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.     

Enzyme attached on polymeric micelles as a nanoscale reactor

Similar to what lipase does, a surface-active enzyme was developed by attaching peroxidase on combshaped polymaleic anhydride-alt-1-tetradecene (PMA-TD) in a microemulsion system composed of n-butyl acetate and buffer solution, and its catalytic characteristics of polyphenol synthesis were investigated in an aqueous solution. The modified peroxidase with PMA-TD tended to form self-assembled aggregates like micelles in the aqueous solution and could be concentrated at solvent/water interfaces without unfolding of the enzyme. The efficiency of conversion of 2,4-dichlorophenol to phenolic oligomers was approximately 2-fold improved with the modified peroxidase compared to native peroxidase. The K _m and V _max values for the modified peroxidase were 1.5-fold lower and 2-fold higher, respectively. The hydrodynamic diameter of the micelle on the modified peroxidase increased with the reaction time, indicating that phenolic products were accumulated in the hydrophobic interior of micelles. In addition, the molecular weight (MW) of phenolic polymers was much larger in the system with the modified peroxidase. These observations implied that the modified peroxidase with hydrophobic side chains formed micellar structures by solubilization of phenolic products and further polymerization reaction could occur in the hydrophobic interior of the micelles.     

Studies on the toxicity of pulp and paper mill effluents—I. Mutagenicity of the sediment samples derived from Kraft paper mills

Sediment samples collected at three different coastal points (Shinguu, Ooigawa and Tagonoura) were extracted with diethylether and then methanol. Each extract was separated into five fractions by high-speed liquid chromatography and they were submitted to mutagenic assay using B. subtilis and S. typhimurium and to GC-MS analysis.The ether fraction of sediment sample from Shinguu showed DNA damaging potency on B. subtilis and exhibited mutagenic effect on S. typhimurium TA 98, TA 100 and TA 1537. 2,4,6-Trichlorophenol, 3,4,5,6-tetrachloroguaiacol, dehydroabietic acid, pyrene and fluoranthene were mutagenic substances among 28 substances identified and tested.     

Stimulation of THP-1 Macrophages with LPS Increased the Production of Osteopontin-Encapsulating Exosome

Osteopontin (OPN) mediates bone remodeling and tissue debridement. The OPN protein is cleaved, but it is unclear how full-length (FL)-OPN or its cleaved form perform their biological activities in target cells. We, therefore, performed the molecular characterization of OPN in exosomes (Exo). The Exo were isolated from lipopolysaccharide (LPS)-stimulated phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages. The Exo were also isolated from PMA-differentiated THP-1 macrophages. The Exo were identified using the qNano multiple analyzer (diameter 59–315 nm) and western blotting with a CD9 antibody. LPS-stimulated cells produced more particles than non-stimulated cells. The presence of the FL or the cleaved form of OPN was confirmed using western blot analysis. A mixture of FL and cleaved OPN was also measured using an ELISA system (Ud-OPN) and their presence in the Exo was confirmed. Ud/FL ratios became low after LPS stimulation, indicating the enhanced encapsulation of FL-OPN in the Exo by LPS. These findings suggest that LPS stimulation of human macrophages facilitates the synthesis of FL-OPN, which is cleaved in cells or the Exo after release. These findings indicate that Exo is a suitable vehicle to transfer OPN to the target cells.     

A robust implicit state observer for multiple-input multiple-output uncertain systems

A new mathematical method of estimating the state for uncertain continuous-time multiple-input multiple-output minimum-phase (with respect to the relation between the disturbance and the output) dynamical systems with arbitrarily relative degrees is presented. For the systems with relative degree one, the state observer which is perfectly robust to disturbances is constructed by using only the input and output information. The estimating error of the state decays to zero exponentially. For the systems with higher relative degrees, the state observer is formulated for the first time, where the input and output information, and the a priori information of the upper and lower bounds of the disturbances are employed. In this case, the estimating error of the state can be controlled to be as small as is needed by the design parameters. The attraction of the proposed observers lies in their robustness to disturbances and insensitivity to the high-frequency noises accompanying the inputs. A design example and its simulation results are presented to illustrate the proposed algorithm.     

Preparation and characterization of nanoporous films derived from alicyclic copolyimides having pendent poly(propyleneglycol) groups

Nanoporous films were prepared with alicyclic copolyimides (coPIs) having polypropylene glycol (PPG) side chains by way of spontaneous phase separation in the film forming process and the subsequent thermal degradation of PPG moieties. PIs having various content (6.5, 11.9, 26.3, 52.7 wt%) and different length (M_w = 1.2 × 10³ and 2.4 × 10³) of PPG side chains were examined in order to clarify the relationship between chemical structure and pore characteristics. Nanopores were formed by heating the coPI films at 200 °C for 9 h under slightly reduced pressure. The size and the number of the pores observed by SEM varied depending on the content and molecular weight of PPG moieties. In many cases, the pore size was larger than those of the reported values for related aromatic copolyimide films. The dielectric constant of the nanoporous films ranged from 2.52 to 3.38.