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.     

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4⁺ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.     

Double-action bending for eliminating springback in hat-shaped bending of advanced high-strength steel sheet

The International Journal of Advanced Manufacturing Technology - This paper presents a novel technology called ‘double-action bending (DAB)’ to eliminate springback in hat-shape forming...     

A Restart Control Method for Position Sensorless PMSM Drive Systems Without Potential Transformer for Railway Vehicle Traction

This paper proposes a restart control method for position sensorless PMSM drive systems without a potential transformer for railway vehicle traction. This method can estimate the initial rotor speed and position under coasting conditions over the entire speed range. The method can also be used when the back‐EMF voltage is higher than the inverter DC link voltage. The proposed method is verified by experiments using a 200‐kW PMSM.     

Application of multiple sensory evaluations to produce fermented beverages made from sole whey using Kluyveromyces marxianus

Various fermented whey-based beverages have been developed to reduce waste. However, approaches to increase the preference of whey-based beverages are required because of the low sensory acceptability of whey. Here, we identified the better starting material (whey type), between raw whey (RW) and demineralised whey (DMW), and determined the optimal initial concentration using multiple sensory evaluations to develop acceptable fermented beverages made from sole whey with pure cultured Kluyveromyces marxianus (i.e. without additional ingredients and processing methods). Acceptance tests showed that fermented beverages made from DMW were superior to RW as the starting material. The amounts of ethanol produced were 5.0%, 7.6% and 9.5% v/v from the different initial DMW concentrations of 10%, 15% and 20% w/v, respectively. We observed a significant positive correlation (r_s = 0.32, P < 0.05) between the assessment attributes, strength of taste as alcohol beverage and overall acceptability, indicating that higher concentrations of DMW yielded a more desirable product.     

Development of Selective TGR5 Ligands Based on the 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalene Skeleton

TGR5, a G-protein-coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N-(2-chlorophenyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC₅₀ value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia.     

Identification and Characterization of D‐Succinylase,and a Proposed Enzymatic Method for D‐Amino Acid Synthesis

Chiral amino acids are important intermediates for the pharmaceutical industry. We have developed a novel one‐pot enzymatic method for D ‐amino acid synthesis by the dynamic kinetic resolution of N‐succinyl‐dl ‐amino acids using D ‐succinylase (DSA) and N‐succinylamino acid racemase (NSAR, EC 4.2.1.113). The DSA from Cupriavidus sp. P4‐10‐C, which hydrolyzes N‐succinyl‐D ‐amino acids enantioselectively to their corresponding D ‐amino acids, was identified for the first time by screening soil microorganisms. Subsequently, the DSA gene was cloned and overexpressed in Escherichia coli. DSA was shown to comprise two subunits with molecular masses of 26 kDa and 60 kDa. Additionally, the NSAR gene from Geobacillus stearothermphilus NCA1503, which racemizes N‐succinylamino acids, was also cloned and overexpressed in E. coli. The highly purified DSA and NSAR prepared from each recombinant E. coli were characterized and used for D ‐amino acid synthesis. A one‐pot enzymatic method converted 100 mM N‐succinyl‐dl ‐phenylalanine to D ‐phenylalanine in 91.1% conversion with 86.7% ee. This novel enzymatic method may be useful for the industrial production of many D ‐amino acids.

     

Recognition and Excision Properties of 8‐Halogenated‐7‐Deaza‐2′‐Deoxyguanosine as 8‐Oxo‐2′‐Deoxyguanosine Analogues and Fpg and hOGG1 Inhibitors

Cellular DNA continuously suffers various types of damage, and unrepaired damage increases disease progression risk. 8‐Oxo‐2′‐deoxyguanine (8‐oxo‐dG) is excised by repair enzymes, and their analogues are of interest as inhibitors and as bioprobes for study of these enzymes. We have developed 8‐halogenated‐7‐deaza‐2′‐deoxyguanosine derivatives that resemble 8‐oxo‐dG in that they adopt the syn conformation. In this study, we investigated their effects on Fpg (formamidopyrimidine DNA glycosylase) and hOGG1 (human 8‐oxoguanine DNA N‐glycosylase 1). Relative to 8‐oxo‐dG, Cl‐ and Br‐deaza‐dG were good substrates for Fpg, whereas they were less efficient substrates for hOGG1. Kinetics and binding experiments indicated that, although hOGG1 effectively binds Cl‐ and Br‐deaza‐dG analogues with low K_m values, their lower k_cat values result in low glycosylase activities. The benefits of the high binding affinities and low reactivities of 8‐oxo‐dG analogues with hOGG1 have been successfully applied to the competitive inhibition of the excision of 8‐oxoguanine from duplex DNA by hOGG1.     

梦露大厦,密西沙加,加拿大

<正>现代主义有一句有名的宣言:建筑是居住的机器。但是我们必须发问,在机器及其所代表的社会基础发生了如此剧变的今天,我们应该怎样理解建筑?如果建筑正在远离工业,那么她更应该表达什么内容?与北美其他迅速发展的近郊城市一样,加拿大多伦多地区的密西沙加市也一直在努力寻找着自己的性格和定位。我们认为这是一个机会,她没有必