High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman’s correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.     

Effect of in-flight particle behavior on the morphology of flame sprayed Er2O3 splats

The morphology and microstructure of splats impact the comprehensive capability of a new coating methodology called chelate flame spraying (CFS). This study addresses the quantitative characterization of the spread morphologies of flame sprayed Er₂O₃ splats directly deposited under different spray conditions on aluminum alloy substrates with a mirror finish. The influence of the in-flight particle temperature and velocity, carrier gas type, and carrier gas ratio on the solidification mechanism of molten droplets was investigated. Image analysis methods were employed to identify single splats from the morphology observed with field-emission scanning electron microscopy (FE-SEM). In addition, Er₂O₃ films were synthesized on an Al–Mg alloy (A5052) substrate using N₂ or O₂ as the carrier gas. When O₂ was used as the carrier gas, 109-μm-thick films were deposited on the A5052 substrate. The cross-sectional porosity of the films was 3.8%. In contrast, films with 101-μm thickness were synthesized on the A5052 substrate when N₂ was used as the carrier gas. The cross-sectional porosity of these films was 13.8%. The results showed that the carrier gas type (N₂) and carrier gas ratio had a significant effect on the flattening behavior of the molten droplets. A spraying method combined with multidimensional modes is proposed to control the morphology of the splats.     

Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

The Function of Sialidase Revealed by Sialidase Activity Imaging Probe

Sialidase cleaves sialic acid residues from glycans such as glycoproteins and glycolipids. In the brain, desorption of the sialic acid by sialidase is essential for synaptic plasticity, learning and memory and synaptic transmission. BTP3-Neu5Ac has been developed for sensitive imaging of sialidase enzyme activity in mammalian tissues. Sialidase activity in the rat hippocampus detected with BTP3-Neu5Ac increases rapidly by neuronal depolarization. It is presumed that an increased sialidase activity in conjunction with neural excitation is involved in the formation of the neural circuit for memory. Since sialidase inhibits the exocytosis of the excitatory neurotransmitter glutamate, the increased sialidase activity by neural excitation might play a role in the negative feedback mechanism against the glutamate release. Mammalian tissues other than the brain have also been stained with BTP3-Neu5Ac. On the basis of information on the sialidase activity imaging in the pancreas, it was found that sialidase inhibitor can be used as an anti-diabetic drug that can avoid hypoglycemia, a serious side effect of insulin secretagogues. In this review, we discuss the role of sialidase in the brain as well as in the pancreas and skin, as revealed by using a sialidase activity imaging probe. We also present the detection of influenza virus with BTP3-Neu5Ac and modification of BTP3-Neu5Ac.     

Involvement of Cytokines in the Pathogenesis of Diabetic Macular Edema

Diabetic macular edema (DME) is a critical complication of diabetic retinopathy, a condition that arises from the breakdown of the blood–retinal barrier and the consequent increase in vascular permeability. Over the years, attempts have been made to treat DME by various approaches, including laser photocoagulation, steroid triamcinolone acetonide, and vitrectomy. However, treatment was unsatisfactory until research identified vascular endothelial growth factor (VEGF) as a factor in the pathogenesis of DME. Intraocular anti-VEGF agents show good efficacy in DME. Nevertheless, in some patients the condition recurs or becomes resistant to treatment, suggesting that other factors may be involved. Because inflammation and retinal hypoxia are seen in DME, research has examined the potential role of cytokines and other inflammatory mediators. In this review, we provide an overview of this research and describe feedback mechanisms that may represent a target for novel treatments.     

Supramolecular Zn(II)-Dipicolylamine-Azobenzene-Aminocyclodextrin-ATP Complex: Design and ATP Recognition in Water

Cyclodextrins (CyDs) are water-soluble host molecules possessing a nanosized hydrophobic cavity. In the realm of molecular recognition, this cavity is used not only as a recognition site but also as a reaction medium, where a hydrophobic sensor recognizes a guest molecule. Based on the latter concept, we have designed a novel supramolecular sensing system composed of Zn(II)-dipicolylamine metal complex-based azobenzene (1-Zn) and 3A-amino-3A-deoxy-(2AS,3AS)-γ-cyclodextrin (3-NH₂-γ-CyD) for sensing adenosine-5′-triphosphate (ATP). 1-Zn showed redshifts in the UV-Vis spectra and induced circular dichroism (ICD) only when both ATP and 3-NH₂-γ-CyD were present. Calculations of equilibrium constants indicated that the amino group of 3-NH₂-γ-CyD was involved in the formation of supramolecular 1-Zn/3-NH₂-γ-CyD/ATP. The Job plot of the ICD spectral response revealed that the stoichiometry of 1-Zn/3-NH₂-γ-CyD/ATP was 2:1:1. The pH effect was examined and 1-Zn/3-NH₂-γ-CyD/ATP was most stable in the neutral condition. The NOESY spectrum suggested the localization of 1-Zn in the 3-NH₂-γ-CyD cavity. Based on the obtained results, the metal coordination interaction of 1-Zn and the electrostatic interaction of 3-NH₂-γ-CyD were found to take place for ATP recognition. The “reaction medium approach” enabled us to develop a supramolecular sensing system that undergoes multi-point interactions in water. This study is the first step in the design of a selective sensing system based on a good understanding of supramolecular structures.     

Design,Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders

Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b , which was designed based on compound 1 , degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1 . These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.     

Evaluation of the containment vessel failure time from operator’s notifications during a severe accident

This paper aims at clarifying the potential and the limit of the method to surmise the timing of the containment vessel (CV) failure utilizing the Emergency Action Levels (EALs) issued as a nuclear operator’s notification in an early phase of the severe accident (SA). We analyzed the timings of the EALs issued in all kinds of the SA sequences of several PWR plant models by using the SA analysis code, MAAP. We found high correlations between the timing of SE41 (EAL issued at CV pressure of 0.5 design pressure) and the timing of the CV failure in the typical scenarios, e.g. over-pressure failures. We could therefore establish an evaluating method to estimate the time for a CV failure. This method has the potential to support the decision-making in nuclear emergency preparedness.