quality compared to the original AP method, particularly in the presence of noise. Experimental results, obtained from mouse kidney cells and label-free blood cells, further affirm the superior 3D imaging efficacy of the FGP-AP method.